ES2884044T3 - Profármaco alquilante de fosforamidato para el tratamiento del cáncer - Google Patents
Profármaco alquilante de fosforamidato para el tratamiento del cáncer Download PDFInfo
- Publication number
- ES2884044T3 ES2884044T3 ES07869800T ES07869800T ES2884044T3 ES 2884044 T3 ES2884044 T3 ES 2884044T3 ES 07869800 T ES07869800 T ES 07869800T ES 07869800 T ES07869800 T ES 07869800T ES 2884044 T3 ES2884044 T3 ES 2884044T3
- Authority
- ES
- Spain
- Prior art keywords
- cancer
- formulation
- dose
- administration
- treatment
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 94
- 238000011282 treatment Methods 0.000 title claims abstract description 67
- 201000011510 cancer Diseases 0.000 title claims abstract description 52
- 239000000651 prodrug Substances 0.000 title description 17
- 229940002612 prodrug Drugs 0.000 title description 17
- 230000002152 alkylating effect Effects 0.000 title description 6
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 title description 6
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 238000009472 formulation Methods 0.000 claims abstract description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 32
- 238000001990 intravenous administration Methods 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims description 32
- 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 claims description 21
- 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 claims description 12
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 9
- 238000001959 radiotherapy Methods 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 8
- 229960004768 irinotecan Drugs 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 229940034982 antineoplastic agent Drugs 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 229960003668 docetaxel Drugs 0.000 claims description 6
- 208000037819 metastatic cancer Diseases 0.000 claims description 5
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 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 claims description 4
- 229960005277 gemcitabine Drugs 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 201000006491 bone marrow cancer Diseases 0.000 claims description 3
- 229960004562 carboplatin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 201000010453 lymph node cancer Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 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 claims description 3
- 238000007865 diluting Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 190000008236 carboplatin Chemical compound 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 34
- 229940079593 drug Drugs 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 26
- 241000700159 Rattus Species 0.000 description 25
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 22
- 241000282472 Canis lupus familiaris Species 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 17
- 231100000419 toxicity Toxicity 0.000 description 17
- 230000001988 toxicity Effects 0.000 description 17
- 201000010099 disease Diseases 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 229940063683 taxotere Drugs 0.000 description 14
- 206010021143 Hypoxia Diseases 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 206010061289 metastatic neoplasm Diseases 0.000 description 12
- 229940109239 creatinine Drugs 0.000 description 11
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- FUNYDODCWWGJJA-UHFFFAOYSA-N bis(2-bromoethylamino)phosphinic acid Chemical compound BrCCNP(=O)(O)NCCBr FUNYDODCWWGJJA-UHFFFAOYSA-N 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- -1 for example Chemical compound 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 241000282412 Homo Species 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 206010061818 Disease progression Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 230000005750 disease progression Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000007954 hypoxia Effects 0.000 description 6
- 238000002483 medication Methods 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 206010047115 Vasculitis Diseases 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000003463 hyperproliferative effect Effects 0.000 description 5
- 230000001146 hypoxic effect Effects 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 230000001394 metastastic effect Effects 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 201000009030 Carcinoma Diseases 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000118 anti-neoplastic effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 206010027452 Metastases to bone Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- HPYIIXJJVYSMCV-MGDXKYBTSA-N astressin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]1C(N[C@@H](C)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@@H](CCCCNC(=O)CC1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)=O)C(C)C)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CNC=N1 HPYIIXJJVYSMCV-MGDXKYBTSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000029918 bioluminescence Effects 0.000 description 3
- 238000005415 bioluminescence Methods 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 208000004235 neutropenia Diseases 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000009597 pregnancy test Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000012766 Growth delay Diseases 0.000 description 2
- 208000032514 Leukocytoclastic vasculitis Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010028813 Nausea Diseases 0.000 description 2
- 229910019213 POCl3 Inorganic materials 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000036772 blood pressure Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 231100000226 haematotoxicity Toxicity 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 208000018875 hypoxemia Diseases 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 238000009121 systemic therapy Methods 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000033116 Asbestos intoxication Diseases 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010051341 Bile duct stenosis Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 206010009137 Chronic sinusitis Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 208000002633 Febrile Neutropenia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 201000004331 Henoch-Schoenlein purpura Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000031814 IgA Vasculitis Diseases 0.000 description 1
- 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 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 208000034624 Leukocytoclastic Cutaneous Vasculitis Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 208000000592 Nasal Polyps Diseases 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000005890 Neuroma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019201 POBr3 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 206010036783 Proctitis ulcerative Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 101150057615 Syn gene Proteins 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 208000037844 advanced solid tumor Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 206010003441 asbestosis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 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 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000021126 eustachian tube disease Diseases 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 201000008361 ganglioneuroma Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 201000006362 hypersensitivity vasculitis Diseases 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 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 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000012028 nasolacrimal duct disease Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003281 pleural cavity Anatomy 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 208000030761 polycystic kidney disease Diseases 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 208000030266 primary brain neoplasm Diseases 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 208000017497 prostate disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000001150 spermicidal effect Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87186506P | 2006-12-26 | 2006-12-26 | |
| PCT/US2007/088645 WO2008083101A1 (en) | 2006-12-26 | 2007-12-21 | Phosphoramidate alkylator prodrugs for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2884044T3 true ES2884044T3 (es) | 2021-12-10 |
Family
ID=39588979
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07869800T Active ES2884044T3 (es) | 2006-12-26 | 2007-12-21 | Profármaco alquilante de fosforamidato para el tratamiento del cáncer |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8552048B2 (enExample) |
| EP (1) | EP2114157B1 (enExample) |
| JP (1) | JP5357049B2 (enExample) |
| ES (1) | ES2884044T3 (enExample) |
| WO (1) | WO2008083101A1 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA200507752B (en) | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
| SI1896040T1 (sl) * | 2005-06-29 | 2012-12-31 | Threshold Pharmaceuticals, Inc. | Fosforamidatna alkilatorska predzdravila |
| ES2884044T3 (es) | 2006-12-26 | 2021-12-10 | Immunogenesis Inc | Profármaco alquilante de fosforamidato para el tratamiento del cáncer |
| JP5765634B2 (ja) | 2008-10-21 | 2015-08-19 | スレッシュホールド ファーマシューティカルズ， インコーポレイテッド | 低酸素活性化型プロドラッグを用いるがんの処置 |
| MX2012014416A (es) * | 2010-06-28 | 2013-02-27 | Threshold Pharmaceuticals Inc | Tratamiento de cancer de sangre. |
| KR20130045341A (ko) | 2010-07-12 | 2013-05-03 | 쓰레솔드 파마슈티컬스, 인코포레이티드 | 암 치료를 위한 저산소증 활성 프로드러그와 항혈관형성제의 투여 |
| KR20140038390A (ko) * | 2011-04-01 | 2014-03-28 | 쓰레솔드 파마슈티컬스, 인코포레이티드 | 암을 치료하는 방법 |
| RU2013147744A (ru) * | 2011-04-15 | 2015-05-20 | Тресхолд Фармасьютикалз, Инк. | Дозированная лекарственная форма для перорального применения |
| JP2015500885A (ja) * | 2011-12-22 | 2015-01-08 | スレッショルド ファーマシューティカルズ，インコーポレイテッド | 癌を治療するためのｃｈｋ１阻害剤と組み合わせた低酸素活性化プロドラッグの投与 |
| EP2817011B1 (en) * | 2012-02-21 | 2022-01-05 | ImmunoGenesis, Inc. | Treatment of cancer |
| WO2014062856A1 (en) | 2012-10-16 | 2014-04-24 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| JP5922791B2 (ja) | 2012-10-29 | 2016-05-24 | 京セラ株式会社 | 弾性表面波センサ |
| CN105792845A (zh) | 2013-07-26 | 2016-07-20 | 施瑞修德制药公司 | 使用低氧活化的前药与紫杉烷类化合物的组合治疗胰腺癌 |
| US10071109B2 (en) | 2013-11-06 | 2018-09-11 | Molecular Templates, Inc. | Predictive biomarker for hypoxia-activated prodrug therapy |
| WO2016011195A1 (en) * | 2014-07-17 | 2016-01-21 | Threshold Pharmaceuticals, Inc. | Th-302 solid forms and methods related thereto |
| SG11201707293VA (en) | 2015-03-10 | 2017-10-30 | Ascenta Pharmaceuticals Ltd | Dna alkylating agents |
| US10829437B2 (en) | 2015-04-02 | 2020-11-10 | Obi Pharma, Inc. | Nitrobenzyl derivatives of anti-cancer agents |
| PL412787A1 (pl) | 2015-06-22 | 2017-01-02 | Magdalena Król | Oparty na makrofagach celowany system dostarczania związków związanych z ferrytyną |
| US20180169064A1 (en) | 2015-06-24 | 2018-06-21 | Threshold Pharmaceuticals, Inc. | Aziridine containing dna alkylating agents |
| EP4549467A3 (en) | 2016-08-01 | 2025-07-23 | ImmunoGenesis, Inc. | Administration of hypoxia activated prodrugs in combination with immune modulatory agents for treating cancer |
| WO2019238886A1 (en) | 2018-06-13 | 2019-12-19 | University Of Dundee | Bifunctional molecules for targeting usp14 |
| KR20210020107A (ko) | 2018-06-13 | 2021-02-23 | 암피스타 테라퓨틱스 엘티디 | UchL5 표적화를 위한 이중작용성 분자 |
| WO2019238817A1 (en) | 2018-06-13 | 2019-12-19 | University Of Dundee | Bifunctional molecules for targeting rpn11 |
| US20210393620A1 (en) * | 2018-09-24 | 2021-12-23 | Sierra Oncology, Inc. | Methods of Treatment of Cancer Comprising CDC7 Inhibitors |
| EP3650046A1 (en) | 2018-11-08 | 2020-05-13 | Cellis AG | Mesenchymal stem cell based targeted active ingredient delivery system |
| AU2021237774A1 (en) | 2020-03-18 | 2022-09-22 | Cellis Ag | Ferritin variants with increased stability, complexation ability and transferrin receptor affinity |
| WO2022195092A1 (en) | 2021-03-18 | 2022-09-22 | Cellis Ag | Ferritin variants with increased stability and complexation ability |
| CN118076359A (zh) * | 2021-08-27 | 2024-05-24 | 深圳艾欣达伟医药科技有限公司 | 使用th-302治疗parp抑制剂耐药的患者 |
| CN117651548A (zh) * | 2021-08-27 | 2024-03-05 | 深圳艾欣达伟医药科技有限公司 | 冻干制剂溶液及冻干制剂、方法和用途 |
| US20250186468A1 (en) | 2022-03-15 | 2025-06-12 | Ascentawits Pharmaceuticals, Ltd. | Method for treating patient with brca-mutated cancer |
| CN119384281A (zh) | 2022-04-15 | 2025-01-28 | 深圳艾欣达伟医药科技有限公司 | 使用th-302单药或联用parp抑制剂治疗癌症的方法 |
| WO2023226959A1 (zh) | 2022-05-23 | 2023-11-30 | 深圳艾欣达伟医药科技有限公司 | 烷化剂前药与细胞周期抑制剂联用治疗癌症的方法 |
| WO2024056413A1 (en) | 2022-09-13 | 2024-03-21 | Cellis Ag | Isolated targeted delivery system for the treatment of glioma |
| CN119894521A (zh) | 2022-09-22 | 2025-04-25 | 深圳艾欣达伟医药科技有限公司 | 乏氧激活的化合物在制备治疗癌症患者的药物中的用途 |
| EP4637829A1 (en) | 2022-12-20 | 2025-10-29 | Cellis Sp. z o.o. ([Ltd.] | Isolated targeted delivery system for the treatment of ovarian cancer |
| WO2024179467A1 (zh) * | 2023-02-27 | 2024-09-06 | 深圳艾欣达伟医药科技有限公司 | 溶液、冻干制剂、冻干制剂单位包装、注射液及注射液配制方法 |
| WO2025083276A1 (en) | 2023-10-19 | 2025-04-24 | Cellis Ag | Improved isolated targeted delivery system |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3652579A (en) | 1969-06-26 | 1972-03-28 | Hoffmann La Roche | 1-methyl-2-substituted 5-nitroimidazoles |
| DE2229248C3 (de) | 1971-07-30 | 1980-03-27 | Gruppo Lepetit S.P.A., Mailand (Italien) | 5-Iminomethyl-2-nitroimidazoI-Derivate und Verfahren zu deren Herstellung |
| US4921963A (en) | 1987-04-13 | 1990-05-01 | British Columbia Cancer Foundation | Platinum complexes with one radiosensitizing ligand |
| JPH0819111B2 (ja) | 1987-10-22 | 1996-02-28 | ポーラ化成工業株式会社 | ２―ニトロイミダゾール誘導体及びこれを有効成分とする放射線増感剤 |
| US4908356A (en) | 1988-05-25 | 1990-03-13 | Research Corporation Technologies, Inc. | Aldophosphamide derivatives useful as antitumor agents |
| US5403932A (en) | 1988-05-25 | 1995-04-04 | Research Corporation Technologies, Inc. | Phosphoramidates useful as antitumor agents |
| US5190929A (en) | 1988-05-25 | 1993-03-02 | Research Corporation Technologies, Inc. | Cyclophosphamide analogs useful as anti-tumor agents |
| DE3835772A1 (de) | 1988-10-20 | 1990-04-26 | Deutsches Krebsforsch | Tumorhemmende saccharid-konjugate |
| KR927003539A (ko) | 1990-01-26 | 1992-12-18 | 스즈끼 쯔네시 | 2-니트로 이미다졸 유도체, 그의 제조방법 및 이를 유효성분으로 하는 방사선 증감제 |
| US5233031A (en) | 1991-09-23 | 1993-08-03 | University Of Rochester | Phosphoramidate analogs of 2'-deoxyuridine |
| EP0638123B1 (en) | 1991-10-23 | 2006-12-27 | Cancer Research Technology Limited | Bacterial nitroreductase for the reduction of cb 1954 and analogues thereof to a cytotoxic form |
| US5750782A (en) | 1992-11-27 | 1998-05-12 | Cancer Research Campaign Technology Limited | Nitroaniline derivatives and their use as anti-tumour agents |
| US5306727A (en) | 1993-04-30 | 1994-04-26 | Research Corporation Technologies, Inc. | Phosphoramidates useful as antitumor agents |
| US5691371A (en) | 1993-05-25 | 1997-11-25 | Auckland Uniservices Limited | Nitrobenzyl mustard quaternary salts and their use as hypoxia-selective cytotoxic agents |
| DE69425356T2 (de) | 1993-09-22 | 2002-04-18 | Hoechst Ag | Pro-Prodrugs, ihre Herstellung und Anwendung |
| JPH07309761A (ja) | 1994-05-20 | 1995-11-28 | Kyowa Hakko Kogyo Co Ltd | デュオカルマイシン誘導体の安定化法 |
| US5659061A (en) | 1995-04-20 | 1997-08-19 | Drug Innovation & Design, Inc. | Tumor protease activated prodrugs of phosphoramide mustard analogs with toxification and detoxification functionalities |
| GB9516943D0 (en) | 1995-08-18 | 1995-10-18 | Cancer Soc Auckland Div Nz Inc | Novel cyclopropylindoles and their secoprecursors,and their use as prodrugs |
| US6218519B1 (en) | 1996-04-12 | 2001-04-17 | Pro-Neuron, Inc. | Compounds and methods for the selective treatment of cancer and bacterial infections |
| US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| US6251933B1 (en) | 1996-12-13 | 2001-06-26 | The Cancer Research Campaign Technology Limited | Seco precursors of cyclopropylindolines and their use as prodrugs |
| DE19720312A1 (de) | 1997-05-15 | 1998-11-19 | Hoechst Ag | Zubereitung mit erhöhter in vivo Verträglichkeit |
| US6240925B1 (en) | 1999-03-23 | 2001-06-05 | Cynosure, Inc. | Photothermal vascular targeting with bioreductive agents |
| GB9909612D0 (en) | 1999-04-26 | 1999-06-23 | Cancer Res Campaign Tech | N-protected amines and their use as prodrugs |
| DE60007120T2 (de) | 1999-05-24 | 2004-09-16 | Southern Research Institute, Birmingham | Isophosphoramide-senfgasanalogen und deren verwendung |
| WO2001004130A1 (en) | 1999-07-14 | 2001-01-18 | Purdue Research Foundation | Phosphoramide compounds |
| WO2001074827A1 (en) | 2000-03-31 | 2001-10-11 | Purdue Research Foundation | Phosphoramidate prodrugs |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US6506739B1 (en) | 2001-05-01 | 2003-01-14 | Telik, Inc. | Bis-(N,N'-bis-(2-haloethyl)amino)phosphoramidates as antitumor agents |
| WO2002096910A1 (en) | 2001-05-31 | 2002-12-05 | Medarex, Inc. | Cytotoxins, prodrugs, linkers and stabilizers useful therefor |
| FR2825926A1 (fr) | 2001-06-14 | 2002-12-20 | Sod Conseils Rech Applic | Derives d'imidazoles modulant les canaux sodiques |
| US7091186B2 (en) | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| KR20030067275A (ko) | 2002-02-07 | 2003-08-14 | 주식회사 하이폭시 | 니트로이미다졸 및 위상 이성질화 효소 저해제를유효성분으로 포함하는 항암제 |
| GB0306907D0 (en) | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Boireductively-activated prodrugs |
| GB0306908D0 (en) | 2003-03-26 | 2003-04-30 | Angiogene Pharm Ltd | Bioreductively activated stilbene prodrugs |
| ZA200507752B (en) * | 2003-03-28 | 2007-01-31 | Threshold Pharmaceuticals Inc | Compositions and methods for treating cancer |
| US6855695B2 (en) | 2003-06-13 | 2005-02-15 | Vion Pharmaceuticals, Inc. | Water-soluble SHPs as novel alkylating agents |
| KR101167335B1 (ko) | 2003-10-31 | 2012-07-19 | 오클랜드 유니서비시즈 리미티드 | 니트로페닐 머스타드, 니트로페닐아지리딘 알코올 및 이에상응하는 포스페이트, 및 타겟화된 세포독성제로서의이들의 용도 |
| NZ549605A (en) | 2004-02-06 | 2010-01-29 | Threshold Pharmaceuticals Inc | Use of glufosfamide to treat chemotherapy-refractory pancreatic cancer |
| US20090042820A1 (en) | 2004-11-22 | 2009-02-12 | Threshold Pharmaceuticals, Inc. | Tubulin Binding Anti Cancer Agents And Prodrugs Thereof |
| SI1896040T1 (sl) * | 2005-06-29 | 2012-12-31 | Threshold Pharmaceuticals, Inc. | Fosforamidatna alkilatorska predzdravila |
| KR100755435B1 (ko) * | 2005-10-04 | 2007-09-04 | 삼성전자주식회사 | 디지털 방송 제한 수신 단말기 및 그 방법 |
| WO2008011588A2 (en) | 2006-07-20 | 2008-01-24 | Threshold Pharmaceuticals, Inc. | Glycoconjugates of phosphoramidate alkylators for treatment of cancer |
| WO2008076826A1 (en) | 2006-12-13 | 2008-06-26 | Threshold Pharmaceuticals, Inc. | Pyrophosphoramide alkylators |
| ES2884044T3 (es) | 2006-12-26 | 2021-12-10 | Immunogenesis Inc | Profármaco alquilante de fosforamidato para el tratamiento del cáncer |
-
2007
- 2007-12-21 ES ES07869800T patent/ES2884044T3/es active Active
- 2007-12-21 EP EP07869800.8A patent/EP2114157B1/en active Active
- 2007-12-21 JP JP2009544230A patent/JP5357049B2/ja not_active Expired - Fee Related
- 2007-12-21 WO PCT/US2007/088645 patent/WO2008083101A1/en not_active Ceased
- 2007-12-21 US US12/521,290 patent/US8552048B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP5357049B2 (ja) | 2013-12-04 |
| EP2114157A4 (en) | 2013-01-23 |
| EP2114157B1 (en) | 2021-05-26 |
| WO2008083101A1 (en) | 2008-07-10 |
| US8552048B2 (en) | 2013-10-08 |
| EP2114157A1 (en) | 2009-11-11 |
| JP2010514787A (ja) | 2010-05-06 |
| US20100183742A1 (en) | 2010-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2884044T3 (es) | Profármaco alquilante de fosforamidato para el tratamiento del cáncer | |
| ES2719091T3 (es) | Terapia de combinación con un inhibidor mitótico | |
| ES2884674T3 (es) | Tratamiento del cáncer con el profármaco activado por hipoxia TH-302 en combinación con docetaxel o pemetrexed | |
| ES2258661T3 (es) | Formulaciones farmaceuticas con un derivado de platino. | |
| ES2261399T3 (es) | Administracion de un compuesto quimioprotector que contiene tiol. | |
| ES2550759T3 (es) | Formulaciones farmacológicas de platino mejoradas | |
| ES2909741T3 (es) | Tratamiento del cáncer | |
| ES2862340T3 (es) | Nuevo uso antitumoral de cabazitaxel | |
| EP2063881B1 (en) | A composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer | |
| US20210267896A1 (en) | Formulations for treating bladder cancer | |
| AU2013308465B2 (en) | Drug delivery systems and methods for treatment of prostate disease comprising gemicitabine | |
| KR20020087456A (ko) | 혈관 손상 활성을 지닌 조합 요법 | |
| ES2745506T3 (es) | Combinación antitumoral que comprende cabazitaxel y cisplatino | |
| CN103623394A (zh) | 一种peg-hm-3和铂类、紫杉醇类或他滨类药物在制备实体瘤药物中的用途 | |
| JP5615189B2 (ja) | ベリノスタットの長期持続注入を用いた治療方法 | |
| ES2774101T3 (es) | Cabazitaxel y su uso para tratar cáncer | |
| JP2009539774A (ja) | 薬物の投与方法 | |
| JP2023520975A (ja) | 塩基性化学療法腫瘍内注射製剤 | |
| WO2022271540A1 (en) | Inhibitors of dot1l | |
| Shinchi et al. | A resected case of effective treatment with gemcitabine for advanced pancreatic cancer with peritoneal metastasis | |
| HK1202419B (en) | Combination therapy with a mitotic inhibitor | |
| HK1202423B (en) | Combination therapy with a topoisomerase inhibitor |