Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H22N4O |
Molecular Weight | 358.4363 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=NNC2=C1C=C(C=C2)C3=CC(OC[C@@H](N)CC4=CC=CC=C4)=CN=C3
InChI
InChIKey=BPNUQXPIQBZCMR-IBGZPJMESA-N
InChI=1S/C22H22N4O/c1-15-21-11-17(7-8-22(21)26-25-15)18-10-20(13-24-12-18)27-14-19(23)9-16-5-3-2-4-6-16/h2-8,10-13,19H,9,14,23H2,1H3,(H,25,26)/t19-/m0/s1
Molecular Formula | C22H22N4O |
Molecular Weight | 358.4363 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15956255 | https://www.ncbi.nlm.nih.gov/pubmed/26920060Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26970307
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15956255 | https://www.ncbi.nlm.nih.gov/pubmed/26920060
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26970307
A-674563 is a potent, orally available Akt1 inhibitor with an IC50 value of 11nM. Also displays activity against PKA and CDK2 with IC50 values of 16nM and 46nM respectively. A-674563 dose-dependently inhibited survival and proliferation of U937 AML cells and six lines of human AML progenitor cells, yet sparing human peripheral blood mononuclear leukocytes (PBMCs). A-674563 activated caspase-3/9 and apoptosis in the AML cells. intraperitoneal injection of A-674563 at well-tolerated doses suppressed U937 leukemic xenograft tumor growth in nude mice, whiling significantly improving the animal survival. A-674563 exerts potent anti-leukemic activity in vitro and in vivo, possibly via concurrent targeting Akt and SphK1 signalings. A-674563 also exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15956255 |
11.0 nM [Ki] | ||
Target ID: CHEMBL2094138 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15956255 |
16.0 nM [Ki] | ||
Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15956255 |
46.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. | 2005 Jun |
|
AKT crystal structure and AKT-specific inhibitors. | 2005 Nov 14 |
|
Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells. | 2016 Apr 15 |
|
Pre-clinical assessment of A-674563 as an anti-melanoma agent. | 2016 Aug 12 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26970307
Mice: In vivo, A-674563 (25 - 100 mg/kg, lavage daily) oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26970307
A-674563 at 10-1000 nM significantly
inhibited A375 cell proliferation
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 12:17:18 GMT 2023
by
admin
on
Sat Dec 16 12:17:18 GMT 2023
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Record UNII |
3W2X0WGW6C
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Record Status |
Validated (UNII)
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Record Version |
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |