sorafenib indications/contra

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 2459 284461-73-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • BAY 43-9006
  • BAY 545-9085
  • BAY-545-9085
  • sorafenib tosilate
  • sorafenib
  • nexavar
  • sorafenib tosylate
inhibits tumor cell proliferation and angiogenesis by targeting RAF KINASES and VEGF RECEPTORS; multikinase inhibitor that targets serine/threonine and receptor tyrosine kinases to decrease tumor growth and angiogenesis; FDA approved orphan drug indication for hepatocellular carcinoma in 2006
  • Molecular weight: 464.83
  • Formula: C21H16ClF3N4O3
  • CLOGP: 5.46
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 3
  • TPSA: 92.35
  • ALOGS: -5.43
  • ROTB: 6

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 2005 FDA BAYER HLTHCARE

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Palmar-plantar erythrodysaesthesia syndrome 6449.37 48.12 1237 8020 5295 3371307
Diarrhoea 2930.49 48.12 1201 8056 103147 3273455
Hepatocellular carcinoma 2834.96 48.12 515 8742 1434 3375168
Hepatic cancer 2115.63 48.12 409 8848 1737 3374865
Hepatic function abnormal 1999.08 48.12 528 8729 10699 3365903
Decreased appetite 1843.62 48.12 672 8585 40818 3335784
Hypertension 1715.02 48.12 625 8632 37841 3338761
Rash 1556.88 48.12 691 8566 70130 3306472
Hepatic encephalopathy 1392.44 48.12 313 8944 3064 3373538
Ascites 1259.85 48.12 354 8903 9023 3367579
Fatigue 1180.18 48.12 654 8603 106586 3270016
Pyrexia 970.55 48.12 524 8733 80591 3296011
Hepatic failure 945.92 48.12 292 8965 10360 3366242
Alopecia 933.45 48.12 333 8924 18653 3357949
Renal cell carcinoma 847.92 48.12 192 9065 1934 3374668
Blister 794.36 48.12 244 9013 8490 3368112
Nausea 734.19 48.12 520 8737 129125 3247477
Abdominal pain 700.68 48.12 351 8906 45874 3330728
Asthenia 680.93 48.12 387 8870 65278 3311324
Stomatitis 627.58 48.12 220 9037 11632 3364970
Weight decreased 617.45 48.12 308 8949 39803 3336799
Vomiting 616.39 48.12 406 8851 89125 3287477
Platelet count decreased 591.58 48.12 266 8991 27202 3349400
Dysphonia 574.80 48.12 184 9073 7320 3369282
Pain in extremity 574.70 48.12 314 8943 48898 3327704
Blood pressure increased 548.63 48.12 237 9020 21993 3354609
Amylase increased 524.96 48.12 132 9125 2134 3374468
Death 501.87 48.12 445 8812 151879 3224723
Skin exfoliation 470.80 48.12 161 9096 7876 3368726
Malaise 455.62 48.12 299 8958 64878 3311724

Pharmacologic Action:

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SourceCodeDescription
ATC L01XE05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:48422 angiogenesis inhibitor

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Liver cell carcinoma indication 109841003
Carcinoma of thyroid indication 448216007
Renal cell carcinoma indication 702391001 DOID:4450
Hypophosphatemia contraindication 4996001
Acute hemorrhage contraindication 8573003
Myocardial infarction contraindication 22298006 DOID:5844
Depressive disorder contraindication 35489007 DOID:2848
Hypertensive disorder contraindication 38341003 DOID:10763
Gastrointestinal perforation contraindication 51875005
Hepatic failure contraindication 59927004
Blood coagulation disorder contraindication 64779008 DOID:1247
Pancreatitis contraindication 75694006 DOID:4989
Angina pectoris contraindication 194828000
Impaired wound healing contraindication 271618001
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Surgical procedure contraindication 387713003
Acute coronary syndrome contraindication 394659003
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Myocardial ischemia contraindication 414795007 DOID:3393

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.84 acidic
pKa2 11.97 acidic
pKa3 12.61 acidic
pKa4 2.76 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 8124630 Jan. 12, 2020 TREATMENT OF CARCINOMA OF THE THYROID
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 8841330 Jan. 12, 2020 TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 8618141 Feb. 11, 2023 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 8877933 Dec. 24, 2027 TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA, ADVANCED RENAL CELL CARCINOMA, OR DIFFERENTIATED THYROID CARCINOMA.
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 9737488 Sept. 10, 2028 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 9737488 Sept. 10, 2028 TREATMENT OF LOCALLY RECURRENT OR METASTATIC, PROGRESSIVE, DIFFERENTIATED THYROID CARCINOMA REFRACTORY TO RADIOACTIVE IODINE TREATMENT
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL 9737488 Sept. 10, 2028 TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 200MG BASE NEXAVAR BAYER HLTHCARE N021923 Dec. 20, 2005 RX TABLET ORAL Nov. 22, 2020 TREATMENT OF PATIENTS WITH LOCALLY RECURRENT OR METASTATIC, PROGRESSIVE, DIFFERENTIATED THYROID CARCINOMA (DCT) THAT IS REFRACTORY TO RADIOACTIVE IODINE TREATMENT.

