Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H17N5.ClH |
Molecular Weight | 291.779 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CC1=CN=C2N1C3=C(C=CC(C)=C3)N=C2NCCN
InChI
InChIKey=MIDKPVLYXNLFGZ-UHFFFAOYSA-N
InChI=1S/C14H17N5.ClH/c1-9-3-4-11-12(7-9)19-10(2)8-17-14(19)13(18-11)16-6-5-15;/h3-4,7-8H,5-6,15H2,1-2H3,(H,16,18);1H
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C14H17N5 |
Molecular Weight | 255.3183 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. BMS-345541 was identified as a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC(50) = 0.3 uM, IKK-1 IC(50) = 4 uM). A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 was shown to have excellent pharmacokinetics in mice, and peroral administration showed the compound to dose-dependently inhibit the production of serum tumor necrosis factor alpha following intraperitoneal challenge with lipopolysaccharide. BMS-345541 is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models. BMS-345541 blocks both joint inflammation and destruction in collagen-induced arthritis in mice.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16286924
Curator's Comment: BMS-345541 apparently does not cross the blood-brain barrier.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12403772
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/13130486
Treatment of collagen-induced arthritis in mice: BMS-345541 was administered perorally daily, either prophylactically (before disease onset) or therapeutically (after disease onset). When administered prophylactically, BMS-345541 (in a dose range of 10-100 mg/kg) was effective, in a dose-dependent manner, in reducing the incidence of disease and inhibiting clinical signs of disease. Dose-dependent efficacy in terms of both disease severity and histologic end points was observed with the therapeutic dosing regimen of BMS-345541, with use of the 100-mg/kg dose resulting in resolution of disease.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16467110
BMS-345541 (10 uM) inhibits growth of Normal human epidermal melanocytes, and metastatic melanoma cells (SK-MEL-5, A375, and Hs 294T) by 96% and 99% at 72h, respectively. Application of 100 uM of BMS-345541 to SK-MEL-5 cell culture results in 87% apoptotic cells at 24 h through caspase-independent and AIF-dependent mitochondria-mediated manner. BMS-345541 treatment (10 uM) results in 76% and 95% reduction in IKK activities and NF-kB activity, as well as CXCL1 production.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:27:38 GMT 2023
by
admin
on
Sat Dec 16 09:27:38 GMT 2023
|
Record UNII |
BXU277OCN5
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DTXSID70203243
Created by
admin on Sat Dec 16 09:27:38 GMT 2023 , Edited by admin on Sat Dec 16 09:27:38 GMT 2023
|
PRIMARY | |||
|
BXU277OCN5
Created by
admin on Sat Dec 16 09:27:38 GMT 2023 , Edited by admin on Sat Dec 16 09:27:38 GMT 2023
|
PRIMARY | |||
|
BMS-345541
Created by
admin on Sat Dec 16 09:27:38 GMT 2023 , Edited by admin on Sat Dec 16 09:27:38 GMT 2023
|
PRIMARY | |||
|
9926054
Created by
admin on Sat Dec 16 09:27:38 GMT 2023 , Edited by admin on Sat Dec 16 09:27:38 GMT 2023
|
PRIMARY | |||
|
547757-23-3
Created by
admin on Sat Dec 16 09:27:38 GMT 2023 , Edited by admin on Sat Dec 16 09:27:38 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |