vismodegib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
SMO receptor antagonists 4227 879085-55-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • erivedge
  • vismodegib
  • GDC-0449
  • RG3616
inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity
  • Molecular weight: 421.29
  • Formula: C19H14Cl2N2O3S
  • CLOGP: 2.74
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 76.13
  • ALOGS: -5.39
  • ROTB: 4
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.23 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.01 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 245 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.035 Moderate 0.67
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.109 Moderate 0.67
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 54.200 10^-6 cm/s Moderate 0.67
dh-clint Dog hepatocyte intrinsic clearance 1.774 uL/min/10^6 cells Moderate 0.67
dppb Dog plasma protein binding (% unbound) 5.300 % Moderate 0.67
fcs-ppb Fetal calf serum protein binding (% unbound) 10.210 % Moderate 0.67
herg hERG pIC50 4.793 pIC50 Moderate 0.67
hh-clint Human hepatocyte intrinsic clearance 1.854 uL/min/10^6 cells Moderate 0.67
hlm-clint Human liver microsomal intrinsic clearance 3.443 uL/min/mg protein Moderate 0.67
hppb Human plasma protein binding (% unbound) 2.010 % Moderate 0.67
kinase-safety-class ACVR2B,CAMK2D,CDK5,CDK9,DDR1,EIF2AK3,ERBB2,GRK2,ITK,MAPK7,PDK1,PDK2,PDK4,PRKDC,TTK 15
kinase-selectivity-class GRK2,PDK4 2
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 7.499 Moderate 0.67
mh-clint Mouse hepatocyte intrinsic clearance 13.459 Moderate 0.67
mppb Mouse plasma protein binding (% unbound) 3.850 Moderate 0.67
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 13.614 Moderate 0.67
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 8.520 % Moderate 0.67
rh-clint Rat hepatocyte intrinsic clearance 4.688 uL/min/10^6 cells Moderate 0.67
rh-fuinc Rat hepatocyte fraction unbound in incubation 34.520 % Moderate 0.67
rppb Rat plasma protein binding (% unbound) 3.530 % Moderate 0.67
solubility-dd Solubility at pH 7.4 in DMSO 13.490 uM Moderate 0.67

Approvals:

DateAgencyCompanyOrphan
July 12, 2013 EMA Roche Registration Ltd
Jan. 30, 2012 FDA GENENTECH

FDA Adverse Event Reporting System (Female)

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
Muscle spasms 506.50 37.86 223 3053 251660 90373511
Dysgeusia 453.84 37.86 137 3139 52423 90572748
Alopecia 398.07 37.86 236 3040 494835 90130336
Ageusia 360.59 37.86 89 3187 15987 90609184
Death 204.85 37.86 152 3124 456399 90168772
Weight decreased 131.94 37.86 109 3167 379801 90245370
Decreased appetite 110.17 37.86 98 3178 376442 90248729
No adverse event 88.58 37.86 45 3231 67937 90557234
Squamous cell carcinoma 76.90 37.86 24 3252 10077 90615094
Fatigue 54.98 37.86 125 3151 1153898 89471273
Nausea 50.33 37.86 118 3158 1110198 89514973

FDA Adverse Event Reporting System (Male)

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
Muscle spasms 1188.04 34.05 419 4369 85625 42530922
Alopecia 877.70 34.05 258 4530 29018 42587529
Ageusia 736.58 34.05 185 4603 11420 42605127
Dysgeusia 554.83 34.05 189 4599 34000 42582547
Weight decreased 219.76 34.05 183 4605 207765 42408782
Squamous cell carcinoma 164.84 34.05 60 4728 12922 42603625
Decreased appetite 142.32 34.05 139 4649 192998 42423549
Death 133.56 34.05 209 4579 470976 42145571
Fatigue 85.91 34.05 165 4623 435476 42181071
No adverse event 78.76 34.05 51 4737 38970 42577577
Taste disorder 75.77 34.05 32 4756 10175 42606372
Myalgia 61.01 34.05 64 4724 96016 42520531
Madarosis 46.99 34.05 11 4777 495 42616052
Constipation 44.05 34.05 71 4717 162220 42454327
Nausea 44.02 34.05 120 4668 396679 42219868
Hypogeusia 38.46 34.05 11 4777 1094 42615453