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR Kd 8.13 CHEMBL CHEMBL
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR Kd 7.80 CHEMBL CHEMBL
Serine/threonine-protein kinase B-raf Kinase INHIBITOR Ki 7.66 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR Kd 7.80 CHEMBL CHEMBL
RAF proto-oncogene serine/threonine-protein kinase Kinase INHIBITOR Ki 8.22 CHEMBL CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase INHIBITOR Kd 8.35 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR Kd 7.51 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR Ki 10.68 CHEMBL CHEMBL
Platelet-derived growth factor receptor beta Kinase INHIBITOR Kd 7.43 CHEMBL CHEMBL
Myosin-IIIb Kinase Kd 5.15 CHEMBL
5-hydroxytryptamine receptor 1A GPCR Ki 5.93 CHEMBL
Cyclin-dependent kinase 15 Kinase Kd 5.54 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5.89 CHEMBL
Ephrin type-B receptor 4 Kinase Kd 5.74 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 5.12 CHEMBL
Aurora kinase A Kinase IC50 5.42 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 6.72 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 8.20 CHEMBL
Homeodomain-interacting protein kinase 3 Kinase Kd 6.41 CHEMBL
Homeodomain-interacting protein kinase 2 Kinase Kd 5.77 CHEMBL
Cyclin-dependent kinase-like 3 Kinase Kd 6.31 CHEMBL
5-hydroxytryptamine receptor 2C GPCR Ki 6.38 CHEMBL
5-hydroxytryptamine receptor 2A GPCR Ki 5.71 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 5.51 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 5.32 CHEMBL
Mitogen-activated protein kinase 15 Kinase Kd 7.34 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 6.64 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 5.11 CHEMBL
Mitogen-activated protein kinase kinase kinase 7 Kinase Kd 6.16 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 6.36 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 5.12 CHEMBL
Homeodomain-interacting protein kinase 1 Kinase Kd 5.96 CHEMBL
Ephrin type-A receptor 8 Kinase Kd 6.02 CHEMBL
Dual specificity protein kinase TTK Kinase Kd 5.46 CHEMBL
Ephrin type-A receptor 2 Kinase Kd 5.70 CHEMBL
Ephrin type-A receptor 3 Kinase Kd 5.72 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 6.85 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 5.47 CHEMBL
Tyrosine-protein kinase JAK3 Kinase Kd 5.14 CHEMBL
Tyrosine-protein kinase CSK Kinase Kd 5.54 CHEMBL
Serine/threonine-protein kinase TAO1 Kinase Kd 6.27 CHEMBL
Serine/threonine-protein kinase TNNI3K Kinase Kd 6.55 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 5.07 CHEMBL
Aurora kinase C Kinase Kd 6.68 CHEMBL
High affinity nerve growth factor receptor Kinase Kd 5.44 CHEMBL
Fibroblast growth factor receptor 1 Kinase Kd 5.60 CHEMBL
Fibroblast growth factor receptor 2 Kinase Kd 5.57 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.21 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 8.57 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 5.80 CHEMBL
Serine/threonine-protein kinase 36 Kinase Kd 5.42 CHEMBL
Ephrin type-A receptor 6 Kinase Kd 6.62 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 5.10 CHEMBL
Aurora kinase B Kinase Kd 6.36 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 6 CHEMBL
5-hydroxytryptamine receptor 2B GPCR Ki 7.25 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 6.89 CHEMBL
Ephrin type-A receptor 7 Kinase Kd 6.17 CHEMBL
Serine/threonine-protein kinase TAO2 Kinase Kd 6.27 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 5.52 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 6.44 CHEMBL
LIM domain kinase 1 Kinase Kd 5.80 CHEMBL
Ephrin type-A receptor 4 Kinase Kd 5.89 CHEMBL
Ephrin type-B receptor 1 Kinase Kd 5.77 CHEMBL
NT-3 growth factor receptor Kinase Kd 6.22 CHEMBL
Cyclin-dependent kinase 2 Kinase Kd 5.06 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 5.89 CHEMBL
