beloranib   Click here for help

GtoPdb Ligand ID: 8445

Synonyms: CKD-732 [2] | O-(4-(2-Dimethylaminoethoxy)-trans-cinnamoyl)fumagillol | ZGN 440 | ZGN-440
Compound class: Synthetic organic
Comment: Beloranib is an investigational drug candidate for the treatment of obesity. The compound is a synthetic derivative of the antimicrobial agent fumagillin, from Aspergillus fumigatus. Beloranib is administered by subcutaneous injection.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 0
Rotatable bonds 12
Topological polar surface area 73.06
Molecular weight 499.29
XLogP 3.91
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COC1C(CCC2(C1C1(C)OC1CC=C(C)C)CO2)OC(=O)C=Cc1ccc(cc1)OCCN(C)C
Isomeric SMILES CO[C@@H]1[C@@H](CC[C@@]2([C@H]1[C@@]1(C)O[C@@H]1CC=C(C)C)CO2)OC(=O)/C=C/c1ccc(cc1)OCCN(C)C
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
InChI Key ZEZFKUBILQRZCK-MJSCXXSSSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Beloranib was advanced to Phase 3 evaluation in patients with Prader-Willi syndrome, following Phase 2 evidence that it helped these obese patients to lose weight. However, patient deaths in Phase 3 forced termination of the development programme, including a study in obese patients with type 2 diabetes mellitus.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Beloranib is a prototype methionine aminopeptidase 2 (MetAP2) inhibitor. MetAP2 inhibitors were originally developed as anti-cancer agents [1,4,6-7] but are now being exploited for their ability to induce significant and sustained weight reduction, without serious side effects [2-3]. Beloranib both decreases the drive to eat and increases the use of stored fat as an energy source to achieve the drug's clinical effects.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02324491 An Efficacy and Safety Study of Beloranib in Obese Subjects With Type 2 Diabetes Mellitus Phase 2 Interventional Zafgen, Inc.
NCT02179151 Double-Blind, Placebo Controlled, Phase 3 Trial of ZGN-440 (Beloranib) in Obese Subjects With Prader-Willi Syndrome Phase 3 Interventional Zafgen, Inc. 5