Identification

Name
Vismodegib
Accession Number
DB08828
Type
Small Molecule
Groups
Approved
Description

Vismodegib inhibits the hedgehog signalling pathway and is indicated for treatment of adult basal cell carcinoma. FDA approved on Jan 30, 2012.

Structure
Thumb
Synonyms
  • Hedgehog Antagonist GDC-0449
  • Vismodegibum
External IDs
GDC-0449 / RG-3616
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ErivedgeCapsule150 mgOralHoffmann La Roche2013-08-09Not applicableCanada
ErivedgeCapsule150 mg/1OralGenentech, Inc.2012-01-30Not applicableUs
International/Other Brands
Erivedge
Categories
UNII
25X868M3DS
CAS number
879085-55-9
Weight
Average: 421.297
Monoisotopic: 420.010218428
Chemical Formula
C19H14Cl2N2O3S
InChI Key
BPQMGSKTAYIVFO-UHFFFAOYSA-N
InChI
InChI=1S/C19H14Cl2N2O3S/c1-27(25,26)13-6-7-14(17(21)11-13)19(24)23-12-5-8-16(20)15(10-12)18-4-2-3-9-22-18/h2-11H,1H3,(H,23,24)
IUPAC Name
2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-methanesulfonylbenzamide
SMILES
CS(=O)(=O)C1=CC(Cl)=C(C=C1)C(=O)NC1=CC=C(Cl)C(=C1)C1=CC=CC=N1

Pharmacology

Indication

Vismodegib is used for treating locally advanced or metastatic basal cell carcinoma in patients whose carcinoma has recurred after surgery, and in patients who are not candidates for surgery or radiation.

Structured Indications
Pharmacodynamics

Vismodegib selectively binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.

Mechanism of action

Mutations of the Hedgehog pathway may results in uncontrolled proliferation of skin basal cells. Vismodegib binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.

TargetActionsOrganism
ASmoothened homolog
antagonist
Human
Absorption

The absolute bioavailability of a single dose is 31.8%. Absorption is saturable and is not affected by food.

Volume of distribution

Vismodegib has a volume of distribution of 16.4 to 26.6 L.

Protein binding

Vismodegib is highly protein bound with plasma protein binding at about 99%. Vismodegib binds to the plasma proteins, albumin and alpha-1-acid glycoprotein (saturable bnding).

Metabolism

The main metabolic enzymes are CYP2C9 and CYP3A4, however more than 98% of total systemic vismodegib is not metabolized. Metabolic pathways of vismodegib in humans include oxidation, glucuronidation, and pyridine ring cleavage. The two most abundant oxidative metabolites recovered in feces are produced in vitro by recombinant CYP2C9 and CYP3A4/5.

Route of elimination

Vismodegib is mostly excreted unchanged, and the main route of elimination is by the feces (82%) and the urine accounts for 4.4%.

Half life

The half-life after a single dose is 12 days, and after continuous daily dosing is 4 days.

Clearance
Not Available
Toxicity

Increased risk of embryo-fetal death and significant birth defects. Common adverse event include muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Vismodegib can be decreased when combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vismodegib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vismodegib.Experimental
AmiodaroneThe metabolism of Vismodegib can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Vismodegib.Approved, Investigational
AprepitantThe serum concentration of Vismodegib can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Vismodegib can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Vismodegib can be decreased when combined with Atomoxetine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Vismodegib.Approved, Investigational
BoceprevirThe metabolism of Vismodegib can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Vismodegib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Vismodegib can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vismodegib.Approved
CapecitabineThe metabolism of Vismodegib can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Vismodegib can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Vismodegib can be increased when it is combined with Ceritinib.Approved
CholecalciferolThe metabolism of Vismodegib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Vismodegib.Approved
ClarithromycinThe metabolism of Vismodegib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Vismodegib can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Vismodegib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Vismodegib can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Vismodegib can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Vismodegib can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Vismodegib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vismodegib.Approved, Investigational
CyclosporineThe metabolism of Vismodegib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Vismodegib.Experimental
DabrafenibThe serum concentration of Vismodegib can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Vismodegib can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Vismodegib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Vismodegib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Vismodegib can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vismodegib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vismodegib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Vismodegib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Vismodegib.Approved
DihydroergotamineThe metabolism of Vismodegib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Vismodegib can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vismodegib.Approved, Investigational
DosulepinThe metabolism of Vismodegib can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Vismodegib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Vismodegib can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Vismodegib can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Vismodegib can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Vismodegib can be decreased when combined with Erythromycin.Approved, Vet Approved
EtravirineThe metabolism of Vismodegib can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Vismodegib can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Vismodegib can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Vismodegib can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Vismodegib can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Vismodegib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Vismodegib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Vismodegib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Vismodegib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Vismodegib can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Vismodegib can be decreased when combined with Gemfibrozil.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Vismodegib.Experimental
IdelalisibThe serum concentration of Vismodegib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Vismodegib can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Vismodegib can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Vismodegib can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Vismodegib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Vismodegib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Vismodegib can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Vismodegib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Vismodegib can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vismodegib.Experimental
LeflunomideThe metabolism of Vismodegib can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Vismodegib can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Vismodegib can be decreased when combined with Lopinavir.Approved
LosartanThe metabolism of Vismodegib can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Vismodegib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Vismodegib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Vismodegib can be decreased when it is combined with Lumacaftor.Approved
ManidipineThe metabolism of Vismodegib can be decreased when combined with Manidipine.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vismodegib.Experimental
MidostaurinThe metabolism of Vismodegib can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Vismodegib can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Vismodegib can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Vismodegib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Vismodegib can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Vismodegib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Vismodegib can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Vismodegib can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Vismodegib can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Vismodegib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Vismodegib.Experimental, Investigational
OmeprazoleThe metabolism of Vismodegib can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Vismodegib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Vismodegib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vismodegib.Approved, Vet Approved
PalbociclibThe serum concentration of Vismodegib can be increased when it is combined with Palbociclib.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Vismodegib.Approved
PentobarbitalThe metabolism of Vismodegib can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vismodegib.Experimental
PhenobarbitalThe metabolism of Vismodegib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Vismodegib can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Vismodegib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Vismodegib can be increased when combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vismodegib.Experimental
PyrimethamineThe metabolism of Vismodegib can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Vismodegib can be decreased when combined with Quinine.Approved
RanolazineThe serum concentration of Vismodegib can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Vismodegib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Vismodegib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Vismodegib can be increased when combined with Rifapentine.Approved
SaquinavirThe metabolism of Vismodegib can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Vismodegib can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Vismodegib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Vismodegib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Vismodegib can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Vismodegib can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Vismodegib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Vismodegib can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Vismodegib can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Vismodegib can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Vismodegib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Vismodegib can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Vismodegib can be decreased when combined with Telithromycin.Approved
TicagrelorThe metabolism of Vismodegib can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Vismodegib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Vismodegib can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Vismodegib can be decreased when combined with Tolbutamide.Approved
TopiroxostatThe metabolism of Vismodegib can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Vismodegib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vismodegib.Approved, Investigational
TrimethoprimThe metabolism of Vismodegib can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Vismodegib can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Vismodegib can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Vismodegib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Vismodegib can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Vismodegib can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Vismodegib can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Vismodegib can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Food does not affect absorption.