FDA Adverse Event Reporting System (Geriatric)

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
Muscle spasms 937.06 32.80 389 5094 277768 110306048
Ageusia 603.51 32.80 149 5334 19496 110564320
Dysgeusia 601.56 32.80 196 5287 69789 110514027
Alopecia 448.47 32.80 257 5226 364496 110219320
Death 233.95 32.80 225 5258 698644 109885172
Weight decreased 205.95 32.80 176 5307 467881 110115935
Squamous cell carcinoma 175.56 32.80 56 5427 18407 110565409
Decreased appetite 173.53 32.80 161 5322 475685 110108131
Fatigue 93.49 32.80 193 5290 1215765 109368051
Myalgia 67.04 32.80 68 5415 222313 110361503
Neutrophil count decreased 62.22 32.80 50 5433 120891 110462925
Embolism 54.88 32.80 23 5460 16266 110567550
No adverse event 54.68 32.80 38 5445 73801 110510015
Madarosis 47.80 32.80 14 5469 3449 110580367
Nausea 40.96 32.80 144 5339 1235546 109348270
Lymphocyte count decreased 38.99 32.80 28 5455 57215 110526601
Disease progression 37.54 32.80 53 5430 243981 110339835
Dehydration 36.22 32.80 56 5427 279455 110304361
Taste disorder 33.53 32.80 27 5456 65360 110518456

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XJ01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Hedgehog pathway inhibitors
FDA MoA N0000184148 Smoothened Receptor Antagonists
FDA EPC N0000184149 Hedgehog Pathway Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50905 teratogenic agent
CHEBI has role CHEBI:66908 SMO receptor antagonist
CHEBI has role CHEBI:140921 Hedgehog signaling pathway inhibitor
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L01XJ Hedgehog pathway inhibitors 2 drugs
glasdegibsonidegib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Basal cell carcinoma of skin indication 254701007
Pregnancy, function contraindication 289908002
Hypericum perforatum extract contraindication 412515006
Breastfeeding (mother) contraindication 413712001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.07 acidic
pKa2 4.25 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
150MG ERIVEDGE GENENTECH N203388 Jan. 30, 2012 RX CAPSULE ORAL 9278961 Dec. 15, 2028 METHOD OF USING VISMODEGIB TO TREAT CANCER IN A MAMMAL

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Smoothened homolog GPCR INHIBITOR Ki 7.79 CHEMBL CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 5.85 CHEMBL
Sonic hedgehog protein Enzyme IC50 7.82 CHEMBL
Sonic hedgehog protein Enzyme IC50 8.52 CHEMBL
Smoothened homolog GPCR IC50 8.30 CHEMBL

External reference:

IDSource
D09992 KEGG_DRUG
4031330 VANDF
CHEBI:66903 CHEBI
VIS PDB_CHEM_ID
CHEMBL473417 ChEMBL_ID
C538724 MESH_SUPPLEMENTAL_RECORD_UI
6975 IUPHAR_LIGAND_ID
DB08828 DRUGBANK_ID
25X868M3DS UNII
1242987 RXNORM
187095 MMSL
28293 MMSL
d07824 MMSL
014152 NDDF
703812008 SNOMEDCT_US
703813003 SNOMEDCT_US
C2987716 UMLSCUI
9311 INN_ID
24776445 PUBCHEM_CID
25X868M3DS INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ERIVEDGE HUMAN PRESCRIPTION DRUG LABEL 1 50242-140 CAPSULE 150 mg ORAL NDA 31 sections