Beloranib (hemioxalate)

Beloranib (ZGN-440) hemioxalate is a selective, irreversible inhibitor of methionine aminopeptidase MetAP2 that suppresses appetite and increases energy expenditure. Beloranib hemioxalate blocks the enzymatic cleavage of N-terminal methionine from nascent proteins by forming a covalent bond with MetAP2, thereby regulating fatty acid metabolism, adrenergic signaling, and hypothalamic NF-κB expression. Beloranib significantly reduces food intake, body weight, and fat accumulation, while improving glucose tolerance, insulin sensitivity, and lipid metabolism. Beloranib hemioxalate also elevates energy expenditure and fat oxidation levels, without affecting body temperature, spontaneous activity, or the inflammatory cytokine IL-1β. Beloranib hemioxalate can be used in research on obesity and hypothalamic obesity^[1][2][3].
In Vitro:Beloranib hemioxalate potently inhibits endothelial cell proliferation via selective inhibition of MetAP2^[2].
Beloranib (24 h pre-incubation; 3 h norepinephrine treatment) hemioxalate enhances norepinephrine-induced lipolysis in primary rat brown adipocytes, increasing glycerol release to 4- to 5-fold relative to vehicle^[3].
Beloranib (24 h pre-incubation) hemioxalate enhances norepinephrine-induced energy expenditure in primary rat brown adipocytes^[3].
Beloranib (24 h concurrent treatment) hemioxalate reverses norepinephrine desensitization in primary rat brown adipocytes, sustaining ucp1 gene expression at 177-fold after 24 h of norepinephrine treatment^[3]. In Vivo:Beloranib (0.1 mg/kg; subcutaneous injection; once daily; for 12 consecutive days) hemioxalate significantly reduces body weight gain, food intake, fasting insulin levels, and hypothalamic NF-κB expression, while increasing circulating α-MSH levels, in male Sprague Dawley rats with obesity induced by CMHL^[1].
Beloranib (0.1 mg/kg; subcutaneous injection; once daily; for 14 consecutive days) hemioxalate induces significant weight loss and reduces food intake by 28% in young adult male MC4rKO obese rats^[1].
Beloranib (0.1 mg/kg, subcutaneous injection, once daily for 21 consecutive days) hemioxalate induces a 10% body weight loss, reduces food intake, and improves insulin sensitivity in weight-stable aged male MC4rKO obese rats^[1].
Administration of Beloranib hemioxalate to nude mice with xenografts inhibits angiogenesis and tumorigenesis^[2].
Beloranib (1 mg/kg; subcutaneous injection; once daily; for 12 consecutive days) hemioxalate reduces body weight by 20-23% over 12 days in high-fat diet-induced obese male C57BL/6 mice^[3].
Beloranib (1 mg/kg; subcutaneous injection; once daily; for 14 consecutive days) hemioxalate reduces body weight by 22-25% within 14 days in high-fat diet-induced obese C57BL/6 mice, while decreasing fat mass and increasing lean mass, but exerts minimal effects on body weight and body composition in lean mice^[3].
Beloranib (0.3 mg/kg; subcutaneous injection; administered twice at 9:00 a.m. on Day 1 and Day 2) hemioxalate inhibits MetAP2 activity in brown adipose tissue of C57BL/6 mice with obesity induced by a high-fat diet^[3].