Patidegib

Summary

Patidegib (CHEMBL538867) is a phase-3 clinical-stage small molecule targeting SMO; indicated across 5 conditions including nevoid basal cell carcinoma syndrome and basal cell carcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. SMO D473H in medulloblastoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (SMO)
• Indications: 5 conditions
• Clinical trials: 8
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 504.8 Da · C29H48N2O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL538867
Name	Patidegib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	25027363
Molecular formula	C29H48N2O3S
Molecular weight	504.8
InChIKey	HZLFFNCLTRVYJG-WWGOJCOQSA-N

SMILES: C[C@H]1C[C@@H]2[C@H]([C@H]([C@]3(O2)CC[C@H]4[C@@H]5CC[C@@H]6C[C@@H](CC[C@@]6([C@H]5CC4=C(C3)C)C)NS(=O)(=O)C)C)NC1

IUPAC name: N-[(3R,3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3’,6’,11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2’-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-3-yl]methanesulfonamide

Also known as: FIN-5, IP-9, IP9 FREE BASE, IPI 926, Ipi-926, IPI-926, IPI-926 FREE BASE, Patidegib, Saridegib, PATIDEGIB

Parent form; salt/anhydrous children: CHEMBL2105764

Patent coverage: 651 distinct patent families (1,695 SureChEMBL compound mentions), from 1 matched compound structure(s). 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).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SMO	SMO	Antagonist	8.85		Q99835

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Protein smoothened.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
SMO	8.85	IC50	1.4	nM	CHEMBL_ACT_2648447

Target pathways

Aggregated over 1 target gene(s): SMO.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	SMO
Organelle biogenesis and maintenance	1	SMO
Signaling by GPCR	1	SMO
Class B/2 (Secretin family receptors)	1	SMO
GPCR ligand binding	1	SMO
Signaling by Hedgehog	1	SMO
Hedgehog ‘off’ state	1	SMO
Cilium Assembly	1	SMO
Cargo trafficking to the periciliary membrane	1	SMO
BBSome-mediated cargo-targeting to cilium	1	SMO
Hedgehog ‘on’ state	1	SMO
Activation of SMO	1	SMO

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
vasculogenesis	1
osteoblast differentiation	1
in utero embryonic development	1
cell fate specification	1
neural crest cell migration	1
negative regulation of protein phosphorylation	1
heart looping	1
positive regulation of neuroblast proliferation	1
positive regulation of mesenchymal cell proliferation	1
determination of left/right asymmetry in lateral mesoderm	1
type B pancreatic cell development	1
protein import into nucleus	1
apoptotic process	1
smoothened signaling pathway	1

Indications & clinical

Indications

5 indications (0 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).

Indication	Trial phase	MONDO	EFO
nevoid basal cell carcinoma syndrome	3	MONDO:0007187	MONDO:0007187
basal cell carcinoma	2	MONDO:0020804	EFO:0004193
chondrosarcoma	2	MONDO:0008977	EFO:0000333
neoplasm	1	MONDO:0005070	EFO:0000616
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE2	4
PHASE1	3
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01310816	PHASE2	COMPLETED	A Safety and Efficacy Study of Patients With Metastatic or Locally Advanced (Unresectable) Chondrosarcoma
NCT01371617	PHASE2	COMPLETED	A Phase 2 Study With IPI-926 in Patients With Myelofibrosis
NCT02762084	PHASE2	COMPLETED	Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients
NCT02828111	PHASE2	COMPLETED	Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas
NCT00761696	PHASE1	COMPLETED	A Phase 1 Study of IPI-926 in Patients With Advanced and/or Metastatic Solid Tumor Malignancies
NCT01255800	PHASE1	COMPLETED	Pilot Study of Cetuximab and the Hedgehog Inhibitor IPI-926 in Recurrent Head and Neck Cancer
NCT01383538	PHASE1	COMPLETED	FOLFIRINOX Plus IPI-926 for Advanced Pancreatic Adenocarcinoma
NCT01609179	Not specified	COMPLETED	IPI-926 Extension Protocol for Continuation of Treatment With IPI-926

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
SMO D473H	Medulloblastoma	Sensitivity/Response	Patidegib	CIViC D	EID1099

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

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:

Molecule	Source	Status	Shared targets
INFIGRATINIB	ChEMBL + PubChem	Phase 4 (approved)	SMO
SONIDEGIB	ChEMBL + PubChem	Phase 4 (approved)	SMO
VISMODEGIB	ChEMBL + PubChem	Phase 4 (approved)	SMO
LINIFANIB	ChEMBL	Phase 3	SMO
CEP-32496	ChEMBL	Phase 2	SMO
FORETINIB	ChEMBL	Phase 2	SMO
TALADEGIB	ChEMBL	Phase 2	SMO
cholecalciferol	PubChem	Approved	SMO
Ergocalciferol	PubChem	Approved	SMO
Glasdegib	PubChem	Approved	SMO