Osugacestat

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H26F6N4O3
Molecular Weight	556.5001
Optical Activity	( - )
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C2=C(C=CC=C2)C(=N[C@H](NC(=O)[C@H](CCC(F)(F)F)[C@H](CCC(F)(F)F)C(N)=O)C1=O)C3=CC=CC=C3

InChI

InChIKey=AYOUDDAETNMCBW-GSHUGGBRSA-N

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

HIDE SMILES / InChI

Molecular Formula	C26H26F6N4O3
Molecular Weight	556.5001
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26005526 | https://www.denovodata.com/pipeline/bristol-myers-squibb-leukemia/

BMS-906024 is a lead candidate of a series of inhibitors of gamma secretase-mediated Notch signalling. BMS-906024 is an orally bioavailable, small-molecule gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon administration, GS/pan-Notch inhibitor BMS-906024 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. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth. BMS-906024 is currently in Phase 1 clinical trials for patients with T-cell acute lymphoblastic leukemia and metastatic solid tumors, including lung cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Neurogenic locus notch homolog protein 1 1 Target ID: CHEMBL2146346 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26005526	Inhibitor 8504	1.6 nM [IC50]
Neurogenic locus notch homolog protein 2 1 Target ID: CHEMBL3407320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26005526	Inhibitor 8504	0.7 nM [IC50]
Neurogenic locus notch homolog protein 3 1 Target ID: CHEMBL3407319 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26005526	Inhibitor 8504	3.4 nM [IC50]
Neurogenic locus notch homolog protein 4 1 Target ID: CHEMBL3407321 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26005526	Inhibitor 8504	2.9 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://clinicaltrials.gov/ct2/show/NCT01292655 http://adisinsight.springer.com/drugs/800034062	Primary		Phase I 438	Unknown Approved Use Unknown
Acute T-cell lymphoblastic leukemia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01363817	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
754 μg/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.3 μg/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg single, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
782 μg/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg 1 times / 4 weeks steady-state, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.5 μg/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg 1 times / 2 weeks multiple, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
155 μg/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
372 μg/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
753 μg/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1740 μg/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
48 μg/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	600 mg single, subcutaneous dose: 600 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
179000 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3530 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg single, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
262000 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg 1 times / 4 weeks steady-state, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10600 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg 1 times / 2 weeks multiple, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18700 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
74400 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
178000 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
438000 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13500 μg × h/mL EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	600 mg single, subcutaneous dose: 600 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
215 h EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
93.8 h EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg single, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
296 h EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	30 mg/kg 1 times / 4 weeks steady-state, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
79 h EXPERIMENT https://investors.alector.com/static-files/3c805bd6-8ba4-4009-855b-2fcda6d38e4f	300 mg 1 times / 2 weeks multiple, subcutaneous dose: 300 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
83.2 h EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
196 h EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
261 h EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
294 h EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
95.8 h EXPERIMENT https://investors.alector.com/static-files/1746ff73-897a-4c27-ad14-8ee3f4680e84	600 mg single, subcutaneous dose: 600 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	BMS-906024 serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
11.3% EXPERIMENT https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.5b00001	10 μmol single, intravenous dose: 10 μmol route of administration: Intravenous experiment type: SINGLE co-administered:		BMS-906024 plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
8.4 mg 1 times / week multiple, intravenous Highest studied dose Dose: 8.4 mg, 1 times / week Route: intravenous Route: multiple Dose: 8.4 mg, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	DLT: Infusion reaction, Vomiting... Dose limiting toxicities: Infusion reaction (grade 3, 14.3%) Vomiting (grade 3, 14.3%) Liver failure (grade 5, 14.3%) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515
4 mg 1 times / week multiple, intravenous MTD Dose: 4 mg, 1 times / week Route: intravenous Route: multiple Dose: 4 mg, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515
6 mg 1 times / 2 weeks multiple, intravenous MTD Dose: 6 mg, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 6 mg, 1 times / 2 weeks Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 16.7%) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515

AEs

AE	Significance	Dose	Population
Infusion reaction	grade 3, 14.3% DLT	8.4 mg 1 times / week multiple, intravenous Highest studied dose Dose: 8.4 mg, 1 times / week Route: intravenous Route: multiple Dose: 8.4 mg, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515
Vomiting	grade 3, 14.3% DLT	8.4 mg 1 times / week multiple, intravenous Highest studied dose Dose: 8.4 mg, 1 times / week Route: intravenous Route: multiple Dose: 8.4 mg, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515
Liver failure	grade 5, 14.3% DLT, Disc. AE	8.4 mg 1 times / week multiple, intravenous Highest studied dose Dose: 8.4 mg, 1 times / week Route: intravenous Route: multiple Dose: 8.4 mg, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515
Diarrhea	grade 3, 16.7% DLT	6 mg 1 times / 2 weeks multiple, intravenous MTD Dose: 6 mg, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 6 mg, 1 times / 2 weeks Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2515

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	HLM 34

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
HLM 34	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26005526/	no [Inhibition 0.5 uM]

Sourcing

Vendor/Aggregator	ID	URL
AstaTech	93506	http://astatechinc.com/CPSResult.php?CRNO=93506
Norris Pharm	NSZB-A218544

PubMed

Title	Date	PubMed
Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma.	2017-12	28978720
Complete hematologic response of early T-cell progenitor acute lymphoblastic leukemia to the γ-secretase inhibitor BMS-906024: genetic and epigenetic findings in an outlier case.	2015-10	27148573
Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors.	2015-05-14	26005526

Patents

Sample Use Guides

In Vivo Use Guide

BMS-906024 escalating doses starting at 0.3 mg solution for intravenous (IV) administration once weekly continuously until disease progression or unacceptable toxicity.

Route of Administration: Intravenous

In Vitro Use Guide

BMS-906024 reduced Notch1 ICD levels in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximal depletion at 50 -100 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:35:51 GMT 2025` Edited by `admin` on `Mon Mar 31 21:35:51 GMT 2025`
Record UNII	DRL23N424R
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Osugacestat

Official Name

English

BMS-906024

Preferred Name

English

Osugacestat [WHO-DD]

Common Name

English

AL101

Code

English

OSUGACESTAT [USAN]

Common Name

English

Butanediamide, N1-[(3S)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)-, (2R,3S)-

Systematic Name

English

osugacestat [INN]

Common Name

English

BM-0018

Code

English

BM0018

Code

English

AL-101

Code

English

(2R,3S)-N-((3S)-1-Methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-2,3-bis(3,3,3-trifluoropropyl)succinamide

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

683819