AKT-IN-1

• CAT Number: M073526
• CAS Number: 1357158-81-6
• Molecular Formula: C22H21N3O
• Molecular Weight: 343.42
• Purity: ≥95%
• Synonyms: 6-[4-(1-aminocyclobutyl)phenyl]-5-phenylpyridine-3-carboxamide
• InChI: InChI=1S/C22H21N3O/c23-21(26)17-13-19(15-5-2-1-3-6-15)20(25-14-17)16-7-9-18(10-8-16)22(24)11-4-12-22/h1-3,5-10,13-14H,4,11-12,24H2,(H2,23,26)
• InChIKey: GIRZDHCBMNHMEH-UHFFFAOYSA-N
• SMILES: C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C(C=N3)C(=O)N)C4=CC=CC=C4)N

AKT-IN-1 is an allosteric AKT inhibitor with an IC50 of 1.042 μM.
AKT-IN-1 is able to potently inhibit phosphorylation of AKT in cells at both Thr308 and Ser473, with IC50s of 0.422 and 0.322 μM, respectively. AKT-IN-1 inhibits the phosphorylation of ribosomal protein S6, a downstream effector of the PI3K-AKT pathway. AKT-IN-1 potently inhibits the phosphorylation of PRAS40[1].
The effects of AKT-IN-1 (Compound 26) in vivo are characterized by measuring the pharmacodynamic activity of AKT-IN-1 in a BT474c breast adenocarcinoma xenograft model. Following acute doses of 100 and 200 mg/kg, AKT-IN-1 potently inhibits the phosphorylation of its downstream substrate GSK3β as well as the phosphorylation of AKT (Ser473), with a potency consistent with its pharmacokinetic profile. The in vivo activity of AKT-IN-1 is further characterized by measuring the effects on the growth of tumor cell xenografts. Continuous (daily) oral dosing of AKT-IN-1 (100 and 200 mg/kg) to nude mice bearing BT474c breast adenocarcinoma xenografts results in inhibition of tumor growth in a dose-dependent manner. When dosed at 200 mg/kg daily, AKT-IN-1 causes significant tumor growth inhibition[1].

Reference

[1]. Kettle JG, et al. Diverse heterocyclic scaffolds as allosteric inhibitors of AKT. J Med Chem. 2012 Feb 9;55(3):1261-73.
 [Content Brief]