ES2991280T3 - Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T - Google Patents
Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T Download PDFInfo
- Publication number
- ES2991280T3 ES2991280T3 ES19735699T ES19735699T ES2991280T3 ES 2991280 T3 ES2991280 T3 ES 2991280T3 ES 19735699 T ES19735699 T ES 19735699T ES 19735699 T ES19735699 T ES 19735699T ES 2991280 T3 ES2991280 T3 ES 2991280T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- group
- ccr2 antagonist
- ctcl
- heteroaryl
- 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
- 239000005557 antagonist Substances 0.000 title claims abstract description 13
- 201000005962 mycosis fungoides Diseases 0.000 title claims description 69
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 title claims description 64
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 title claims description 62
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 title claims description 62
- 238000011282 treatment Methods 0.000 title description 49
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 title description 19
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 title description 19
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 95
- 239000002604 chemokine receptor CCR2 antagonist Substances 0.000 claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 20
- 102000009410 Chemokine receptor Human genes 0.000 claims abstract description 6
- 108050000299 Chemokine receptor Proteins 0.000 claims abstract description 6
- 229940125904 compound 1 Drugs 0.000 claims description 63
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- -1 arylC1-4alkyl Chemical group 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- 229910003827 NRaRb Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 229960003301 nivolumab Drugs 0.000 claims description 9
- 239000012271 PD-L1 inhibitor Substances 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229940121656 pd-l1 inhibitor Drugs 0.000 claims description 8
- 229960002621 pembrolizumab Drugs 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 6
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 6
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 6
- 239000012270 PD-1 inhibitor Substances 0.000 claims description 5
- 239000012668 PD-1-inhibitor Substances 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 229950009791 durvalumab Drugs 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 229940121655 pd-1 inhibitor Drugs 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 229950002916 avelumab Drugs 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 229940121497 sintilimab Drugs 0.000 claims description 4
- HFOBENSCBRZVSP-LKXGYXEUSA-N C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O Chemical compound C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O HFOBENSCBRZVSP-LKXGYXEUSA-N 0.000 claims description 3
- 229960003852 atezolizumab Drugs 0.000 claims description 3
- 229940126214 compound 3 Drugs 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229950010773 pidilizumab Drugs 0.000 claims description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 abstract description 31
- 230000001965 increasing effect Effects 0.000 abstract description 15
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 description 67
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 59
- 108010074708 B7-H1 Antigen Proteins 0.000 description 56
- 241000699670 Mus sp. Species 0.000 description 52
- 210000004027 cell Anatomy 0.000 description 32
- 101001056128 Homo sapiens Mannose-binding protein C Proteins 0.000 description 24
- 102100026553 Mannose-binding protein C Human genes 0.000 description 24
- LOTKRQAVGJMPNV-UHFFFAOYSA-N 1-fluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C([N+]([O-])=O)=C1 LOTKRQAVGJMPNV-UHFFFAOYSA-N 0.000 description 21
- 239000003981 vehicle Substances 0.000 description 21
- 210000003491 skin Anatomy 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 239000000203 mixture Substances 0.000 description 17
- 210000001165 lymph node Anatomy 0.000 description 16
- 210000001744 T-lymphocyte Anatomy 0.000 description 15
- 230000004614 tumor growth Effects 0.000 description 15
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 13
- 210000005069 ears Anatomy 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 230000008685 targeting Effects 0.000 description 13
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 12
- 238000002513 implantation Methods 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- 208000009129 Ear Neoplasms Diseases 0.000 description 11
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 11
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 11
- 150000003384 small molecules Chemical class 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229940045513 CTLA4 antagonist Drugs 0.000 description 10
- 229910018828 PO3H2 Inorganic materials 0.000 description 10
- 229910006074 SO2NH2 Inorganic materials 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000002648 combination therapy Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 210000000440 neutrophil Anatomy 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 230000005740 tumor formation Effects 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 6
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 6
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 6
- 102100022338 Integrin alpha-M Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 206010042971 T-cell lymphoma Diseases 0.000 description 6
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 6
- 239000000090 biomarker Substances 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 239000006285 cell suspension Substances 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 5
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 5
- 102000019034 Chemokines Human genes 0.000 description 5
- 108010012236 Chemokines Proteins 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 208000009359 Sezary Syndrome Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 229960000106 biosimilars Drugs 0.000 description 5
- 125000004404 heteroalkyl group Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 238000011532 immunohistochemical staining Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000001616 monocyte Anatomy 0.000 description 5
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 5
- 230000007115 recruitment Effects 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 108091030071 RNAI Proteins 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000005809 anti-tumor immunity Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000000779 depleting effect Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000890 drug combination Substances 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000009368 gene silencing by RNA Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- 239000012275 CTLA-4 inhibitor Substances 0.000 description 3
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 239000012269 PD-1/PD-L1 inhibitor Substances 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940121653 pd-1/pd-l1 inhibitor Drugs 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 206010015548 Euthanasia Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 2
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 101150030213 Lag3 gene Proteins 0.000 description 2
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 2
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 240000001307 Myosotis scorpioides Species 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 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
- 125000004452 carbocyclyl group Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000005206 flow analysis Methods 0.000 description 2
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 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
- 230000012010 growth Effects 0.000 description 2
- 125000004474 heteroalkylene group Chemical group 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 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
- 239000012442 inert solvent Substances 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000010212 intracellular staining Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 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 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- ZNSVOHSYDRPBGI-CBQRAPNFSA-N n-[2-[(3s)-3-[[4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexyl]amino]pyrrolidin-1-yl]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H](C1)NC2CCC(CC2)(O)C=2N=CC(=CC=2)C=2N=CC=CN=2)CN1C(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZNSVOHSYDRPBGI-CBQRAPNFSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 2
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008279 sol Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- 229950007217 tremelimumab Drugs 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- SRWQVWAIVQXPJY-QGZVFWFLSA-N 4-[(2r)-4-tert-butylpiperazine-2-carbonyl]-n-(4-chloro-3-fluorophenyl)piperazine-1-carboxamide Chemical compound C1N(C(C)(C)C)CCN[C@H]1C(=O)N1CCN(C(=O)NC=2C=C(F)C(Cl)=CC=2)CC1 SRWQVWAIVQXPJY-QGZVFWFLSA-N 0.000 description 1
- LUUMLYXKTPBTQR-UHFFFAOYSA-N 4-chloro-n-[5-methyl-2-(7h-pyrrolo[2,3-d]pyrimidine-4-carbonyl)pyridin-3-yl]-3-(trifluoromethyl)benzenesulfonamide Chemical compound C=1C(C)=CN=C(C(=O)C=2C=3C=CNC=3N=CN=2)C=1NS(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 LUUMLYXKTPBTQR-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-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
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 239000004475 Arginine Substances 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
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 102100022716 Atypical chemokine receptor 3 Human genes 0.000 description 1
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 101001042041 Bos taurus Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm 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
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 102000004497 CCR2 Receptors Human genes 0.000 description 1
- 108010017312 CCR2 Receptors Proteins 0.000 description 1
- 229940125429 CCR2 chemokine receptor antagonist Drugs 0.000 description 1
- 108010062802 CD66 antigens Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
- 102100028914 Catenin beta-1 Human genes 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010055124 Chemokine CCL7 Proteins 0.000 description 1
- 102000001304 Chemokine CCL7 Human genes 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 description 1
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
- 206010014967 Ependymoma Diseases 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
- 229940125570 FS118 Drugs 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102100030708 GTPase KRas Human genes 0.000 description 1
- 102100039788 GTPase NRas Human genes 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 1
- 101150112743 HSPA5 gene Proteins 0.000 description 1
- 101150046249 Havcr2 gene Proteins 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101000678890 Homo sapiens Atypical chemokine receptor 3 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 1
- 101000916173 Homo sapiens Catenin beta-1 Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 1
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 1
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 101000960234 Homo sapiens Isocitrate dehydrogenase [NADP] cytoplasmic Proteins 0.000 description 1
- 101000599886 Homo sapiens Isocitrate dehydrogenase [NADP], mitochondrial Proteins 0.000 description 1
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 1
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 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
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000004556 Interleukin-15 Receptors Human genes 0.000 description 1
- 108010017535 Interleukin-15 Receptors Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 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
- 102100039905 Isocitrate dehydrogenase [NADP] cytoplasmic Human genes 0.000 description 1
- 102100037845 Isocitrate dehydrogenase [NADP], mitochondrial Human genes 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
- 102000017578 LAG3 Human genes 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 229940122142 Lipoxygenase inhibitor Drugs 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 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
- 229940125568 MGD013 Drugs 0.000 description 1
- 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- PJTGSIKANITYOO-RCOXNQKVSA-N N-[(1R,2S,5R)-5-[methyl(propan-2-yl)amino]-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]methanesulfonamide Chemical compound CC(C)N(C)[C@@H]1CC[C@@H]([C@@H](C1)NS(C)(=O)=O)N1CC[C@H](Nc2ncnc3ccc(cc23)C(F)(F)F)C1=O PJTGSIKANITYOO-RCOXNQKVSA-N 0.000 description 1
- RRMJMHOQSALEJJ-UHFFFAOYSA-N N-[5-[[4-[4-[(dimethylamino)methyl]-3-phenylpyrazol-1-yl]pyrimidin-2-yl]amino]-4-methoxy-2-morpholin-4-ylphenyl]prop-2-enamide Chemical compound CN(C)CC=1C(=NN(C=1)C1=NC(=NC=C1)NC=1C(=CC(=C(C=1)NC(C=C)=O)N1CCOCC1)OC)C1=CC=CC=C1 RRMJMHOQSALEJJ-UHFFFAOYSA-N 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
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 229940123134 Nitric oxide inhibitor Drugs 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 102000001759 Notch1 Receptor Human genes 0.000 description 1
- 108010029755 Notch1 Receptor Proteins 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 229910018830 PO3H Inorganic materials 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920001774 Perfluoroether Polymers 0.000 description 1
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 1
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102000003711 Syndecan-2 Human genes 0.000 description 1
- 108090000054 Syndecan-2 Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
- 230000027029 T-helper 2 cell chemotaxis Effects 0.000 description 1
- 101150056647 TNFRSF4 gene Proteins 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- MCRWZBYTLVCCJJ-DKALBXGISA-N [(1s,3r)-3-[[(3s,4s)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[(1s,4s)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)[C@@]1(C[C@@H](CC1)N[C@@H]1[C@@H](COCC1)OC)C(C)C)[H])N2C1=CC(C(F)(F)F)=NC=N1 MCRWZBYTLVCCJJ-DKALBXGISA-N 0.000 description 1
- MTMDXAIUENDNDL-RJSMDTJLSA-N [(1s,3r)-3-[[(3s,4s)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[3-(trifluoromethyl)-7,8-dihydro-5h-1,6-naphthyridin-6-yl]methanone Chemical compound CO[C@@H]1COCC[C@@H]1N[C@H]1C[C@](C(=O)N2CC3=CC(=CN=C3CC2)C(F)(F)F)(C(C)C)CC1 MTMDXAIUENDNDL-RJSMDTJLSA-N 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 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
- 230000006229 amino acid addition Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001656 angiogenetic effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000008365 aqueous carrier 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
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect 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
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 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
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 238000004364 calculation method Methods 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
- 229950011033 cenicriviroc Drugs 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 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
- 230000001684 chronic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper 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
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 229940029030 dendritic cell vaccine Drugs 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 1
- 238000000375 direct analysis in real time Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000012063 dual-affinity re-targeting Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 208000037828 epithelial carcinoma Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- 101150098622 gag gene Proteins 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 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 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 101150028578 grp78 gene Proteins 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin 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
- 229930195733 hydrocarbon Natural products 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical class N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000005746 immune checkpoint blockade Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 210000005008 immunosuppressive cell Anatomy 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
- 208000012804 lymphangiosarcoma Diseases 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000028550 monocyte chemotaxis Effects 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- CMVHFGNTABZQJU-HCXYKTFWSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-3-[(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino]-2-oxopyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2N3N=C(C=C3N=CN=2)C(C)(C)C)CC1 CMVHFGNTABZQJU-HCXYKTFWSA-N 0.000 description 1
- NXZNYBUBXWWKCP-JMOWIOHXSA-N n-[2-[[(3r)-1-[4-hydroxy-4-(6-methoxypyridin-3-yl)cyclohexyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1C1(O)CCC(N2C[C@@H](CC2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)CC1 NXZNYBUBXWWKCP-JMOWIOHXSA-N 0.000 description 1
- 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 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000000174 oncolytic effect Effects 0.000 description 1
