MK-2206

Modify Date: 2024-01-02 17:08:26

MK-2206 Structure
MK-2206 structure
Common Name MK-2206
CAS Number 1032349-77-1 Molecular Weight 443.92800
Density N/A Boiling Point N/A
Molecular Formula C25H22ClN5O Melting Point N/A
MSDS N/A Flash Point N/A

 Use of MK-2206


MK-2206 is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206. Anticancer activities[1][2].

 Names

Name 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one,hydrochloride
Synonym More Synonyms

 MK-2206 Biological Activity

Description MK-2206 is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206. Anticancer activities[1][2].
Related Catalog
Target

Akt1:8 nM ()

Akt2:12 nM ()

Akt3:65 nM ()

In Vitro MK-2206 (0-10 μM; 72 and 96 hours) inhibits the nasopharyngeal carcinoma (NPC) cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 proliferation in dose- and time-dependent manner[3]. MK-2206 (0-10 μM; 24 and 48 hours) results in a dose-dependent increase in the percentage of cells in G0/G1 phase and a concomitant reduction of cell numbers in S phase in CNE-2 and HONE-1 cells[3]. MK-2206 (0-10 μM; 24 hours) attenuates phosphorylation levels of PRAS40 and S6 in a dose-dependent manner. MK-2206 does not affect phosphorylation of GSKα/β and AKT[3]. MK-2206 (0-10 μM; 24 hours) increases the appearance of LC3-II in CNE-2 cells dose-dependently. Microtubule-associated protein 1 LC3 is an essential autophagy protein[3]. Cell Proliferation Assay[3] Cell Line: The NPC cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 Concentration: 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10 μM Incubation Time: 72 and 96 hours Result: At 72 and 96 hours, the IC50 values in CNE-1, CNE-2, and HONE-1 cell lines were 3-5 μM, and in SUNE-1, they were less than 1 μM. Cell Cycle Analysis[3] Cell Line: CNE-2 and HONE-1 cells Concentration: 0.625, 1.25, 2.5, 5, 10 μM Incubation Time: 24 or 48 hours Result: Induced cell cycle arrest at G1 in a dose-dependent manner. Western Blot Analysis[3] Cell Line: SUNE-1 and CNE-2 cells Concentration: 0.625, 1.25, 2.5, 5, 10 μM Incubation Time: 24 hours Result: Inhibited phosphorylation of AKT downstream targets. Cell Autophagy Assay[3] Cell Line: CNE-2 cells Concentration: 0.625, 1.25, 2.5, 5, 10 μM Incubation Time: 24 hours Result: Induced autophagy.
In Vivo Both MK-2206 doses (oral gavage; 480 mg/kg once a week and 240 mg/kg three times a week; for 2 weeks) can inhibit the growth of human CNE-2 xenografts in nude mice. No other obvious toxicity is observed in mice[3]. MK-2206 (orally; 120 mg/kg; alternate days; for 3 weeks) significantly inhibits tumor growth in 3-5 week old athymic nude mice with GEO colon carcinoma cells[4]. Animal Model: Four- to 6-week-old male BALB/c nude mice with CNE-2 xenografts[3] Dosage: 240 mg/kg and 480 mg/kg Administration: Oral gavage; 240 mg/kg for three times a week; 480 mg/kg for once a week; for 2 weeks Result: Both doses inhibited the growth of human CNE-2 xenografts in nude mice.
References

[1]. Li Yan, et al. Abstract #DDT01-1: MK-2206: A potent oral allosteric AKT inhibitor. 2009.

[2]. Xing Y, et al. Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation. Breast Cancer Res. 2019 Jul 5;21(1):78.

[3]. Zhao YY, et al. Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo. Drug Des Devel Ther. 2014 Oct 10;8:1827-37.

[4]. Agarwal E, et al. Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer. BMC Cancer. 2014 Mar 1;14:145.

 Chemical & Physical Properties

Molecular Formula C25H22ClN5O
Molecular Weight 443.92800
Exact Mass 443.15100
PSA 89.33000
LogP 6.15730

 Synonyms

unii-4ha45s22zz