ES2941630T3 - Forma cristalina de sulfato de hidrógeno de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida - Google Patents
Forma cristalina de sulfato de hidrógeno de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida Download PDFInfo
- Publication number
- ES2941630T3 ES2941630T3 ES20169707T ES20169707T ES2941630T3 ES 2941630 T3 ES2941630 T3 ES 2941630T3 ES 20169707 T ES20169707 T ES 20169707T ES 20169707 T ES20169707 T ES 20169707T ES 2941630 T3 ES2941630 T3 ES 2941630T3
- Authority
- ES
- Spain
- Prior art keywords
- trka
- crystalline form
- trk
- cancer
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 title abstract description 28
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title description 63
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 218
- 201000011510 cancer Diseases 0.000 claims abstract description 132
- 208000002193 Pain Diseases 0.000 claims abstract description 99
- 230000036407 pain Effects 0.000 claims abstract description 83
- 238000011282 treatment Methods 0.000 claims abstract description 66
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 14
- 206010061218 Inflammation Diseases 0.000 claims abstract description 13
- 230000004054 inflammatory process Effects 0.000 claims abstract description 13
- 238000013519 translation Methods 0.000 claims abstract description 9
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 8
- 206010001935 American trypanosomiasis Diseases 0.000 claims abstract description 7
- 208000024699 Chagas disease Diseases 0.000 claims abstract description 7
- 101100517381 Rattus norvegicus Ntrk1 gene Proteins 0.000 claims description 172
- 101100261976 Drosophila melanogaster trk gene Proteins 0.000 claims description 158
- 101100537955 Schizosaccharomyces pombe (strain 972 / ATCC 24843) trk1 gene Proteins 0.000 claims description 158
- 108090000623 proteins and genes Proteins 0.000 claims description 107
- 230000014509 gene expression Effects 0.000 claims description 90
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 82
- 101150111783 NTRK1 gene Proteins 0.000 claims description 81
- 230000000694 effects Effects 0.000 claims description 80
- 230000008482 dysregulation Effects 0.000 claims description 66
- 230000004927 fusion Effects 0.000 claims description 50
- 101150056950 Ntrk2 gene Proteins 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 230000035772 mutation Effects 0.000 claims description 38
- 108700026220 vif Genes Proteins 0.000 claims description 32
- 108020001507 fusion proteins Proteins 0.000 claims description 30
- 102000037865 fusion proteins Human genes 0.000 claims description 30
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 24
- 230000004913 activation Effects 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 230000002018 overexpression Effects 0.000 claims description 10
- 230000003321 amplification Effects 0.000 claims description 9
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 9
- 230000003831 deregulation Effects 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- 230000002759 chromosomal effect Effects 0.000 claims description 3
- 102200049395 rs2070863 Human genes 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- PXHANKVTFWSDSG-QLOBERJESA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 PXHANKVTFWSDSG-QLOBERJESA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 101
- 210000004027 cell Anatomy 0.000 description 75
- 238000000034 method Methods 0.000 description 73
- 239000000203 mixture Substances 0.000 description 67
- 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 60
- 239000000523 sample Substances 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- 101000596894 Homo sapiens High affinity nerve growth factor receptor Proteins 0.000 description 54
- 239000000243 solution Substances 0.000 description 50
- 239000003814 drug Substances 0.000 description 46
- 238000003556 assay Methods 0.000 description 45
- 150000003839 salts Chemical class 0.000 description 41
- 239000007787 solid Substances 0.000 description 41
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 36
- 238000002360 preparation method Methods 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 33
- 101150117329 NTRK3 gene Proteins 0.000 description 32
- 239000013078 crystal Substances 0.000 description 32
- 239000003112 inhibitor Substances 0.000 description 30
- -1 4-methylpiperidinyl Chemical group 0.000 description 29
- 201000010099 disease Diseases 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000000843 powder Substances 0.000 description 27
- 239000000725 suspension Substances 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 26
- 208000004296 neuralgia Diseases 0.000 description 23
- 239000003826 tablet Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000008186 active pharmaceutical agent Substances 0.000 description 22
- 108700024394 Exon Proteins 0.000 description 21
- 238000007792 addition Methods 0.000 description 21
- 108010025020 Nerve Growth Factor Proteins 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 230000005764 inhibitory process Effects 0.000 description 20
- 230000001105 regulatory effect Effects 0.000 description 20
- 238000002411 thermogravimetry Methods 0.000 description 20
- 101000850794 Homo sapiens Tropomyosin alpha-3 chain Proteins 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 238000001907 polarising light microscopy Methods 0.000 description 19
- 238000010384 proximity ligation assay Methods 0.000 description 19
- 230000008859 change Effects 0.000 description 18
- 230000037430 deletion Effects 0.000 description 17
- 238000012217 deletion Methods 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 229940124597 therapeutic agent Drugs 0.000 description 17
- 239000000463 material Substances 0.000 description 15
- 208000021722 neuropathic pain Diseases 0.000 description 15
- 238000001179 sorption measurement Methods 0.000 description 15
- 239000012535 impurity Substances 0.000 description 14
- 208000005615 Interstitial Cystitis Diseases 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- 108091000080 Phosphotransferase Proteins 0.000 description 12
- 201000005249 lung adenocarcinoma Diseases 0.000 description 12
- 102000020233 phosphotransferase Human genes 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000002775 capsule Substances 0.000 description 11
- 230000001684 chronic effect Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 230000037361 pathway Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 206010009944 Colon cancer Diseases 0.000 description 10
- 102000015336 Nerve Growth Factor Human genes 0.000 description 10
- 102000007072 Nerve Growth Factors Human genes 0.000 description 10
- 238000002441 X-ray diffraction Methods 0.000 description 10
- 238000007906 compression Methods 0.000 description 10
- 230000006835 compression Effects 0.000 description 10
- 229940053128 nerve growth factor Drugs 0.000 description 10
- 238000007481 next generation sequencing Methods 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 230000011664 signaling Effects 0.000 description 10
- 238000001356 surgical procedure Methods 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 208000000094 Chronic Pain Diseases 0.000 description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000001154 acute effect Effects 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 8
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- 101001003584 Homo sapiens Prelamin-A/C Proteins 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 206010065390 Inflammatory pain Diseases 0.000 description 8
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 8
- 238000010240 RT-PCR analysis Methods 0.000 description 8
- 206010039491 Sarcoma Diseases 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 8
- 208000005298 acute pain Diseases 0.000 description 8
- 238000001574 biopsy Methods 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 8
- 239000008108 microcrystalline cellulose Substances 0.000 description 8
- 210000004940 nucleus Anatomy 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229960003787 sorafenib Drugs 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000005945 translocation Effects 0.000 description 8
- FTNWXGFYRHWUKG-UHFFFAOYSA-N triflupromazine hydrochloride Chemical compound [H+].[Cl-].C1=C(C(F)(F)F)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 FTNWXGFYRHWUKG-UHFFFAOYSA-N 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 7
- 208000008035 Back Pain Diseases 0.000 description 7
- 208000035473 Communicable disease Diseases 0.000 description 7
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 7
- 206010029240 Neuritis Diseases 0.000 description 7
- 102100026531 Prelamin-A/C Human genes 0.000 description 7
- 206010045515 Undifferentiated sarcoma Diseases 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 238000000099 in vitro assay Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- 230000005855 radiation Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 208000022810 undifferentiated (embryonal) sarcoma Diseases 0.000 description 7
- NCXSNNVYILYEBC-SNVBAGLBSA-N (2r)-2-(2,5-difluorophenyl)pyrrolidine Chemical compound FC1=CC=C(F)C([C@@H]2NCCC2)=C1 NCXSNNVYILYEBC-SNVBAGLBSA-N 0.000 description 6
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 6
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 6
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 6
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 102000002015 Transforming Protein 1 Src Homology 2 Domain-Containing Human genes 0.000 description 6
- 108010040625 Transforming Protein 1 Src Homology 2 Domain-Containing Proteins 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000008367 deionised water Substances 0.000 description 6
- 229910021641 deionized water Inorganic materials 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000004817 gas chromatography Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 230000004580 weight loss Effects 0.000 description 6
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 238000001712 DNA sequencing Methods 0.000 description 5
- 206010018338 Glioma Diseases 0.000 description 5
- 206010019233 Headaches Diseases 0.000 description 5
