Abiraterone

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Abiraterone
175px
219px
Systematic (IUPAC) name
(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(pyridin-3-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
Identifiers
CAS Number 154229-19-3
ATC code none
PubChem CID 132971
ChemSpider 117349
Chemical data
Formula C24H31NO
Molar mass 349.509 g/mol[[Script error: No such module "String".]]
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Abiraterone is a drug currently under investigation for use in castration-resistant prostate cancer (formerly hormone-resistant or hormone-refractory prostate cancer) (prostate cancer not responding to androgendeprivation or treatment with antiandrogens).

It blocks the formation of testosterone by inhibiting CYP17A1 (CYP450c17), an enzyme also known as 17α-hydroxylase/17,20 lyase.[1] This enzyme is involved in the formation of DHEA and androstenedione, which may ultimately be metabolized into testosterone.

This drug was initially discovered and developed at the Institute of Cancer Research in London. Cougar Biotechnology is the biotechnology company conducting the research.[2] It has been announced that Cougar will be acquired by Johnson & Johnson in 2009. Subsequent to merger, J&J will conduct trials.[3]

Clinical studies

The first study run at the Royal Marsden Hospital, London, in patients who had not received chemotherapy reported in 2007 that abiraterone acetate induced decline in prostate specific antigen (PSA) in up to 70% of patients as well as radiological shrinkage of tumors, symptom improvement, normalization of lactate dehydrogenase.[4] However others cautioned in 2008 that it was too early to know whether abiraterone treatment will have long term benefit.[5][6]

Results of two Phase II trials indicate that abiraterone may reduce prostate specific antigen (PSA) levels, as well as shrink tumors.[7] Many of the 21 men in the Phase II trial reported significant improvements in their quality of life and several were able to stop taking morphine, used to control the pain caused after the cancer spread into their bones.[8] On average, progression-free survival (PFS) was prolonged by 161 days in patients which had been treated with chemotherapy, and by 236 days in chemotherapy naive patients.[9]

A Phase III trial in subjects previously treated with docetaxel started in 2008 and is now closed to accrual.[10] A placebo-controlled randomized phase III clincal trial in patients with castration-refractory prostate cancer who are chemotherapy-naive opened to accrual in April 2009.[11] Encouraging results to be presented in Oct 2010.[12]

A Phase I/II clinical trial evaluating abiraterone acetate in advanced breast cancer patients is also underway.[12]

References

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News reports

See also

  • MDV3100, an oral anti-androgen currently being tested in a phase III clinical trial for use in hormone-refractory prostate cancer (HRPC)
  • TOK-001, a small molecule, oral drug, that is both an androgen receptor antagonist and CYP17 inhibitor (a combination MOA of abiraterone and mdv3100). Currently being tested in early phase I/II clinical trials for HRPC and sponsored by Tokai Pharmaceuticals.
Agonist
SARM
Antiandrogen
Enzyme inhibitors
CYP17A1 inhibitors
Abiraterone
de:Abirateron pt:Abiraterone
  1. ↑ Attard G, Belldegrun AS, de Bono JS (2005). "Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer". BJU Int. 96 (9): 1241–6. doi:10.1111/j.1464-410X.2005.05821.x. PMID 16287438. 
  2. ↑ "Abiraterone Acetate (CB7630)". Research and Development Pipeline. Cougar Biotechnology, Inc. Retrieved 2008-08-20. 
  3. ↑ "Johnson & Johnson Announces Definitive Agreement to Acquire Cougar Biotechnology, Inc". Press Release. Cougar Biotechnology, Inc. 2009-05-11. Retrieved 2009-06-03. 
  4. ↑ Attard G, Reid AHM, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper CS, Kaye SB, Dearnaley D, Lee G, de Bono JS (2008). "Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven". Journal of Clinical Oncology. 26 (28): 4563. doi:10.1200/JCO.2007.15.9749. PMID 18645193. 
  5. ↑ Cole A (2008). "Cancer expert doubts claims about prostate cancer trial". BMJ. 337: a979. doi:10.1136/bmj.a979. PMID 18653636. 
  6. ↑ Attard G, Reid AH, Dearnaley D, De Bono JS (2008). "New prostate cancer drug: Prostate cancer's day in the sun". BMJ. 337: a1249. doi:10.1136/bmj.a979. PMID 18694888. 
  7. ↑ "Hormone inhibitor promising for hard-to-treat prostate cancer". Press release. European Society for Medical Oncology. 2007-07-08. Retrieved 2008-07-22. 
  8. ↑ "Drug for deadly prostate cancer". Health. BBC NEWS. 2008-07-21. Retrieved 2008-08-20. 
  9. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. edit
  10. ↑ "NCT00638690". ClinicalTrials.gov. Retrieved 2008-08-22. Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy 
  11. ↑ "NCT00887198". ClinicalTrials.gov. Retrieved 2009-12-29. Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer 
  12. ↑ 12.0 12.1 http://www.genengnews.com/gen-news-highlights/btg-and-ortho-biotech-s-prostate-cancer-trial-unblinded/81243905/
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