MK-2206 HCl | CAS#1032350-13-2 | AKT inhibitor

MedKoo Cat#: 201913 | Name: MK-2206 2HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

MK2206 is an Akt inhibitor. MK-2206 significantly increased the efficacy of anticancer compounds that were substrates for the ABCG2 but not the ABCB1 transporter. MK-2206 alone (0.03-1 μM) did not significantly alter the viability of H460/MX20 and S1-M1-80 cancer cells, which overexpress the ABCG2 transporter, compared to cells incubated with vehicle. However, MK-2206 (0.3 and 1 μM) significantly increased the anticancer efficacy of mitoxantrone, SN-38 and topotecan, in H460/MX20 and S1-M1-80 cancer cells, as indicated by a significant decrease in their IC50 values,

Chemical Structure

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: 0.0000

Molecular Weight: 409.48

Elemental Analysis: C, 62.24; H, 5.22; Cl, 14.70; N, 14.52; O, 3.32

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 180.00	Ready to ship
50mg	USD 300.00	Ready to ship
100mg	USD 500.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,750.00	Ready to ship

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Related CAS #

1032349-93-1 (free base) 1032350-13-2 (2HCl) 1032349-77-1 (HCl)

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

More Info

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC50512

View CoA: current batch, Lot#A20T07K20

View CoA: current batch, Lot#C21R07B30

QC Data

View QC data: current batch, Lot#A20T07K20

View QC data: current batch, Lot#TZC50512.

View QC data: current batch, Lot#C21R07B30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 409.48 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.

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:

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.

