At dosages of 1 nM or greater, vamorolone (VBP15) suppresses TNFα-induced pro-inflammatory NF-κB activation in C2C12 ablated cells. Human macrophages that are exposed to vamorolone (0.1, 1 μM) for 30 minutes produce less IL1β and CCL5 mediators in their main tissue [2]. Today's dissociative glucose requirement (GR) ligand and mineralocorticoid receptor (MR)-restricted antagonist is vamorolone [3].

When compared to pharmaceutical glucocorticoids, vamolodone (5–30 mg/kg; Cherry) has been demonstrated to cause more substantial side effects in MDX [1]. In mice with experimental autoimmune encephalitis, vamolodone (30 mg/kg; lateral; once daily for 20 days) decreases inflammation of the central nervous system [2].

Animal/Disease Models: C57BL/6 mice (experimental autoimmune encephalomyelitis) [2]
Doses: 30 mg/kg one time/day for 20 days (starting the day before MOG 33-55 peptide immunization and continuing)
Experimental Results: Small diminished central nervous system inflammation in murine experimental autoimmune encephalomyelitis.

Absorption, Distribution and Excretion
Following oral administration with food, the median Tmax of vamorolone is approximately 2 hours. The co-administration of vamorolone with a high-fat, high-calorie meal reduced Cmax by 18%, increased AUC by 13%, and delayed Tmax by one hour. The co-administration of vamorolone with a low-fat, low-calorie meal reduced Cmax by 4%, increased AUC by 14%, and delayed Tmax by one hour.
Approximately 30% of a given vamorolone dose is excreted in the feces (15.4% as unchanged parent drug) and 48% is excreted in the urine (<1% as unchanged parent drug).
Based on population pharmacokinetic analysis, the apparent volume of distribution of vamorolone when administered with a meal to a 20 kg patient with DMD is 162 L.
Based on population pharmacokinetic analysis, the clearance of vamorolone when administered with a meal to a 20 kg patient with DMD is 58 L/h.

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Metabolism / Metabolites
Vamorolone is subject to multiple metabolic pathways, including glucuronidation, hydroxylation, and reduction. Its metabolism is mediated through CYP3A4, CYP3A5, CYP2C8, UGT1A3, UGT2B7, and UGT2B17. Glucuronides - formed via direct glucuronidation and hydrogenation with subsequent glucuronidation - are the main metabolites in the plasma and urine.

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Biological Half-Life
The terminal elimination half-life of vamorolone is approximately 2 hours.

Protein Binding
The _in vitro_ protein binding of vamorolone is 88.1%.

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

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

Vamorolone is a 3-oxo-Delta(1),Delta(4)-steroid that is pregna-1,4,9(11)-trien-17-ol substituted by oxo, oxo, and hydroxy groups at positions 3, 20, and 21, respectively. It is approved by the FDA for the treatment of patients with Duchenne muscular dystrophy aged 2 years and older. It has a role as an anti-inflammatory drug, an immunosuppressive agent and a glucocorticoid receptor agonist. It is a corticosteroid, a 3-oxo-Delta(1),Delta(4)-steroid, a 20-oxo steroid, a 17alpha-hydroxy steroid, a 21-hydroxy steroid, a primary alpha-hydroxy ketone and a tertiary alpha-hydroxy ketone.
Vamorolone is a novel and fully synthetic glucocorticoid developed by Santhera Pharmaceuticals. It is used to manage inflammation and immune dysregulation in patients with Duchenne muscular dystrophy (DMD), a neuromuscular disorder characterized by the insidious regression of neuromuscular function and the most common form of muscular dystrophy in the United States. Corticosteroid therapy is the current standard of care for DMD despite relatively high rates of adverse effects. Vamorolone is positioned as having a more tolerable adverse effect profile than other corticosteroids owing to its unique receptor binding profile, thus providing an additional treatment option in patients for whom corticosteroid adverse effects are intolerable or otherwise unacceptable. Vamorolone was approved by the FDA in October 2023 for the management of DMD in patients ≥2 years of age. In December 2023, it was approved in the EU for the treatment of patients ≥4 years of age.
Vamorolone is a Corticosteroid. The mechanism of action of vamorolone is as a Corticosteroid Hormone Receptor Agonist.

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Drug Indication
Vamorolone is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients ≥2 years of age in the US and in patients ≥4 years of age in the EU.
Treatment of Duchenne muscular dystrophy

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Mechanism of Action
Vamorolone is a synthetic corticosteroid that acts as an agonist at the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. It is also an antagonist of the mineralocorticoid receptor. The precise mechanism by which vamorolone exerts its therapeutic effects in patients with DMD is unclear.

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Pharmacodynamics
In clinical studies, treatment with vamorolone induced a dose-dependent decrease in morning cortisol levels and a dose-dependent increase in leukocyte and lymphocyte counts.

C22H28O4

356.45532

356.199

13209-41-1

3035000

White to yellow solid powder

1.24g/cm3

548.3ºC at 760 mmHg

299.4ºC

2.63E-14mmHg at 25°C

1.603

2.752

2

4

2

26

775

6

C[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@@]4(C3=CC[C@@]2([C@]1(C(=O)CO)O)C)C

ZYTXTXAMMDTYDQ-DGEXFFLYSA-N

InChI=1S/C22H28O4/c1-13-10-18-16-5-4-14-11-15(24)6-8-20(14,2)17(16)7-9-21(18,3)22(13,26)19(25)12-23/h6-8,11,13,16,18,23,26H,4-5,9-10,12H2,1-3H3/t13-,16-,18+,20+,21+,22+/m1/s1

(8S,10S,13S,14S,16R,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-7,8,12,14,15,16-hexahydro-6H-cyclopenta[a]phenanthren-3-one

Agamree

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~62.5 mg/mL (~175.34 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)