From Wikipedia, the free encyclopedia
Chemical compound
Onapristone
Other names ZK-89299; ZK-299; AR-18; IVV-1001; 11β-(4-(Dimethylamino)phenyl)-17α-hydroxy-17β-(3-hydroxypropyl)-13α-estra-4,9-dien-3-one
Drug class
Antiprogestogen
(8S ,11R ,13R ,14S ,17S )-11-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a ]phenanthren-3-one
CAS Number
PubChem
CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.233.493
Formula C 29 H 39 N O 3
Molar mass 449.635 g·mol−1 3D model (
JSmol )
C[C@@]12C[C@@H](C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]1CC[C@@]2(CCCO)O)C5=CC=C(C=C5)N(C)C
InChI=1S/C29H39NO3/c1-28-18-25(19-5-8-21(9-6-19)30(2)3)27-23-12-10-22(32)17-20(23)7-11-24(27)26(28)13-15-29(28,33)14-4-16-31/h5-6,8-9,17,24-26,31,33H,4,7,10-16,18H2,1-3H3/t24-,25+,26-,28+,29+/m0/s1
Key:IEXUMDBQLIVNHZ-YOUGDJEHSA-N
Onapristone (
INN Tooltip International Nonproprietary Name ) (developmental code names ZK-89299 , ZK-299 ) is a
synthetic and
steroidal
antiprogestogen with additional
antiglucocorticoid activity which was developed by
Schering
[1] and described in 1984 but was never marketed.
[2]
[3] It is a
silent antagonist of the
progesterone receptor (PR), in contrast to the related antiprogestogen
mifepristone (which is a weak
partial agonist of the
receptor ).
[4] Moreover, compared to mifepristone, onapristone has reduced antiglucocorticoid activity, shows little
antiandrogenic activity, and has 10- to 30-fold greater
potency as an antiprogestogen.
[4] The medication was under development for clinical use, for instance in the treatment of
breast cancer and as an
endometrial
contraceptive , but was discontinued during
phase III
clinical trials in 1995 due to findings that
liver function abnormalities developed in a majority patients.
[5]
[6]
[7]
Onapristone has been found to be effective in the treatment of
breast cancer .
[8]
[5]
[9]
As of 2016, onapristone has re-emerged and is under development for the treatment of
prostate cancer , currently in
phase II
clinical trials .
[10] It was also under development for the treatment of
endometrial cancer , breast cancer,
ovarian cancer , and
uterine cancer , but was discontinued for these indications in favor of focusing on prostate cancer.
[10]
See also
References
^ Lange CA, Sartorius CA, Abdel-Hafiz H, Spillman MA, Horwitz KB, Jacobsen BM (2008). "Progesterone receptor action: translating studies in breast cancer models to clinical insights". Advances in Experimental Medicine and Biology . Vol. 630. Springer. pp. 94–111.
doi :
10.1007/978-0-387-78818-0_7 .
ISBN
978-0-387-78817-3 .
PMID
18637487 .
Onapristone , p. 102, at
Google Books
^ Elks J, Ganellin CR (1990). "O". Dictionary of Drugs . Springer. pp. 892–927.
doi :
10.1007/978-1-4757-2085-3_15 .
ISBN
978-1-4757-2087-7 .
Onapristone , p. 903, at
Google Books
^ Morton IK, Hall JM (1999). "O". Concise Dictionary of Pharmacological Agents . Springer. pp. 206–213.
doi :
10.1007/978-94-011-4439-1_14 .
ISBN
978-94-010-5907-7 .
Onapristone , p. 207, at
Google Books
^
a
b Pavlik EJ, Nelson K, Srinivasan S, Depriest PD, Kenady DE (1997). "Antiestrogen Resistance in Human Breast Cancer". Estrogens, Progestins, and Their Antagonists . Hormones in Health and Disease. Birkhäuser. pp. 115–160.
doi :
10.1007/978-1-4612-4096-9_5 .
ISBN
978-1-4612-8650-9 .
Onapristone , p. 134, at
Google Books
^
a
b Robertson JF, Willsher PC, Winterbottom L, Blamey RW, Thorpe S (February 1999). "Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer". European Journal of Cancer . 35 (2): 214–218.
doi :
10.1016/S0959-8049(98)00388-8 .
PMID
10448262 .
^ Katkam RR, Gopalkrishnan K, Chwalisz K, Schillinger E, Puri CP (September 1995). "Onapristone (ZK 98.299): a potential antiprogestin for endometrial contraception". American Journal of Obstetrics and Gynecology . 173 (3 Pt 1): 779–787.
doi :
10.1016/0002-9378(95)90341-0 .
PMID
7573244 .
^ Howell SJ, Howell A (2010). "Endocrine Therapy". Management of Breast Diseases . Springer. pp. 329–352.
doi :
10.1007/978-3-540-69743-5_18 .
ISBN
978-3-540-69742-8 .
Onapristone , p. 338, at
Google Books
^ Klijn JG, Setyono-Han B, Foekens JA (2000). "Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer". Steroids . 65 (10–11): 825–830.
doi :
10.1016/S0039-128X(00)00195-1 .
PMID
11108894 .
S2CID
25524094 .
^ Cottu PH, Bonneterre J, Varga A, Campone M, Leary A, Floquet A, et al. (2018).
"Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers" . PLOS ONE . 13 (10): e0204973.
Bibcode :
2018PLoSO..1304973C .
doi :
10.1371/journal.pone.0204973 .
PMC
6179222 .
PMID
30304013 .
^
a
b
"Onapristone - Context Therapeutics" . Adis Insight . Springer Nature Switzerland AG.
GR Tooltip Glucocorticoid receptor
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins:
6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
Chloroethynylnorgestrel
Cingestol
Danazol
Desogestrel
Dienogest
Ethinylandrostenediol
Ethisterone
Ethynerone
Etonogestrel
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel
Levonorgestrel esters (e.g.,
levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g.,
norethisterone acetate ,
norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids:
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione
Dimethisterone
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g.,
nandrolone decanoate ,
nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g.,
trenbolone acetate ,
trenbolone enanthate )
Trendione
Trestolone
Trestolone acetate
Mixed (
SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )