WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H327030
CAS#: 13209-41-1 (free base)
Description: Vamorolone, also known as VBP-15, is an anti-inflammatory compound used in the treatment of muscular dystrophy. Vamorolone is hoped to retain the beneficial anti-inflammatory and muscle strengthening aspects of corticosteroids, while decreasing or eliminating many of the undesirable side effects (bone fragility, stunted growth, insulin resistance).
Hodoodo Cat#: H327030
Name: Vamorolone
CAS#: 13209-41-1 (free base)
Chemical Formula: C22H28O4
Exact Mass: 356.20
Molecular Weight: 356.462
Elemental Analysis: C, 74.13; H, 7.92; O, 17.95
Related CAS #: 10106-41-9 (acetate) 13209-41-1 (free base)
Synonym: Vamorolone, VBP-15, VBP15, VBP 15
IUPAC/Chemical Name: (8S,10S,13S,14S,16R,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one
InChi Key: ZYTXTXAMMDTYDQ-DGEXFFLYSA-N
InChi Code: 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
SMILES Code: C[C@@]12[C@](C(CO)=O)(O)[C@H](C)C[C@@]1([H])[C@]3([H])CCC4=CC(C=C[C@]4(C)C3=CC2)=O
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Vamorolone (VBP15) is a first-in-class, orally active dissociative steroidal anti-inflammatory drug and membrane-stabilizer. |
| In vitro activity: | VBP15 has protective physicochemical effects on the plasma membrane, protecting cells from injury and promoting membrane repair. This sub-activity is likely to be particularly important in duchenne muscular dystrophy (DMD) where disease pathogenesis is clearly linked to membrane instability and myofibre injury. A key anti-inflammatory activity, the inhibition of TNFα-induced NF-κB, is retained by VBP15. This mechanism occurs through protein–protein interactions of the VBP15 ligand-activated GR, independently of DNA binding, GRE activation, or upregulation of inhibitory transcripts. NF-κB activation is among the earliest histological features of DMD neonates (Chen et al, 2005; Porter et al, 2002, 2003), years before symptoms appear. Reference: EMBO Mol Med. 2013 Oct;5(10):1569-85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799580/ |
| In vivo activity: | The EAE model shows that VBP15 does, indeed, reduce CNS inflammation to a similar degree to that of prednisolone. VBP15 was able to reduce both the incidence and severity of disease which was assessed based on the degree of paralysis. This anti-inflammatory effect was confirmed via histological studies which showed a significant reduction of inflammatory foci. It was found that that a 5-week treatment regimen of VBP15 did not decrease trabecular thickness in mdx mouse model of Duchenne Muscular Dystrophy (Heier et al. 2013). With regard to muscle atrophy, it was determined that a 5 week treatment with prednisolone significantly upregulated expression of MurF1 and FBXO32, two genes known to play a key role in GC-mediated muscle catabolism, whereas VBP15 did not. Additionally, the weight of the diaphragms in prednisolone-treated mice was significantly less than that of VBP15-treated mice, providing further evidence that VBP15 may not induce the muscle-wasting processes associated with long-term glucocorticoid use. Reference: Cell Mol Neurobiol. 2015 Apr;35(3):377-387. https://link-springer-com.libproxy.lib.unc.edu/article/10.1007/s10571-014-0133-y |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Soluble in DMSO | 62.5 | 175.34 |
The following data is based on the product molecular weight 356.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. 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. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med. 2013 Oct;5(10):1569-85. doi: 10.1002/emmm.201302621. Epub 2013 Sep 9. PMID: 24014378; PMCID: PMC3799580. 2. Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. PMID: 30745312; PMCID: PMC6371196. 3. Dillingham BC, Knoblach SM, Many GM, Harmon BT, Mullen AM, Heier CR, Bello L, McCall JM, Hoffman EP, Connor EM, Nagaraju K, Reeves EKM, Damsker JM. 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. doi: 10.1007/s10571-014-0133-y. Epub 2014 Nov 13. PMID: 25392236. 4. Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. PMID: 30745312; PMCID: PMC6371196. |
| In vitro protocol: | 1. 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. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med. 2013 Oct;5(10):1569-85. doi: 10.1002/emmm.201302621. Epub 2013 Sep 9. PMID: 24014378; PMCID: PMC3799580. 2. Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. PMID: 30745312; PMCID: PMC6371196. |
| In vivo protocol: | 1. Dillingham BC, Knoblach SM, Many GM, Harmon BT, Mullen AM, Heier CR, Bello L, McCall JM, Hoffman EP, Connor EM, Nagaraju K, Reeves EKM, Damsker JM. 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. doi: 10.1007/s10571-014-0133-y. Epub 2014 Nov 13. PMID: 25392236. 2. Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. PMID: 30745312; PMCID: PMC6371196. |
1: Damsker JM, Conklin LS, Sadri S, Dillingham BC, Panchapakesan K, Heier CR, McCall JM, Sandler AD. VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis. Inflamm Res. 2016 Sep;65(9):737-43. doi: 10.1007/s00011-016-0956-8. Epub 2016 Jun 3. PubMed PMID: 27261270.
2: Garvin LM, Chen Y, Damsker JM, Rose MC. A novel dissociative steroid VBP15 reduces MUC5AC gene expression in airway epithelial cells but lacks the GRE mediated transcriptional properties of dexamethasone. Pulm Pharmacol Ther. 2016 Jun;38:17-26. doi: 10.1016/j.pupt.2016.04.004. Epub 2016 Apr 29. PubMed PMID: 27133900.
3: Freishtat RJ, Nino G, Tsegaye Y, Alcala SE, Benton AS, Watson AM, Reeves EK, Haider SK, Damsker JM. Pharmacologically-induced mitotic synchrony in airway epithelial cells as a mechanism of action of anti-inflammatory drugs. Respir Res. 2015 Oct 29;16:132. doi: 10.1186/s12931-015-0293-4. PubMed PMID: 26511361; PubMed Central PMCID: PMC4625853.
4: Dillingham BC, Knoblach SM, Many GM, Harmon BT, Mullen AM, Heier CR, Bello L, McCall JM, Hoffman EP, Connor EM, Nagaraju K, Reeves EK, Damsker JM. VBP15, a novel anti-inflammatory, is effective at reducing the severity of murine experimental autoimmune encephalomyelitis. Cell Mol Neurobiol. 2015 Apr;35(3):377-87. doi: 10.1007/s10571-014-0133-y. Epub 2014 Nov 13. PubMed PMID: 25392236.
5: 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. Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. J Cell Biol. 2014 Oct 13;207(1):139-58. doi: 10.1083/jcb.201402079. PubMed PMID: 25313409; PubMed Central PMCID: PMC4195829.
6: 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. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med. 2013 Oct;5(10):1569-85. doi: 10.1002/emmm.201302621. Epub 2013 Sep 9. PubMed PMID: 24014378; PubMed Central PMCID: PMC3799580.
7: Ruegg UT. Pharmacological prospects in the treatment of Duchenne muscular dystrophy. Curr Opin Neurol. 2013 Oct;26(5):577-84. doi: 10.1097/WCO.0b013e328364fbaf. Review. PubMed PMID: 23995279.
8: Damsker JM, Dillingham BC, Rose MC, Balsley MA, Heier CR, Watson AM, Stemmy EJ, Jurjus RA, Huynh T, Tatem K, Uaesoontrachoon K, Berry DM, Benton AS, Freishtat RJ, Hoffman EP, McCall JM, Gordish-Dressman H, Constant SL, Reeves EK, Nagaraju K. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice. PLoS One. 2013 May 7;8(5):e63871. doi: 10.1371/journal.pone.0063871. Print 2013. PubMed PMID: 23667681; PubMed Central PMCID: PMC3646769.
9: Reeves EK, Hoffman EP, Nagaraju K, Damsker JM, McCall JM. VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid. Bioorg Med Chem. 2013 Apr 15;21(8):2241-9. doi: 10.1016/j.bmc.2013.02.009. Epub 2013 Feb 18. Erratum in: Bioorg Med Chem. 2015 Apr 1;23(7):1664. PubMed PMID: 23498916; PubMed Central PMCID: PMC4088988.
