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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H23N5O
Molecular Weight 397.4723
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of A-443654

SMILES

CC1=NNC2=CC=C(C=C12)C3=CC(OC[C@@H](N)CC4=CNC5=CC=CC=C45)=CN=C3

InChI

InChIKey=YWTBGJGMTBHQTM-IBGZPJMESA-N
InChI=1S/C24H23N5O/c1-15-22-10-16(6-7-24(22)29-28-15)17-9-20(13-26-11-17)30-14-19(25)8-18-12-27-23-5-3-2-4-21(18)23/h2-7,9-13,19,27H,8,14,25H2,1H3,(H,28,29)/t19-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19208828 | https://www.ncbi.nlm.nih.gov/pubmed/15956255

A-443654 is a potent and selective AKT inhibitor. A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition. A-443654 interferes with mitotic progression by regulating aurora a kinase expression. A-443654 inhibits all three Akt isoforms in FL5.12 cells stably transfected with constitutively active myristoylated Akt1/2/3, and showed moderate selectivity when screened against related kinases in the AGC family, such as PKA and PKC20. A-443654 has being shown to extend survival in an intracranial glioma animal model. A-443654, either alone or in combination with existing drugs, may be a useful therapy for primary and drug-resistant T-ALL.

Approval Year

PubMed

PubMed

TitleDatePubMed
Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells.
2009 Feb
Inhibitor hijacking of Akt activation.
2009 Jul
Rapamycin reverses pulmonary artery smooth muscle cell proliferation in pulmonary hypertension.
2013 May
Patents

Sample Use Guides

Mice: A-443654 was given s.c. in a vehicle of 0.2% HPMC.
Route of Administration: Other
Treatment with A-443654 (0.5 uM), reduced FCS-stimulated growth of PA-SMCs (pulmonary artery smooth muscle cells) from MCT-PH rats to the level in control rats while inhibiting Akt, GSK3, and S6K activation.
Name Type Language
A-443654
Code English
1H-Indole-3-ethanamine, α-[[[5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy]methyl]-, (αS)-
Systematic Name English
A-443644
Code English
(2S)-1-(1H-Indol-3-yl)-3-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxypropan-2-amine
Systematic Name English
A 443654
Code English
A 443644
Code English
Code System Code Type Description
FDA UNII
Q4UG565ZYH
Created by admin on Sat Dec 16 19:56:51 GMT 2023 , Edited by admin on Sat Dec 16 19:56:51 GMT 2023
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PUBCHEM
10172943
Created by admin on Sat Dec 16 19:56:51 GMT 2023 , Edited by admin on Sat Dec 16 19:56:51 GMT 2023
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CAS
552325-16-3
Created by admin on Sat Dec 16 19:56:51 GMT 2023 , Edited by admin on Sat Dec 16 19:56:51 GMT 2023
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