Osugacestat 

DRACPC ID  DRACPC0063

Active Ingredients   Osugacestat 

Description  A small-molecule gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon intravenous administration, osugacestat binds to GS and blocks activation of Notch receptors, which may inhibit the proliferation of tumor cells with an overly-active Notch pathway. 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 that lead to their activation. Overactivation of the Notch signaling pathway, often triggered by activating mutations, has been correlated with increased cellular proliferation and poor prognosis in certain tumor types.

Synonyms  AL-101; AL101; BM-0018; BM0018; BMS-906024; GS/pan-Notch Inhibitor AL101; Osugacestat 

Type  Small Molecule

Disease  Leukemia, Lymphoma

Classification

  

GS/pan-Notch Inhibitor Amino acid and derivative

Structure Information


Molecular Formula  C26H26F6N4O3

Molecular Weight  556.5

Active Sequence  Not available

Sequence Length  Not available

Modification  Not available

Structure

 

Show IUPAC/InChI/SMILES

IUPAC Name  (2S,3R)-N'-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide

InChI  InChI=1S/C26H26F6N4O3/c1-36-19-10-6-5-9-18(19)20(15-7-3-2-4-8-15)34-22(24(36)39)35-23(38)17(12-14-26(30,31)32)16(21(33)37)11-13-25(27,28)29/h2-10,16-17,22H,11-14H2,1H3,(H2,33,37)(H,35,38)/t16-,17+,22+/m0/s1

InChI_Key AYOUDDAETNMCBW-GSHUGGBRSA-N

SMILES  O=C(N)[C@@H](CCC(F)(F)F)[C@@H](CCC(F)(F)F)C(N[C@@H]1C(N(C)C2=CC=CC=C2C(C3=CC=CC=C3)=N1)=O)=O

External Codes


PubChem CID  66550890

DrugBank Accession Number  DB12006

NCI Thesaurus Code  C116872  

UNII  DRL23N424R   GSRS

CAS  1401066-79-2



Drug approval


Drug indication
    Osugacestat (BMS-906024) has been used in trials studying the treatment of Cancer, Lymphoblastic Leukemia, Acute T-cell, and Precursor T-Cell Lymphoblastic Lymphoma.

    The drug is not approved.

ClinicalTrials.gov Identifier Title Condition or disease Phase Purpose
NCT04461600 A Phase 2, Multi-center, Open-label, Single Arm Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer Triple Negative Breast Cancer Phase 2 Treatment
NCT03691207 A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations Adenoid Cystic Carcinoma Phase 2 Treatment
NCT04973683 AL101 Prior to Standard-of-Care Surgery in Patients With Notch Activated Adenoid Cystic Carcinoma (ACC) Adenoid Cystic Carcinoma; Metastatic Adenoid Cystic Carcinoma Phase 1 Treatment

    More clinical information is obtained from ClinicalTrials.gov.





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