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'''Beloranib''' is a former drug candidate for the treatment of obesity. It was discovered by CKD Pharmaceuticals and its clinical development was led by Zafgen.<ref>{{cite web | url = http://www.zafgen.com/PDF/zafgen-series-c-070711.pdf | title = News Release: Zafgen Secures $33 Million Series C Financing | publisher = Zafgen, Inc. | date = July 7, 2011 | url-status = dead | archive-url = https://web.archive.org/web/20111210094436/http://www.zafgen.com/PDF/zafgen-series-c-070711.pdf | archive-date = December 10, 2011 }}</ref> Drug development was halted in 2016 after deaths during clinical trials.<ref name=nasdaq>{{cite news | url = http://www.nasdaq.com/article/zafgen-halts-development-of-beloranib-to-cut-jobs-by-34-cm651992 | publisher = nasdaq.com | title = Zafgen Halts Development of Beloranib, to Cut Jobs by ~34% | date = July 20, 2016}}</ref>
==Mechanism of action== Beloranib, an analog of the natural chemical compound fumagillin, is an inhibitor of the enzyme METAP2.<ref>{{cite journal | vauthors = Chun E, Han CK, Yoon JH, Sim TB, Kim YK, Lee KY | title = Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude model | journal = International Journal of Cancer | volume = 114 | issue = 1 | pages = 124–30 | date = March 2005 | pmid = 15523682 | doi = 10.1002/ijc.20687 | doi-access = free }}</ref> It was originally designed as angiogenesis inhibitor for the treatment of cancer.<ref>{{cite journal | vauthors = Kim EJ, Shin WH | title = General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system | journal = Biological & Pharmaceutical Bulletin | volume = 28 | issue = 2 | pages = 217–23 | date = February 2005 | pmid = 15684472 | doi = 10.1248/bpb.28.217 | doi-access = free }}</ref> However, once the potential anti-obesity effects of METAP2 inhibition became apparent, the clinical development began to focus on these effects and beloranib has shown positive results in preliminary clinical trials for this indication.<ref>{{cite web | url = https://www.drugs.com/clinical_trials/zafgen-announces-positive-topline-phase-1b-data-zgn-433-obesity-10955.html | title = Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity | date = 5 January 2011 | work = MedNews | publisher = Drugs.com }}</ref>
==Clinical trials== A Phase I trial was published in 2013,<ref>{{cite journal | vauthors = Hughes TE, Kim DD, Marjason J, Proietto J, Whitehead JP, Vath JE | title = Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women | journal = Obesity | volume = 21 | issue = 9 | pages = 1782–8 | date = September 2013 | pmid = 23512440 | doi = 10.1002/oby.20356 | s2cid = 2352854 }}</ref> finding a dose that led to weight loss in obese women in comparison to placebo. Results from a Phase II clinical trial for obesity were promising with clinically meaningful weight loss and improvements in cardiometabolic risk factors in the treated group.<ref>{{cite journal | vauthors = Kim DD, Krishnarajah J, Lillioja S, de Looze F, Marjason J, Proietto J, Shakib S, Stuckey BG, Vath JE, Hughes TE | display-authors = 6 | title = Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial | journal = Diabetes, Obesity & Metabolism | volume = 17 | issue = 6 | pages = 566–572 | date = June 2015 | pmid = 25732625 | doi = 10.1111/dom.12457 | s2cid = 205076412 }}</ref> Zafgen continued with a Phase III trial for Prader–Willi syndrome.<ref>{{Cite web|url = http://www.zafgen.com/zafgen/clinical-trials|title = Clinical Trials |access-date = 2014-11-18}}</ref>
In December 2015, Zafgen halted the Phase III clinical trial of beloranib for Prader–Willi syndrome after a second patient death in order to determine whether the deaths were treatment-related.<ref>{{Cite news|url = https://www.reuters.com/article/zafgen-study-idUSL3N13R3OQ20151203|title = UPDATE 4-Zafgen halts obesity drug trial after second patient death| newspaper=Reuters | date=3 December 2015 |access-date = 2015-12-03|archive-date = 2015-12-03|archive-url = https://web.archive.org/web/20151203084512/http://www.reuters.com/article/2015/12/03/zafgen-study-idUSL3N13R3OQ20151203|url-status = live}}</ref> After discussions with the Food and Drug Administration indicated that the obstacles to gaining approval were insurmountable, product development for beloranib was ended.<ref name=nasdaq/>
== References == {{reflist}}
{{Antiobesity preparations}}
Category:Epoxides Category:Cinnamate esters Category:Abandoned drugs Category:2-Phenoxyethanamines Category:Dimethylamino compounds Category:Ethanolamines Category:Methoxy compounds Category:METAP2 inhibitors