Details
Stereochemistry | ACHIRAL |
Molecular Formula | C34H39N9O3 |
Molecular Weight | 621.732 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(=CC=C1NC(=O)C2=CC3=C(C=CC=C3)N2C)C4=NN([C@H]5CC[C@@H](CC5)N6CCN(CC6)C(C)=O)C7=NC=NC(N)=C47
InChI
InChIKey=ZMNWFTYYYCSSTF-SOAUALDESA-N
InChI=1S/C34H39N9O3/c1-21(44)41-14-16-42(17-15-41)24-9-11-25(12-10-24)43-33-30(32(35)36-20-37-33)31(39-43)23-8-13-26(29(19-23)46-3)38-34(45)28-18-22-6-4-5-7-27(22)40(28)2/h4-8,13,18-20,24-25H,9-12,14-17H2,1-3H3,(H,38,45)(H2,35,36,37)/t24-,25-
Molecular Formula | C34H39N9O3 |
Molecular Weight | 621.732 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/16014572 | https://www.ncbi.nlm.nih.gov/pubmed/16216497Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800017763
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16014572 | https://www.ncbi.nlm.nih.gov/pubmed/16216497
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800017763
A- 770041 is a src-family selective lck inhibitor with greater than 90% inhibition of IL-2 in vivo at 8 h when dosed at ED90 in mice and rats. A-770041 is greater than 300-fold selective against fyn, the other src-family kinase involved in T-cell signaling. A-770041 exhibits >60-fold selectivity versus the src-family members src and fgr, and >8-fold versus lyn and hck. Selectivity against the receptor tyrosine kinases tie-2 and kdr was >340-fold. In the anti-CD3 stimulated human whole blood assay, A-770041 inhibited IL-2 production with an IC50 of 0.08 uM. In rats, a correlation of concanavalin A-induced serum IL-2 levels to A-770041 concentrations was observed. Inhibition of IL-2 production was shown to be dependent upon in vivo plasma concentration of A-770041 with an in vivo EC50 of 0.078 uM. A-770041 represents the most selective lck inhibitor described to date and represents an advance not only in the understanding of structural features important for src-family selectivity, but also in the potential arsenal for the treatment of immunological conditions, in particular transplant rejection.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16014572 |
147.0 nM [IC50] | ||
Target ID: CHEMBL5880 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16216497 |
0.08 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
A-770041, a novel and selective small-molecule inhibitor of Lck, prevents heart allograft rejection. | 2005 Oct |
|
Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection. | 2006 Jan 1 |
|
Small molecule inhibitors of Lck: the search for specificity within a kinase family. | 2008 Jun |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16014572
Doses of A-770041 at or above 10 mg/kg/day prevent rejection of hearts transplanted heterotopically in rats from Brown Norway donors to Lewis recipients across a major histocompatibility barrier for least 65 days.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16216497
In the anti-CD3 stimulated human whole blood assay, A-770041 inhibited IL-2 production with an IC50 of 0.08 uM.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:00:03 GMT 2023
by
admin
on
Sat Dec 16 11:00:03 GMT 2023
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Record UNII |
U9855G2ZPR
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Record Status |
Validated (UNII)
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Record Version |
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Systematic Name | English |
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869748-10-7
Created by
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9549184
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1140478-96-1
Created by
admin on Sat Dec 16 11:00:03 GMT 2023 , Edited by admin on Sat Dec 16 11:00:03 GMT 2023
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NON-SPECIFIC STEREOCHEMISTRY | |||
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U9855G2ZPR
Created by
admin on Sat Dec 16 11:00:03 GMT 2023 , Edited by admin on Sat Dec 16 11:00:03 GMT 2023
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ACTIVE MOIETY |