Beloranib

Beloranib
Names
IUPAC name
[(3R,6R,7S,8S)-7-methoxy-8-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-2-oxaspiro[2.5]octan-6-yl] (E)-3-[4-[2-(dimethylamino)ethoxy]phenyl]prop-2-enoate
Other names
CKD-732; ZGN-433
Identifiers
251111-30-5 YesY
529511-79-3 (hemioxalate) YesY
3D model (Jmol) Interactive image
ChemSpider 5293699 N
PubChem 6918502
UNII FI471K8BU6 YesY
Properties
C29H41NO6
Molar mass 499.65 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

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.[1] Drug development for the product was halted in 2016.[2]

Mechanism of action

Beloranib, an analog of the natural chemical compound fumagillin, is an inhibitor of the enzyme METAP2.[3] It was originally designed as angiogenesis inhibitor for the treatment of cancer.[4] 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.[5][6]

Clinical trials

A Phase I trial was published in 2013,[7] 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.[8] Zafgen continued with a Phase III trial for Prader–Willi syndrome.[9]

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.[10] After discussions with the Food and Drug Administration indicated that the obstacles to gaining approval were insurmountable, product development for beloranib was ended.[2]

References

  1. ↑ "News Release: Zafgen Secures $33 Million Series C Financing" (PDF). Zafgen, Inc. July 7, 2011.
  2. 1 2 "Zafgen Halts Development of Beloranib, to Cut Jobs by ~34%". nasdaq.com. July 20, 2016.
  3. ↑ Chun, E; Han, CK; Yoon, JH; Sim, TB; Kim, YK; Lee, KY (2005). "Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude model". International Journal of Cancer. Journal International Du Cancer. 114 (1): 124–30. doi:10.1002/ijc.20687. PMID 15523682.
  4. ↑ Kim, EJ; Shin, WH (2005). "General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system". Biological & Pharmaceutical Bulletin. 28 (2): 217–23. doi:10.1248/bpb.28.217. PMID 15684472.
  5. ↑ "Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity". MedNews. Drugs.com. 5 January 2011.
  6. ↑ "Fat-busting pill helps obese to shed two pounds a week - without changing their diets". UK Daily Mail. 11 January 2011.
  7. ↑ Hughes, T. E.; Kim, D. D.; Marjason, J; Proietto, J; Whitehead, J. P.; Vath, J. E. (Sep 2013). "Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women". Obesity. 21 (9): 1782–8. doi:10.1002/oby.20356. PMID 23512440.
  8. ↑ Kim, D. D.; Krishnarajah, J; Lillioja, S; De Looze, F; Marjason, J; Proietto, J; Shakib, S; Stuckey, B. G.; Vath, J. E.; Hughes, T. E. (2015). "Efficacy and Safety of Beloranib for Weight Loss in Obese Adults: A Randomized Controlled Trial". Diabetes, Obesity and Metabolism: n/a. doi:10.1111/dom.12457. PMID 25732625.
  9. ↑ "Clinical Trials". Retrieved 2014-11-18.
  10. ↑ "UPDATE 4-Zafgen halts obesity drug trial after second patient death". Retrieved 2015-12-03.
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