U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C24H21ClF3NO4S
Molecular Weight 511.941
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BMS-299897

SMILES

C[C@@H](N(C1=CC(F)=CC=C1F)S(=O)(=O)C2=CC=C(Cl)C=C2)C3=C(CCCC(O)=O)C=C(F)C=C3

InChI

InChIKey=IZAOBRWCUGOKNH-OAHLLOKOSA-N
InChI=1S/C24H21ClF3NO4S/c1-15(21-11-7-18(26)13-16(21)3-2-4-24(30)31)29(23-14-19(27)8-12-22(23)28)34(32,33)20-9-5-17(25)6-10-20/h5-15H,2-4H2,1H3,(H,30,31)/t15-/m1/s1

HIDE SMILES / InChI
Molecular Formula C24H21ClF3NO4S
Molecular Weight 511.941
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15670587

BMS-299897 is an orally bioavailable, sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP). BMS-299897 has the potential for treatment of Alzheimer's disease.

CNS Activity

CNS Active
3913
Curator's Comment: BMS-299897 markedly reduced both brain and plasma Abeta(1-40) in APP-YAC mice and in guinea pigs. Readily crosses blood–brain barrier.

Originator

Bristol-Myers Squibb
145
Curator's Comment: # Bristol-Myers Squibb

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 12.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897.
2005 Feb 15
A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.
2015
Patents

Patents

US2008045499
1
US6967196
1
US8637493
1
WO2014039781A1
1

Sample Use Guides

In Vivo Use Guide
Mice: 100 mg/kg po, guinea pigs: 30 mg/kg intraperitoneally
Route of Administration: Other
In Vitro Use Guide
At ∼1.0 uM, BMS-299897 decreased Aβ42, Aβ40 and Aβ38 peptides to levels ranging from 20 to 50% of the vehicle control in rat neuronal cultures.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:34:18 UTC 2023
Edited
by admin
on Sat Dec 16 16:34:18 UTC 2023
Record UNII
QK855F579S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BMS-299897
Common Name English
2-((1R)-1-((4-CHLOROPHENYL)SULFONYL)(2,5-DIFLUOROPHENYL) AMINO)ETHYL-5-FLUOROBENZENEBUTANOIC ACID
Common Name English
Code System Code Type Description
PUBCHEM
11249248
Created by admin on Sat Dec 16 16:34:18 UTC 2023 , Edited by admin on Sat Dec 16 16:34:18 UTC 2023
PRIMARY
EPA CompTox
DTXSID50460039
Created by admin on Sat Dec 16 16:34:18 UTC 2023 , Edited by admin on Sat Dec 16 16:34:18 UTC 2023
PRIMARY
FDA UNII
QK855F579S
Created by admin on Sat Dec 16 16:34:18 UTC 2023 , Edited by admin on Sat Dec 16 16:34:18 UTC 2023
PRIMARY
CAS
290315-45-6
Created by admin on Sat Dec 16 16:34:18 UTC 2023 , Edited by admin on Sat Dec 16 16:34:18 UTC 2023
PRIMARY
Related Record Type Details
.GAMMA.-SECRETASE
TARGET -> INHIBITOR
IC50
Related Record Type Details
Structure of BMS-299897
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966