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 5
- 239000002138 L01XE21 - Regorafenib Substances 0.000 description 5
- 239000002176 L01XE26 - Cabozantinib Substances 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 206010027452 Metastases to bone Diseases 0.000 description 5
- 206010029260 Neuroblastoma Diseases 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000003305 autocrine Effects 0.000 description 5
- 229960001292 cabozantinib Drugs 0.000 description 5
- ONIQOQHATWINJY-UHFFFAOYSA-N cabozantinib Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 ONIQOQHATWINJY-UHFFFAOYSA-N 0.000 description 5
- 238000002591 computed tomography Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 239000004744 fabric Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 231100000869 headache Toxicity 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 231100000590 oncogenic Toxicity 0.000 description 5
- 230000002246 oncogenic effect Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 229920001155 polypropylene Polymers 0.000 description 5
- 229960004836 regorafenib Drugs 0.000 description 5
- FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 229960001796 sunitinib Drugs 0.000 description 5
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 5
- 238000002626 targeted therapy Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 4
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 4
- QIZHVCUPPAMGIW-UHFFFAOYSA-N 5-(2,5-difluorophenyl)-3,4-dihydro-2h-pyrrole Chemical compound FC1=CC=C(F)C(C=2CCCN=2)=C1 QIZHVCUPPAMGIW-UHFFFAOYSA-N 0.000 description 4
- MZRUFMBFIKGOAL-UHFFFAOYSA-N 5-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C1=CC=NN1 MZRUFMBFIKGOAL-UHFFFAOYSA-N 0.000 description 4
- 206010003571 Astrocytoma Diseases 0.000 description 4
- 208000010392 Bone Fractures Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 4
- 208000001640 Fibromyalgia Diseases 0.000 description 4
- 208000032612 Glial tumor Diseases 0.000 description 4
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 208000008930 Low Back Pain Diseases 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 208000003076 Osteolysis Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 4
- 108020004459 Small interfering RNA Proteins 0.000 description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000011374 additional therapy Methods 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000003119 immunoblot Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 229960005386 ipilimumab Drugs 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 229960003301 nivolumab Drugs 0.000 description 4
- 201000008482 osteoarthritis Diseases 0.000 description 4
- 229960002621 pembrolizumab Drugs 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 201000002510 thyroid cancer Diseases 0.000 description 4
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 4
- 206010044652 trigeminal neuralgia Diseases 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 3
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 3
- WLAVZAAODLTUSW-UHFFFAOYSA-N 1-n'-[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=O)C4(CC4)C(=O)NC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 WLAVZAAODLTUSW-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 206010002515 Animal bite Diseases 0.000 description 3
- 108010006654 Bleomycin Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 206010058019 Cancer Pain Diseases 0.000 description 3
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 3
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 208000034951 Genetic Translocation Diseases 0.000 description 3
- 208000027747 Kennedy disease Diseases 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 3
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 3
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 3
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 3
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 3
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 3
- 206010027458 Metastases to lung Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 3
- 206010061934 Salivary gland cancer Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 3
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 3
- IKWTVSLWAPBBKU-UHFFFAOYSA-N a1010_sial Chemical compound O=[As]O[As]=O IKWTVSLWAPBBKU-UHFFFAOYSA-N 0.000 description 3
- 229960002833 aflibercept Drugs 0.000 description 3
- 108010081667 aflibercept Proteins 0.000 description 3
- 229960005310 aldesleukin Drugs 0.000 description 3
- 108700025316 aldesleukin Proteins 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 229960002594 arsenic trioxide Drugs 0.000 description 3
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 3
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 3
- 229960000397 bevacizumab Drugs 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229960001561 bleomycin Drugs 0.000 description 3
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 3
- 229960001573 cabazitaxel Drugs 0.000 description 3
- 229960004117 capecitabine Drugs 0.000 description 3
- 229960004562 carboplatin Drugs 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 229960005061 crizotinib Drugs 0.000 description 3
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 3
- 239000002178 crystalline material Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 229960000684 cytarabine Drugs 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 229960003901 dacarbazine Drugs 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 229960000975 daunorubicin Drugs 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229960003668 docetaxel Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229960001433 erlotinib Drugs 0.000 description 3
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 3
- IDNUEBSJWINEMI-UHFFFAOYSA-N ethyl nitrate Chemical compound CCO[N+]([O-])=O IDNUEBSJWINEMI-UHFFFAOYSA-N 0.000 description 3
- 229960005420 etoposide Drugs 0.000 description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
- 229960005167 everolimus Drugs 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 229960002584 gefitinib Drugs 0.000 description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 3
- 229960005277 gemcitabine Drugs 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 229960002411 imatinib Drugs 0.000 description 3
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
- 229960004768 irinotecan Drugs 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229960004891 lapatinib Drugs 0.000 description 3
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 229960002247 lomustine Drugs 0.000 description 3
- 229920001684 low density polyethylene Polymers 0.000 description 3
- 239000004702 low-density polyethylene Substances 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 229960001346 nilotinib Drugs 0.000 description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 108091008819 oncoproteins Proteins 0.000 description 3
- 102000027450 oncoproteins Human genes 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 230000000010 osteolytic effect Effects 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 229960000639 pazopanib Drugs 0.000 description 3
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 3
- 229960005079 pemetrexed Drugs 0.000 description 3
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 3
- SZFPYBIJACMNJV-UHFFFAOYSA-N perifosine Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1 SZFPYBIJACMNJV-UHFFFAOYSA-N 0.000 description 3
- 229950010632 perifosine Drugs 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 229960002087 pertuzumab Drugs 0.000 description 3
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 208000037821 progressive disease Diseases 0.000 description 3
- 229960005562 radium-223 Drugs 0.000 description 3
- HCWPIIXVSYCSAN-OIOBTWANSA-N radium-223 Chemical compound [223Ra] HCWPIIXVSYCSAN-OIOBTWANSA-N 0.000 description 3
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000002271 resection Methods 0.000 description 3
- 239000013557 residual solvent Substances 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 229960000714 sipuleucel-t Drugs 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- 229960002930 sirolimus Drugs 0.000 description 3
- 229950010611 sitravatinib Drugs 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- GXISRYWBYOPHFY-UHFFFAOYSA-M sodium;pyrazolo[1,5-a]pyrimidin-5-olate Chemical compound [Na+].N1=C([O-])C=CN2N=CC=C21 GXISRYWBYOPHFY-UHFFFAOYSA-M 0.000 description 3
- 230000000153 supplemental effect Effects 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 229960004964 temozolomide Drugs 0.000 description 3
- 229960000235 temsirolimus Drugs 0.000 description 3
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 3
- GJJYYMXBCYYXPQ-UHFFFAOYSA-N tert-butyl 2-oxopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1=O GJJYYMXBCYYXPQ-UHFFFAOYSA-N 0.000 description 3
- QUXRUQHCVUUDHV-UHFFFAOYSA-N tert-butyl N-[4-(2,5-difluorophenyl)-4-oxobutyl]carbamate Chemical compound FC1=C(C=C(C=C1)F)C(CCCNC(OC(C)(C)C)=O)=O QUXRUQHCVUUDHV-UHFFFAOYSA-N 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 description 3
- 229960004066 trametinib Drugs 0.000 description 3
- 229960000575 trastuzumab Drugs 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 108010064884 trkA Receptor Proteins 0.000 description 3
- 102000015533 trkA Receptor Human genes 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 229960003862 vemurafenib Drugs 0.000 description 3
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 3
- 229960004528 vincristine Drugs 0.000 description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- KMLXGOHWKMHXAE-SBHYBIRFSA-N (2R)-2-(2,5-difluorophenyl)pyrrolidine (2R)-2-hydroxybutanedioic acid Chemical compound O[C@H](CC(O)=O)C(O)=O.Fc1ccc(F)c(c1)[C@H]1CCCN1 KMLXGOHWKMHXAE-SBHYBIRFSA-N 0.000 description 2
- KCOYQXZDFIIGCY-CZIZESTLSA-N (3e)-4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1,3-dihydrobenzimidazol-2-ylidene]quinolin-2-one Chemical compound C1CN(C)CCN1C1=CC=C(N\C(N2)=C/3C(=C4C(F)=CC=CC4=NC\3=O)N)C2=C1 KCOYQXZDFIIGCY-CZIZESTLSA-N 0.000 description 2
- NXNQLECPAXXYTR-LCYFTJDESA-N (3z)-3-[(1-methylindol-3-yl)methylidene]-1h-pyrrolo[3,2-b]pyridin-2-one Chemical compound C12=CC=CC=C2N(C)C=C1\C=C/1C2=NC=CC=C2NC\1=O NXNQLECPAXXYTR-LCYFTJDESA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- YYDUWLSETXNJJT-MTJSOVHGSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-methyl-3-[[(3z)-2-oxo-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-6-yl]amino]phenyl]urea Chemical compound C1=C(NC=2C=C3NC(=O)C(=C\C=4NC=CC=4)/C3=CC=2)C(C)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1F YYDUWLSETXNJJT-MTJSOVHGSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- WSTUJEXAPHIEIM-UHFFFAOYSA-N 4-fluoro-n-[6-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]-1-[4-(propan-2-ylcarbamoyl)cyclohexyl]benzimidazol-2-yl]benzamide Chemical compound C1CC(C(=O)NC(C)C)CCC1N(C=1C(=CC=C(CN2CCC(CC2)C(C)(C)O)C=1)N\1)C/1=N/C(=O)C1=CC=C(F)C=C1 WSTUJEXAPHIEIM-UHFFFAOYSA-N 0.000 description 2
- LBVKEEFIPBQIMD-JTQLQIEISA-N 5-chloro-2-n-[(1s)-1-(5-fluoropyridin-2-yl)ethyl]-4-n-(3-propan-2-yloxy-1h-pyrazol-5-yl)pyrimidine-2,4-diamine Chemical compound N1C(OC(C)C)=CC(NC=2C(=CN=C(N[C@@H](C)C=3N=CC(F)=CC=3)N=2)Cl)=N1 LBVKEEFIPBQIMD-JTQLQIEISA-N 0.000 description 2
- 102100034452 Alternative prion protein Human genes 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- 206010006002 Bone pain Diseases 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 208000016718 Chromosome Inversion Diseases 0.000 description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 208000001730 Familial dysautonomia Diseases 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VWVYILCFSYNJHF-UHFFFAOYSA-N Goe 6976 Chemical compound C1=CC=C2N(CCC#N)C3=C4N(C)C5=CC=CC=C5C4=C(C(=O)NC4)C4=C3C2=C1 VWVYILCFSYNJHF-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 description 2
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 2
- 206010023256 Juvenile melanoma benign Diseases 0.000 description 2
- 238000003109 Karl Fischer titration Methods 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 230000037364 MAPK/ERK pathway Effects 0.000 description 2
- 206010026673 Malignant Pleural Effusion Diseases 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- XKFTZKGMDDZMJI-HSZRJFAPSA-N N-[5-[(2R)-2-methoxy-1-oxo-2-phenylethyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methyl-1-piperazinyl)benzamide Chemical compound O=C([C@H](OC)C=1C=CC=CC=1)N(CC=12)CC=1NN=C2NC(=O)C(C=C1)=CC=C1N1CCN(C)CC1 XKFTZKGMDDZMJI-HSZRJFAPSA-N 0.000 description 2
- 241000232901 Nephroma Species 0.000 description 2
- 208000007256 Nevus Diseases 0.000 description 2
- 208000004983 Phantom Limb Diseases 0.000 description 2
- 201000007286 Pilocytic astrocytoma Diseases 0.000 description 2
- 208000002151 Pleural effusion Diseases 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 238000003559 RNA-seq method Methods 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 2
- 201000001638 Riley-Day syndrome Diseases 0.000 description 2
- 208000026137 Soft tissue injury Diseases 0.000 description 2
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- JVDOKQYTTYUYDV-UHFFFAOYSA-N TG101209 Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C)C(NC=2C=C(C=CC=2)S(=O)(=O)NC(C)(C)C)=N1 JVDOKQYTTYUYDV-UHFFFAOYSA-N 0.000 description 2
- 208000033781 Thyroid carcinoma Diseases 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 241000223109 Trypanosoma cruzi Species 0.000 description 2
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 2
- 230000009692 acute damage Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229960001686 afatinib Drugs 0.000 description 2
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000005775 apoptotic pathway Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000008267 autocrine signaling Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 201000007452 breast secretory carcinoma Diseases 0.000 description 2
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000037011 constitutive activity Effects 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 229960002465 dabrafenib Drugs 0.000 description 2
- BFSMGDJOXZAERB-UHFFFAOYSA-N dabrafenib Chemical compound S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 BFSMGDJOXZAERB-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000002074 deregulated effect Effects 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
- 229950005778 dovitinib Drugs 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000037442 genomic alteration Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003979 granulating agent Substances 0.000 description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229960003507 interferon alfa-2b Drugs 0.000 description 2
- 208000037906 ischaemic injury Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 208000030173 low grade glioma Diseases 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- HAYYBYPASCDWEQ-UHFFFAOYSA-N n-[5-[(3,5-difluorophenyl)methyl]-1h-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide Chemical compound C1CN(C)CCN1C(C=C1NC2CCOCC2)=CC=C1C(=O)NC(C1=C2)=NNC1=CC=C2CC1=CC(F)=CC(F)=C1 HAYYBYPASCDWEQ-UHFFFAOYSA-N 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 208000025351 nephroma Diseases 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000005959 oncogenic signaling Effects 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 208000002320 spinal muscular atrophy Diseases 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000011301 standard therapy Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 238000004441 surface measurement Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 101150111535 trk gene Proteins 0.000 description 2
- 108010064892 trkC Receptor Proteins 0.000 description 2
- 102000047459 trkC Receptor Human genes 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- DWYRIWUZIJHQKQ-SANMLTNESA-N (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine Chemical compound Cn1cc(cn1)-c1cc2c(ncnn2c1)N1CCN(CC1)c1ncc(cn1)[C@@](C)(N)c1ccc(F)cc1 DWYRIWUZIJHQKQ-SANMLTNESA-N 0.000 description 1
- JUTDHSGANMHVIC-SNVBAGLBSA-N (2r)-2-phenylpyrrolidine Chemical group C1CCN[C@H]1C1=CC=CC=C1 JUTDHSGANMHVIC-SNVBAGLBSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- YYACLQUDUDXAPA-MRXNPFEDSA-N (3r)-n-[3-[5-(2-cyclopropylpyrimidin-5-yl)-1h-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]-3-fluoropyrrolidine-1-sulfonamide Chemical compound C1[C@H](F)CCN1S(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=NC(=NC=2)C2CC2)=C1F YYACLQUDUDXAPA-MRXNPFEDSA-N 0.000 description 1
- NYNZQNWKBKUAII-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-RDTXWAMCSA-N 0.000 description 1
- JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
- JGSMCYNBVCGIHC-QPEQYQDCSA-N (3z)-3-[(4-hydroxyphenyl)methylidene]-5,6-dimethoxy-1h-indol-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(=O)\C1=C/C1=CC=C(O)C=C1 JGSMCYNBVCGIHC-QPEQYQDCSA-N 0.000 description 1
- SWDZPNJZKUGIIH-QQTULTPQSA-N (5z)-n-ethyl-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-[4-(morpholin-4-ylmethyl)phenyl]-2h-1,2-oxazole-3-carboxamide Chemical compound O1NC(C(=O)NCC)=C(C=2C=CC(CN3CCOCC3)=CC=2)\C1=C1/C=C(C(C)C)C(O)=CC1=O SWDZPNJZKUGIIH-QQTULTPQSA-N 0.000 description 1
- LCFFREMLXLZNHE-GBOLQPHISA-N (e)-2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(/C#N)=C/C(C)(C)N2CCN(CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LCFFREMLXLZNHE-GBOLQPHISA-N 0.000 description 1
- XEMRAKSQROQPBR-UHFFFAOYSA-N (trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=CC=C1 XEMRAKSQROQPBR-UHFFFAOYSA-N 0.000 description 1
- QHLVBNKYJGBCQJ-UHFFFAOYSA-N 1-(2-hydroxyethyl)-8-[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)anilino]-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(OC(F)(F)F)C(NC=2N=C3C=4N(CCO)N=C(C=4CCC3=CN=2)C(N)=O)=C1 QHLVBNKYJGBCQJ-UHFFFAOYSA-N 0.000 description 1
- DKNUPRMJNUQNHR-UHFFFAOYSA-N 1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1OC(C=1)=CC=CC=1NC(=O)NC=1C=C(C(C)(C)C(F)(F)F)ON=1 DKNUPRMJNUQNHR-UHFFFAOYSA-N 0.000 description 1
- ODPGGGTTYSGTGO-UHFFFAOYSA-N 1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1CN(CC)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(NC)=NC=N1 ODPGGGTTYSGTGO-UHFFFAOYSA-N 0.000 description 1
- ZXFDJWMFCAEGED-UHFFFAOYSA-N 1-chlorocycloocta-1,5-diene;iridium Chemical class [Ir].ClC1=CCCC=CCC1 ZXFDJWMFCAEGED-UHFFFAOYSA-N 0.000 description 1
- GNNDEPIMDAZHRQ-UHFFFAOYSA-N 1-n'-[4-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-2,5-difluorophenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C(=CC(OC=3C=C(NC(=O)C4CC4)N=CC=3)=C(F)C=2)F)CC1 GNNDEPIMDAZHRQ-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- KTBSXLIQKWEBRB-UHFFFAOYSA-N 2-[1-[1-[3-fluoro-2-(trifluoromethyl)pyridine-4-carbonyl]piperidin-4-yl]-3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile Chemical compound C1=CN=C(C(F)(F)F)C(F)=C1C(=O)N1CCC(N2CC(CC#N)(C2)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CC1 KTBSXLIQKWEBRB-UHFFFAOYSA-N 0.000 description 1
- KPACBFJTZSMBKD-OAQYLSRUSA-N 2-[2-[(4-carbamimidoylphenyl)carbamoyl]-6-methoxypyridin-3-yl]-5-[[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]carbamoyl]benzoic acid Chemical compound C=1C=C(C(N)=N)C=CC=1NC(=O)C1=NC(OC)=CC=C1C1=CC=C(C(=O)N[C@H](CO)C(C)(C)C)C=C1C(O)=O KPACBFJTZSMBKD-OAQYLSRUSA-N 0.000 description 1
- XCRCSPKQEDMVBO-UHFFFAOYSA-N 2-bromo-1,4-difluorobenzene Chemical compound FC1=CC=C(F)C(Br)=C1 XCRCSPKQEDMVBO-UHFFFAOYSA-N 0.000 description 1
- LIOLIMKSCNQPLV-UHFFFAOYSA-N 2-fluoro-n-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1C1=NN2C(CC=3C=C4C=CC=NC4=CC=3)=CN=C2N=C1 LIOLIMKSCNQPLV-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- JQOIRTDBHMDWMT-UHFFFAOYSA-N 3-(2-phenylethynyl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)N=C1C#CC1=CC=CC=C1 JQOIRTDBHMDWMT-UHFFFAOYSA-N 0.000 description 1
- YWFPGZXICYWLAP-UHFFFAOYSA-N 3-hydroxypyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCC(O)C1 YWFPGZXICYWLAP-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- NVSHVYGIYPBTEZ-UHFFFAOYSA-N 4,5-dimethyl-n-(2-phenyl-1h-pyrrolo[2,3-b]pyridin-5-yl)-1h-pyrazole-3-carboxamide Chemical compound CC1=NNC(C(=O)NC=2C=C3C=C(NC3=NC=2)C=2C=CC=CC=2)=C1C NVSHVYGIYPBTEZ-UHFFFAOYSA-N 0.000 description 1
- JFUAWXPBHXKZGA-IBGZPJMESA-N 4-fluoro-2-[(4r)-5,5,5-trifluoro-4-hydroxy-2-methyl-4-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-yl]phenol Chemical compound C([C@@](O)(CC=1NC2=CN=CC=C2C=1)C(F)(F)F)C(C)(C)C1=CC(F)=CC=C1O JFUAWXPBHXKZGA-IBGZPJMESA-N 0.000 description 1
