Stem definition | Drug id | CAS RN |
---|---|---|
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors | 4654 | 755037-03-7 |
Dose | Unit | Route |
---|---|---|
0.12 | g | O |
None
Date | Agency | Company | Orphan |
---|---|---|---|
Aug. 26, 2013 | EMA | ||
Sept. 27, 2012 | FDA | BAYER HLTHCARE |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
---|---|---|---|---|---|---|
Palmar-plantar erythrodysaesthesia syndrome | 1120.61 | 26.37 | 340 | 11425 | 21266 | 53316035 |
Dysphonia | 410.19 | 26.37 | 195 | 11570 | 41743 | 53295558 |
Colorectal cancer metastatic | 381.08 | 26.37 | 76 | 11689 | 771 | 53336530 |
Colon cancer | 293.47 | 26.37 | 102 | 11663 | 9723 | 53327578 |
Colorectal cancer | 283.58 | 26.37 | 65 | 11700 | 1327 | 53335974 |
Off label use | 236.69 | 26.37 | 393 | 11372 | 471819 | 52865482 |
Decreased appetite | 233.56 | 26.37 | 261 | 11504 | 214713 | 53122588 |
Hepatocellular carcinoma | 200.76 | 26.37 | 58 | 11707 | 3022 | 53334279 |
Metastases to lung | 160.50 | 26.37 | 69 | 11696 | 11635 | 53325666 |
Fatigue | 152.40 | 26.37 | 426 | 11339 | 730080 | 52607221 |
Blister | 118.27 | 26.37 | 114 | 11651 | 78639 | 53258662 |
Hyperkeratosis | 105.61 | 26.37 | 41 | 11724 | 5325 | 53331976 |
Skin exfoliation | 103.66 | 26.37 | 76 | 11689 | 36007 | 53301294 |
Metastases to liver | 99.71 | 26.37 | 61 | 11704 | 21435 | 53315866 |
Carcinoembryonic antigen increased | 95.61 | 26.37 | 28 | 11737 | 1529 | 53335772 |
Diarrhoea | 95.60 | 26.37 | 328 | 11437 | 625218 | 52712083 |
Asthenia | 93.33 | 26.37 | 222 | 11543 | 343368 | 52993933 |
Pyrexia | 92.26 | 26.37 | 244 | 11521 | 402949 | 52934352 |
Pain in extremity | 89.36 | 26.37 | 195 | 11570 | 284855 | 53052446 |
Gastrointestinal stromal tumour | 89.02 | 26.37 | 25 | 11740 | 1174 | 53336127 |
Hypertension | 86.88 | 26.37 | 168 | 11597 | 225263 | 53112038 |
Neuropathy peripheral | 86.40 | 26.37 | 110 | 11655 | 103077 | 53234224 |
Rectal cancer | 85.69 | 26.37 | 27 | 11738 | 1890 | 53335411 |
Blood bilirubin increased | 84.44 | 26.37 | 67 | 11698 | 35663 | 53301638 |
Stomatitis | 79.60 | 26.37 | 103 | 11662 | 98055 | 53239246 |
Oral pain | 73.63 | 26.37 | 55 | 11710 | 26782 | 53310519 |
Weight decreased | 68.22 | 26.37 | 156 | 11609 | 234792 | 53102509 |
Dehydration | 66.63 | 26.37 | 127 | 11638 | 168283 | 53169018 |
Dry skin | 64.44 | 26.37 | 64 | 11701 | 45696 | 53291605 |
Rash | 63.57 | 26.37 | 229 | 11536 | 445962 | 52891339 |
Blood pressure increased | 61.91 | 26.37 | 111 | 11654 | 140368 | 53196933 |
Platelet count decreased | 57.64 | 26.37 | 93 | 11672 | 108006 | 53229295 |
Hepatic function abnormal | 48.99 | 26.37 | 50 | 11715 | 36849 | 53300452 |
Hospitalisation | 47.63 | 26.37 | 68 | 11697 | 70944 | 53266357 |
Drug ineffective | 46.49 | 26.37 | 68 | 11697 | 817177 | 52520124 |
Skin fissures | 46.21 | 26.37 | 27 | 11738 | 8718 | 53328583 |
Condition aggravated | 45.33 | 26.37 | 6 | 11759 | 297128 | 53040173 |
Colon cancer metastatic | 45.06 | 26.37 | 15 | 11750 | 1250 | 53336051 |
Disseminated intravascular coagulation | 44.48 | 26.37 | 36 | 11729 | 19683 | 53317618 |
Erythema | 43.04 | 26.37 | 102 | 11663 | 156867 | 53180434 |
Mucosal inflammation | 42.88 | 26.37 | 50 | 11715 | 42734 | 53294567 |
Gait inability | 42.17 | 26.37 | 47 | 11718 | 38264 | 53299037 |
Plantar erythema | 41.23 | 26.37 | 10 | 11755 | 262 | 53337039 |
Tumour marker increased | 40.44 | 26.37 | 19 | 11746 | 3934 | 53333367 |
Dry mouth | 38.43 | 26.37 | 56 | 11709 | 59494 | 53277807 |
Exercise tolerance decreased | 38.00 | 26.37 | 20 | 11745 | 5275 | 53332026 |
Palmoplantar keratoderma | 37.79 | 26.37 | 8 | 11757 | 111 | 53337190 |
Abdominal pain | 37.70 | 26.37 | 133 | 11632 | 255770 | 53081531 |
Skin toxicity | 36.79 | 26.37 | 18 | 11747 | 4075 | 53333226 |
Hepatic encephalopathy | 31.44 | 26.37 | 23 | 11742 | 10836 | 53326465 |
Drug hypersensitivity | 30.93 | 26.37 | 10 | 11755 | 265232 | 53072069 |
Feeding disorder | 28.33 | 26.37 | 22 | 11743 | 11332 | 53325969 |
Drug interaction | 27.91 | 26.37 | 7 | 11758 | 219322 | 53117979 |
Constipation | 26.55 | 26.37 | 100 | 11665 | 198312 | 53138989 |
Jaundice | 26.40 | 26.37 | 33 | 11732 | 30280 | 53307021 |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
---|---|---|---|---|---|---|
Palmar-plantar erythrodysaesthesia syndrome | 1870.55 | 23.38 | 560 | 14985 | 15189 | 32482792 |
Hepatocellular carcinoma | 739.39 | 23.38 | 250 | 15295 | 10020 | 32487961 |
Dysphonia | 712.38 | 23.38 | 293 | 15252 | 20391 | 32477590 |
Colorectal cancer | 499.53 | 23.38 | 131 | 15414 | 2122 | 32495859 |
Colorectal cancer metastatic | 471.64 | 23.38 | 109 | 15436 | 1008 | 32496973 |
Colon cancer | 319.77 | 23.38 | 130 | 15415 | 8736 | 32489245 |
Decreased appetite | 316.81 | 23.38 | 386 | 15159 | 160427 | 32337554 |
Metastases to lung | 308.99 | 23.38 | 125 | 15420 | 8292 | 32489689 |
Off label use | 300.32 | 23.38 | 528 | 15017 | 305792 | 32192189 |
Fatigue | 254.29 | 23.38 | 532 | 15013 | 350169 | 32147812 |
Blister | 192.39 | 23.38 | 124 | 15421 | 21967 | 32476014 |
Diarrhoea | 187.55 | 23.38 | 484 | 15061 | 364318 | 32133663 |
Metastases to liver | 176.48 | 23.38 | 97 | 15448 | 12835 | 32485146 |
Gastrointestinal stromal tumour | 165.33 | 23.38 | 49 | 15496 | 1261 | 32496720 |
Carcinoembryonic antigen increased | 149.52 | 23.38 | 40 | 15505 | 700 | 32497281 |
Hypertension | 141.01 | 23.38 | 237 | 15308 | 131513 | 32366468 |
Pain in extremity | 132.71 | 23.38 | 218 | 15327 | 118683 | 32379298 |
Rectal cancer | 125.06 | 23.38 | 46 | 15499 | 2351 | 32495630 |
Skin exfoliation | 115.66 | 23.38 | 96 | 15449 | 25061 | 32472920 |
Blood bilirubin increased | 110.06 | 23.38 | 113 | 15432 | 38671 | 32459310 |
Skin fissures | 103.35 | 23.38 | 46 | 15499 | 3857 | 32494124 |
Asthenia | 98.61 | 23.38 | 291 | 15254 | 235653 | 32262328 |
Dry skin | 95.91 | 23.38 | 86 | 15459 | 24892 | 32473089 |
Neuropathy peripheral | 93.76 | 23.38 | 147 | 15398 | 76835 | 32421146 |
Weight decreased | 86.36 | 23.38 | 221 | 15324 | 164597 | 32333384 |
Hyperkeratosis | 85.42 | 23.38 | 39 | 15506 | 3470 | 32494511 |
Stomatitis | 82.65 | 23.38 | 99 | 15446 | 40130 | 32457851 |
Alpha 1 foetoprotein increased | 82.02 | 23.38 | 25 | 15520 | 709 | 32497272 |
Tumour marker increased | 79.39 | 23.38 | 23 | 15522 | 545 | 32497436 |
Ascites | 73.04 | 23.38 | 93 | 15452 | 40098 | 32457883 |
Blood pressure increased | 70.80 | 23.38 | 132 | 15413 | 79222 | 32418759 |
Hospitalisation | 61.63 | 23.38 | 95 | 15450 | 48876 | 32449105 |
Hepatic function abnormal | 59.27 | 23.38 | 89 | 15456 | 44751 | 32453230 |
Oral pain | 58.58 | 23.38 | 44 | 15501 | 9934 | 32488047 |
Colon cancer metastatic | 57.01 | 23.38 | 24 | 15521 | 1756 | 32496225 |
Hepatic encephalopathy | 50.76 | 23.38 | 48 | 15497 | 14847 | 32483134 |
Toxicity to various agents | 47.86 | 23.38 | 13 | 15532 | 178028 | 32319953 |
Abdominal pain | 44.78 | 23.38 | 165 | 15380 | 149364 | 32348617 |
Abdominal pain upper | 44.55 | 23.38 | 99 | 15446 | 67239 | 32430742 |
Dehydration | 44.38 | 23.38 | 149 | 15396 | 128809 | 32369172 |
Glossodynia | 44.19 | 23.38 | 25 | 15520 | 3491 | 32494490 |
Metastases to lymph nodes | 43.87 | 23.38 | 27 | 15518 | 4401 | 32493580 |
Drug interaction | 43.81 | 23.38 | 25 | 15520 | 218160 | 32279821 |
Aphonia | 43.29 | 23.38 | 24 | 15521 | 3222 | 32494759 |
Febrile neutropenia | 40.07 | 23.38 | 5 | 15540 | 119561 | 32378420 |
Colorectal cancer recurrent | 39.92 | 23.38 | 8 | 15537 | 34 | 32497947 |
Metastases to peritoneum | 38.93 | 23.38 | 18 | 15527 | 1648 | 32496333 |
Acute kidney injury | 36.95 | 23.38 | 52 | 15493 | 293416 | 32204565 |
Dry mouth | 36.41 | 23.38 | 51 | 15494 | 24068 | 32473913 |
Colon cancer recurrent | 35.25 | 23.38 | 9 | 15536 | 130 | 32497851 |
Drug ineffective | 34.10 | 23.38 | 84 | 15461 | 383393 | 32114588 |
Hypotension | 32.82 | 23.38 | 33 | 15512 | 216077 | 32281904 |
Condition aggravated | 32.43 | 23.38 | 17 | 15528 | 155644 | 32342337 |
Malaise | 31.99 | 23.38 | 168 | 15377 | 176970 | 32321011 |
Cardiac arrest | 30.20 | 23.38 | 5 | 15540 | 96771 | 32401210 |
Biliary obstruction | 28.66 | 23.38 | 17 | 15528 | 2592 | 32495389 |
Overdose | 28.31 | 23.38 | 4 | 15541 | 87073 | 32410908 |
Angular cheilitis | 28.30 | 23.38 | 8 | 15537 | 173 | 32497808 |
Constipation | 27.16 | 23.38 | 126 | 15419 | 126247 | 32371734 |
Proteinuria | 26.64 | 23.38 | 37 | 15508 | 17318 | 32480663 |
Plantar erythema | 25.61 | 23.38 | 6 | 15539 | 59 | 32497922 |
Protein induced by vitamin K absence or antagonist II increased | 25.61 | 23.38 | 5 | 15540 | 18 | 32497963 |
Gait inability | 25.35 | 23.38 | 39 | 15506 | 20008 | 32477973 |
Pneumonia | 24.87 | 23.38 | 87 | 15458 | 355165 | 32142816 |
Neutropenia | 24.83 | 23.38 | 19 | 15526 | 142156 | 32355825 |
Rectal cancer metastatic | 24.50 | 23.38 | 8 | 15537 | 285 | 32497696 |
Rectal cancer stage IV | 24.35 | 23.38 | 4 | 15541 | 3 | 32497978 |
Metastases to adrenals | 23.73 | 23.38 | 11 | 15534 | 1013 | 32496968 |
Source | Code | Description |
---|---|---|
ATC | L01EX05 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors |
FDA MoA | N0000175076 | Protein Kinase Inhibitors |
FDA EPC | N0000175605 | Kinase Inhibitor |
FDA MoA | N0000185504 | Cytochrome P450 2C9 Inhibitors |
CHEBI has role | CHEBI:35610 | cytostatic |
CHEBI has role | CHEBI:38637 | protein tyrosine kinase inhibitor |
CHEBI has role | CHEBI:50908 | agente hepatotoxico |
Disease | Relation | SNOMED_ID | DOID |
---|---|---|---|
Liver cell carcinoma | indication | 109841003 | DOID:684 |
Metastasis from malignant tumor of colon | indication | 314998002 | |
Gastrointestinal stromal tumor | indication | 420120006 | DOID:9253 |
Dissociation level | Dissociation constant | Type (acidic/basic) |
---|---|---|
pKa1 | 11.41 | acidic |
pKa2 | 11.83 | acidic |
pKa3 | 12.52 | acidic |
pKa4 | 2.76 | Basic |
Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
---|---|---|---|---|---|---|---|---|---|---|
40MG | STIVARGA | BAYER HLTHCARE | N203085 | Sept. 27, 2012 | RX | TABLET | ORAL | 8680124 | June 2, 2030 | TREATMENT OF PATIENTS WITH GASTROINTESTINAL STROMAL TUMOR (GIST), INCLUDING BUT NOT LIMITED TO PATIENTS PREVIOUSLY TREATED WITH IMATINIB AND PATIENTS WITH GIST HAVING RESISTANCE TO A KIT TYROSINE KINASE INHIBITOR |
Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
---|---|---|---|---|---|---|---|---|---|
40MG | STIVARGA | BAYER HLTHCARE | N203085 | Sept. 27, 2012 | RX | TABLET | ORAL | April 27, 2024 | TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC OR LIVER CANCER) WHO HAVE BEEN PREVIOUSLY TREATED WITH THE DRUG SORAFENIB. |
Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
---|---|---|---|---|---|---|---|---|---|
Serine/threonine-protein kinase B-raf | Kinase | INHIBITOR | IC50 | 7.55 | CHEMBL | CHEMBL | |||
Vascular endothelial growth factor receptor 2 | Kinase | INHIBITOR | IC50 | 7.90 | IUPHAR | CHEMBL | |||
Tyrosine-protein kinase ABL1 | Kinase | Kd | 6.12 | CHEMBL | |||||
Mast/stem cell growth factor receptor Kit | Kinase | IC50 | 8.21 | CHEMBL | |||||
Breakpoint cluster region protein | Kinase | Kd | 6.13 | CHEMBL | |||||
