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Vismodegib

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Also known as ErivedgeGDC-0449NSC-747691NSC-755986SID137275857Vismodegib, Erivedge(TM)VismodegibÊVismodegibÂ

Summary

Vismodegib (CHEMBL473417) is an approved small-molecule antineoplastic agent (ATC L01XJ01) targeting SMO; indicated across 30 conditions including basal cell carcinoma and neoplasm; with CIViC clinical evidence for 28 variant-indication associations (e.g. PTCH1 Loss-of-function in basal cell carcinoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XJ01
  • Targets: 1 (SMO)
  • Indications: 30 conditions
  • Clinical trials: 82
  • Precision-oncology evidence (CIViC): 28 variant–indication associations
  • Chemistry: 421.3 Da · C19H14Cl2N2O3S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL473417
NameVismodegib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID24776445
ChEBICHEBI:66903
ATCL01XJ01
Molecular formulaC19H14Cl2N2O3S
Molecular weight421.3
InChIKeyBPQMGSKTAYIVFO-UHFFFAOYSA-N

SMILES: CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl

IUPAC name: 2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide

ChEBI definition: A benzamide obtained by formal condensation between the carboxy group of 2-chloro-4-(methylsulfonyl)benzoic acid and the anilino group of 4-chloro-3-(pyridin-2-yl)aniline. Used for the treatment metastatic basal cell carcinoma.

Pharmacological roles (ChEBI): antineoplastic agent, SMO receptor antagonist, Hedgehog signaling pathway inhibitor, teratogenic agent.

Also known as: Erivedge, GDC-0449, NSC-747691, NSC-755986, Vismodegib, VISMODEGIB, vismodegib, SID137275857, Vismodegib, Erivedge(TM), VismodegibÊ, VismodegibÂ

Parent form; salt/anhydrous children: CHEMBL4125998, CHEMBL4127241, CHEMBL4129312

Patent coverage: 2,817 distinct patent families (6,714 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 6,189 (92%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
SMOSMOAntagonist7.79Q99835

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Equilibrative nucleoside transporter 1, 5-hydroxytryptamine receptor 1A, Ubiquitin carboxyl-terminal hydrolase 28, Sodium-dependent noradrenaline transporter, Mu-type opioid receptor, D(3) dopamine receptor, Sodium-dependent dopamine transporter, 3’,5’-cyclic-AMP phosphodiesterase 4A, 3’,5’-cyclic-AMP phosphodiesterase 4D.

Bioactivity

ChEMBL activities: 39 potent at pChembl ≥ 5 of 47 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
SMO9.4IC500.4nMCHEMBL_ACT_20631882
P567268.82IC501.5nMCHEMBL_ACT_12076096
SMO8.7EC502nMCHEMBL_ACT_20631812
P567268.7EC502nMCHEMBL_ACT_20631881
SMO8.52EC503nMCHEMBL_ACT_20631880
Q622268.52IC503nMCHEMBL_ACT_2517608
P567268.33EC504.7nMCHEMBL_ACT_20631663
P567268.3IC505nMCHEMBL_ACT_10923871
SMO8.29IC505.1nMCHEMBL_ACT_16627640
SMO8.22IC506nMCHEMBL_ACT_16406805
P567268.22IC506nMCHEMBL_ACT_18542389
SMO8.15IC507nMCHEMBL_ACT_10887750
SMO8.15IC507nMCHEMBL_ACT_10888029
Q622268.14IC507.2nMCHEMBL_ACT_13843840
SMO7.91Ki12.2nMCHEMBL_ACT_18188705
Q622267.89IC5013nMCHEMBL_ACT_16406815
Q622267.89IC5013nMCHEMBL_ACT_3004844
SMO7.88IC5013.06nMCHEMBL_ACT_20705188
SHH7.82IC5015nMCHEMBL_ACT_6187155
P567267.8IC5016nMCHEMBL_ACT_15679155
SMO7.79Ki16.2nMCHEMBL_ACT_12076104
Q622267.77IC5017nMCHEMBL_ACT_16406801
SMO7.7IC5020nMCHEMBL_ACT_13941632
SMO7.64IC5023nMCHEMBL_ACT_14645553
SMO7.48IC5033nMCHEMBL_ACT_13941653
P567267.41IC5039.2nMCHEMBL_ACT_16774918
P567267.34IC5046nMCHEMBL_ACT_18429769
P567267.34IC5046nMCHEMBL_ACT_19217425
SMO7.13IC5074nMCHEMBL_ACT_19217429
SMO7.01Kd97.5nMCHEMBL_ACT_20692451

Target pathways

Aggregated over 1 target gene(s): SMO.

Top Reactome pathways

12 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction1SMO
Organelle biogenesis and maintenance1SMO
Signaling by GPCR1SMO
Class B/2 (Secretin family receptors)1SMO
GPCR ligand binding1SMO
Signaling by Hedgehog1SMO
Hedgehog ‘off’ state1SMO
Cilium Assembly1SMO
Cargo trafficking to the periciliary membrane1SMO
BBSome-mediated cargo-targeting to cilium1SMO
Hedgehog ‘on’ state1SMO
Activation of SMO1SMO

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II1
vasculogenesis1
osteoblast differentiation1
in utero embryonic development1
cell fate specification1
neural crest cell migration1
negative regulation of protein phosphorylation1
heart looping1
positive regulation of neuroblast proliferation1
positive regulation of mesenchymal cell proliferation1
determination of left/right asymmetry in lateral mesoderm1
type B pancreatic cell development1
protein import into nucleus1
apoptotic process1
smoothened signaling pathway1

Indications & clinical

Indications

30 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
basal cell carcinoma4MONDO:0020804EFO:0004193
neoplasm4MONDO:0005070EFO:0000616
medulloblastoma2MONDO:0007959EFO:0002939
idiopathic pulmonary fibrosis2MONDO:0800504EFO:0000768
plasma cell myeloma2MONDO:0009693EFO:0001378
gliosarcoma2MONDO:0016681EFO:1001465
acute myeloid leukemia2MONDO:0018874EFO:0000222
glioblastoma2MONDO:0018177EFO:0000519
small cell lung carcinoma2MONDO:0008433EFO:0000702
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
gastric neoplasm2MONDO:0021085EFO:0003897
breast neoplasm2MONDO:0021100MONDO:0007254
ovarian cancer2MONDO:0008170MONDO:0008170
mesenchymal chondrosarcoma2MONDO:0006853EFO:1001041
nevoid basal cell carcinoma syndrome2MONDO:0007187MONDO:0007187
breast carcinoma2MONDO:0004989EFO:0000305
paraganglioma2MONDO:0000448EFO:1000453
pancreatic ductal adenocarcinoma2MONDO:0005184MONDO:0005184
meningioma2MONDO:0016642MONDO:0850302
prostate adenocarcinoma1MONDO:0005082EFO:0000673
primary myelofibrosis1MONDO:0009692MONDO:0044903
triple-negative breast carcinoma1MONDO:0005494EFO:0005537
skin neoplasm0MONDO:0002531MONDO:0002898

7 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 82.

Phase distribution

PhaseTrials
PHASE249
PHASE117
PHASE1/PHASE26
EARLY_PHASE14
Not specified4
PHASE42

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02436408PHASE4COMPLETEDVISmodegib for ORbital and Periocular Basal Cell Carcinoma
NCT03610022PHASE4COMPLETEDRelationship Between Pharmacokinetics and Safety of Vismodegib - OPTIVISMO-1
NCT01267955PHASE2ACTIVE_NOT_RECRUITINGVismodegib in Treating Patients With Advanced Chondrosarcomas
NCT01878617PHASE2ACTIVE_NOT_RECRUITINGA Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02523014PHASE2RECRUITINGVismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03297606PHASE2RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
NCT04341181PHASE2RECRUITINGProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling
NCT05159245PHASE2RECRUITINGThe Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
NCT05538091PHASE2RECRUITINGVismodegib Combined With Atezolizumab in Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
NCT05561634PHASE2RECRUITINGRadiotherapy by Sonic Hedgehog Pathway Inhibitors in Basal Cell Carcinoma
NCT06344052PHASE2RECRUITINGTo Assess the Safety and Efficacy of SP-002 with Vismodegib for the Treatment of Locally Advanced Basal Cell Carcinoma
NCT06357988PHASE2ACTIVE_NOT_RECRUITINGTesting GDC-0449 (Vismodegib) as Potentially Targeted Treatment in Cancers With Smoothened or Patched 1 Mutant Tumors (MATCH - Subprotocol T)
NCT00636610PHASE2COMPLETEDA Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer
NCT00739661PHASE2COMPLETEDA Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission
NCT00833417PHASE2COMPLETEDA Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma
NCT00887159PHASE2COMPLETEDA Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients With Extensive Stage
NCT00939484PHASE2COMPLETEDVismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma
NCT00957229PHASE2COMPLETEDTo Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
NCT00959647PHASE2COMPLETEDA Study of Vismodegib (GDC-0449) in Patients Treated With Vismodegib in a Previous Genentech-sponsored Phase I or II Cancer Study
NCT00980343PHASE2COMPLETEDGDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
NCT00982592PHASE2COMPLETEDCombination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer
NCT01064622PHASE2COMPLETEDGemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer
NCT01088815PHASE2COMPLETEDHedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas
NCT01096732PHASE2TERMINATEDHedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)
NCT01154452PHASE1/PHASE2COMPLETEDVismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma
NCT01163084PHASE1/PHASE2TERMINATEDLeuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer
NCT01174264PHASE1/PHASE2COMPLETEDEvaluation of Food Effect on Pharmacokinetics of Vismodegib
NCT01195415PHASE2COMPLETEDVismodegib and Gemcitabine Hydrochloride in Treating Patients With Advanced Pancreatic Cancer
NCT01201915PHASE2COMPLETEDA Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449) in Operable Basal Cell Carcinoma
NCT01239316PHASE2COMPLETEDVismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma
NCT01367665PHASE2COMPLETEDSTEVIE: A Study of Vismodegib in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma
NCT01543581PHASE2COMPLETEDVismodegib for Treatment of Basal Cell Carcinoma
NCT01556009PHASE2COMPLETEDTrial Comparing the Effects of Intermittent Vismodegib vs. PDT in Patients With Multiple Basal Cell Carcinomas
NCT01601184PHASE1/PHASE2TERMINATEDStudy of Vismodegib in Combination With Temozolomide Versus Temozolomide Alone in Patients With Medulloblastomas With an Activation of the Sonic Hedgehog Pathway
NCT01774253PHASE2TERMINATEDErivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma
NCT01815840PHASE2COMPLETEDA Study of Two Vismodegib Regimens in Participants With Multiple Basal Cell Carcinomas
NCT01835626PHASE2COMPLETEDPhase II Study of Radiation Therapy and Vismodegib for Advanced Head/Neck Basal Cell Carcinoma
NCT01880437PHASE2TERMINATEDA Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome

Clinical evidence (CIViC)

Variant × indication × effect (28 predictive associations from 35 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
PTCH1 Loss-of-functionBasal Cell CarcinomaSensitivity/ResponseVismodegibCIViC AEID11607
PTCH1 LOHMedulloblastomaSensitivity/ResponseVismodegibCIViC BEID749
PTCH1 MutationCancerSensitivity/ResponseVismodegibCIViC BEID5978
SMO MutationCancerSensitivity/ResponseVismodegibCIViC BEID5979
SMO MutationBasal Cell CarcinomaResistanceVismodegib + SonidegibCIViC BEID1477
SMO MutationBasal Cell CarcinomaResistanceVismodegibCIViC BEID746
PTCH1 Q17XBasal Cell CarcinomaSensitivity/ResponseVismodegibCIViC CEID4684
PTCH1 Q787XBasal Cell CarcinomaSensitivity/ResponseVismodegibCIViC CEID4683
PTCH1 W170XBasal Cell CarcinomaSensitivity/ResponseVismodegibCIViC CEID4681
PTCH1 W712XBasal Cell CarcinomaSensitivity/ResponseVismodegibCIViC CEID4682
TP53 MutationMedulloblastoma SHH Activated And TP53 MutantSensitivity/ResponseVismodegibCIViC CEID8348
SMO L412FBasal Cell CarcinomaResistanceVismodegibCIViC CEID4654 +2
SMO V321MBasal Cell CarcinomaResistanceVismodegibCIViC CEID4660 +2
SMO D473HMedulloblastomaResistanceVismodegibCIViC CEID745 +1
SMO W535LBasal Cell CarcinomaResistanceVismodegibCIViC CEID3735 +1
SMO D473GBasal Cell CarcinomaResistanceVismodegibCIViC CEID4634
SMO D473YBasal Cell CarcinomaResistanceVismodegibCIViC CEID4635
SMO G497WBasal Cell CarcinomaResistanceVismodegibCIViC CEID4675
SMO S278IBasal Cell CarcinomaResistanceVismodegibCIViC CEID4636
SMO W281LBasal Cell CarcinomaResistanceVismodegibCIViC CEID4674
SMO W281CBasal Cell CarcinomaResistanceVismodegibCIViC DEID4637 +1
SMO A459VBasal Cell CarcinomaResistanceVismodegibCIViC DEID4679
SMO C469YBasal Cell CarcinomaResistanceVismodegibCIViC DEID4677
SMO D473HBasal Cell CarcinomaResistanceVismodegibCIViC DEID755
SMO I408VBasal Cell CarcinomaResistanceVismodegibCIViC DEID4676
SMO Q477EBasal Cell CarcinomaResistanceVismodegibCIViC DEID4639
SMO S533NBasal Cell CarcinomaResistanceVismodegibCIViC DEID4680
SMO T241MBasal Cell CarcinomaResistanceVismodegibCIViC DEID4678

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

10 molecules share ≥1 primary target. Top 10 by shared-target count:

MoleculeSourceStatusShared targets
INFIGRATINIBChEMBL + PubChemPhase 4 (approved)SMO
SONIDEGIBChEMBL + PubChemPhase 4 (approved)SMO
LINIFANIBChEMBLPhase 3SMO
PATIDEGIBChEMBLPhase 3SMO
CEP-32496ChEMBLPhase 2SMO
FORETINIBChEMBLPhase 2SMO
TALADEGIBChEMBLPhase 2SMO
cholecalciferolPubChemApprovedSMO
ErgocalciferolPubChemApprovedSMO
GlasdegibPubChemApprovedSMO

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot