Delving into the Latest Updates on MK-2206 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [4]

Target

Akt

Mechanism

Akt inhibitors(Proto-oncogene proteins c-akt inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

Recurrent Prostate CarcinomaBreast CancerNon-Small Cell Lung Cancer+ [2]

Inactive Indication

Acute Erythroblastic LeukemiaAcute Lymphoblastic LeukemiaAcute Megakaryoblastic Leukemia+ [124]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization

National Cancer Institute

Merck Sharp & Dohme Corp.

Inactive Organization

Merck Sharp & Dohme LLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC25H21N5O

InChIKeyULDXWLCXEDXJGE-UHFFFAOYSA-N

CAS Registry1032349-93-1

This phase II trial studies how well v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor MK2206 works in treating patients with previously treated colon or rectal cancer that has spread from the primary site to other places in the body or nearby tissue or lymph nodes and cannot be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date01 Mar 2013

Sponsor / Collaborator

National Cancer Institute

NCT01783171 / CompletedPhase 1IIT

A Phase I Trial of Dinaciclib (SCH727965) and MK-2206 in Metastatic Pancreatic Cancer With an Expansion Cohort in Advanced Pancreatic Cancer

This randomized phase I trial studies the side effects and best dose of dinaciclib and Akt inhibitor MK2206 in treating patients with pancreatic cancer that cannot be removed by surgery. Dinaciclib and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date15 Jan 2013

Sponsor / Collaborator

National Cancer Institute

NCT01776008 / TerminatedPhase 2IIT

A Phase II Trial of Neoadjuvant MK-2206 in Combination With Either Anastrozole if Postmenopausal or Anastrozole and Goserelin if Premenopausal in Women With Clinical Stage 2 or 3 PIK3CA Mutant Estrogen Receptor Positive and HER2 Negative Invasive Breast Cancer

This phase II trial studies how well Akt inhibitor MK-2206 (MK-2206) and anastrozole with or without goserelin acetate works in treating patients with stage II-III breast cancer. MK-2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole and goserelin acetate may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving MK-2206, anastrozole, and goserelin acetate together may kill more tumor cells.

Start Date01 Jan 2013

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with MK-2206

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100 Translational Medicine associated with MK-2206

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100 Patents (Medical) associated with MK-2206

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952

Literatures (Medical) associated with MK-2206

01 Dec 2024·International Immunopharmacology

Monotropein alleviates septic acute liver injury by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway

Article

Author: Xu, Xiaolong ; Pan, Shoujie ; Dong, Zibo ; Wang, Feibiao ; Ma, Zhihao ; Wang, Xinyan ; Wang, Junyao ; Yang, Yue ; Xiao, Nan ; Xie, Kunmei

Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.

01 Dec 2024·Biomaterials

Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy

Article

Author: Tao, Yu ; Li, Mingqiang ; Wang, Haixia ; Zheng, Chunxiong ; Xu, Yanteng ; Luo, Xing ; Ma, Limin ; Fang, Youqiang ; Liu, Zheng ; Lv, Shixian ; Zhou, Xiangfu ; Yuan, Qing ; Lao, Yeh-Hsing

Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.

01 Dec 2024·Journal of Molecular Histology

Halofuginone ameliorates the susceptibility to atrial fibrillation by activating the PI3K/Akt signaling pathway

Article

Author: Zhao, Xiaolong ; Shen, Chunjian ; Zhang, Jing ; Xu, Feng

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Halofuginone (HF) exerts beneficial effects on organ fibrosis, periodontitis, and cancer. However, the effect of HF against AF remains unknown. During the induction of AF, the rats were intragastrically administered HF (5 mg/kg and 10 mg/kg) daily for 7 consecutive days. Cardiac function was evaluated through echocardiographic analysis. The presence of pathological changes and interstitial fibrosis in the left atrial tissues were investigated. Intracellular Ca²⁺ homeostasis and mitochondrial function in atrial tissues were evaluated. The activation of the PI3K/Akt signaling pathway was examined, and an allosteric Akt inhibitor, MK-2206, was applied to confirm the involvement of the PI3K/Akt signaling pathway in the protection against AF by HF. The administration of HF resulted in a prolongation of the atrial effective refractory period (AERP), a reduction in both the duration and inducibility of AF, and a decrease in atrial weight, heart weight, atrial weight/body weight ratio, and heart weight/body weight ratio in rats with AF. In addition, the administration of HF resulted in a reduction in left atrial diameter (LAD) and an increase in left ventricular internal diameter diastolic (LVIDd), ejection fraction (EF), and fractional shortening (FS), while having no effect on left ventricular internal diameter systolic (LVIDs). The pathological changes and cardiac fibrosis observed in rats with AF were mitigated by HF. Moreover, HF enhanced mitochondrial function, suppressed cardiomyocyte apoptosis, and activated the PI3K/Akt pathway in AF rats. Furthermore, the protective effect against AF was also observed in an in vitro model. The effects of HF on fibrosis markers, intracellular Ca²⁺ homeostasis, mitochondrial function, and cardiac apoptosis were blocked by MK-2206. HF alleviated the susceptibility to AF in vivo and in vitro via the activation of the PI3K/Akt signaling pathway.

