Roxibolone

Roxibolone (INN; development code BR-906; also known as 11β,17β-dihydroxy-17α-methyl-3-oxoandrosta-1,4-diene-2-carboxylic acid) is a steroidal antiglucocorticoid described as an anticholesterolemic (cholesterol-lowering) and anabolic drug which was never marketed.^[1][2] Roxibolone is closely related to formebolone, which shows antiglucocorticoid activity similarly and, with the exception of having a carboxaldehyde group at the C2 position instead of a carboxylic acid group, roxibolone is structurally almost identical to.^[2] The 2-decyl ester of roxibolone, decylroxibolone (development code BR-917), is a long-acting prodrug of roxibolone with similar activity.^[1][2]

Roxibolone

Clinical data
Other names	BR-906; 11β,17β-Dihydroxy-17α-methyl-3-oxoandrosta-1,4-diene-2-carboxylic acid
Identifiers
IUPAC name (8S,9S,10R,11S,13S,14S,17S)-11,17-dihydroxy-10,13,17-trimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-2-carboxylic acid
CAS Number	60023-92-9 Y
PubChem CID	68795
ChemSpider	62035 N
UNII	3R7NLP419C
CompTox Dashboard (EPA)	DTXSID20208728
Chemical and physical data
Formula	C21H28O5
Molar mass	360.450 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)C(=C[C@]34C)C(=O)O)O)C)O
InChI InChI=1S/C21H28O5/c1-19-9-13(18(24)25)15(22)8-11(19)4-5-12-14-6-7-21(3,26)20(14,2)10-16(23)17(12)19/h8-9,12,14,16-17,23,26H,4-7,10H2,1-3H3,(H,24,25)/t12-,14-,16-,17+,19-,20-,21-/m0/s1 N Key:JOFBZBDWOWPUMO-QARKFJNLSA-N N
NY (what is this?)  (verify)

In rats, roxibolone counteracts the catabolic effects (control of nitrogen balance) and increased alkaline phosphatase levels induced by the potent glucocorticoid dexamethasone phosphate.^[2] It does not bind to the glucocorticoid receptor however, and its antiglucocorticoid activity may instead be mediated by enzyme inhibition.^[3] In accordance, 11α- and 11β-hydroxyprogesterone are known to be potent inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD), which is responsible for the biosynthesis of the potent endogenous glucocorticoids cortisol and corticosterone (from the precursors deoxycortisol and deoxycorticosterone, respectively).^[4][5] As roxibolone is 11β-hydroxylated similarly, it may act in a likewise fashion. However, formebolone was found to be a very weak inhibitor of 11β-HSD type 2, although this specific isoenzyme is responsible for the inactivation of glucocorticoids rather than their production.^[6]

Unlike formebolone, which is additionally an anabolic-androgenic steroid (AAS), roxibolone is devoid of affinity for the androgen receptor and possesses no androgenic or myotrophic activity in animal assays.^[2] For this reason, it has been said that roxibolone may be much better tolerated in comparison.^[2]