- VYEUPRYCLWAOMU-UHFFFAOYSA-N 5-chloro-3-nitropyrazolo[1,5-a]pyrimidine Chemical compound C1=CC(Cl)=NC2=C([N+](=O)[O-])C=NN21 VYEUPRYCLWAOMU-UHFFFAOYSA-N 0.000 description 1
- AILRADAXUVEEIR-UHFFFAOYSA-N 5-chloro-4-n-(2-dimethylphosphorylphenyl)-2-n-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1P(C)(C)=O AILRADAXUVEEIR-UHFFFAOYSA-N 0.000 description 1
- YLLPAAYZOKXPDB-UHFFFAOYSA-N 5-pyrimidin-2-yl-1h-pyrazol-4-amine Chemical compound NC1=CNN=C1C1=NC=CC=N1 YLLPAAYZOKXPDB-UHFFFAOYSA-N 0.000 description 1
- PUIXMSRTTHLNKI-UHFFFAOYSA-N 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidin-7-one Chemical compound C(C=C)(=O)N1CCN(CC1)CCCN1C(C(=CC2=C1N=C(N=C2)NC)C2=C(C(=CC(=C2Cl)OC)OC)Cl)=O PUIXMSRTTHLNKI-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 206010073360 Appendix cancer Diseases 0.000 description 1
- 206010003399 Arthropod bite Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 102000007371 Ataxin-3 Human genes 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102100035080 BDNF/NT-3 growth factors receptor Human genes 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 201000006390 Brachial Plexus Neuritis Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006542 Bulbar palsy Diseases 0.000 description 1
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 101100417166 Caenorhabditis elegans rpi-1 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000001387 Causalgia Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010058842 Cerebrovascular insufficiency Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008513 Child maltreatment syndrome Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- UDHXJZHVNHGCEC-UHFFFAOYSA-N Chlorophacinone Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)C(=O)C1C(=O)C2=CC=CC=C2C1=O UDHXJZHVNHGCEC-UHFFFAOYSA-N 0.000 description 1
- 102100036956 Chromatin target of PRMT1 protein Human genes 0.000 description 1
- 206010061764 Chromosomal deletion Diseases 0.000 description 1
- 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013971 Dyspnoea exertional Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 102100030708 GTPase KRas Human genes 0.000 description 1
- 208000037767 Gallbladder pain Diseases 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
- 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 206010063491 Herpes zoster oticus Diseases 0.000 description 1
- 101000596896 Homo sapiens BDNF/NT-3 growth factors receptor Proteins 0.000 description 1
- 101000737958 Homo sapiens Chromatin target of PRMT1 protein Proteins 0.000 description 1
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 1
- 101001048464 Homo sapiens Homer protein homolog 2 Proteins 0.000 description 1
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 101000807561 Homo sapiens Tyrosine-protein kinase receptor UFO Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 201000003803 Inflammatory myofibroblastic tumor Diseases 0.000 description 1
- 206010067917 Inflammatory myofibroblastic tumour Diseases 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- 206010049949 Intercostal neuralgia Diseases 0.000 description 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 1
- 239000002137 L01XE24 - Ponatinib Substances 0.000 description 1
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 description 1
- 208000007914 Labor Pain Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 208000019090 Machado-Joseph disease type 3 Diseases 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- 206010070665 Mesoblastic nephroma Diseases 0.000 description 1
- 208000037848 Metastatic bone disease Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 206010027910 Mononeuritis Diseases 0.000 description 1
- 208000002472 Morton Neuroma Diseases 0.000 description 1
- 208000020059 Morton neuralgia Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 208000006907 Multiple Pulmonary Nodules Diseases 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102100029166 NT-3 growth factor receptor Human genes 0.000 description 1
- 206010028836 Neck pain Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 102100033857 Neurotrophin-4 Human genes 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010062501 Non-cardiac chest pain Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- DGVCEXQFNYYRQI-BTJKTKAUSA-N OC(=O)\C=C/C(O)=O.CNC(=O)C1=NN(C)C(C2=N3)=C1C(C)(C)CC2=CN=C3NC(C=C1)=CC=C1N1CCN(C)CC1 Chemical compound OC(=O)\C=C/C(O)=O.CNC(=O)C1=NN(C)C(C2=N3)=C1C(C)(C)CC2=CN=C3NC(C=C1)=CC=C1N1CCN(C)CC1 DGVCEXQFNYYRQI-BTJKTKAUSA-N 0.000 description 1
- NYNZQNWKBKUAII-KDOFPFPSSA-N O[C@@H]1CCN(C1)C(=O)Nc1cnn2ccc(nc12)N1CCC[C@H]1c1cc(F)ccc1F Chemical compound O[C@@H]1CCN(C1)C(=O)Nc1cnn2ccc(nc12)N1CCC[C@H]1c1cc(F)ccc1F NYNZQNWKBKUAII-KDOFPFPSSA-N 0.000 description 1
- 206010068106 Occipital neuralgia Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 206010030973 Oral discomfort Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- YFNWWNRZJGMDBR-LJQANCHMSA-N PF-00477736 Chemical compound C1=NN(C)C=C1C1=NC2=CC(NC(=O)[C@H](N)C3CCCCC3)=CC3=C2C1=CNNC3=O YFNWWNRZJGMDBR-LJQANCHMSA-N 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010033885 Paraparesis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000000450 Pelvic Pain Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010054048 Postoperative ileus Diseases 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 description 1
- 206010037075 Protozoal infections Diseases 0.000 description 1
- 208000032225 Proximal spinal muscular atrophy type 1 Diseases 0.000 description 1
- 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010056342 Pulmonary mass Diseases 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- 208000002108 Shaken Baby Syndrome Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000004078 Snake Bites Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 208000002548 Spastic Paraparesis Diseases 0.000 description 1
- 206010054874 Sphenopalatine neuralgia Diseases 0.000 description 1
- 208000003589 Spider Bites Diseases 0.000 description 1
- 206010041549 Spinal cord compression Diseases 0.000 description 1
- 208000020339 Spinal injury Diseases 0.000 description 1
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
- 206010072450 Spitzoid melanoma Diseases 0.000 description 1
- 208000005250 Spontaneous Fractures Diseases 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 206010043220 Temporomandibular joint syndrome Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000026481 Werdnig-Hoffmann disease Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 description 1
- VIUODKCIIYIXHC-UHFFFAOYSA-L [I-].[I-].[Ra+2] Chemical compound [I-].[I-].[Ra+2] VIUODKCIIYIXHC-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 208000037844 advanced solid tumor Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229960001611 alectinib Drugs 0.000 description 1
- KDGFLJKFZUIJMX-UHFFFAOYSA-N alectinib Chemical compound CCC1=CC=2C(=O)C(C3=CC=C(C=C3N3)C#N)=C3C(C)(C)C=2C=C1N(CC1)CCC1N1CCOCC1 KDGFLJKFZUIJMX-UHFFFAOYSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229950005952 altiratinib Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 229960003982 apatinib Drugs 0.000 description 1
- 229940076005 apoptosis modulator Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 208000021780 appendiceal neoplasm Diseases 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229950000971 baricitinib Drugs 0.000 description 1
- XUZMWHLSFXCVMG-UHFFFAOYSA-N baricitinib Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2C=3C=CNC=3N=CN=2)=C1 XUZMWHLSFXCVMG-UHFFFAOYSA-N 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 description 1
- 229950003054 binimetinib Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 201000004571 bone carcinoma Diseases 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 208000024883 bone remodeling disease Diseases 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 201000007983 brain glioma Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229950004272 brigatinib Drugs 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 229940002226 buccal film Drugs 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- HFCFMRYTXDINDK-WNQIDUERSA-N cabozantinib malate Chemical compound OC(=O)[C@@H](O)CC(O)=O.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 HFCFMRYTXDINDK-WNQIDUERSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 229950005852 capmatinib Drugs 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- NMMGUHANGUWNBN-OGLOGDKOSA-N cep-751 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1C[C@](OC)(CO)[C@]4(C)O1 NMMGUHANGUWNBN-OGLOGDKOSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 201000008168 congenital mesoblastic nephroma Diseases 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 208000012790 cranial neuralgia Diseases 0.000 description 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
- 230000002559 cytogenic effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229950002966 danusertib Drugs 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical class CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- OUQSAXROROGQEE-QFIPXVFZSA-N diphenyl-[2-[(4r)-4-propan-2-yl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]phosphane Chemical compound CC(C)[C@@H]1COC(C=2C(=CC=CC=2)P(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 OUQSAXROROGQEE-QFIPXVFZSA-N 0.000 description 1
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 229950009791 durvalumab Drugs 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000002003 electron diffraction Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 208000023965 endometrium neoplasm Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000012055 enteric layer Substances 0.000 description 1
- 229950000521 entrectinib Drugs 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 208000004967 femoral neuropathy Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- MGZKYOAQVGSSGC-DLBZAZTESA-N fisogatinib Chemical compound COc1cc(OC)c(Cl)c(c1Cl)-c1ccc2nc(N[C@@H]3COCC[C@@H]3NC(=O)C=C)ncc2c1 MGZKYOAQVGSSGC-DLBZAZTESA-N 0.000 description 1
- 239000012054 flavored emulsion Substances 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 201000011349 geniculate herpes zoster Diseases 0.000 description 1