References

General References
  1. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2. [PubMed:19726763]
  2. Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. [PubMed:23662017]
External Links
KEGG Drug
D09992
PubChem Compound
24776445
PubChem Substance
175427109
ChemSpider
23337846
BindingDB
50249522
ChEBI
66903
ChEMBL
CHEMBL473417
PharmGKB
PA166048558
HET
VIS
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vismodegib
ATC Codes
L01XX43 — Vismodegib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
5l7i
FDA label
Download (211 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentProstate Cancer1
0CompletedTreatmentBasal Cell Carcinoma of the Skin / Recurrent Skin Cancer1
0Unknown StatusTreatmentPancreatic Adenocarcinoma Resectable1
1Active Not RecruitingTreatmentAdult Solid Neoplasm / Pancreatic Acinar Cell Carcinoma / Pancreatic Ductal Adenocarcinoma / Recurrent Pancreatic Carcinoma / Stage IV Pancreatic Cancer / Stage IV Pancreatic Cancer AJCC v6 and v71
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentCancers / Solid Cancers1
1CompletedTreatmentDS Stage I Plasma Cell Myeloma / DS Stage II Plasma Cell Myeloma / DS Stage III Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
1CompletedTreatmentRecurrent Childhood Medulloblastoma1
1CompletedTreatmentSolid Cancers2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingTreatmentBasal Cell Carcinoma (BCC)1
1SuspendedTreatmentAcinar Cell Adenocarcinoma of the Pancreas / Duct Cell Adenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage IV Pancreatic Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentEstrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma1
1, 2Active Not RecruitingTreatmentAdenocarcinoma, Prostate / Stage IIA Prostate Cancer / Stage IIB Prostate Cancer1
1, 2Active Not RecruitingTreatmentNeoplasms, Malignant1
1, 2CompletedTreatmentAdenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage IV Pancreatic Cancer1
1, 2CompletedTreatmentAdult Alveolar Soft Part Sarcoma / Adult Angiosarcoma / Adult Desmoplastic Small Round Cell Tumor / Adult Epithelioid Hemangioendothelioma / Adult Epithelioid Sarcoma / Adult Extraskeletal Myxoid Chondrosarcoma / Adult Extraskeletal Osteosarcoma / Adult Fibrosarcoma / Adult Leiomyosarcoma / Adult Liposarcoma / Adult Malignant Mesenchymoma / Adult Malignant Peripheral Nerve Sheath Tumor / Adult Rhabdomyosarcoma / Adult Synovial Sarcoma / Adult Unclassified Pleomorphic Sarcoma / Chondrosarcomas / Clear Cell Sarcoma of the Kidney / Conjunctival Kaposi Sarcoma / Dermatofibrosarcoma Protuberans / Gastrointestinal Stromal Tumors / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Metastatic Osteosarcoma / Ovarian Sarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Kaposi's Sarcoma / Recurrent Osteosarcoma / Recurrent Uterine Corpus Sarcoma / Small Intestine Leiomyosarcoma / Stage III Adult Soft Tissue Sarcoma / Stage III Uterine Sarcoma / Stage IV Adult Soft Tissue Sarcoma / Stage IV Uterine Sarcoma / Unclassified Pleomorphic Sarcoma of Bone1
1, 2Not Yet RecruitingTreatmentGlioblastoma, Adult1
1, 2RecruitingTreatmentActivation of the Sonic Hedgehog (SHH) Pathway / Histologically Confirmed Medulloblastoma1
1, 2RecruitingTreatmentAgnogenic Myeloid Metaplasia1
2Active Not RecruitingTreatmentBasal Cell Carcinoma (BCC)1
2Active Not RecruitingTreatmentChondrosarcoma, Mesenchymal / Chondrosarcomas / Clear Cell Chondrosarcoma / Dedifferentiated Chondrosarcoma / Metastatic Chondrosarcoma / Primary Central Chondrosarcoma1
2Active Not RecruitingTreatmentExtensive Stage Small Cell Lung Cancer / Extensive Stage Small Cell Lung Carcinoma / Recurrent Small Cell Lung Cancer / Recurrent Small Cell Lung Carcinoma1
2Active Not RecruitingTreatmentKeratocystic Odontogenic Tumor1
2Active Not RecruitingTreatmentPancreatic Cancer Metastatic1
2Active Not RecruitingTreatmentRecurrent Pancreatic Carcinoma / Stage IV Pancreatic Cancer1
2CompletedPreventionBasal Cell Carcinoma (BCC)1
2CompletedTreatmentAdenocarcinoma of the Stomach / Adenocarcinomas of the Gastroesophageal Junction / Recurrent Gastric Cancer / Stage IIIA Gastric Cancer / Stage IIIB Gastric Cancer / Stage IIIC Gastric Cancer / Stage IV Gastric Cancer1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
2CompletedTreatmentAdult Medulloblastoma1
2CompletedTreatmentBasal Cell Carcinoma (BCC)6
2CompletedTreatmentBasal Cell Carcinoma (BCC) / Cancer, Ovarian / Metastatic Colorectal Cancers1
2CompletedTreatmentBasal Cell Nevus Syndrome / Gorlin's Syndrome2
2CompletedTreatmentCancer, Ovarian1
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentRecurrent Childhood Medulloblastoma1
2Not Yet RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentBasal Cell Carcinoma (BCC)1
2RecruitingTreatmentAdvanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Bladder Carcinoma / Carcinoma, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Endometrial Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Uterine Neoplasm / Melanoma / Oesophageal Carcinoma / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Carcinoma / Refractory Lymphomas / Refractory Malignant Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Solid Neoplasms / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentBasal Cell Carcinoma (BCC)2
2RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentCutaneous Malignancy / Locally Advanced Basal Cell Carcinoma / Skin Cancers1
2RecruitingTreatmentIntracranial Meningioma / NF2 Gene Mutation / Recurrent Meningiomas1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentMedulloblastomas1
2RecruitingTreatmentNeoplasms1
2RecruitingTreatmentSkin Basal Cell Carcinoma1
2RecruitingTreatmentStomach Neoplasms1
2TerminatedTreatment"Indolent" Non-hodgkin Lymphoma / Chronic Lymphocytic Leukaemia (CLL) / Indolent Non-Hodgkin's Lymphomas / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Primary Central Nervous System Lymphoma (PCNSL)1
2TerminatedTreatmentMyelodysplastic Syndromes, Myelogenous Leukemia, Acute1
2TerminatedTreatmentPancreatic Ductal Adenocarcinoma1
2TerminatedTreatmentPontine Glioma1
2WithdrawnTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
4Approved for MarketingNot AvailableBasal Cell Carcinoma (BCC)1
4RecruitingTreatmentBasal Cell Carcinoma (BCC)1
Not AvailableActive Not RecruitingNot AvailableBasal Cell Carcinoma (BCC) / Locally Advanced Basal Cell Carcinoma1
Not AvailableRecruitingNot AvailableBasal Cell Carcinoma (BCC)1
Not AvailableRecruitingTreatmentChronic Graft Versus Host Disease / Progressive cGVHD1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral150 mg
CapsuleOral150 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9278961No2008-12-152028-12-15Us
US7888364No2008-11-112028-11-11Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.1 μg/mL and is pH dependent FDA label
logP2.7 FDA label
pKa3.8FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00173 mg/mLALOGPS
logP4.22ALOGPS
logP3.93ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)10.27ChemAxon
pKa (Strongest Basic)3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area76.13 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity107.81 m3·mol-1ChemAxon
Polarizability39.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9547
Blood Brain Barrier+0.9387
Caco-2 permeable+0.6048
P-glycoprotein substrateNon-substrate0.8443
P-glycoprotein inhibitor INon-inhibitor0.8663
P-glycoprotein inhibitor IINon-inhibitor0.9558
Renal organic cation transporterNon-inhibitor0.8925
CYP450 2C9 substrateNon-substrate0.6009
CYP450 2D6 substrateNon-substrate0.63
CYP450 3A4 substrateNon-substrate0.5083
CYP450 1A2 substrateNon-inhibitor0.6067
CYP450 2C9 inhibitorInhibitor0.9078
CYP450 2D6 inhibitorNon-inhibitor0.6638
CYP450 2C19 inhibitorInhibitor0.8515
CYP450 3A4 inhibitorInhibitor0.8452
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9282
Ames testNon AMES toxic0.8271
CarcinogenicityNon-carcinogens0.6746
BiodegradationNot ready biodegradable0.9956
Rat acute toxicity2.0840 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9973
hERG inhibition (predictor II)Non-inhibitor0.8224
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0212900000-190a5fdca2d781122e92

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Phenylpyridines / 2-halobenzoic acids and derivatives / Benzamides / Benzenesulfonyl compounds / Benzoyl derivatives / Chlorobenzenes / Aryl chlorides / Vinylogous halides / Sulfones / Heteroaromatic compounds
show 8 more
Substituents
Benzanilide / 2-phenylpyridine / 2-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Benzenesulfonyl group / Benzoyl / Chlorobenzene / Halobenzene
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfone, benzamides, pyridines, monochlorobenzenes (CHEBI:66903)

Targets

Details
1. Smoothened homolog
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Wnt-protein binding
Specific Function
G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought t...
Gene Name
SMO
Uniprot ID
Q99835
Uniprot Name
Smoothened homolog
Molecular Weight
86395.95 Da
References
  1. Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. [PubMed:23662017]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. [PubMed:23662017]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. [PubMed:23662017]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da

Carriers

Details
1. Serum albumin
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. [PubMed:23662017]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da

Drug created on January 04, 2013 14:48 / Updated on November 22, 2017 12:37