Vamorolone

Vamorolone (VBP15) is a first-in-class, orally active dissociative steroidal anti-inflammatory drug and membrane-stabilizer. Vamorolone improves muscular dystrophy without side effects. Vamorolone shows potent NF-κB inhibition and substantially reduces hormonal effects[1][2].

Signaling Pathways >> Metabolic Enzyme/Protease >> Mineralocorticoid Receptor

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Glucocorticoid Receptor

Vamorolone (VBP15) inhibits TNFα-induced pro-inflammatory NF-κB signaling in C2C12 muscle cells at 1 nM or more. Vamorolone binds the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) with similar affinity[1]. Vamorolone (0.1, 1μM; 30 minutes) reduces production of IL1βand CCL5 inflammatory mediators in primary human macrophages[2]. Vamorolone is a first-in-class mineralocorticoid receptor (MR) antagonist/dissociative glucocorticoid receptor (GR) ligand[3].

Vamorolone (5-30 mg/kg; cherry syrup) shows a superior side effect profile compared to pharmacological glucocorticoids in mdx mice[1]. Vamorolone (30 mg/kg; orally; daily for 20 days) reduces CNS Inflammation in murine experimental autoimmune encephalomyelitis[2]. Animal Model: C57BL/6 mice (experimental autoimmune encephalomyelitis)[2] Dosage: 30 mg/kg Administration: Orally; daily for 20 days (starting one day prior to MOG 33-55 peptide immunization and continuing) Result: Reduced CNS inflammation in murine experimental autoimmune encephalomyelitis.

[1]. Heier CR, et al. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med. 2013 Oct;5(10):1569-85.

[2]. Dillingham BC, et al. VBP15, a novel anti-inflammatory, is effective at reducing the severity of murine experimental autoimmune encephalomyelitis. Cell Mol Neurobiol. 2015 Apr;35(3):377-387.

[3]. Heier CR, et al. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1). pii: e201800186.