Akt1 and Akt2-IN-1

• CAT Number: I005347
• CAS Number: 893422-47-4
• Molecular Formula: C33H29N7O
• Molecular Weight: 539.63
• Purity: ≥95%
• Target: Akt
• Solubility: DMSO: ≥ 35 mg/mL
• Storage: Store at -20°C
• IC50: 3.5 nM (Akt1), 42 nM (Akt2)

Akt1 and Akt2-IN-1 is an allosteric inhibitor of Akt1 (IC50 = 3.5 nM) and Akt2 (IC50 = 42 nM), with potent and balanced activity.IC50 value: 3.5 nM (Akt1), 42 nM (Akt2)Target: Aktin vitro: Akt1 and Akt2-IN-1 is dependent on the PH-domain for Akt inhibition, is selective for Akt1/2 over Akt3 (IC50 = 1900 nM), andis highly selective over other members of the AGC familyof kinases (>50 lM vs PKA, PKC, SGK). Akt1 and Akt2-IN-1 has moderate activity in an hERG binding assay (IC50 = 5610 nM) and is a substrate for human P-glycoprotein (MDR1 Directional Transport Ratio (B to A/A to B) = 17.6). Akt1 and Akt2-IN-1 also shows good physical properties with a human plasma protein binding of 97.3% and a logP = 3.51.in vivo: Akt1 and Akt2-IN-1 has potent inhibitory activity against Akt1 and Akt 2 in vivo in a mouse lung and efficacy in atumor xenograft model. Akt1 and Akt2-IN-1 shows good pharmacokinetics in rat with a low clearance of 4.6 mL/min/kg and a half-life of 3.8 h.

Reference

[1]. Bilodeau MT, et al. Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3178-3182.
[2]. Li Y, et al. Allosteric inhibitors of Akt1 and Akt2: discovery of [1,2,4]triazolo[3,4-f][1,6]naphthyridines with potent and balanced activity. Bioorg Med Chem Lett. 2009 Feb 1;19(3):834-836.