- 239000003402 opiate agonist Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229960005547 pelareorep Drugs 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003893 phenacetin Drugs 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 210000003429 pore cell Anatomy 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 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
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 231100000205 reproductive and developmental toxicity Toxicity 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- FECGNJPYVFEKOD-VMPITWQZSA-N resminostat Chemical compound C1=CC(CN(C)C)=CC=C1S(=O)(=O)N1C=C(\C=C\C(=O)NO)C=C1 FECGNJPYVFEKOD-VMPITWQZSA-N 0.000 description 1
- 229950002821 resminostat Drugs 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 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 1
- 229960003676 tenidap Drugs 0.000 description 1
- LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 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
- 230000005748 tumor development Effects 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61K31/536—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 ortho- or peri-condensed with carbocyclic ring systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862614923P | 2018-01-08 | 2018-01-08 | |
| PCT/US2019/012515 WO2019136368A2 (en) | 2018-01-08 | 2019-01-07 | Methods of treating solid tumors with ccr2 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2991280T3 true ES2991280T3 (es) | 2024-12-03 |
Family
ID=67139234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19735699T Active ES2991280T3 (es) | 2018-01-08 | 2019-01-07 | Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US11154556B2 (https=) |
| EP (1) | EP3737367B1 (https=) |
| JP (1) | JP7442141B2 (https=) |
| CN (1) | CN112105353B (https=) |
| AU (1) | AU2019205784B2 (https=) |
| CA (1) | CA3087765A1 (https=) |
| ES (1) | ES2991280T3 (https=) |
| IL (1) | IL275898B2 (https=) |
| MA (1) | MA50423A (https=) |
| TW (1) | TWI882953B (https=) |
| WO (1) | WO2019136368A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3297438T3 (da) | 2015-05-21 | 2022-01-17 | Chemocentryx Inc | Ccr2-modulatorer |
| US20190275015A1 (en) * | 2017-09-25 | 2019-09-12 | Chemocentryx, Inc. | Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor |
| CA3293051A1 (en) | 2017-09-25 | 2026-03-02 | Chemocentryx, Inc. | Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor |
| US20190269664A1 (en) | 2018-01-08 | 2019-09-05 | Chemocentryx, Inc. | Methods of treating solid tumors with ccr2 antagonists |
| CN111334575A (zh) * | 2020-02-18 | 2020-06-26 | 至本医疗科技（上海）有限公司 | Notch家族基因变异在预测实体瘤患者对免疫检查点抑制剂疗法敏感性中的应用 |
Family Cites Families (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004517805A (ja) | 2000-06-30 | 2004-06-17 | ブリストル−マイヤーズ・スクイブ・ファーマ・カンパニー | ケモカイン受容体活性調節剤としてのｎ−ウレイドヘテロシクロアルキル−ピペリジン |
| EP1318811B1 (en) | 2000-08-17 | 2006-08-30 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| ATE319703T1 (de) | 2001-07-02 | 2006-03-15 | Piperidinverbindungen, die sich als modulatoren der chemokinrezeptoraktivität eignen | |
| JO2479B1 (en) | 2002-04-29 | 2009-01-20 | ميرك شارب اند دوم ليمتد | Rates for the activity of the chemokine receptor of tetrahydrobranyl cycloneptil tetrahydrobredo predine |
| US20060030582A1 (en) | 2002-04-29 | 2006-02-09 | Demartino Julie | Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity |
| EP1501507B1 (en) | 2002-04-29 | 2008-05-28 | Merck & Co., Inc. | Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity |
| DE60322877D1 (de) | 2002-04-29 | 2008-09-25 | Merck Sharp & Dohme | Tetrahydropyranylcyclopentyltetrahydroisochino-linmodulatoren der chemokinrezeptoraktivität |
| EP1558599A4 (en) | 2002-10-30 | 2007-06-27 | Merck & Co Inc | HETEROARYLPIPERIDINE MODULATORS DERCHEMOKIN RECEPTORACTIVITY |
| WO2004076411A2 (en) | 2003-02-24 | 2004-09-10 | Merck & Co., Inc. | Aminocyclopentyl fused heterotricylicamide modulators of chemokine receptor activity |
| AU2004222336B2 (en) | 2003-03-18 | 2010-06-03 | Merck Sharp & Dohme Corp. | Amino cyclobutylamide modulators of chemokine receptor activity |
| AU2004231087B2 (en) | 2003-04-15 | 2007-01-04 | Merck Sharp & Dohme Corp. | Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors |
| AU2004232939A1 (en) | 2003-04-17 | 2004-11-04 | Merck Sharp & Dohme Corp. | Heterocyclic cyclopentyl tetrahydroisoquinoline and tetrahydropyridopyridine modulators of chemokine receptor activity |
| WO2004110376A2 (en) | 2003-06-06 | 2004-12-23 | Merck & Co., Inc. | Ccr-2 antagonists for treatment of neuropathic pain |
| MXPA06004647A (es) | 2003-10-27 | 2006-06-27 | Merck & Co Inc | Sal antagonista de ccr-2. |
| AR045875A1 (es) | 2003-10-27 | 2005-11-16 | Merck & Co Inc | Procedimiento para la preparacion del antagonista ccr-2 |
| US20070117797A1 (en) | 2004-01-02 | 2007-05-24 | Goble Stephen D | Alkylamino, arylamino, and sulfonamido cyclopentyl amide modulators of chemokine receptor activity |
| JP2007522219A (ja) | 2004-02-12 | 2007-08-09 | メルク エンド カムパニー インコーポレーテッド | ケモカイン受容体活性のアミノ複素環式調節物質 |
| BRPI0510665A (pt) | 2004-05-11 | 2007-12-04 | Incyte Corp | 3-(4-heteroarilcicloexilamino) ciclopentano-carboxiamidas como moduladores de receptores de quimiocinas |
| PA8653301A1 (es) | 2004-11-22 | 2006-11-09 | Incyte Corp Incyte Corp | Sales de la n-[2-({(3r)-1-[trans-4-hidroxi-4-(6-metoxipiridin-3-il) ciclohexil)pirrolidin |
| WO2006074265A2 (en) | 2005-01-06 | 2006-07-13 | Merck & Co., Inc. | Drug combination therapy and pharmaceutical compositions for treating inflammatory disorders |
| US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
| US7671062B2 (en) | 2006-07-28 | 2010-03-02 | Bristol-Myers Squibb Company | Modulators of chemokine receptor activity, crystalline forms and process |
| BR122017025062B8 (pt) | 2007-06-18 | 2021-07-27 | Merck Sharp & Dohme | anticorpo monoclonal ou fragmento de anticorpo para o receptor de morte programada humano pd-1, polinucleotídeo e composição compreendendo o referido anticorpo ou fragmento |
| JP5306344B2 (ja) | 2007-07-12 | 2013-10-02 | ケモセントリックス， インコーポレイテッド | 炎症の治療のためのｃｃｒ２モジュレーターとしての縮合ヘテロアリールピリジルおよびフェニルベンゼンスルホンアミド |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| US8552154B2 (en) | 2008-09-26 | 2013-10-08 | Emory University | Anti-PD-L1 antibodies and uses therefor |
| MX2011006226A (es) | 2008-12-10 | 2011-06-24 | Janssen Pharmaceutica Nv | Antagonistas de 4-azetidinil-1-heteroaril-ciclohexanol del receptor 2 de citocina quimioatrayente. |
| JP5844159B2 (ja) | 2009-02-09 | 2016-01-13 | ユニヴェルシテ デクス−マルセイユＵｎｉｖｅｒｓｉｔｅ Ｄ’Ａｉｘ−Ｍａｒｓｅｉｌｌｅ | Ｐｄ−１抗体およびｐｄ−ｌ１抗体ならびにその使用 |
| TW201105649A (en) | 2009-04-16 | 2011-02-16 | Janssen Pharmaceutica Nv | 4-azetidinyl-1-heteroaryl-cyclohexane antagonists of CCR2 |
| EP2419419B1 (en) | 2009-04-17 | 2014-12-03 | Janssen Pharmaceutica NV | 4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 |
| ES2674275T3 (es) | 2009-12-17 | 2018-06-28 | Centrexion Therapeutics Corporation | Antagonistas del receptor CCR2 y usos de los mismos |
| US9040526B2 (en) | 2010-02-09 | 2015-05-26 | Bristol-Myers Squibb Company | Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity |
| WO2011141474A1 (en) | 2010-05-12 | 2011-11-17 | Boehringer Ingelheim International Gmbh | Novel ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| US8642622B2 (en) | 2010-06-16 | 2014-02-04 | Bristol-Myers Squibb Company | Piperidinyl compound as a modulator of chemokine receptor activity |
| US8518969B2 (en) | 2010-06-17 | 2013-08-27 | Janssen Pharmaceutica Nv | Cyclohexyl-azetidinyl antagonists of CCR2 |
| SG193002A1 (en) | 2011-03-10 | 2013-09-30 | Daiichi Sankyo Co Ltd | Dispiropyrrolidine derivative |
| KR101764096B1 (ko) | 2011-11-28 | 2017-08-02 | 메르크 파텐트 게엠베하 | 항-ｐｄ-ｌ1 항체 및 그의 용도 |
| US8822460B2 (en) | 2012-04-06 | 2014-09-02 | Janssen Pharmaceutica Nv | Fused cyclopentyl antagonists of CCR2 |
| HK1203971A1 (en) | 2012-05-15 | 2015-11-06 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| RU2689760C2 (ru) | 2012-05-31 | 2019-05-30 | Дженентек, Инк. | Способы лечения рака с применением антагонистов аксиального связывания pd-1 и vegf антагонистов |
| WO2013192596A2 (en) * | 2012-06-22 | 2013-12-27 | Sorrento Therapeutics Inc. | Antigen binding proteins that bind ccr2 |
| US9308236B2 (en) | 2013-03-15 | 2016-04-12 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
| SI3010503T1 (sl) * | 2013-06-21 | 2020-07-31 | Zenith Epigenetics Ltd. | Novi biciklični inhibitorji bromodomene |
| AU2014309199B2 (en) | 2013-08-20 | 2018-04-19 | Merck Sharp & Dohme Llc | Treating cancer with a combination of a PD-1 antagonist and dinaciclib |
| CN105705489B (zh) | 2013-09-04 | 2019-04-26 | 百时美施贵宝公司 | 用作免疫调节剂的化合物 |
| TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗ｐｄ-ｌ１之人類抗體 |
