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

Structure

 

Show IUPAC/InChI/SMILES

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.





DRACP is developed by Dr.Zheng's team.