1032349-77-1
1032349-77-1 structure
- Name: MK-2206
- Chemical Name: 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one,hydrochloride
- CAS Number: 1032349-77-1
- Molecular Formula: C25H22ClN5O
- Molecular Weight: 443.92800
- Catalog: Signaling Pathways Apoptosis Apoptosis
- Create Date: 2017-04-17 19:11:35
- Modify Date: 2024-01-02 17:08:26
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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].
| Name | 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one,hydrochloride |
|---|---|
| Synonyms | unii-4ha45s22zz |
| 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]. |
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| 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. |
| Molecular Formula | C25H22ClN5O |
|---|---|
| Molecular Weight | 443.92800 |
| Exact Mass | 443.15100 |
| PSA | 89.33000 |
| LogP | 6.15730 |