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
CAS Registry Number	251111-30-5^Y 529511-79-3 (hemioxalate)^Y
ChemSpider	5293699^N
InChI InChI=1S/C29H41NO6/c1-20(2)7-13-24-28(3,36-24)27-26(32-6)23(15-16-29(27)19-34-29)35-25(31)14-10-21-8-11-22(12-9-21)33-18-17-30(4)5/h7-12,14,23-24,26-27H,13,15-19H2,1-6H3/b14-10+/t23-,24-,26-,27-,28+,29+/m1/s1^N Key: ZEZFKUBILQRZCK-MJSCXXSSSA-N^N InChI=1/C29H41NO6/c1-20(2)7-13-24-28(3,36-24)27-26(32-6)23(15-16-29(27)19-34-29)35-25(31)14-10-21-8-11-22(12-9-21)33-18-17-30(4)5/h7-12,14,23-24,26-27H,13,15-19H2,1-6H3/b14-10+/t23-,24-,26-,27-,28+,29+/m1/s1 Key: ZEZFKUBILQRZCK-MJSCXXSSBU
Jmol-3D images	Image
PubChem	6918502
SMILES O=C(O[C@H]2[C@@H](OC)[C@@H]([C@]1(OC1)CC2)[C@]3(O[C@@H]3C\C=C(/C)C)C)\C=C\c4ccc(OCCN(C)C)cc4
UNII	FI471K8BU6^Y
Properties
Molecular formula	C₂₉H₄₁NO₆
Molar mass	499.64 g·mol⁻¹
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
N verify (what is: Y/N?)
Infobox references

Beloranib is an experimental injectable^[1] drug candidate for the treatment of obesity. It was discovered by CKD Pharmaceuticals and is currently being developed by Zafgen.^[2]

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]

An ascending dose trial of 31 obese women was published in 2013,^[7] finding a dose that led to weight loss vs placebo. Zafgen is running a phase 3 trial for Prader–Willi syndrome and phase 2 trials for obesity.^[8]

Results from the Phase II clinical trial for obesity mentioned earlier were promising with clinically meaningful weight loss and improvements in cardiometabolic risk factors in the treated group.^[9]

References

↑ Zafgen Announces New Weight Loss and Safety Data from Phase 2 Trial of Beloranib in Hypothalamic Injury Associated Obesity at ENDO 2015 (2015)
↑ "News Release: Zafgen Secures $33 Million Series C Financing" (PDF). Zafgen, Inc. July 7, 2011.
↑ 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.
↑ 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.
↑ "Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity". MedNews. Drugs.com. 5 January 2011.
↑ "Fat-busting pill helps obese to shed two pounds a week - without changing their diets". UK Daily Mail. 11 January 2011.
↑ 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.
↑ "CLINICAL TRIALS". Retrieved 2014-11-18.
↑ 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.