Metapristone

Metapristone

Clinical data
Other names	RU-42633; Desmethylmifepristone; 17β-Hydroxy-11β-[4-(methylamino)phenyl]-17α-(prop-1-yn-1-yl)estra-4,9-dien-3-one
Identifiers
IUPAC name (8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-11-[4-(methylamino)phenyl]-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one
CAS Number	104004-96-8
PubChem CID	10070462
ChemSpider	8246002
UNII	K1P8OGJ86J
ChEMBL	ChEMBL1608
CompTox Dashboard (EPA)	DTXSID60146216
Chemical and physical data
Formula	C28H33NO2
Molar mass	415.577 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC#C[C@@]1(CC[C@@H]2[C@@]1(C[C@@H](C3=C4CCC(=O)C=C4CC[C@@H]23)C5=CC=C(C=C5)NC)C)O
InChI InChI=1S/C28H33NO2/c1-4-14-28(31)15-13-25-23-11-7-19-16-21(30)10-12-22(19)26(23)24(17-27(25,28)2)18-5-8-20(29-3)9-6-18/h5-6,8-9,16,23-25,29,31H,7,10-13,15,17H2,1-3H3/t23-,24+,25-,27-,28-/m0/s1 Key:IBLXOBHABOVXDY-WKWWZUSTSA-N

Metapristone (developmental code name RU-42633; also known as desmethylmifepristone) is the major metabolite of mifepristone (RU-486, RU-38486) and a selective progesterone receptor modulator (SPRM) which itself was never marketed. ^{[1] [2] [3] [4]} It is formed from mifepristone in the liver by the enzyme CYP3A4 via monodemethylation, and circulates at concentrations higher than those of mifepristone. ^{[1] [5]} The metabolite retains partial but considerable affinity for the progesterone receptor (PR) and the glucocorticoid receptor (GR) (RBA Tooltip relative binding affinity = 21% and 61% of that of mifepristone for the human forms of these receptors, respectively). ^{[6] [1]} On the basis of actions that are apparently independent of its hormonal activity, metapristone is being researched as a potential cancer metastatic chemopreventive agent. ^{[2] [3] [4]}

References

1. Heikinheimo O (July 1997). "Clinical pharmacokinetics of mifepristone". Clin Pharmacokinet. 33 (1): 7–17. doi:10.2165/00003088-199733010-00002. PMID   9250420. S2CID   25101911.
2. Wang J, Chen J, Wan L, Shao J, Lu Y, Zhu Y, Ou M, Yu S, Chen H, Jia L (March 2014). "Synthesis, spectral characterization, and in vitro cellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486)". AAPS J. 16 (2): 289–98. doi:10.1208/s12248-013-9559-2. PMC   3933578 . PMID   24442753.
3. Wang J, Chen J, Zhu Y, Zheng N, Liu J, Xiao Y, Lu Y, Dong H, Xie J, Yu S, Shao J, Jia L (March 2016). "In vitro and in vivo efficacy and safety evaluation of metapristone and mifepristone as cancer metastatic chemopreventive agents". Biomed. Pharmacother. 78: 291–300. doi:10.1016/j.biopha.2016.01.017. PMID   26898454.
4. Chen W, Xiao Y, Chen J, Liu J, Shao J, Li T, Zhu Y, Ma J, Gao Y, Wang J, Xu J, Lu Y, Jia L (December 2017). "Sex-related pharmacokinetic differences and mechanisms of metapristone (RU486 metabolite)". Sci Rep. 7 (1) 17190. Bibcode:2017NatSR...717190C. doi:10.1038/s41598-017-17225-0. PMC   5719405 . PMID   29215040.
5. United States Pharmacopeial Convention (2006). USP DI: United States Pharmacopeia Dispensing Information. United States Pharmacopeial Convention. p. 1992. ISBN   978-1-56363-574-8.
6. Heikinheimo O, Kekkonen R, Lähteenmäki P (December 2003). "The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action". Contraception. 68 (6): 421–6. doi:10.1016/S0010-7824(03)00077-5. PMID   14698071.