MK-2206 2HCl
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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.


Chemical Structure

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MK-2206 2HCl
CAS# 1032350-13-2 (2HCl)

Theoretical Analysis

MedKoo Cat#: 201913
Name: MK-2206 2HCl
CAS#: 1032350-13-2 (2HCl)
Chemical Formula: C25H25Cl2N5O
Exact Mass:
Molecular Weight: 409.48483
Elemental Analysis: C, 62.24; H, 5.22; Cl, 14.70; N, 14.52; O, 3.32

Price and Availability

Size Price Availability Quantity
25.0mg USD 90.0 Ready to ship
50.0mg USD 150.0 Ready to ship
100.0mg USD 250.0 Ready to ship
200.0mg USD 450.0 Ready to ship
500.0mg USD 950.0 Ready to ship
1.0g USD 1750.0 Ready to ship
2.0g USD 3250.0 Ready to ship
5.0g USD 5850.0 Ready to ship
10.0g USD 8950.0 2 weeks
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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

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: MK-2206 dihydrochloride (MK-2206 (2HCl)) is an allosteric AKT inhibitor with IC50s of 5 nM, 12 nM, and 65 nM for AKT1, AKT2, and AKT3, respectively.
In vitro activity: The effect of MK-2206 on Akt phosphorylation was subsequently examined. Treatment with MK-2206 was performed at 0.1 and 1 µM for 48 h. As presented in Fig. 1B, MK-2206 treatment reduced the expression p-Akt in all pancreatic cancer cell lines. No changes in the levels of total Akt protein were observed. These results demonstrated that MK-2206 inhibited Akt phosphorylation in pancreatic cancer cells. Reference: Oncol Lett. 2020 Mar; 19(3): 1999–2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039141/
In vivo activity: Consistent with previous reports, the results of the present study demonstrated that MK2206 inhibited the phosphorylation of AKT and production of cytokines (IL-4, −5, −6 and −13) in a mouse model of TDI-induced asthma. In addition, the present study also revealed that MK2206 inhibited the phosphorylation of AKT in vitro. These results indicated a potential role for MK2206 in a clinical setting for the management of TDI-induced asthma. Reference: Mol Med Rep. 2020 Nov; 22(5): 3723–3734. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533517/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 11.5 28.08
DMF 0.2 0.49
DMF:PBS (pH 7.2) (1:3) 0.2 0.49
Water 1.0 2.44

Preparing Stock Solutions

The following data is based on the product molecular weight 409.48483 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wang Z, Luo G, Qiu Z. Akt inhibitor MK-2206 reduces pancreatic cancer cell viability and increases the efficacy of gemcitabine. Oncol Lett. 2020 Mar;19(3):1999-2004. doi: 10.3892/ol.2020.11300. Epub 2020 Jan 14. PMID: 32194695; PMCID: PMC7039141. 2. Djuzenova CS, Fiedler V, Memmel S, Katzer A, Sisario D, Brosch PK, Göhrung A, Frister S, Zimmermann H, Flentje M, Sukhorukov VL. Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells. BMC Cancer. 2019 Apr 3;19(1):299. doi: 10.1186/s12885-019-5517-4. PMID: 30943918; PMCID: PMC6446411. 3. Cui H, Cheng Y, He Y, Cheng W, Zhao W, Zhao H, Zhou FH, Wang L, Dong J, Cai S. The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Mol Med Rep. 2020 Nov;22(5):3723-3734. doi: 10.3892/mmr.2020.11450. Epub 2020 Aug 21. PMID: 33000187; PMCID: PMC7533517. 4. Al-Saffar NMS, Troy H, Wong Te Fong AC, Paravati R, Jackson LE, Gowan S, Boult JKR, Robinson SP, Eccles SA, Yap TA, Leach MO, Chung YL. Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma. Br J Cancer. 2018 Oct;119(9):1118-1128. doi: 10.1038/s41416-018-0242-3. Epub 2018 Oct 31. PMID: 30377337; PMCID: PMC6219501.
In vitro protocol: 1. Wang Z, Luo G, Qiu Z. Akt inhibitor MK-2206 reduces pancreatic cancer cell viability and increases the efficacy of gemcitabine. Oncol Lett. 2020 Mar;19(3):1999-2004. doi: 10.3892/ol.2020.11300. Epub 2020 Jan 14. PMID: 32194695; PMCID: PMC7039141. 2. Djuzenova CS, Fiedler V, Memmel S, Katzer A, Sisario D, Brosch PK, Göhrung A, Frister S, Zimmermann H, Flentje M, Sukhorukov VL. Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells. BMC Cancer. 2019 Apr 3;19(1):299. doi: 10.1186/s12885-019-5517-4. PMID: 30943918; PMCID: PMC6446411.
In vivo protocol: 1. Cui H, Cheng Y, He Y, Cheng W, Zhao W, Zhao H, Zhou FH, Wang L, Dong J, Cai S. The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Mol Med Rep. 2020 Nov;22(5):3723-3734. doi: 10.3892/mmr.2020.11450. Epub 2020 Aug 21. PMID: 33000187; PMCID: PMC7533517. 2. Al-Saffar NMS, Troy H, Wong Te Fong AC, Paravati R, Jackson LE, Gowan S, Boult JKR, Robinson SP, Eccles SA, Yap TA, Leach MO, Chung YL. Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma. Br J Cancer. 2018 Oct;119(9):1118-1128. doi: 10.1038/s41416-018-0242-3. Epub 2018 Oct 31. PMID: 30377337; PMCID: PMC6219501.

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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.



Additional Information

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.