regorafenib indications/contra

Stem definitionDrug idCAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors 4654 755037-03-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • regorafenib monohydrate
  • Stivarga
  • regorafenib
  • regorafenib hydrate
  • anhydrous regorafenib
  • BAY 73-4506
a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment
  • Molecular weight: 482.82
  • Formula: C21H15ClF4N4O3
  • CLOGP: 5.19
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 3
  • TPSA: 92.35
  • ALOGS: -5.67
  • ROTB: 6

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 26, 2013 EMA
Sept. 27, 2012 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 2353.41 53.19 445 2661 6087 3376666
Fatigue 1353.17 53.19 509 2597 106731 3276022
Dysphonia 1140.91 53.19 251 2855 7253 3375500
Decreased appetite 1109.99 53.19 348 2758 41142 3341611
Colorectal cancer metastatic 885.63 53.19 128 2978 220 3382533
Diarrhoea 860.14 53.19 367 2739 103981 3278772
Asthenia 665.89 53.19 269 2837 65396 3317357
Colon cancer 615.43 53.19 130 2976 3022 3379731
Colorectal cancer 608.71 53.19 99 3007 480 3382273
Pyrexia 581.67 53.19 260 2846 80855 3301898
Pain in extremity 579.38 53.19 225 2881 48987 3333766
Hypertension 550.38 53.19 203 2903 38263 3344490
Weight decreased 520.12 53.19 197 2909 39914 3342839
Blister 507.43 53.19 135 2971 8599 3374154
Dehydration 434.54 53.19 165 2941 33484 3349269
Stomatitis 413.60 53.19 123 2983 11729 3371024
Blood pressure increased 398.49 53.19 139 2967 22091 3360662
Nausea 384.78 53.19 230 2876 129415 3253338
Blood bilirubin increased 379.35 53.19 112 2994 10397 3372356
Rash 357.61 53.19 179 2927 70642 3312111
Abdominal pain 357.46 53.19 157 2949 46068 3336685
Skin exfoliation 313.36 53.19 91 3015 7946 3374807
Constipation 301.99 53.19 124 2982 30688 3352065
General physical health deterioration 286.87 53.19 107 2999 20482 3362271
Malaise 271.46 53.19 145 2961 65032 3317721
Rectal cancer 268.33 53.19 52 3054 760 3381993
Vomiting 264.53 53.19 159 2947 89372 3293381
Dry skin 249.84 53.19 76 3030 7767 3374986
Erythema 245.36 53.19 105 3001 28705 3354048
Platelet count decreased 240.14 53.19 102 3004 27366 3355387

Pharmacologic Action:

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SourceCodeDescription
ATC L01XE21 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Liver cell carcinoma indication 109841003
Metastasis from malignant tumor of colon indication 314998002
Gastrointestinal stromal tumor indication 420120006 DOID:9253

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.41 acidic
pKa2 11.83 acidic
pKa3 12.52 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
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

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
40MG STIVARGA BAYER HLTHCARE N203085 Sept. 27, 2012 RX TABLET ORAL Feb. 25, 2020 TREATMENT OF PATIENTS WITH LOCALLY ADVANCED, UNRESECTABLE OR METASTATIC GASTROINTESTINAL STROMAL TUMOR (GIST) WHO HAVE BEEN PREVIOUSLY TREATED WITH IMATINIB MESYLATE AND SUNITINIB MALATE.
40MG STIVARGA BAYER HLTHCARE N203085 Sept. 27, 2012 RX TABLET ORAL April 27, 2020 TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB
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.

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 7.90 IUPHAR CHEMBL
Serine/threonine-protein kinase B-raf Kinase INHIBITOR IC50 7.55 CHEMBL CHEMBL
Bifunctional epoxide hydrolase 2 Enzyme INHIBITOR IC50 9.30 CHEMBL
Glycine receptor subunit alpha-1 Ion channel EC50 5.74 CHEMBL

External reference:

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IDSource
CHEBI:68647 CHEBI
5891 IUPHAR_LIGAND_ID
D10137 KEGG_DRUG
C3537697 UMLSCUI
24T2A1DOYB UNII
9026 INN_ID
1312397 RXNORM
014656 NDDF
4031721 VANDF
28887 MMSL
d07913 MMSL
N0000185731 NDFRT
702804006 SNOMEDCT_US
703808002 SNOMEDCT_US
DB08896 DRUGBANK_ID
CHEMBL1946170 ChEMBL_ID
1019206-88-2 SECONDARY_CAS_RN
C559147 MESH_SUPPLEMENTAL_RECORD_UI
11167602 PUBCHEM_CID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Stivarga HUMAN PRESCRIPTION DRUG LABEL 1 50419-171 TABLET, FILM COATED 40 mg ORAL NDA 19 sections