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MedKoo CAT#: 201913
CAS#: 1032350-13-2 (2HCl)
Description: MK2206 is a Akt inhibitor, is also an orally bioavailable allosteric inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor MK2206 binds to and inhibits the activity of Akt in a non-ATP competitive manner, which may result in the inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis.
MedKoo Cat#: 201913
Name: MK-2206 2HCl
CAS#: 1032350-13-2 (2HCl)
Chemical Formula: C25H25Cl2N5O
Exact Mass: 481.14362
Molecular Weight: 409.48483
Elemental Analysis: C, 62.24; H, 5.22; Cl, 14.70; N, 14.52; O, 3.32
Related CAS #: 1032350-13-2 (2HCl) 1032349-77-1 (HCl) 1032349-93-1 (free base)
Synonym: MK2206; MK-2206; MK 2206; MK2206 dihydrochloride; MK2206 HCl.
IUPAC/Chemical Name: 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-8,9-dihydro-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one dihydrochloride
InChi Key: AVWUIYMDWOYEFM-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H23N5O.2ClH/c26-25(12-4-13-25)18-9-7-17(8-10-18)22-19(16-5-2-1-3-6-16)15-20-21(27-22)11-14-30-23(20)28-29-24(30)31;;/h1-3,5-11,14-15,19,22H,4,12-13,26H2,(H,29,31);2*1H
SMILES Code: O=C1NN=C2C3=CC(C4=CC=CC=C4)C(C5=CC=C(C6(N)CCC6)C=C5)N=C3C=CN21.[H]Cl.[H]Cl
MK-2206 is a novel allosteric Akt inhibitor. In vitro, MK-2206 synergistically inhibited cell proliferation of human cancer cell lines in combination with molecular targeted agents such as erlotinib (an epidermal growth factor receptor inhibitor) or lapatinib (a dual epidermal growth factor receptor/human epidermal growth factor receptor 2 inhibitor). Complementary inhibition of erlotinib-insensitive Akt phosphorylation by MK-2206 was one mechanism of synergism, and a synergistic effect was found even in erlotinib-insensitive cell lines. MK-2206 also showed synergistic responses in combination with cytotoxic agents such as topoisomerase inhibitors (doxorubicin, camptothecin), antimetabolites (gemcitabine, 5-fluorouracil), anti-microtubule agents (docetaxel), and DNA cross-linkers (carboplatin) in lung NCI-H460 or ovarian A2780 tumor cells. The synergy with docetaxel depended on the treatment sequence; a schedule of MK-2206 dosed before docetaxel was not effective. MK-2206 suppressed the Akt phosphorylation that is induced by carboplatin and gemcitabine. In vivo, MK-2206 in combination with these agents exerted significantly more potent tumor inhibitory activities than each agent in the monotherapy setting. These findings suggest that Akt inhibition may augment the efficacy of existing cancer therapeutics; thus, MK-2206 is a promising agent to treat cancer patients who receive these cytotoxic and/or molecular targeted agents.
1: Meng J, Majidi M, Fang B, Ji L, Bekele BN, Minna JD, Roth JA. The tumor suppressor gene TUSC2 (FUS1) sensitizes NSCLC to the AKT inhibitor MK2206 in LKB1-dependent manner. PLoS One. 2013 Oct 17;8(10):e77067. doi: 10.1371/journal.pone.0077067. eCollection 2013. PubMed PMID: 24146957; PubMed Central PMCID: PMC3798310.
2: Ding W, Shanafelt TD, Lesnick CE, Erlichman C, Leis JF, Secreto C, Sassoon TR, Call TG, Bowen DA, Conte M, Kumar S, Kay NE. Akt inhibitor MK2206 selectively targets CLL B-cell receptor induced cytokines, mobilizes lymphocytes and synergizes with bendamustine to induce CLL apoptosis. Br J Haematol. 2013 Sep 20. doi: 10.1111/bjh.12564. [Epub ahead of print] PubMed PMID: 24111951.
3: Liu R, Liu D, Xing M. The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF(V600E) inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. J Clin Endocrinol Metab. 2012 Feb;97(2):E173-82. doi: 10.1210/jc.2011-1054. Epub 2011 Nov 16. PubMed PMID: 22090271; PubMed Central PMCID: PMC3275354.
4: Liu R, Liu D, Trink E, Bojdani E, Ning G, Xing M. The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway. J Clin Endocrinol Metab. 2011 Apr;96(4):E577-85. doi: 10.1210/jc.2010-2644. Epub 2011 Feb 2. PubMed PMID: 21289267; PubMed Central PMCID: PMC3070256.