Onapristone

Onapristone
Clinical data
Synonyms 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
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C29H39NO3
Molar mass 449.635 g/mol
3D model (JSmol)

Onapristone (INN) (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 drug 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]

As of 2016, onapristone has re-emerged and is under development for the treatment of prostate cancer, currently in phase II clinical trials.[8] 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.[8]

See also

References

  1. Lev M. Berstein; Richard J. Santen (4 December 2009). Innovative Endocrinology of Cancer. Springer Science & Business Media. pp. 102–. ISBN 978-0-387-78818-0.
  2. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 903–. ISBN 978-1-4757-2085-3.
  3. I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 207–. ISBN 978-0-7514-0499-9.
  4. 1 2 Edward J. Pavlik (6 December 2012). Estrogens, Progestins, and Their Antagonists: Health Issues. Springer Science & Business Media. pp. 134–. ISBN 978-1-4612-4096-9.
  5. Robertson JF, Willsher PC, Winterbottom L, Blamey RW, Thorpe S (1999). "Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer". Eur. J. Cancer. 35 (2): 214–8. PMID 10448262.
  6. Katkam RR, Gopalkrishnan K, Chwalisz K, Schillinger E, Puri CP (1995). "Onapristone (ZK 98.299): a potential antiprogestin for endometrial contraception". Am. J. Obstet. Gynecol. 173 (3 Pt 1): 779–87. PMID 7573244.
  7. Ismail Jatoi; Manfred Kaufmann (11 February 2010). Management of Breast Diseases. Springer Science & Business Media. pp. 338–. ISBN 978-3-540-69743-5.
  8. 1 2 http://adisinsight.springer.com/drugs/800000877



This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.