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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
Structure of A-674563

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

HIDE SMILES / InChI

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

Description
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

Targets

Primary TargetPharmacologyConditionPotency
11.0 nM [Ki]
16.0 nM [Ki]
46.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo.
2005 Jun
Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells.
2016 Apr 15
Patents

Sample Use Guides

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
A-674563 at 10-1000 nM significantly inhibited A375 cell proliferation
Substance Class Chemical
Created
by admin
on Sat Dec 16 12:17:18 UTC 2023
Edited
by admin
on Sat Dec 16 12:17:18 UTC 2023
Record UNII
3W2X0WGW6C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
A-674563
Common Name English
(.ALPHA.S)-.ALPHA.-(((5-(3-METHYL-1H-INDAZOL-5-YL)-3-PYRIDINYL)OXY)METHYL)BENZENEETHANAMINE
Systematic Name English
A674563
Code English
5-(5-((2S)-2-AMINO-3-PHENYLPROPOXY)PYRIDIN-3-YL)-3-METHYL-1H-INDAZOLE
Systematic Name English
BENZENEETHANAMINE, .ALPHA.-(((5-(3-METHYL-1H-INDAZOL-5-YL)-3-PYRIDINYL)OXY)METHYL)-, (.ALPHA.S)-
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID10462115
Created by admin on Sat Dec 16 12:17:18 UTC 2023 , Edited by admin on Sat Dec 16 12:17:18 UTC 2023
PRIMARY
FDA UNII
3W2X0WGW6C
Created by admin on Sat Dec 16 12:17:18 UTC 2023 , Edited by admin on Sat Dec 16 12:17:18 UTC 2023
PRIMARY
PUBCHEM
11314340
Created by admin on Sat Dec 16 12:17:18 UTC 2023 , Edited by admin on Sat Dec 16 12:17:18 UTC 2023
PRIMARY
CAS
552325-73-2
Created by admin on Sat Dec 16 12:17:18 UTC 2023 , Edited by admin on Sat Dec 16 12:17:18 UTC 2023
PRIMARY
DRUG BANK
DB08568
Created by admin on Sat Dec 16 12:17:18 UTC 2023 , Edited by admin on Sat Dec 16 12:17:18 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR