Osugacestat
DCTPepD ID DCTPepD0063
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
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
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.