100 Deals associated with MK-2206

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	-
Non-Small Cell Lung Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	-
Acute Erythroblastic Leukemia	Phase 1	US	National Cancer Institute	01 Oct 2010
Acute Myelomonocytic Leukemia	Phase 1	US	National Cancer Institute	01 Oct 2010
Colonic Cancer	Phase 1	US	Merck Sharp & Dohme Corp.	01 Aug 2010
KRAS Wild-type Colorectal Cancer	Phase 1	US	Merck Sharp & Dohme Corp.	01 Aug 2010
Rectal Cancer	Phase 1	US	Merck Sharp & Dohme Corp.	01 Aug 2010
Rectal Cancer	Phase 1	US	Merck Sharp & Dohme Corp.	01 Aug 2010
Neuroendocrine Tumors	Phase 1	US	Merck Sharp & Dohme Corp.	01 Jul 2010
Pancreatic Diseases	Phase 1	US	Merck Sharp & Dohme Corp.	01 Jul 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01306045 (CTgov)	Phase 2	Thymoma, Familial \| Small Cell Lung Cancer \| Advanced Lung Non-Small Cell Carcinoma \| thymic carcinoma	647	Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Non-Small Cell Lung Cancer (NSCLC))	knpopevibb(yvnhxhcsbp) = lyxpscofxn kgsovktssf (guwnojymxe, xtmgwtsamh - kjtpebxfez) View more	-	11 Apr 2023
				Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Small Cell Lung Cancer (SCLC))	knpopevibb(yvnhxhcsbp) = kdwxkadnjz kgsovktssf (guwnojymxe, gxfqfrimvq - ujvpagaqmm) View more
AACR2023	Not Applicable	Triple Negative Breast Cancer	-	Tazmetostat	lzayqkuira(zkjhhbqpvo) = 8µM Tazmetostat and 5μM MK2206 significantly suppressed EZH2 activity susclljtoz (awubeogyab ) View more	-	04 Apr 2023
				MK2206
NCT01248247 (BATTLE-2, CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	334	Erlotinib (Arm 1 - Erlotinib)	(pbdbdovovm) = zbgagtuzqe wrpwndlsey (xikinsldgd, zcinhxtdrb - vuuxowabdy) View more	-	12 Jan 2022
				Erlotinib+MK-2206 (Arm 2 - Erlotinib + MK-2206)	(pbdbdovovm) = jaamplkndi wrpwndlsey (xikinsldgd, pszxfmwuks - pdpijjwoql) View more
NCT01783171 (Pubmed \| Clin Transl Sci) Manual	Phase 1	Pancreatic Cancer	39	MK-2206+Dinaciclib	(csdjwrieqn) = dinaciclib 9 mg/m2 and MK-2206 135 mg ckezvfuabj (pohjdslida ) View more	Negative	01 Nov 2020
NCT01307631 (Pubmed \| Int J Cancer) Manual	Phase 2	Recurrent Endometrial Cancer PIK3CA Mutation	36	MK-2206	(lpwbzaflsv) = uwgxebjdhf cvoqketvkk (uvovliirqw ) View more	Negative	15 Jul 2020
NCT01251861 (E2809, CTgov)	Phase 2	Recurrent Prostate Carcinoma	108	Clinical Observation+Bicalutamide (Arm A (Observation and Bicalutamide))	yvaobwakrl(sevolfblgs) = rfeqbdtcqx xxtviqeqby (znlrtystii, ryxiqknvkj - vmdiziyomm) View more	-	05 Dec 2019
				Laboratory Biomarker Analysis+Akt Inhibitor MK2206+Bicalutamide (Arm B (Akt Inhibitor MK2206 and Bicalutamide))	yvaobwakrl(sevolfblgs) = mcidtoujbb xxtviqeqby (znlrtystii, psbenkxenh - micixdueuu) View more
NCT01277757 (Pubmed) Manual	Phase 2	Advanced breast cancer PIK3CA mutations \| AKT mutations \| PTEN mutation	27	MK-2206 (PIK3CA/AKT1 mutation)	(khckpwfryz) = gpmvxhgfun iiupffdmar (tbfrhgewmr ) View more	Negative	05 Jul 2019
				MK-2206 (PTEN loss/mutation)	(khckpwfryz) = lvacshggag iiupffdmar (tbfrhgewmr ) View more
NCT01021748 (2206-010, CTgov)	Phase 1	Solid tumor \| Advanced Malignant Solid Neoplasm	63	AZD6244+MK-2206 (MK-2206 45 mg QOD + AZD6244 75 mg QD)	hasgyylueu(fcyetrjmaf) = ljsgsumzng dsieecbxnd (ymyqhjocsj, lvcbodnxoz - gwvfnfsfha) View more	-	07 Aug 2018
				AZD6244+MK-2206 (MK-2206 45 mg QOD + AZD6244 75 mg BID)	hasgyylueu(fcyetrjmaf) = tvpglnizwl dsieecbxnd (ymyqhjocsj, uqrsdykibw - snyzhblauc) View more
NCT01776008 (CTgov)	Phase 2	Breast cancer recurrent \| PIK3CA positive/ER positive/HER2 negative/breast cancer \| Breast Cancer 3	16	Neoadjuvant Therapy+Akt Inhibitor MK2206+Goserelin Acetate+anastrozole	qepmqarhtu(onbrdwzhnq) = kfvtjgvioo xmkxybrbvn (anrmvtffvg, woerdsfcrs - vytgiraekk) View more	-	08 May 2018
NCT01243762 (0646-027, CTgov)	Phase 1	Advanced cancer	47	MK-0752+dalotuzumab (Dalotuzumab 7.5 mg/kg + MK-0752 1800 mg)	ojsxdoypur(fvgsskivzv) = rzwwfwqzez ovmpscwvqs (xzotiqrqla, ikjchcgusx - trzlqcakwy) View more	-	30 Oct 2017
				MK-0752+dalotuzumab (Dalotuzumab 10 mg/kg + MK-0752 1800 mg)	ojsxdoypur(fvgsskivzv) = fidakfvvme ovmpscwvqs (xzotiqrqla, makdipdxln - rptpfrwvtc) View more