- 229950007540 glesatinib Drugs 0.000 description 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
- 229940124750 glucocorticoid receptor agonist Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 101150098203 grb2 gene Proteins 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 229960001507 ibrutinib Drugs 0.000 description 1
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000007850 in situ PCR Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000010978 in-process monitoring Methods 0.000 description 1
- 238000010949 in-process test method Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 208000037805 labour Diseases 0.000 description 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 description 1
- 229950003970 larotrectinib Drugs 0.000 description 1
- 238000000370 laser capture micro-dissection Methods 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 229960003784 lenvatinib Drugs 0.000 description 1
- WOSKHXYHFSIKNG-UHFFFAOYSA-N lenvatinib Chemical compound C=12C=C(C(N)=O)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1CC1 WOSKHXYHFSIKNG-UHFFFAOYSA-N 0.000 description 1
- 229950001845 lestaurtinib Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229950005069 luminespib Drugs 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000028830 lung neuroendocrine neoplasm Diseases 0.000 description 1
- 238000007403 mPCR Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 208000032184 meralgia paresthetica Diseases 0.000 description 1
- 229960004635 mesna Drugs 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000037843 metastatic solid tumor Diseases 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 229950009655 milciclib Drugs 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 229940015637 mobocertinib Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 208000013734 mononeuritis simplex Diseases 0.000 description 1
- 201000005518 mononeuropathy Diseases 0.000 description 1
- 229950003968 motesanib Drugs 0.000 description 1
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- RXZMYLDMFYNEIM-UHFFFAOYSA-N n,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5h-pyrazolo[4,3-h]quinazoline-3-carboxamide Chemical compound CNC(=O)C1=NN(C)C(C2=N3)=C1C(C)(C)CC2=CN=C3NC(C=C1)=CC=C1N1CCN(C)CC1 RXZMYLDMFYNEIM-UHFFFAOYSA-N 0.000 description 1
- AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- WPEWQEMJFLWMLV-UHFFFAOYSA-N n-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NCC=2C=CN=CC=2)C=1C(=O)NC(C=C1)=CC=C1C1(C#N)CCCC1 WPEWQEMJFLWMLV-UHFFFAOYSA-N 0.000 description 1
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000019382 nerve compression syndrome Diseases 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 201000002120 neuroendocrine carcinoma Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 201000009985 neuronitis Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229960004378 nintedanib Drugs 0.000 description 1
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
- 231100001222 nononcogenic Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 230000005969 oncogenic driver mutation Effects 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 229940127013 pan-TRK inhibitor Drugs 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000014306 paracrine signaling Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- JGWRKYUXBBNENE-UHFFFAOYSA-N pexidartinib Chemical compound C1=NC(C(F)(F)F)=CC=C1CNC(N=C1)=CC=C1CC1=CNC2=NC=C(Cl)C=C12 JGWRKYUXBBNENE-UHFFFAOYSA-N 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 229950010773 pidilizumab Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- 208000019629 polyneuritis Diseases 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229960001131 ponatinib Drugs 0.000 description 1
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 208000001282 primary progressive aphasia Diseases 0.000 description 1
- 208000032207 progressive 1 supranuclear palsy Diseases 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- AZSRSNUQCUDCGG-UHFFFAOYSA-N propan-2-yl 2-[4-[2-(dimethylamino)ethyl-methylamino]-2-methoxy-5-(prop-2-enoylamino)anilino]-4-(1-methylindol-3-yl)pyrimidine-5-carboxylate Chemical compound C(C=C)(=O)NC=1C(=CC(=C(C=1)NC1=NC=C(C(=N1)C1=CN(C2=CC=CC=C12)C)C(=O)OC(C)C)OC)N(C)CCN(C)C AZSRSNUQCUDCGG-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 201000000196 pseudobulbar palsy Diseases 0.000 description 1
- 210000002097 psoas muscle Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 229910001642 radium iodide Inorganic materials 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000026749 regulation of bone remodeling Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 102000027483 retinoid hormone receptors Human genes 0.000 description 1
- 108091008679 retinoid hormone receptors Proteins 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000001359 rheumatologic effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229940018008 rilzabrutinib Drugs 0.000 description 1
- 238000009490 roller compaction Methods 0.000 description 1
- 229960000215 ruxolitinib Drugs 0.000 description 1
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 208000007771 sciatic neuropathy Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 229950010746 selumetinib Drugs 0.000 description 1
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 1
- 229950003647 semaxanib Drugs 0.000 description 1
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000003755 striatonigral degeneration Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 239000003558 transferase inhibitor Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000000411 transmission spectrum Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 102000015534 trkB Receptor Human genes 0.000 description 1
- 108010064880 trkB Receptor Proteins 0.000 description 1
- 208000025421 tumor of uterus Diseases 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 208000032471 type 1 spinal muscular atrophy Diseases 0.000 description 1
- 208000032527 type III spinal muscular atrophy Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 229940126496 utatrectinib Drugs 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 238000002460 vibrational spectroscopy Methods 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
- C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/10—Protein-tyrosine kinases (2.7.10)
- C12Y207/10001—Receptor protein-tyrosine kinase (2.7.10.1)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Communicable Diseases (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462080374P | 2014-11-16 | 2014-11-16 | |
| US201562169545P | 2015-06-01 | 2015-06-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2941630T3 true ES2941630T3 (es) | 2023-05-24 |
Family
ID=54848892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES20169707T Active ES2941630T3 (es) | 2014-11-16 | 2015-11-16 | Forma cristalina de sulfato de hidrógeno de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida |
Country Status (30)
| Country | Link |
|---|---|
| US (5) | US10799505B2 (OSRAM) |
| EP (2) | EP3218380B1 (OSRAM) |
| JP (2) | JP6914834B2 (OSRAM) |
| KR (1) | KR102649887B1 (OSRAM) |
| CN (2) | CN113354649B (OSRAM) |
| AU (1) | AU2015346046B2 (OSRAM) |
| BR (1) | BR112017010141A2 (OSRAM) |
| CA (1) | CA2967951C (OSRAM) |
| CL (1) | CL2017001249A1 (OSRAM) |
| CO (1) | CO2017005483A2 (OSRAM) |
| CR (1) | CR20170263A (OSRAM) |
| DK (1) | DK3699181T3 (OSRAM) |
| ES (1) | ES2941630T3 (OSRAM) |
| FI (1) | FI3699181T3 (OSRAM) |
| HK (1) | HK1244483A1 (OSRAM) |
| HR (1) | HRP20230271T1 (OSRAM) |
| HU (1) | HUE061448T2 (OSRAM) |
| IL (2) | IL290905B2 (OSRAM) |
| LT (1) | LT3699181T (OSRAM) |
| MX (2) | MX376478B (OSRAM) |
| PH (2) | PH12017500900A1 (OSRAM) |
| PL (1) | PL3699181T3 (OSRAM) |
| PT (1) | PT3699181T (OSRAM) |
| RS (1) | RS64122B1 (OSRAM) |
| SG (1) | SG11201703962XA (OSRAM) |
| SI (1) | SI3699181T1 (OSRAM) |
| TW (2) | TWI767858B (OSRAM) |
| UA (1) | UA123044C2 (OSRAM) |
| WO (1) | WO2016077841A1 (OSRAM) |
| ZA (1) | ZA201703501B (OSRAM) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8450322B2 (en) | 2008-09-22 | 2013-05-28 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as Trk kinase inhibitors |
| TR201807039T4 (tr) | 2008-10-22 | 2018-06-21 | Array Biopharma Inc | Trk kinaz inhibitörleri olarak sübstitüe edilmiş pirazolo[1,5-]pirimidin bileşikleri. |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| EP3628749A1 (en) * | 2013-07-30 | 2020-04-01 | Blueprint Medicines Corporation | Ntrk2 fusions |
| US20160053301A1 (en) | 2014-08-22 | 2016-02-25 | Clearfork Bioscience, Inc. | Methods for quantitative genetic analysis of cell free dna |
| PT3699181T (pt) | 2014-11-16 | 2023-04-05 | Array Biopharma Inc | Forma cristalina de hidrogenossulfato de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| TN2017000502A1 (en) | 2015-06-01 | 2019-04-12 | Loxo Oncology Inc | Methods of diagnosing and treating cancer |
| RS61485B1 (sr) | 2015-07-16 | 2021-03-31 | Array Biopharma Inc | Supstituisana pirazolo [1,5-a] piridinska jedinjenja kao inhibitori ret kinaze |
| TN2018000138A1 (en) | 2015-10-26 | 2019-10-04 | Array Biopharma Inc | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| RS65988B1 (sr) * | 2016-04-04 | 2024-10-31 | Loxo Oncology Inc | Postupak lečenja pedijatrijskih karcinoma |
| CN109414442B (zh) * | 2016-04-04 | 2024-03-29 | 洛克索肿瘤学股份有限公司 | 一种化合物的液体制剂 |
| DK3800189T3 (da) * | 2016-05-18 | 2023-07-31 | Loxo Oncology Inc | Fremstilling af (s)-n-(5-((r)-2-(2,5-difluorphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| EP3571203B1 (en) | 2017-01-18 | 2023-06-07 | Array BioPharma Inc. | Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| US10180422B1 (en) | 2017-08-22 | 2019-01-15 | Scripps Health | Methods of treating a neuroendocrine tumor |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| EP3700576A1 (en) | 2017-10-26 | 2020-09-02 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
| HRP20251226T1 (hr) | 2017-10-31 | 2025-12-05 | Assia Chemical Industries Ltd. | Soli i oblici larotrectiniba u čvrstom stanju |
| CN107987082B (zh) * | 2017-11-14 | 2019-09-20 | 苏州东南药业股份有限公司 | 一种Larotrectinib的制备方法及其中间体 |
| CN109456331B (zh) * | 2017-12-22 | 2020-06-05 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的吡唑并[1,5-a]嘧啶化合物及其药物组合物及用途 |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| CN111615514B (zh) | 2018-01-18 | 2022-10-11 | 奥瑞生物药品公司 | 作为ret激酶抑制剂的取代的吡唑并[4,3-c]吡啶化合物 |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| CN111848622A (zh) | 2018-01-23 | 2020-10-30 | 深圳市塔吉瑞生物医药有限公司 | 取代的吡唑并[1,5-a]嘧啶类的大环化合物 |
| MX2020008273A (es) * | 2018-02-06 | 2020-11-24 | Univ Miami | Inhibidores de la cinasa del complejo de activacion transcripcional notch ("nack") y metodos para el uso de los mismos. |
| CA3095366A1 (en) | 2018-03-29 | 2019-10-03 | Loxo Oncology, Inc. | Treatment of trk-associated cancers |
| WO2019220352A1 (en) * | 2018-05-15 | 2019-11-21 | Dr. Reddy’S Laboratories Limited | Amorphous solid dispersion of larotrectinib sulfate and process thereof |
| CN110294761B (zh) * | 2018-06-08 | 2020-09-08 | 南京雷正医药科技有限公司 | 作为Trk激酶抑制剂的取代的吡唑并[1,5-a]嘧啶化合物 |
| CA3224945C (en) | 2018-07-31 | 2025-11-18 | Loxo Oncology, Inc. | SPRAY DRIED DISPERSIONS, FORMULATIONS AND POLYMORPHIES OF (S)-5-AMINO-3-(4-((5-FLUORO-2-METHOXYBENZAMIDO)METHYL)PHENYL)(1,1,1-TRIFLUOROPROPAN-2-YL)-1H-PYRAZOLE-4-CARBOXAMIDE |
| CN110857304B (zh) * | 2018-08-24 | 2021-05-18 | 北京富龙康泰生物技术有限公司 | Trk抑制剂、其制备方法和用途 |
| JP2022500383A (ja) | 2018-09-10 | 2022-01-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての縮合複素環式化合物 |
| CN111138333B (zh) * | 2018-11-02 | 2023-05-23 | 上海复星星泰医药科技有限公司 | 一种(r)-2-(2,5-二氟苯基)-吡咯烷的制备方法 |
| CN109232582B (zh) * | 2018-11-28 | 2021-02-05 | 安礼特（上海）医药科技有限公司 | 拉洛替尼硫酸氢盐晶型及其制备和应用 |
| BR112021009057A2 (pt) | 2018-11-29 | 2021-08-10 | Pfizer Inc. | pirazóis como moduladores de hemoglobina |
| CN109608464B (zh) * | 2018-12-12 | 2021-09-24 | 上海健康医学院 | 一种放射性碘标记Larotrectinib化合物及其制备方法和应用 |
| CN113474337A (zh) | 2018-12-19 | 2021-10-01 | 奥瑞生物药品公司 | 作为fgfr抑制剂用于治疗癌症的7-((3，5-二甲氧基苯基)氨基)喹喔啉衍生物 |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| CN109593803A (zh) * | 2018-12-24 | 2019-04-09 | 上海健康医学院 | (r)-2-(2,5-二氟苯基)吡咯烷或其盐的制备方法 |
| CN111057729B (zh) * | 2019-06-03 | 2023-08-29 | 弈柯莱生物科技(上海)股份有限公司 | 一种(r)-2-(2,5-二氟苯基)吡咯烷及其制备方法和应用 |
| CN110804059B (zh) * | 2019-09-30 | 2024-03-12 | 郑州泰基鸿诺医药股份有限公司 | 氨基甲酸酯类化合物、药物组合物及其应用 |
| CN110981779B (zh) * | 2019-11-23 | 2021-02-26 | 武汉理工大学 | R-2-(2,5-二氟苯基)吡咯烷的合成方法 |
| CN111087398A (zh) * | 2019-12-24 | 2020-05-01 | 上海万巷制药有限公司 | 一种制备拉罗替尼中间体的清洁工艺 |
| CN111302997B (zh) * | 2020-04-15 | 2022-03-29 | 江苏恒沛药物科技有限公司 | “一锅法”制备拉罗替尼中间体的方法 |
| BR112022025065A2 (pt) * | 2020-06-10 | 2022-12-27 | Epics Therapeutics | Síntese de ácido (2s,5r)-5-(2-clorofenil)-1-(2'-metoxi-[1,1'-bifenil]-4- carbonil)pirrolidina-2-carboxílico |
| CN111763211A (zh) * | 2020-08-05 | 2020-10-13 | 安庆多辉生物科技有限公司 | 拉罗替尼盐酸盐、制备方法与应用 |
| RU2764955C1 (ru) * | 2021-01-11 | 2022-01-24 | Федеральное государственное бюджетное научное учреждение "Томский национальный исследовательский медицинский центр" Российской академии наук ("Томский НИМЦ") | Способ комбинированного лечения метастатического колоректального рака у больных с резектабельными метастазами в печени и при отсутствии мутаций в генах KRAS и BRAF |
| RU2760174C1 (ru) * | 2021-01-11 | 2021-11-22 | Федеральное государственное бюджетное научное учреждение "Томский национальный исследовательский медицинский центр" Российской академии наук ("Томский НИМЦ") | Способ комбинированного лечения метастатического колоректального рака у больных с резектабельными метастазами в печени и при наличии мутаций в генах KRAS и BRAF |
| WO2022168115A1 (en) * | 2021-02-05 | 2022-08-11 | Mylan Laboratories Limited | A process for the preparation of larotrectinib or its salts |
| IT202100003887A1 (it) | 2021-02-19 | 2022-08-19 | Olon Spa | Procedimento per la preparazione di larotrectinib ad elevato grado di purezza |
| CN114478345B (zh) * | 2022-02-10 | 2024-06-14 | 中瀚(齐河县)生物医药科技有限公司 | 一种(r)-2-(2,5-二氟苯基)吡咯烷的制备方法 |
| WO2024023836A1 (en) * | 2022-07-27 | 2024-02-01 | Mylan Laboratories Limited | Polymorphic form of larotrectinib sulfate |
Family Cites Families (198)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ234143A (en) | 1989-06-28 | 1991-10-25 | Mcneil Ppc Inc | Aqueous pharmaceutical suspension formulation for administering substantially insoluble pharmaceutical agents |
| KR100263817B1 (ko) | 1993-11-30 | 2000-08-16 | 윌리암스 로저 에이 | 염증치료용 치환 피라졸일벤젠술폰아미드 |
| US5877016A (en) | 1994-03-18 | 1999-03-02 | Genentech, Inc. | Human trk receptors and neurotrophic factor inhibitors |
| US5430021A (en) | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
| US5844092A (en) | 1994-03-18 | 1998-12-01 | Genentech, Inc. | Human TRK receptors and neurotrophic factor inhibitors |
| CA2206201A1 (en) | 1996-05-29 | 1997-11-29 | Yoshiaki Isobe | Pyrazole derivatives and their pharmaceutical use |
| JP3898296B2 (ja) | 1996-08-28 | 2007-03-28 | ポーラ化成工業株式会社 | ピロロピラゾロピリミジン化合物及びこれを有効成分とする医薬 |
| EP0979231B1 (en) | 1997-04-25 | 2004-11-24 | Takeda Chemical Industries, Ltd. | Condensed pyridazine derivatives, their production and use |
| UA74546C2 (en) | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| US6534085B1 (en) | 1999-09-23 | 2003-03-18 | Bioresponse L.L.C. | Phytochemicals for promoting weight loss |
| IL153375A0 (en) | 2000-06-22 | 2003-07-06 | Genentech Inc | Agonist anti-trk-c monoclonal antibodies |
| TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
| ATE522229T1 (de) | 2001-05-30 | 2011-09-15 | Genentech Inc | Anti-ngf-antikörper zur behandlung verschiedener erkrankungen |
| US7101572B2 (en) | 2001-12-07 | 2006-09-05 | Unilab Pharmatech, Ltd. | Taste masked aqueous liquid pharmaceutical composition |
| US20030199525A1 (en) | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
| WO2003091256A1 (en) | 2002-04-23 | 2003-11-06 | Shionogi & Co., Ltd. | PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVE AND NAD(P)H OXIDASE INHIBITOR CONTAINING THE SAME |
| US7449488B2 (en) | 2002-06-04 | 2008-11-11 | Schering Corporation | Pyrazolopyrimidines as protein kinase inhibitors |
| ITMI20021620A1 (it) | 2002-07-23 | 2004-01-23 | Novuspharma Spa | Composto ad ativita' antitumorale |
| JP4024624B2 (ja) | 2002-08-26 | 2007-12-19 | 富士通株式会社 | 半導体装置の製造方法及び製造装置 |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| US7196078B2 (en) | 2002-09-04 | 2007-03-27 | Schering Corpoartion | Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| US7119200B2 (en) | 2002-09-04 | 2006-10-10 | Schering Corporation | Pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| AU2003263071B2 (en) | 2002-09-04 | 2007-03-15 | Merck Sharp & Dohme Llc | Pyrazolopyrimidines as cyclin-dependent kinase inhibitors |
| US7550470B2 (en) | 2002-12-11 | 2009-06-23 | Merck & Co. Inc. | Substituted pyrazolo[1,5-A]pyrimidines as tyrosine kinase inhibitors |
| WO2004052286A2 (en) | 2002-12-11 | 2004-06-24 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB0303910D0 (en) | 2003-02-20 | 2003-03-26 | Merck Sharp & Dohme | Therapeutic agents |
| US20070037150A1 (en) | 2003-02-21 | 2007-02-15 | The Johns Hopkins University | Tyrosine kinome |
| JP2004277337A (ja) | 2003-03-14 | 2004-10-07 | Sumitomo Pharmaceut Co Ltd | ピラゾロ［１，５−ａ］ピリミジン誘導体 |
| WO2004087707A1 (en) | 2003-03-31 | 2004-10-14 | Vernalis (Cambridge) Limited | Pyrazolopyrimidine compounds and their use in medicine |
| WO2004089471A2 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | NEW PYRAZOLO[1,5-a] PYRIMIDINES DERIVATIVES AND PHARMACEUTICAL USE THEREOF |
| US20060094699A1 (en) | 2003-04-11 | 2006-05-04 | Kampen Gita Camilla T | Combination therapy using an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist to minimize the side effects associated with glucocorticoid receptor agonist therapy |
| WO2004089415A2 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | COMBINATIONS OF AN 11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITOR AND A GLUCOCORTICOID RECEPTOR AGONIST |
| CA2523508A1 (en) | 2003-04-28 | 2004-11-11 | Galpharma Co., Ltd. | Galectin 9-inducing factors |
| PA8603801A1 (es) | 2003-05-27 | 2004-12-16 | Janssen Pharmaceutica Nv | Derivados de la quinazolina |
| JP2005008581A (ja) | 2003-06-20 | 2005-01-13 | Kissei Pharmaceut Co Ltd | 新規なピラゾロ［１，５−ａ］ピリミジン誘導体、それを含有する医薬組成物およびそれらの用途 |
| EA009517B1 (ru) | 2003-06-27 | 2008-02-28 | Байер Кропсайенс Аг | Пиразолопиримидины |
| DK1648509T3 (da) | 2003-07-15 | 2013-01-07 | Amgen Inc | Humane anti-NGF-neutraliserende antistoffer som selektive NGF-pathway-inhibitorer |
| US7491794B2 (en) | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| WO2005044835A1 (en) | 2003-10-27 | 2005-05-19 | Genelabs Technologies, Inc. | METHODS FOR PREPARING 7-(2'-SUBSTITUTED-ß-D-RIBOFURANOSYL)-4-(NR2R3)-5-(SUBSTITUTED ETHYN-1-YL)-PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| RU2006122853A (ru) | 2003-11-28 | 2008-01-10 | Новартис АГ (CH) | Производные диарилмочевины для лечения заболеваний, зависимых от протеинкиназы |
| UA83881C2 (en) | 2003-12-18 | 2008-08-26 | Янссен Фармацевтика Н.В. | Pyrido- and pyrimidopyrimidine derivatives as anti-proliferative agents |
| US7504509B2 (en) | 2003-12-19 | 2009-03-17 | Plexxikon, Inc. | Compounds and methods for development of Ret modulators |
| WO2005068424A1 (en) | 2004-01-20 | 2005-07-28 | Cell Therapeutics Europe S.R.L. | Indolinone derivatives as receptor tyrosine kinase ihibitors |
| US20050222171A1 (en) | 2004-01-22 | 2005-10-06 | Guido Bold | Organic compounds |
| WO2005099363A2 (en) | 2004-03-26 | 2005-10-27 | Whitehead Institute For Biomedical Research | Methods of diagnosing, preventing and treating cancer metastasis |
| CN1938311A (zh) | 2004-03-30 | 2007-03-28 | 因特蒙公司 | 作为病毒复制抑制剂的大环化合物 |
| PE20060664A1 (es) | 2004-09-15 | 2006-08-04 | Novartis Ag | Amidas biciclicas como inhibidores de cinasa |
| DK1812440T3 (da) | 2004-11-04 | 2011-01-31 | Vertex Pharma | Pyrazolo[1,5-a]pyrimidiner, der kan anvendes som inhibistorer af proteinkinaser |
| JO3088B1 (ar) | 2004-12-08 | 2017-03-15 | Janssen Pharmaceutica Nv | مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف |
| DE102005003687A1 (de) | 2005-01-26 | 2006-07-27 | Sphingo Tec Gmbh | Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation |
| SI1853602T1 (sl) | 2005-02-16 | 2010-11-30 | Astrazeneca Ab | Kemične spojine |
| CN101119996A (zh) | 2005-02-16 | 2008-02-06 | 阿斯利康(瑞典)有限公司 | 化学化合物 |
