Roxibolone

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 ;
PubChem CID	68795;
ChemSpider	62035 ;
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 ; Key:JOFBZBDWOWPUMO-QARKFJNLSA-N ;
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Roxibolone (INN) (developmental code name 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 (developmental code name BR-917), is a long-acting prodrug of roxibolone with similar activity.^[1]^[2]

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]

References

^ ^a ^b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 1082. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c ^d ^e ^f Felippone F, Resnati G, Scolastico C, Tronconi G (1984). "Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds". Steroids. 43 (3): 271–82. doi:10.1016/0039-128x(84)90045-x. PMID 6523544. S2CID 54289377.
^ Dahlberg E, Snochowski M, Gustafsson JA (1981). "Regulation of the androgen and glucocorticoid receptors in rat and mouse skeletal muscle cytosol". Endocrinology. 108 (4): 1431–40. doi:10.1210/endo-108-4-1431. PMID 6970661.
^ Souness GW, Latif SA, Laurenzo JL, Morris DJ (1995). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat". Endocrinology. 136 (4): 1809–12. doi:10.1210/endo.136.4.7895695. PMID 7895695.
^ Souness GW, Morris DJ (1996). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat". Hypertension. 27 (3 Pt 1): 421–5. doi:10.1161/01.hyp.27.3.421. PMID 8698448.
^ Fürstenberger C, Vuorinen A, Da Cunha T, Kratschmar DV, Saugy M, Schuster D, Odermatt A (2012). "The anabolic androgenic steroid fluoxymesterone inhibits 11β-hydroxysteroid dehydrogenase 2-dependent glucocorticoid inactivation". Toxicol. Sci. 126 (2): 353–61. doi:10.1093/toxsci/kfs022. PMID 22273746.

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[Elks2014-1] J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 1082. ISBN 978-1-4757-2085-3.

[pmid6523544-2] ^ ^a ^b ^c ^d ^e ^f Felippone F, Resnati G, Scolastico C, Tronconi G (1984). "Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds". Steroids. 43 (3): 271–82. doi:10.1016/0039-128x(84)90045-x. PMID 6523544. S2CID 54289377.

[pmid6970661-3] Dahlberg E, Snochowski M, Gustafsson JA (1981). "Regulation of the androgen and glucocorticoid receptors in rat and mouse skeletal muscle cytosol". Endocrinology. 108 (4): 1431–40. doi:10.1210/endo-108-4-1431. PMID 6970661.

[pmid7895695-4] Souness GW, Latif SA, Laurenzo JL, Morris DJ (1995). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat". Endocrinology. 136 (4): 1809–12. doi:10.1210/endo.136.4.7895695. PMID 7895695.

[pmid8698448-5] Souness GW, Morris DJ (1996). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat". Hypertension. 27 (3 Pt 1): 421–5. doi:10.1161/01.hyp.27.3.421. PMID 8698448.

[pmid22273746-6] Fürstenberger C, Vuorinen A, Da Cunha T, Kratschmar DV, Saugy M, Schuster D, Odermatt A (2012). "The anabolic androgenic steroid fluoxymesterone inhibits 11β-hydroxysteroid dehydrogenase 2-dependent glucocorticoid inactivation". Toxicol. Sci. 126 (2): 353–61. doi:10.1093/toxsci/kfs022. PMID 22273746.

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