:MK-2206
{{Chembox
| ImageFile = MK-2206.svg
| ImageSize = 200px
| ImageAlt =
| PIN = 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f] [1,6]naphthyridin-3(2H)-one
| OtherNames =
| Section1 = {{Chembox Identifiers
| CASNo = 1032349-93-1
| CASNo_Ref = {{Cascite|correct|CAS}}
| ChEMBL = 1079175
| ChEBI = 67271
| EINECS = 682-246-4
| PubChem = 24964624
| UNII = 51HZG6MP1K
| SMILES = C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N
| ChemSpiderID = 24658140
| InChI = 1/C25H21N5O/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/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31)
| InChIKey = ULDXWLCXEDXJGE-UHFFFAOYAX
| StdInChI = 1S/C25H21N5O/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/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31)
| StdInChIKey = ULDXWLCXEDXJGE-UHFFFAOYSA-N
}}
| Section2 = {{Chembox Properties
| C=25|H=21|N=5|O=1
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility =
}}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
MK-2206 is a drug candidate being investigated to help treat cancer. Its chemical formula is C25H21N5O.[http://www.scbt.com/datasheet-364537-CASNumber-1032350-13-2.html MK-2206 dihydrochloride (CAS 1032350-13-2)] inc structure diagram It acts as an allosteric AKT inhibitor.[http://mct.aacrjournals.org/content/9/7/1956 MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted Drugs In vitro and In vivo. Hirai et al. 2010]
It is a highly selective inhibitor of pan-Akt, namely, of all three Akt isoforms Akt1, Akt2, and Akt3.
It is intended to be used with other cancer therapies that advanced tumours may become resistant to.
__TOC__
Clinical trials
2011: A phase 1 clinical trial of MK-2206 alone has reported it was well tolerated.{{cite journal | vauthors = Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW | display-authors = 6 | title = First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors | journal = Journal of Clinical Oncology | volume = 29 | issue = 35 | pages = 4688–4695 | date = December 2011 | pmid = 22025163 | doi = 10.1200/JCO.2011.35.5263 }}
2014: A phase 1 clinical trial of MK-2206 with a variety of other agents in 72 patients with advanced cancer reported acceptable side-effects.[http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-mk2206-with-chemotherapy-or-erlotinib-for-advanced-cancer A trial of MK-2206 with chemotherapy or erlotinib for advanced cancer]
2016: MK-2206 is one of the treatments in the I-SPY2 Adaptive clinical trial for breast cancer that had been selected for later stage trials.[http://www.medpagetoday.com/reading-room/asco/breast-cancer/58805 Novel Agents are Targeting Drivers of TNBC - Several drug candidates in I-SPY2 have 'graduated' to later-phase studies. June 2016 ]
{{as of|2017|8}} 31 phase II clinical trials are registered, many completed.[https://clinicaltrials.gov/ct2/results?term=MK-2206&type=&rslt=&age_v=&gndr=&cond=&intr=&titles=&outc=&spons=&lead=&id=&cntry1=&state1=&cntry2=&state2=&cntry3=&state3=&locn=&phase=1&rcv_s=&rcv_e=&lup_s=&lup_e= MK-2206 phase=2 trials] e.g. in colorectal cancer, breast cancer, and many others.
MK-2206 and COVID-19
Data shown in a study preprint suggest that SARS-CoV-2 infection decreases cellular autophagy and that MK-2206, which induces autophagy, reduced virus replication by up to 88% in vitro. The study's authors propose that MK-2206 should be tested in clinical trials as a potential treatment for COVID-19.{{cite journal | vauthors = Gassen NC, Papies J, Bajaj T, Emanuel J, Dethloff F, Chua RL, Trimpert J, Heinemann N, Niemeyer C, Weege F, Hönzke K, Aschman T, Heinz DE, Weckmann K, Ebert T, Zellner A, Lennarz M, Wyler E, Schroeder S, Richter A, Niemeyer D, Hoffmann K, Meyer TF, Heppner FL, Corman VM, Landthaler M, Hocke AC, Morkel M, Osterrieder N, Conrad C, Eils R, Radbruch H, Giavalisco P, Drosten C, Müller MA | display-authors = 6 | title = SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals | journal = Nature Communications | volume = 12 | issue = 1 | pages = 3818 | date = June 2021 | pmid = 34155207 | pmc = 8217552 | doi = 10.1038/s41467-021-24007-w }}
References
{{reflist}}
Category:Protein kinase inhibitors
Category:Experimental cancer drugs
Category:Nitrogen heterocycles
Category:Heterocyclic compounds with 3 rings
{{antineoplastic-drug-stub}}