Details
Stereochemistry | ACHIRAL |
Molecular Formula | C27H24O2 |
Molecular Weight | 380.4783 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1(C)CC=C(C2=CC=CC=C2)C3=CC(\C=C\C4=CC=C(C=C4)C(O)=O)=CC=C13
InChI
InChIKey=VUODRPPTYLBGFM-CMDGGOBGSA-N
InChI=1S/C27H24O2/c1-27(2)17-16-23(21-6-4-3-5-7-21)24-18-20(12-15-25(24)27)9-8-19-10-13-22(14-11-19)26(28)29/h3-16,18H,17H2,1-2H3,(H,28,29)/b9-8+
Molecular Formula | C27H24O2 |
Molecular Weight | 380.4783 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
BMS-453 (BMS-189453) is a potent and selective RAR agonist and a potent testicular toxin. In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase levels, and marked testicular degeneration and atrophy at all doses. BMS-189453 reduced MMP-1 expression in HIG-82 synovial fibroblasts in culture. BMS-189453 treatment blocked the clinical progression of arthritis beyond soft tissue inflammation in the CIA model. In the SCWA model, BMS-189453 treatment resulted in significantly reduced swelling with no notable progression to joint distortion/destruction. Improvement in clinical and histologic variables in 2 separate animal models, along with simultaneous reduction in MMP expression in the affected joint, suggests that RAR antagonists such as BMS-189453 may be useful as agents to treat rheumatoid arthritis and for determining the role of MMP in disease progression.
Originator
Sources: http://adisinsight.springer.com/drugs/800019546 | https://www.ncbi.nlm.nih.gov/pubmed/18417366
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2055 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27261179 |
7.7 nM [Ki] | ||
Target ID: CHEMBL2008 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27261179 |
16.7 nM [Ki] | ||
Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27261179 |
17.3 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs. | 2005 |
|
Retinoic acid via RARalpha inhibits the expression of 24-hydroxylase in human prostate stromal cells. | 2005 Dec 30 |
|
Retinoid receptor antagonists alter the pattern of apoptosis in organogenesis stage mouse limbs. | 2006 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11158723
Rats: In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase levels, and marked testicular degeneration and atrophy at all doses. Significant overt signs of toxicity and deaths occurred at 240 mg/kg, whereas body-weight and food-consumption decreases occurred at 60 and 240 mg/kg.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12660332
BMS-453 (0-10 uM) canceled the ATRA-dependent transactivation of human nephrin gene (NPHS1) contained three putative retinoic acid response elements (RARE) in a dose-dependent manner.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:23:12 GMT 2023
by
admin
on
Sat Dec 16 09:23:12 GMT 2023
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Record UNII |
M531IV9E0V
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Record Status |
Validated (UNII)
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Record Version |
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