Nirogacestat
DRACPC ID DRACPC0070
Active Ingredients Nirogacestat
Description A selective gamma secretase (GS) inhibitor with potential antitumor activity. Nirogacestat binds to GS, blocking proteolytic activation of Notch receptors; Notch signaling pathway inhibition may follow, which may result in the induction of apoptosis in tumor cells that overexpress Notch. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth and survival.
Synonyms PF-03084014; (S)-2-(((S)-6,8-Difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide; Nirogacestat
Type Small Molecule
Disease Breast Cancer, HIV Infection, Desmoid Tumors, Advanced Solid Tumors
Classification
GS inhibitor Amino acid and derivative
Structure Information
Molecular Formula C27H41F2N5O
Molecular Weight 489.6
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name (2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-N-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide
InChI InChI=1S/C27H41F2N5O/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35)/t20-,23-/m0/s1
InChI_Key VFCRKLWBYMDAED-REWPJTCUSA-N
SMILES CCC[C@H](N[C@@H]1CC2=C(C=C(F)C=C2F)CC1)C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)=O
External Codes
PubChem CID 46224413
DrugBank Accession Number DB12005
NCI Thesaurus Code C82383
UNII QZ62892OFJ GSRS
CAS 1290543-63-3
Drug approval
Drug indication
Nirogacestat has been used in trials studying the treatment of Breast Cancer, HIV Infection, Desmoid Tumors, Advanced Solid Tumors, and Aggressive Fibromatosis, among others.
The drug is not approved.
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT03785964 | A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF) | Desmoid Tumor; Aggressive Fibromatosis | Phase 3 | Treatment |
| NCT05348356 | A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors | Ovarian Granulosa-Stromal Tumor; Ovarian Granulosa Cell Tumor; Ovarian Cancer | Phase 2 | Treatment |
| NCT05556798 | Belantamab Mafodotin in Combination With Nirogacestat in Patients With Relapsed or Refractory Multiple Myeloma | Multiple Myeloma | Phase 1 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
