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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
Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor.
2005 Feb
Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897.
2005 Feb 15
Advances in recent patent and clinical trial drug development for Alzheimer's disease.
2014 Jul
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 GMT 2023
Edited
by admin
on Sat Dec 16 16:34:18 GMT 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 GMT 2023 , Edited by admin on Sat Dec 16 16:34:18 GMT 2023
PRIMARY
EPA CompTox
DTXSID50460039
Created by admin on Sat Dec 16 16:34:18 GMT 2023 , Edited by admin on Sat Dec 16 16:34:18 GMT 2023
PRIMARY
FDA UNII
QK855F579S
Created by admin on Sat Dec 16 16:34:18 GMT 2023 , Edited by admin on Sat Dec 16 16:34:18 GMT 2023
PRIMARY
CAS
290315-45-6
Created by admin on Sat Dec 16 16:34:18 GMT 2023 , Edited by admin on Sat Dec 16 16:34:18 GMT 2023
PRIMARY
Related Record Type Details
.GAMMA.-SECRETASE
TARGET -> INHIBITOR
IC50
Related Record Type Details
Structure of BMS-299897
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