| US9850225B2 (en) | 2014-04-14 | 2017-12-26 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| WO2016039749A1 (en) | 2014-09-11 | 2016-03-17 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the pd-1/pd-l1 and cd80 (b7-1)/pd-li protein/protein interactions |
| US9732119B2 (en) | 2014-10-10 | 2017-08-15 | Bristol-Myers Squibb Company | Immunomodulators |
| US9856292B2 (en) | 2014-11-14 | 2018-01-02 | Bristol-Myers Squibb Company | Immunomodulators |
| US9861680B2 (en) | 2014-12-18 | 2018-01-09 | Bristol-Myers Squibb Company | Immunomodulators |
| US9944678B2 (en) | 2014-12-19 | 2018-04-17 | Bristol-Myers Squibb Company | Immunomodulators |
| US20160222060A1 (en) | 2015-02-04 | 2016-08-04 | Bristol-Myers Squibb Company | Immunomodulators |
| US9809625B2 (en) | 2015-03-18 | 2017-11-07 | Bristol-Myers Squibb Company | Immunomodulators |
| DK3297438T3 (da) | 2015-05-21 | 2022-01-17 | Chemocentryx Inc | Ccr2-modulatorer |
| WO2017165125A1 (en) * | 2016-03-24 | 2017-09-28 | Millennium Pharmaceuticals, Inc. | Use of a pd-1 antagonist and an anti-ccr2 antibody in the treatment of cancer |
| US10195188B2 (en) | 2016-06-13 | 2019-02-05 | Chemocentryx, Inc. | Method of treating pancreatic cancer |
| US10251888B2 (en) | 2016-06-13 | 2019-04-09 | Chemocentryx, Inc. | Method of treating pancreatic cancer |
| US10639284B2 (en) * | 2016-06-27 | 2020-05-05 | Chemocentryx, Inc. | Immunomodulator compounds |
| US20190275015A1 (en) | 2017-09-25 | 2019-09-12 | Chemocentryx, Inc. | Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor |
| CA3293051A1 (en) | 2017-09-25 | 2026-03-02 | Chemocentryx, Inc. | Combination therapy using a chemokine receptor 2 (ccr2) antagonist and a pd-1/pd-l1 inhibitor |
| US20190269664A1 (en) | 2018-01-08 | 2019-09-05 | Chemocentryx, Inc. | Methods of treating solid tumors with ccr2 antagonists |
-
2019
- 2019-01-07 CN CN201980017482.2A patent/CN112105353B/zh active Active
- 2019-01-07 WO PCT/US2019/012515 patent/WO2019136368A2/en not_active Ceased
- 2019-01-07 US US16/241,391 patent/US11154556B2/en active Active
- 2019-01-07 AU AU2019205784A patent/AU2019205784B2/en active Active
- 2019-01-07 JP JP2020537565A patent/JP7442141B2/ja active Active
- 2019-01-07 EP EP19735699.1A patent/EP3737367B1/en active Active
- 2019-01-07 MA MA050423A patent/MA50423A/fr unknown
- 2019-01-07 IL IL275898A patent/IL275898B2/en unknown
- 2019-01-07 ES ES19735699T patent/ES2991280T3/es active Active
- 2019-01-07 CA CA3087765A patent/CA3087765A1/en active Pending
- 2019-01-08 TW TW108100692A patent/TWI882953B/zh active
-
2021
- 2021-09-22 US US17/481,829 patent/US20220241290A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| TW201938160A (zh) | 2019-10-01 |
| CA3087765A1 (en) | 2019-07-11 |
| TWI882953B (zh) | 2025-05-11 |
| WO2019136368A2 (en) | 2019-07-11 |
| US20220241290A1 (en) | 2022-08-04 |
| AU2019205784A1 (en) | 2020-07-30 |
| JP7442141B2 (ja) | 2024-03-04 |
| IL275898B2 (en) | 2025-05-01 |
| AU2019205784B2 (en) | 2024-07-25 |
| US20190209573A1 (en) | 2019-07-11 |
| EP3737367A2 (en) | 2020-11-18 |
| IL275898B1 (en) | 2025-01-01 |
| IL275898A (en) | 2020-08-31 |
| MA50423A (fr) | 2020-08-26 |
| CN112105353A (zh) | 2020-12-18 |
| CN112105353B (zh) | 2024-04-19 |
| US11154556B2 (en) | 2021-10-26 |
| EP3737367A4 (en) | 2022-11-09 |
| JP2021509678A (ja) | 2021-04-01 |
| WO2019136368A3 (en) | 2020-04-16 |
| EP3737367B1 (en) | 2024-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2991280T3 (es) | Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T | |
| JP7611189B2 (ja) | Ｐｄ－１阻害剤又はｐｄ－ｌ１阻害剤と組み合わせてｃｃｒ１アンタゴニストを投与することによる腫瘍負荷の低減 | |
| US11986466B2 (en) | Methods of treating solid tumors with CCR2 antagonists | |
| JP7847576B2 (ja) | がんの治療のための組み合わせ | |
| CN111712242B (zh) | 使用趋化因子受体2(ccr2)拮抗剂和pd-1/pd-l1抑制剂的联合治疗 | |
| JP2020517652A5 (https=) | ||
| CN110536703A (zh) | 使用抗axl抗体-药物缀合物的组合疗法 | |
| CN121889152A (zh) | 用于治疗费城染色体阳性血癌的sos1抑制剂 | |
| TW202315873A (zh) | 二醯基甘油激酶調節化合物 | |
| CA3196535A1 (en) | Combination of an ahr inhibitor with a pdx inhibitor or doxorubicine | |
| WO2025190251A1 (zh) | 抗trop2抗体药物偶联物和pd-1拮抗剂联合治疗实体瘤的用途 | |
| WO2025190318A1 (zh) | 抗her2抗体药物偶联物和her二聚化抑制剂联合治疗实体瘤 | |
| WO2025232801A1 (zh) | 抗FRα抗体药物偶联物和PD-1拮抗剂在治疗肿瘤中的应用 | |
| WO2025247187A1 (zh) | 抗trop2抗体药物偶联物和抗pd-l1/cd47双特异抗体联合治疗肿瘤的用途 | |
| BR122024013223A2 (pt) | Composição de antagonistas do ccr1 e inibidores de pd-1 ou inibidores de pd-l1, kit e seus usos |