Angiopoietin-1 receptor Kinase Kd 5.68 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 6.62 CHEMBL
5-hydroxytryptamine receptor 5A GPCR Ki 5.48 CHEMBL
Bifunctional epoxide hydrolase 2 Enzyme IC50 7.92 CHEMBL
5-hydroxytryptamine receptor 6 GPCR Ki 5.21 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 5.57 CHEMBL
Tyrosine-protein kinase Srms Kinase Kd 5.01 CHEMBL
Casein kinase I isoform alpha Kinase IC50 6.60 CHEMBL
Cyclin-dependent kinase 3 Kinase Kd 5.42 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 6.85 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 5.08 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 7.55 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 8.18 CHEMBL
Cyclin-dependent kinase 17 Kinase Kd 5.80 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 7.17 CHEMBL
Cyclin-dependent kinase 14 Kinase Kd 5.54 CHEMBL
TGF-beta receptor type-2 Kinase Kd 5.16 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 8.82 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4 Kinase Kd 5.32 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 5.57 CHEMBL
Mitogen-activated protein kinase 13 Kinase Kd 5.18 CHEMBL
Myosin light chain kinase 2, skeletal/cardiac muscle Kinase Kd 5.89 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 7 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 5.35 CHEMBL
BDNF/NT-3 growth factors receptor Kinase Kd 5.68 CHEMBL
Ephrin type-B receptor 2 Kinase Kd 5.72 CHEMBL
Mitogen-activated protein kinase 11 Kinase Kd 6.70 CHEMBL
LIM domain kinase 2 Kinase Kd 5.02 CHEMBL
Myosin light chain kinase 3 Kinase Kd 5.02 CHEMBL
5-hydroxytryptamine receptor 7 GPCR Ki 5.15 CHEMBL
Cyclin-dependent-like kinase 5 Kinase Kd 5.21 CHEMBL
Cyclin-dependent kinase 19 Kinase Kd 6.60 CHEMBL
Serine/threonine-protein kinase 33 Kinase Kd 5.62 CHEMBL
Serine/threonine-protein kinase NLK Kinase Kd 6.19 CHEMBL
Mitogen-activated protein kinase 12 Kinase Kd 5.12 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 5.44 CHEMBL
Mitogen-activated protein kinase 14 Kinase Kd 6.59 CHEMBL
Non-receptor tyrosine-protein kinase TNK1 Kinase Kd 5.64 CHEMBL
Mitogen-activated protein kinase 3 Kinase IC50 7.74 CHEMBL
Mitogen-activated protein kinase 1 Kinase IC50 6.96 CHEMBL
Cyclin-dependent kinase 8 Kinase Kd 6.51 CHEMBL
Cyclin-dependent kinase-like 2 Kinase Kd 6.89 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.89 CHEMBL
Muscle, skeletal receptor tyrosine-protein kinase Kinase Kd 6.89 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.44 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 6.41 CHEMBL
Fibroblast growth factor receptor 3 Kinase Kd 5.38 CHEMBL
Insulin receptor Kinase AGONIST IC50 5.28 CHEMBL
Platelet-derived growth factor receptor alpha Kinase Kd 7.21 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.59 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 6.65 CHEMBL
Calcium-dependent protein kinase 1 Kinase Kd 6.66 CHEMBL
Purine nucleoside phosphorylase Unclassified IC50 7.90 CHEMBL
Platelet-derived growth factor receptor beta Unclassified INHIBITOR IC50 7.24 IUPHAR
Vascular endothelial growth factor receptor 3 Unclassified INHIBITOR IC50 7.70 IUPHAR

External reference:

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IDSource
DB00398 DRUGBANK_ID
4025077 VUID
N0000175349 NUI
C1516119 UMLSCUI
5711 IUPHAR_LIGAND_ID
D06272 KEGG_DRUG
5T62Q3B36J UNII
475207-59-1 SECONDARY_CAS_RN
495881 RXNORM
20792 MMSL
420681006 SNOMEDCT_US
422042001 SNOMEDCT_US
4025077 VANDF
N0000175349 NDFRT
N0000171742 NDFRT
d05691 MMSL
011160 NDDF
8234 INN_ID
CHEMBL1336 ChEMBL_ID
216239 PUBCHEM_CID
CHEMBL1200485 ChEMBL_ID
C471405 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:50924 CHEBI
BAX PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Nexavar HUMAN PRESCRIPTION DRUG LABEL 1 50419-488 TABLET, FILM COATED 200 mg ORAL NDA 17 sections