A-674563

• CAT Number: I004050
• CAS Number: 552325-73-2
• Molecular Formula: C22H22N4O
• Molecular Weight: 358.4
• Purity: ≥95%
• Synonyms: (2S)-1-[5-(3-methyl-2H-indazol-5-yl)pyridin-3-yl]oxy-3-phenylpropan-2-amine
• Target: Akt
• Solubility: DMSO ≥70mg/mL Water ≥70mg/mL Ethanol ≥10mg/mL
• Storage: 3 years -20C powder
• IC50: 14 nM (Akt1)
• InChI: 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
• InChIKey: BPNUQXPIQBZCMR-IBGZPJMESA-N
• SMILES: CC1=NNC(C1=C2)=CC=C2C3=CN=CC(OC[C@@H](N)CC4=CC=CC=C4)=C3

A-674563 is a potent selective Akt1 inhibitor with an IC50 of 14 nM; also shows inhibitory activity against PKA and CDK2 with IC50 of 16 and 46 nM, respectively.IC50 value: 14 nM (Akt1)Target: Akt1; PKAin vitro: A-674563 is achieved from A-443654 by replacing the indole with a phenyl moiety and getting oral activity. A-674563 slows proliferation of tumor cells with EC50 of 0.4 μM [1]. A-674563 does not inhibit Akt phosphorylation per se, but blocks the phosphorylation of Akt downstream targets in a dose-dependent manner. A-674563 induced Akt blockade results in decreased STS cell downstream target phosphorylation and tumor cell growth inhibiton. A-674563 induces G2 cell cycle arrest and apoptosis in STS cells [2].in vivo: 20 mg/kg A-674563 increases plasma insulin in an oral glucose tolerance test. A-674563 shows no significant monotherapy tumor inhibitory activity; the efficacy of the combination therapy is significantly improved compared to paclitaxel monotherapy [1]. A674563-treated (20 mg/kg/bid, p.o.) mice exhibits slower tumor growth and more than 50% decrease in the tumor volume at the termination of the study compared with that in control group. [2] A-674563 is identified to have drastically improved PK profile with oral bioavailability of 67% in mouse, but is 70-fold less active than A-443654 [3].

Reference

1:Pre-clinical assessment of A-674563 as an anti-melanoma agent. Zou Y, Fan G, Wang X.Biochem Biophys Res Commun. 2016 Aug 12;477(1):1-8. doi: 10.1016/j.bbrc.2016.03.020. Epub 2016 Mar 10. PMID: 26970307 2:Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells. Xu L, Zhang Y, Gao M, Wang G, Fu Y.Biochem Biophys Res Commun. 2016 Apr 15;472(4):662-8. doi: 10.1016/j.bbrc.2016.02.094. Epub 2016 Feb 23. PMID: 26920060