| DK1869049T3 (da) | 2005-03-21 | 2009-05-18 | Lilly Co Eli | Imidazopyridazinforbindelser |
| CN101208093A (zh) | 2005-04-27 | 2008-06-25 | 阿斯利康(瑞典)有限公司 | 吡唑-嘧啶衍生物在治疗疼痛中的用途 |
| JP2008540622A (ja) | 2005-05-16 | 2008-11-20 | アストラゼネカ アクチボラグ | 化合物 |
| CN100406650C (zh) | 2005-06-05 | 2008-07-30 | 徐斌 | 一种抗特大变位的模块式梳型桥梁伸缩缝装置 |
| ITRM20050290A1 (it) | 2005-06-07 | 2006-12-08 | Lay Line Genomics Spa | Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato. |
| US20070025540A1 (en) | 2005-07-07 | 2007-02-01 | Roger Travis | Call center routing based on talkativeness |
| GEP20105124B (en) | 2005-07-25 | 2010-11-25 | Array Biopharma Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
| EP1910369A1 (en) | 2005-07-29 | 2008-04-16 | Astellas Pharma Inc. | Fused heterocycles as lck inhibitors |
| JP2009503071A (ja) | 2005-08-03 | 2009-01-29 | イーストマン ケミカル カンパニー | トコフェリルポリエチレングリコールスクシネート粉末及びその製造方法 |
| WO2007024680A1 (en) | 2005-08-22 | 2007-03-01 | Amgen Inc. | Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators |
| EA017318B1 (ru) | 2005-08-25 | 2012-11-30 | Креабилис Терапеутикс С.П.А. | Полимерные конъюгаты индолокарбазола и его производных |
| WO2007025090A2 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase |
| DE102005042742A1 (de) | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| JP5102212B2 (ja) | 2005-10-06 | 2012-12-19 | メルク・シャープ・アンド・ドーム・コーポレーション | プロテインキナーゼインヒビターとしてのピラゾロピリミジン |
| WO2007044441A2 (en) | 2005-10-06 | 2007-04-19 | Schering Corporation | Use of pyrazolo [1 , 5 -a] pyrimidine derivatives for inhibiting protein kinases methods for inhibiting protein kinases |
| CA2624772C (en) | 2005-10-11 | 2011-11-29 | Centre National De La Recherche Scientifique (Cnrs) | Compounds and kits for the detection and the quantification of cell apoptosis |
| BRPI0617274A2 (pt) | 2005-10-11 | 2011-07-19 | Intermune Inc | compostos e métodos para a inibição de replicação viral de hepatite c |
| ATE517874T1 (de) | 2005-10-21 | 2011-08-15 | Exelixis Inc | Pyrimidinone als modulatoren von caseinkinase ii (ck2) |
| WO2007057399A2 (en) | 2005-11-15 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Treatment of cancer with indole derivatives |
| GB0524436D0 (en) | 2005-11-30 | 2006-01-11 | Novartis Ag | Organic compounds |
| EP1968579A1 (en) | 2005-12-30 | 2008-09-17 | Astex Therapeutics Limited | Pharmaceutical compounds |
| WO2007084815A2 (en) | 2006-01-19 | 2007-07-26 | Janssen Pharmaceutica, N.V. | Substituted thienopyrimidine kinase inhibitors |
| EP1978958A4 (en) | 2006-01-24 | 2009-12-02 | Merck & Co Inc | RET tyrosine kinase Inhibition |
| KR100846988B1 (ko) | 2006-03-06 | 2008-07-16 | 제일약품주식회사 | 신규한 티에노피리미딘 유도체 또는 이의 약학적으로허용가능한 염, 이의 제조방법 및 이를 함유하는 약학조성물 |
| WO2007103308A2 (en) | 2006-03-07 | 2007-09-13 | Array Biopharma Inc. | Heterobicyclic pyrazole compounds and methods of use |
| GB0606805D0 (en) | 2006-04-04 | 2006-05-17 | Novartis Ag | Organic compounds |
| BRPI0710874A2 (pt) | 2006-04-26 | 2012-02-14 | Hoffmann La Roche | compostos de tienopirimidina, processos de produção dos referidos compostos, composições farmacêuticas contendo os mesmos, kit, produto, e usos dos compostos |
| AU2007252506C1 (en) | 2006-05-18 | 2012-07-19 | Eisai R & D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| EP1873157A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| TWI419889B (zh) | 2006-07-05 | 2013-12-21 | Mitsubishi Tanabe Pharma Corp | 吡唑并〔１，５-ａ〕嘧啶化合物 |
| EP2058309A4 (en) | 2006-08-04 | 2010-12-22 | Takeda Pharmaceutical | CONDENSED HETEROCYCLIC COMPOUND |
| US7531539B2 (en) | 2006-08-09 | 2009-05-12 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| CA2663091A1 (en) | 2006-09-07 | 2008-03-13 | Biogen Idec Ma Inc. | Modulators of interleukin-1 receptor-associated kinase |
| EP2067039A2 (en) | 2006-09-12 | 2009-06-10 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute for Biomedical Research | Non-neuroendocrine cancer therapy |
| AU2007302263A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as P13K lipid kinase inhibitors |
| WO2008052734A1 (en) | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
| MY146474A (en) | 2006-11-06 | 2012-08-15 | Supergen Inc | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
| US20080234267A1 (en) | 2007-03-20 | 2008-09-25 | Karen Elizabeth Lackey | Compounds and Methods of Treatment |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| US20080255153A1 (en) | 2007-03-28 | 2008-10-16 | Biovitrum Ab (Publ) | New compounds |
| HRP20130660T1 (en) | 2007-04-03 | 2013-08-31 | Array Biopharma, Inc. | Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors |
| AU2008247442B2 (en) | 2007-05-04 | 2013-01-10 | Irm Llc | Compounds and compositions as c-kit and PDGFR kinase inhibitors |
| ES2435454T3 (es) | 2007-06-21 | 2013-12-19 | Janssen Pharmaceutica, N.V. | Indolin-2-onas y aza-indolin-2-onas |
| PH12013501594A1 (en) | 2007-07-20 | 2014-05-12 | Nerviano Medical Sciences Srl | Substituted indazole derivatives active as kinase inhibitors |
| WO2009017838A2 (en) | 2007-08-01 | 2009-02-05 | Exelixis, Inc. | Combinations of jak-2 inhibitors and other agents |
| BRPI0815370B8 (pt) | 2007-08-10 | 2021-05-25 | Regeneron Pharma | anticorpos humanos de alta afinidade contra o fator de crescimento neural humano e seu uso, molécula de ácido nucleico, vetor de expressão, método para produção de um anticorpo anti-ngf humano e composiçao farmacêutica |
| MX2010004260A (es) | 2007-10-16 | 2010-04-30 | Wyeth Llc | Compuestos de tienopirimidina y pirazolopirimidina y su uso como inhibidores de mtor cinasa y pi3 cinasa. |
| KR20100089851A (ko) | 2007-10-23 | 2010-08-12 | 노파르티스 아게 | 호흡기 질환의 치료를 위한 ｔｒｋｂ 항체의 용도 |
| US20110046127A1 (en) | 2007-11-08 | 2011-02-24 | Paolo Pevarello | Imidazopyridazines for Use as Protein Kinase Inhibitors |
| JP2011504931A (ja) | 2007-11-28 | 2011-02-17 | シェーリング コーポレイション | プロテインキナーゼ阻害剤としての２−フルオロピラゾロ［１，５−ａ］ピリミジン |
| JP5420568B2 (ja) | 2008-01-17 | 2014-02-19 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 改良された抗ＴｒｋＢ抗体 |
| JP2009203226A (ja) | 2008-01-31 | 2009-09-10 | Eisai R & D Management Co Ltd | ピリジン誘導体およびピリミジン誘導体を含有するレセプターチロシンキナーゼ阻害剤 |
| AU2009246687B2 (en) | 2008-05-13 | 2012-08-09 | Irm Llc | Fused nitrogen containing heterocycles and compositions thereof as kinase inhibitors |
| US8946226B2 (en) | 2008-07-29 | 2015-02-03 | Nerviano Medical Sciences S.R.L. | Use of CDK inhibitor for the treatment of glioma |
| US8450322B2 (en) | 2008-09-22 | 2013-05-28 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as Trk kinase inhibitors |
| TR201807039T4 (tr) | 2008-10-22 | 2018-06-21 | Array Biopharma Inc | Trk kinaz inhibitörleri olarak sübstitüe edilmiş pirazolo[1,5-]pirimidin bileşikleri. |
| JP5769199B2 (ja) | 2008-10-31 | 2015-08-26 | ジェネンテック， インコーポレイテッド | ピラゾロピリミジンｊａｋ阻害剤化合物と方法 |
| JP2012509859A (ja) | 2008-11-24 | 2012-04-26 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 中皮腫の治療のためのｃｄｋ阻害物質 |
| DK2881402T3 (en) | 2009-02-12 | 2017-08-28 | Cell Signaling Technology Inc | Mutant ROS expression in human liver cancer |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| DK2536414T3 (en) | 2010-02-18 | 2016-10-03 | Inserm (Institut Nat De La Santé Et De La Rech Médicale) | METHOD FOR PREVENTING cancer metastasis |
| WO2011127219A1 (en) | 2010-04-06 | 2011-10-13 | Caris Life Sciences Luxembourg Holdings | Circulating biomarkers for disease |
| US8383793B2 (en) | 2010-04-15 | 2013-02-26 | St. Jude Children's Research Hospital | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors |
| TWI619713B (zh) | 2010-04-21 | 2018-04-01 | 普雷辛肯公司 | 用於激酶調節的化合物和方法及其適應症 |
| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| JP6121903B2 (ja) | 2010-08-19 | 2017-04-26 | ゾエティス・ベルジャム・エス・アー | 抗ｎｇｆ抗体およびその使用 |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| JP2014005206A (ja) | 2010-10-22 | 2014-01-16 | Astellas Pharma Inc | アリールアミノヘテロ環カルボキサミド化合物 |
| MX359070B (es) | 2010-12-01 | 2018-09-13 | Alderbio Holdings Llc | Composiciones anti-ngf y uso de las mismas. |
| CA2828219A1 (en) | 2011-02-25 | 2012-08-30 | Irm Llc | Pyrazolo [1,5-a] pyridines as trk inhibitors |
| WO2012125667A1 (en) * | 2011-03-17 | 2012-09-20 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| WO2012125668A1 (en) * | 2011-03-17 | 2012-09-20 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| SG10201913053QA (en) | 2011-05-13 | 2020-03-30 | Array Biopharma Inc | Pyrrolidinyl urea and pyrrolidinyl thiourea compounds as trka kinase inhibitors |
| US8656365B2 (en) | 2011-09-01 | 2014-02-18 | Infosys Limited | Systems, methods, and computer-readable media for measuring quality of application programming interfaces |
| TW201312526A (zh) | 2011-09-02 | 2013-03-16 | Wintek Corp | 觸控顯示面板 |
| WO2013059740A1 (en) | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Novel alk and ntrk1 fusion molecules and uses thereof |
| JP2014533286A (ja) | 2011-11-14 | 2014-12-11 | テサロ， インコーポレイテッド | 特定のチロシンキナーゼの調節 |
| US9045478B2 (en) | 2011-12-12 | 2015-06-02 | Dr. Reddy's Laboratories Ltd. | Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (Trk) inhibitors |
| US9242977B2 (en) | 2012-04-26 | 2016-01-26 | Ono Pharmaceutical Co., Ltd. | Trk-inhibiting compound |
| ES2751944T3 (es) | 2012-05-23 | 2020-04-02 | Nerviano Medical Sciences Srl | Proceso para la preparación de N-[5-(3,5-difluoro-bencil)-1H-indazol-3-il]-4-(4-metil-piperazin-1-il)-2-(tetrahidro-piran-4-ilamino)-benzamida |
| TWI585088B (zh) | 2012-06-04 | 2017-06-01 | 第一三共股份有限公司 | 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物 |
| EP2689778A1 (en) | 2012-07-27 | 2014-01-29 | Pierre Fabre Medicament | Derivatives of azaindoles or diazaindoles for treating pain |
| US20150218652A1 (en) | 2012-08-31 | 2015-08-06 | The Regents Of The Unversity Of Colorado, A Body Corporate | Methods for diagnosis and treatment of cancer |
| US20150238477A1 (en) | 2012-09-07 | 2015-08-27 | Exelixis, Inc. | Method of Treating Lung Adenocarcinoma |
| US20140084039A1 (en) | 2012-09-24 | 2014-03-27 | Electro Scientific Industries, Inc. | Method and apparatus for separating workpieces |
| JP2014082984A (ja) | 2012-10-23 | 2014-05-12 | Astellas Pharma Inc | 新規ｎｔｒｋ２活性化変異の検出法 |
| US11230589B2 (en) | 2012-11-05 | 2022-01-25 | Foundation Medicine, Inc. | Fusion molecules and uses thereof |
| WO2014072220A1 (en) | 2012-11-07 | 2014-05-15 | Nerviano Medical Sciences S.R.L. | Substituted pyrimidinyl and pyridinyl-pyrrolopyridinones, process for their preparation and their use as kinase inhibitors |
| US9809578B2 (en) | 2012-11-13 | 2017-11-07 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors |
| WO2014078408A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078331A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(arylalkyl)-n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078328A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078372A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9981959B2 (en) | 2012-11-13 | 2018-05-29 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| SMT201800169T1 (it) | 2012-11-13 | 2018-05-02 | Array Biopharma Inc | Composti di n-pirrolidinile, n'-pirazolile-urea, tiourea, guanidina e cianoguanidina come inibitore di chinasi trka |
| RS55593B1 (sr) | 2012-11-13 | 2017-06-30 | Array Biopharma Inc | Jedinjenja biciklične uree, tiouree, guanidina i cijanoguanidina korisna za lečenje bola |
| WO2014078325A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| HK1213189A1 (zh) | 2012-11-29 | 2016-06-30 | 耶达研究及发展有限公司 | 预防肿瘤转移、癌症治疗和预後及鉴定为推定转移抑制剂的试剂的方法 |
| US9127055B2 (en) | 2013-02-08 | 2015-09-08 | Astellas Pharma Inc. | Method of treating pain with anti-human NGF antibody |
| MX353336B (es) | 2013-02-19 | 2018-01-09 | Ono Pharmaceutical Co | Compuesto inhibidor de cinasa del receptor de tropomiosina (trk). |
| WO2014130975A1 (en) | 2013-02-22 | 2014-08-28 | Bastian Boris C | Fusion polynucleotides and fusion polypeptides associated with cancer and particularly melanoma and their uses as therapeutic and diagnostic targets |
| US20140243332A1 (en) | 2013-02-27 | 2014-08-28 | Oregon Health & Science University | Methods of treating cancers characterized by aberrent ros1 activity |
| WO2014152777A2 (en) | 2013-03-15 | 2014-09-25 | Insight Genetics, Inc. | Methods and compositions for the diagnosis and treatment of cancers resistant to ros1 inhibitors |
| US8937071B2 (en) | 2013-03-15 | 2015-01-20 | Glaxosmithkline Intellectual Property Development Limited | Compounds as rearranged during transfection (RET) inhibitors |
| WO2014150751A2 (en) | 2013-03-15 | 2014-09-25 | Novartis Ag | Biomarkers associated with brm inhibition |
| WO2014151734A1 (en) | 2013-03-15 | 2014-09-25 | The Trustees Of Columbia University In The City Of New York | Fusion proteins and methods thereof |
| CN105518151B (zh) | 2013-03-15 | 2021-05-25 | 莱兰斯坦福初级大学评议会 | 循环核酸肿瘤标志物的鉴别和用途 |
| EP2986736B1 (en) | 2013-04-17 | 2019-09-18 | Life Technologies Corporation | Gene fusions and gene variants associated with cancer |
| US9682083B2 (en) | 2013-05-14 | 2017-06-20 | Nerviano Medical Sciences S.R.L. | Pyrrolo[2,3-D]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors |
| JP6510510B2 (ja) | 2013-07-11 | 2019-05-08 | ベータ ファーマシューティカルズ カンパニー リミテッド | プロテインチロシンキナーゼモジュレーター及び使用方法 |
| JP6534930B2 (ja) | 2013-07-26 | 2019-06-26 | 公益財団法人がん研究会 | Ｎｔｒｋ３融合体の検出法 |
| EP3628749A1 (en) | 2013-07-30 | 2020-04-01 | Blueprint Medicines Corporation | Ntrk2 fusions |
| MX2016004678A (es) | 2013-10-24 | 2017-03-10 | Univ Georgetown | Composiciones para el tratamiento del cancer. |
| JPWO2015064621A1 (ja) | 2013-10-29 | 2017-03-09 | 公益財団法人がん研究会 | 新規融合体及びその検出法 |
| LT3636649T (lt) | 2014-01-24 | 2024-04-10 | Turning Point Therapeutics, Inc. | Diarilo makrociklai kaip proteinkinazių moduliatoriai |
| CA2934043C (en) | 2014-02-05 | 2019-03-12 | VM Oncology LLC | Trka receptor tyrosine kinase antagonists and uses thereof |
| TWI672141B (zh) | 2014-02-20 | 2019-09-21 | 美商醫科泰生技 | 投予ｒｏｓ１突變癌細胞之分子 |
| EP3154959B1 (en) | 2014-05-15 | 2019-07-10 | Array Biopharma, Inc. | 1-((3s,4r)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1h-pyrazol-5-yl)urea as a trka kinase inhibitor |
| WO2015183837A1 (en) | 2014-05-27 | 2015-12-03 | Brian Haynes | Compositions, methods, and uses related to ntrk2-tert fusions |
| US20170114415A1 (en) | 2014-05-30 | 2017-04-27 | The Regents Of The University Of Colorado, A Body Corporate | Activating ntrk1 gene fusions predictive of kinase inhibitor therapy |
| KR20170042614A (ko) | 2014-08-01 | 2017-04-19 | 파마싸이클릭스 엘엘씨 | Btk 저해제를 이용한 치료에 대한 dlbcl의 반응을 예측하기 위한 바이오마커 |
| AU2015304438B2 (en) | 2014-08-18 | 2019-06-20 | Ono Pharmaceutical Co., Ltd. | Acid-addition salt of Trk-inhibiting compound |
| EP3206711B1 (en) | 2014-10-14 | 2023-05-31 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
| PT3699181T (pt) | 2014-11-16 | 2023-04-05 | Array Biopharma Inc | Forma cristalina de hidrogenossulfato de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| HRP20240937T1 (hr) | 2014-12-15 | 2024-10-25 | Cmg Pharmaceutical Co., Ltd. | Heteroaril spoj sa kondeziranim prstenom i njihova primjena kao trk inhibitora |
| CN108025048B (zh) | 2015-05-20 | 2022-10-25 | 博德研究所 | 共有的新抗原 |
| US20180177792A1 (en) | 2015-05-29 | 2018-06-28 | Ignyta, Inc. | Compositions and methods for treating patients with rtk mutant cells |
| TN2017000502A1 (en) | 2015-06-01 | 2019-04-12 | Loxo Oncology Inc | Methods of diagnosing and treating cancer |
| AU2015101722A4 (en) | 2015-06-19 | 2016-05-19 | Macau University Of Science And Technology | Oncogenic ros1 and alk kinase inhibitor |
| US9782400B2 (en) | 2015-06-19 | 2017-10-10 | Macau University Of Science And Technology | Oncogenic ROS1 and ALK kinase inhibitor |
| GB201511546D0 (en) | 2015-07-01 | 2015-08-12 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers |
| US10316044B2 (en) | 2015-07-02 | 2019-06-11 | Tp Therapeutics, Inc. | Chiral diaryl macrocycles as modulators of protein kinases |
| TN2018000138A1 (en) | 2015-10-26 | 2019-10-04 | Array Biopharma Inc | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US20170224662A1 (en) | 2016-01-22 | 2017-08-10 | The Medicines Company | Aqueous Formulations and Methods of Preparation and Use Thereof |
| WO2017155018A1 (ja) | 2016-03-11 | 2017-09-14 | 小野薬品工業株式会社 | Ｔｒｋ阻害剤抵抗性の癌治療剤 |
| CN109414442B (zh) | 2016-04-04 | 2024-03-29 | 洛克索肿瘤学股份有限公司 | 一种化合物的液体制剂 |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| EP3445361A1 (en) | 2016-04-19 | 2019-02-27 | Exelixis, Inc. | Triple negative breast cancer treatment method |
| DK3800189T3 (da) | 2016-05-18 | 2023-07-31 | Loxo Oncology Inc | Fremstilling af (s)-n-(5-((r)-2-(2,5-difluorphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid |
| WO2017201156A1 (en) | 2016-05-18 | 2017-11-23 | Duke University | Method of treating kras wild-type metastatic colorectal cell carcinoma using cabozantinib plus panitumumab |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| EP3700576A1 (en) | 2017-10-26 | 2020-09-02 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
-
2015
- 2015-11-16 PT PT201697075T patent/PT3699181T/pt unknown
- 2015-11-16 BR BR112017010141-6A patent/BR112017010141A2/pt not_active Application Discontinuation
- 2015-11-16 RS RS20230253A patent/RS64122B1/sr unknown
- 2015-11-16 WO PCT/US2015/060953 patent/WO2016077841A1/en not_active Ceased
- 2015-11-16 FI FIEP20169707.5T patent/FI3699181T3/fi active
- 2015-11-16 ES ES20169707T patent/ES2941630T3/es active Active
- 2015-11-16 SI SI201531931T patent/SI3699181T1/sl unknown
- 2015-11-16 CA CA2967951A patent/CA2967951C/en active Active
- 2015-11-16 UA UAA201705913A patent/UA123044C2/uk unknown
- 2015-11-16 HU HUE20169707A patent/HUE061448T2/hu unknown
- 2015-11-16 DK DK20169707.5T patent/DK3699181T3/da active
- 2015-11-16 CR CR20170263A patent/CR20170263A/es unknown
- 2015-11-16 EP EP15808300.6A patent/EP3218380B1/en active Active
- 2015-11-16 AU AU2015346046A patent/AU2015346046B2/en active Active
- 2015-11-16 US US14/943,014 patent/US10799505B2/en active Active
- 2015-11-16 LT LTEP20169707.5T patent/LT3699181T/lt unknown
- 2015-11-16 CN CN202110402862.7A patent/CN113354649B/zh active Active
- 2015-11-16 HR HRP20230271TT patent/HRP20230271T1/hr unknown
- 2015-11-16 EP EP20169707.5A patent/EP3699181B1/en active Active
- 2015-11-16 KR KR1020177016115A patent/KR102649887B1/ko active Active
- 2015-11-16 PL PL20169707.5T patent/PL3699181T3/pl unknown
- 2015-11-16 IL IL290905A patent/IL290905B2/en unknown
- 2015-11-16 TW TW110139370A patent/TWI767858B/zh active
- 2015-11-16 SG SG11201703962XA patent/SG11201703962XA/en unknown
- 2015-11-16 CN CN201580073515.7A patent/CN107428760B/zh active Active
- 2015-11-16 TW TW104137812A patent/TWI746426B/zh active
- 2015-11-16 MX MX2017006412A patent/MX376478B/es active IP Right Grant
- 2015-11-16 JP JP2017526116A patent/JP6914834B2/ja active Active
- 2015-11-16 HK HK18103883.4A patent/HK1244483A1/zh unknown
-
2017
- 2017-01-05 US US15/399,207 patent/US9782414B2/en active Active
- 2017-05-14 IL IL252270A patent/IL252270B/en unknown
- 2017-05-15 PH PH12017500900A patent/PH12017500900A1/en unknown
- 2017-05-16 MX MX2020011079A patent/MX2020011079A/es unknown
- 2017-05-16 CL CL2017001249A patent/CL2017001249A1/es unknown
- 2017-05-22 ZA ZA2017/03501A patent/ZA201703501B/en unknown
- 2017-05-31 CO CONC2017/0005483A patent/CO2017005483A2/es unknown
- 2017-09-15 US US15/706,062 patent/US10285993B2/en active Active
-
2018
- 2018-01-16 US US15/872,769 patent/US10172861B2/en active Active
-
2019
- 2019-03-27 US US16/366,368 patent/US10813936B2/en active Active
-
2021
- 2021-04-12 PH PH12021550809A patent/PH12021550809A1/en unknown
- 2021-07-14 JP JP2021116073A patent/JP2021169496A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2941630T3 (es) | Forma cristalina de sulfato de hidrógeno de (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida | |
| AU2017246554B2 (en) | Liquid formulations of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo(1,5-a)pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide | |
| HK40036794A (en) | Crystalline form of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate | |
| HK40036794B (en) | Crystalline form of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate | |
| RU2723990C9 (ru) | Кристаллическая форма (s)-n-(5-((r)-2-(2,5-дифторфенил)-пирролидин-1-ил)-пиразоло[1,5-a]пиримидин-3-ил)-3-гидроксипирролидин-1-карбоксамида гидросульфата | |
| BR112018070304B1 (pt) | Formulações líquidas de (s)-n-(5-((r)-2-(2,5- difluorofenil)-pirrolidin-1-il) -pirazolo[1,5-a]pirimidin-3- il)-3-hidroxipirrolidina-1-carboxamida, e seu uso". referência cruzada aos pedidos relacionados |