VAMOROLONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H28O4
Molecular Weight	356.4553
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)CC=C3[C@@]2([H])CCC4=CC(=O)C=C[C@]34C

InChI

InChIKey=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

HIDE SMILES / InChI

Description
Sources: https://vision-dmd.info/history-of-vbp15/ | https://musculardystrophynews.com/2018/09/19/potential-dmd-therapy-vamorolone-shows-positive-results-phase-2a-trial/ | https://www.ncbi.nlm.nih.gov/pubmed/29524454

VBP-15 FREE ALCOHOL, also known as Vamorolone and VBP-15, is an anti-inflammatory compound used in the treatment of muscular dystrophy. Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day. Vamorolone is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. Vamorolone has received Orphan Drug Designation in the US and Europe and is being developed for chronic treatment of boys with Duchenne Muscular Dystrophy (DMD).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nuclear factor NF-kappa-B complex 11 Target ID: CHEMBL2094258 Sources: patents.google.com/patent/WO2009155056A2	Modulator 828

PubMed

Title	Date	PubMed
Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor.	2017 Feb 7	28030841
The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice.	2018 Apr 17	29666400
Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes.	2018 Jun	29524454

Patents

Sample Use Guides

In Vivo Use Guide

2-week, open-label Phase IIa multiple ascending dose study (0.25, 0.75, 2.0, and 6.0 mg/kg/day) enrolled 48 boys with Duchenne muscular dystrophy. Vamorolone was safe and well-tolerated through the highest dose tested (6.0 mg/kg/day) and pharmacokinetics of vamorolone were similar to prednisolone.

Route of Administration: Oral

In Vitro Use Guide

Primary human intestinal epithelial cells were treated with VBP-15 (10 uM) for 24 h. VBP-15 significantly reduced the in vitro production of CCL5 , IL-6, IL-8.

Name

Type

Language

VAMOROLONE

Official Name

English

VAMOROLONE [USAN]

Common Name

English

17,21-DIHYDROXY-16.ALPHA.-METHYLPREGNA-1,4,9(11)-TRIENE- 3,20-DIONE

Systematic Name

English

DEXAMETHASONE IMPURITY E [EP IMPURITY]

Common Name

English

DELTA-1,4,9(11)-PREGNATRIENE-17-ALPHA,21-DIHYDROXY-16-ALPHA-METHYL-3,20-DIONE

Common Name

English

9,11-DEHYDRO DEXAMETHASONE

Common Name

English

vamorolone [INN]

Common Name

English

PREGNA-1,4,9(11)-TRIENE-3,20-DIONE, 17,21-DIHYDROXY-16-METHYL-, (16.ALPHA.)-

Systematic Name

English

AGAMREE

Brand Name

English

Vamorolone [WHO-DD]

Common Name

English

16.ALPHA.-METHYL-9,11-DEHYDROPREDNISOLONE

Common Name

English

VBP-15 FREE ALCOHOL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C521