1: Ho AL, Foster NR, Deraje Vasudeva S, Katabi N, Antonescu CR, Frenette GP, Pfister DG, Erlichman C, Schwartz GK. A phase 2 study of MK-2206 in patients with incurable adenoid cystic carcinoma (Alliance A091104). Cancer. 2024 Mar 1;130(5):702-712. doi: 10.1002/cncr.35103. Epub 2023 Nov 10. PMID: 37947157; PMCID: PMC10922149. 2: Gao HL, Cui Q, Wang JQ, Ashby CR Jr, Chen Y, Shen ZX, Chen ZS. The AKT inhibitor, MK-2206, attenuates ABCG2-mediated drug resistance in lung and colon cancer cells. Front Pharmacol. 2023 Jul 13;14:1235285. doi: 10.3389/fphar.2023.1235285. PMID: 37521473; PMCID: PMC10373739. 3: Xu LN, Liu SL, Yang Y, Shu L, Sun Y. CircLASP1 silence strengthens the therapeutic effects of MK-2206 on nasopharyngeal cancer through upregulating miR-625. Cancer Sci. 2023 May;114(5):2123-2138. doi: 10.1111/cas.15725. Epub 2023 Mar 1. PMID: 36644819; PMCID: PMC10154807. 4: Chen M, Yu Y, Mi T, Guo Q, Xiang B, Tian X, Jin L, Long C, Shen L, Liu X, Pan J, Zhang Y, Xu T, Zhang D, Wei G. MK-2206 Alleviates Renal Fibrosis by Suppressing the Akt/mTOR Signaling Pathway In Vivo and In Vitro. Cells. 2022 Nov 5;11(21):3505. doi: 10.3390/cells11213505. PMID: 36359901; PMCID: PMC9655032. 5: Guvenir Celik E, Eroglu O. Combined treatment with ruxolitinib and MK-2206 inhibits the JAK2/STAT5 and PI3K/AKT pathways via apoptosis in MDA-MB-231 breast cancer cell line. Mol Biol Rep. 2023 Jan;50(1):319-329. doi: 10.1007/s11033-022-08034-4. Epub 2022 Nov 4. PMID: 36331743. 6: Gong B, Zhang J, Hua Z, Liu Z, Thiele CJ, Li Z. Corrigendum: Downregulation of ATXN3 enhances the sensitivity to AKT inhibitors (Perifosine or MK-2206), but decreases the sensitivity to chemotherapeutic drugs (etoposide or cisplatin) in neuroblastoma cells. Front Oncol. 2022 Aug 3;12:984514. doi: 10.3389/fonc.2022.984514. Erratum for: Front Oncol. 2021 Jul 12;11:686898. doi: 10.3389/fonc.2021.686898. PMID: 35992874; PMCID: PMC9382292. 7: Savaee M, Bakhshi A, Yaghoubi F, Pourrajab F, Goodarzvand Chegini K. Evaluating the Effects of Separate and Concomitant Use of MK-2206 and Salinomycin on Prostate Cancer Cell Line. Rep Biochem Mol Biol. 2022 Apr;11(1):157-165. doi: 10.52547/rbmb.11.1.157. PMID: 35765523; PMCID: PMC9208569. 8: Ma Y, Sender S, Sekora A, Kong W, Bauer P, Ameziane N, Al-Ali R, Krake S, Radefeldt M, Weiss FU, Lerch MM, Parveen A, Zechner D, Junghanss C, Murua Escobar H. The Inhibitory Response to PI3K/AKT Pathway Inhibitors MK-2206 and Buparlisib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines. Int J Mol Sci. 2022 Apr 13;23(8):4295. doi: 10.3390/ijms23084295. PMID: 35457111; PMCID: PMC9029322. 9: Stover EH, Xiong N, Myers AP, Tayob N, Engvold V, Polak M, Broaddus RR, Makker V, Drapkin R, Liu JF, Horowitz NS, Meric-Bernstam F, Aghajanian C, Coleman RL, Mills GB, Cantley LC, Matulonis UA, Westin SN, Konstantinopoulos PA. A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma. Gynecol Oncol Rep. 2022 Mar 31;40:100974. doi: 10.1016/j.gore.2022.100974. PMID: 35434236; PMCID: PMC9011027. 10: Wang C, Hu X, Wan Y, Wang S, Qi K, Li Y, Qiao J, Zeng L, Li Z, Fu C, Xu K. The Synergistic Inhibitory Effect of Combining MK-2206 and AZD 6244 in MARIMO Cells Harboring a Calreticulin Gene Mutation. Chemotherapy. 2021;66(5-6):169-178. doi: 10.1159/000518921. Epub 2021 Oct 19. PMID: 34666331. 11: Gong B, Zhang J, Hua Z, Liu Z, Thiele CJ, Li Z. Downregulation of ATXN3 Enhances the Sensitivity to AKT Inhibitors (Perifosine or MK-2206), but Decreases the Sensitivity to Chemotherapeutic Drugs (Etoposide or Cisplatin) in Neuroblastoma Cells. Front Oncol. 2021 Jul 12;11:686898. doi: 10.3389/fonc.2021.686898. Erratum in: Front Oncol. 2022 Aug 03;12:984514. doi: 10.3389/fonc.2022.984514. PMID: 34322387; PMCID: PMC8311598. 12: Bouzeyen R, Chugh S, Gosain TP, Barbouche MR, Haoues M, Rao KVS, Essafi M, Singh R. Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine Against Mycobacterium tuberculosis in Mice and Guinea Pigs. Front Immunol. 2021 May 27;12:645962. doi: 10.3389/fimmu.2021.645962. PMID: 34122406; PMCID: PMC8190480. 13: Richter A, Fischer E, Holz C, Schulze J, Lange S, Sekora A, Knuebel G, Henze L, Roolf C, Murua Escobar H, Junghanss C. Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021 Mar 9;22(5):2771. doi: 10.3390/ijms22052771. PMID: 33803402; PMCID: PMC7967241. 14: Zhong W, Chebolu S, Darmani NA. Central and peripheral emetic loci contribute to vomiting evoked by the Akt inhibitor MK-2206 in the least shrew model of emesis. Eur J Pharmacol. 2021 Jun 5;900:174065. doi: 10.1016/j.ejphar.2021.174065. Epub 2021 Mar 26. PMID: 33775646; PMCID: PMC8085164. 15: Murphy AG, Zahurak M, Shah M, Weekes CD, Hansen A, Siu LL, Spreafico A, LoConte N, Anders NM, Miles T, Rudek MA, Doyle LA, Nelkin B, Maitra A, Azad NS; ETCTN-9231 Study Team. A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer. Clin Transl Sci. 2020 Nov;13(6):1178-1188. doi: 10.1111/cts.12802. Epub 2020 Aug 1. PMID: 32738099; PMCID: PMC7719383. 16: 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. 17: Dong Y, Gong W, Hua Z, Chen B, Zhao G, Liu Z, Thiele CJ, Li Z. Combination of Rapamycin and MK-2206 Induced Cell Death via Autophagy and Necroptosis in MYCN-Amplified Neuroblastoma Cell Lines. Front Pharmacol. 2020 Feb 14;11:31. doi: 10.3389/fphar.2020.00031. PMID: 32116708; PMCID: PMC7033642. 18: Lee EK, Tan-Wasielewski Z, Aghajanian C, Coleman RL, Curtis J, Hirsch MS, Matulonis UA, Cantley LC, Mills GB, Doyle LA, Liu JF. Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum- resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035). Gynecol Oncol Rep. 2020 Feb 3;32:100546. doi: 10.1016/j.gore.2020.100546. PMID: 32083163; PMCID: PMC7021536. 19: Chien AJ, Tripathy D, Albain KS, Symmans WF, Rugo HS, Melisko ME, Wallace AM, Schwab R, Helsten T, Forero-Torres A, Stringer-Reasor E, Ellis ED, Kaplan HG, Nanda R, Jaskowiak N, Murthy R, Godellas C, Boughey JC, Elias AD, Haley BB, Kemmer K, Isaacs C, Clark AS, Lang JE, Lu J, Korde L, Edmiston KK, Northfelt DW, Viscusi RK, Yee D, Perlmutter J, Hylton NM, Van't Veer LJ, DeMichele A, Wilson A, Peterson G, Buxton MB, Paoloni M, Clennell J, Berry S, Matthews JB, Steeg K, Singhrao R, Hirst GL, Sanil A, Yau C, Asare SM, Berry DA, Esserman LJ; I-SPY 2 Consortium. MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial. J Clin Oncol. 2020 Apr 1;38(10):1059-1069. doi: 10.1200/JCO.19.01027. Epub 2019 Feb 7. PMID: 32031889; PMCID: PMC7106976. 20: Li YL, Weng HC, Hsu JL, Lin SW, Guh JH, Hsu LC. The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells. Front Pharmacol. 2019 Nov 6;10:1311. doi: 10.3389/fphar.2019.01311. PMID: 31780937; PMCID: PMC6856645.

E Bosdriesz, JMF Neto, A Sieber, R Bernards… - scholar.archive.org. Identifying selective drug combinations using Comparative Network Reconstruction. ttps://scholar.archive.org/work/jl7db26ckrhajm2albm55dsl4y/access/wayback/https://www.biorxiv.org/content/biorxiv/early/2020/12/18/2020.12.17.423240.full.pdf