BMS-986115
DRACPC ID DRACPC0052
Active Ingredients BMS-986115
Description An orally bioavailable, gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon administration, GS/pan-Notch inhibitor AL102 binds to GS and blocks the proteolytic cleavage and release of the Notch intracellular domain (NICD), which would normally follow ligand binding to the extracellular domain of the Notch receptor. This prevents both the subsequent translocation of NICD to the nucleus to form a transcription factor complex and the expression of Notch-regulated genes. This results in the induction of apoptosis and the inhibition of growth of tumor cells that overexpress Notch. Overexpression of the Notch signaling pathway plays an important role in tumor cell proliferation and survival. 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 and leads to their activation.
Synonyms GS/pan-Notch Inhibitor AL102; AL 102; AL-102; BMS-986115
Type Small Molecule
Disease Various Advanced Cancer
Classification
GS/pan-Notch Inhibitor Amino acid and derivative
Structure Information
Molecular Formula C26H25F7N4O3
Molecular Weight 574.5
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name (2S,3R)-N'-[(3S)-5-(3-fluorophenyl)-9-methyl-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)butanediamide
InChI InChI=1S/C26H25F7N4O3/c1-13-4-2-7-18-19(13)36-24(40)22(35-20(18)14-5-3-6-15(27)12-14)37-23(39)17(9-11-26(31,32)33)16(21(34)38)8-10-25(28,29)30/h2-7,12,16-17,22H,8-11H2,1H3,(H2,34,38)(H,36,40)(H,37,39)/t16-,17+,22+/m0/s1
InChI_Key SRJNRAQUSAVENA-GSHUGGBRSA-N
SMILES O=C(N)[C@@H](CCC(F)(F)F)[C@@H](CCC(F)(F)F)C(N[C@@H]1C(NC2=C(C)C=CC=C2C(C3=CC=CC(F)=C3)=N1)=O)=O
External Codes
PubChem CID 73388393
DrugBank Accession Number DB13126
NCI Thesaurus Code C118573
UNII LSK1L593UU GSRS
CAS 1584647-27-7
Drug approval
Drug indication
BMS-986115 has been used in trials studying the treatment of Various Advanced Cancer.
The drug is not approved.
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT01986218 | Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors | Various Advanced Cancer | Phase 1 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
