Vamorolone

Vamorolone (developmental code names VBP-15) is a synthetic steroid, which is under development for the treatment of duchenne muscular dystrophy.[1][2][3][4][5]

vamorolone
Clinical data
Other namesVBP; VBP-15; 17α,21-Dihydroxy-16α-methylpregna-1,4,9(11)-triene-3,20-dione
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard100.032.874
Chemical and physical data
FormulaC22H28O4
Molar mass356.462 g·mol−1
3D model (JSmol)

Anti-inflammatory drugs of the corticosteroid class show a carbonyl (=O) or hydroxyl (-OH) group on the C11 carbon of the steroid backbone. In contrast, vamorolone contains a delta9,11 double bond between the C9 and C11 carbons.

In Phase 1 clinical trials of adult volunteers, vamorolone was shown to be safe and well-tolerated, with blood biomarker data suggesting possible loss of safety concerns of the corticosteroid class[6]

In Phase 2a clinical trial of children with Duchenne muscular dystrophy, vamorolone was shown to be safe and well-tolerated, and showed blood biomarker data consistent with an anti-inflammatory effect, and possible loss of safety concerns[7]

References

  1. "Vamorolone - ReveraGen Biopharma". AdisInsight.
  2. Reeves EK, Hoffman EP, Nagaraju K, Damsker JM, McCall JM (April 2013). "VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid". Bioorganic & Medicinal Chemistry. 21 (8): 2241–2249. doi:10.1016/j.bmc.2013.02.009. PMC 4088988. PMID 23498916.
  3. Heier CR, Damsker JM, Yu Q, Dillingham BC, Huynh T, Van der Meulen JH, Sali A, Miller BK, Phadke A, Scheffer L, Quinn J, Tatem K, Jordan S, Dadgar S, Rodriguez OC, Albanese C, Calhoun M, Gordish-Dressman H, Jaiswal JK, Connor EM, McCall JM, Hoffman EP, Reeves EK, Nagaraju K (October 2013). "VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects". EMBO Molecular Medicine. 5 (10): 1569–85. doi:10.1002/emmm.201302621. PMC 3799580. PMID 24014378.
  4. Dadgar S, Wang Z, Johnston H, Kesari A, Nagaraju K, Chen YW, Hill DA, Partridge TA, Giri M, Freishtat RJ, Nazarian J, Xuan J, Wang Y, Hoffman EP (October 2014). "Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy". The Journal of Cell Biology. 207 (1): 139–58. doi:10.1083/jcb.201402079. PMC 4195829. PMID 25313409.
  5. Damsker JM, Conklin LS, Sadri S, Dillingham BC, Panchapakesan K, Heier CR, McCall JM, Sandler AD (September 2016). "VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis". Inflammation Research. 65 (9): 737–43. doi:10.1007/s00011-016-0956-8. PMID 27261270.
  6. Hoffman EP, Riddle V, Siegler MA, Dickerson D, Backonja M, Kramer WG, Nagaraju K, Gordish-Dressman H, Damsker JM, McCall JM (June 2018). "Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes". Steroids. 134: 43–52. doi:10.1016/j.steroids.2018.02.010. PMC 6136660. PMID 29524454.
  7. Conklin LS, Damsker JM, Hoffman EP, Jusko WJ, Mavroudis PD, Schwartz BD, Mengle-Gaw LJ, Smith EC, Mah JK, Guglieri M, Nevo Y, Kuntz N, McDonald CM, Tulinius M, Ryan MM, Webster R, Castro D, Finkel RS, Smith AL, Morgenroth LP, Arrieta A, Shimony M, Jaros M, Shale P, McCall JM, Hathout Y, Nagaraju K, van den Anker J, Ward LM, Ahmet A, Cornish MR, Clemens PR (October 2018). "Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug". Pharmacological Research. 136: 140–150. doi:10.1016/j.phrs.2018.09.007. PMC 6218284. PMID 30219580.
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