Ephrin type-A receptor 2 | Kinase | Kd | 6.08 | CHEMBL | |||||
RAF proto-oncogene serine/threonine-protein kinase | Kinase | IC50 | 8.82 | CHEMBL | |||||
Receptor-type tyrosine-protein kinase FLT3 | Kinase | IC50 | 7.09 | CHEMBL | |||||
Proto-oncogene tyrosine-protein kinase receptor Ret | Kinase | Kd | 6.90 | CHEMBL | |||||
Vascular endothelial growth factor receptor 1 | Kinase | IC50 | 8.82 | CHEMBL | |||||
Angiopoietin-1 receptor | Kinase | IC50 | 8.82 | CHEMBL | |||||
LIM domain kinase 1 | Kinase | Kd | 6.21 | CHEMBL | |||||
Fibroblast growth factor receptor 1 | Kinase | IC50 | 8.82 | CHEMBL | |||||
Dual specificity protein kinase TTK | Kinase | Kd | 5.41 | CHEMBL | |||||
Mitogen-activated protein kinase 11 | Kinase | Kd | 5.72 | CHEMBL | |||||
Ephrin type-A receptor 5 | Kinase | Kd | 5.95 | CHEMBL | |||||
Mitogen-activated protein kinase 14 | Kinase | Kd | 6.15 | CHEMBL | |||||
Dual specificity protein kinase CLK1 | Kinase | Kd | 5.68 | CHEMBL | |||||
Receptor-interacting serine/threonine-protein kinase 2 | Kinase | Kd | 6.12 | CHEMBL | |||||
Epithelial discoidin domain-containing receptor 1 | Kinase | Kd | 6.45 | CHEMBL | |||||
Bifunctional epoxide hydrolase 2 | Enzyme | INHIBITOR | IC50 | 9.30 | CHEMBL | ||||
MAP kinase-activated protein kinase 2 | Kinase | Kd | 6.17 | CHEMBL | |||||
Cyclin-dependent kinase 17 | Kinase | Kd | 6.14 | CHEMBL | |||||
Mitogen-activated protein kinase kinase kinase MLT | Kinase | Kd | 6.56 | CHEMBL | |||||
Discoidin domain-containing receptor 2 | Kinase | Kd | 6.38 | CHEMBL | |||||
Ephrin type-A receptor 1 | Kinase | Kd | 8.15 | CHEMBL | |||||
Mitogen-activated protein kinase kinase kinase 1 | Kinase | Kd | 6.33 | CHEMBL | |||||
Glycine receptor subunit alpha-1 | Ion channel | EC50 | 5.74 | CHEMBL | |||||
Receptor-interacting serine/threonine-protein kinase 3 | Kinase | Kd | 6.43 | CHEMBL | |||||
Platelet-derived growth factor receptor beta | Kinase | IC50 | 8.82 | CHEMBL | |||||
Vascular endothelial growth factor receptor 2 | Kinase | IC50 | 8.82 | CHEMBL | |||||
Vascular endothelial growth factor receptor 3 | Kinase | IC50 | 8.82 | CHEMBL |
ID | Source |
---|---|
D10137 | KEGG_DRUG |
1019206-88-2 | SECONDARY_CAS_RN |
4031721 | VANDF |
CHEBI:68647 | CHEBI |
CHEMBL1946170 | ChEMBL_ID |
C559147 | MESH_SUPPLEMENTAL_RECORD_UI |
5891 | IUPHAR_LIGAND_ID |
DB08896 | DRUGBANK_ID |
MGN125FS9D | UNII |
11167602 | PUBCHEM_CID |
1312397 | RXNORM |
193440 | MMSL |
28887 | MMSL |
d07913 | MMSL |
014656 | NDDF |
702804006 | SNOMEDCT_US |
703808002 | SNOMEDCT_US |
C2980094 | UMLSCUI |
Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
---|---|---|---|---|---|---|---|---|
Stivarga | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50419-171 | TABLET, FILM COATED | 40 mg | ORAL | NDA | 29 sections |