DIMP (antiandrogen) explained

DIMP (developmental code name Ro 7-8117), or N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide, is a nonsteroidal antiandrogen (NSAA) structurally related to thalidomide (which also binds to and antagonizes the androgen receptor (AR))^{[1] [2] [3]} that was first described in 1973 and was never marketed.^[4] Along with flutamide, it was one of the earliest NSAAs to be discovered,^[5] and for this reason, has been described as a "classical" NSAA. The drug is a selective, competitive, silent antagonist of the AR,^[6] although it is described as an "only relatively weak competitor".^{[7] [8]} Its relative binding affinity for the androgen receptor is about 2.6% of that of metribolone.^[9] DIMP possesses no androgenic, estrogenic, progestogenic, or antigonadotropic activity, but it does reverse the antigonadotropic effects of testosterone, indicating that, like other pure AR antagonists, it is progonadotropic.

DIMP is the lead antiandrogen of the phthalimide group of nonsteroidal AR ligands, and a variety of AR ligands with higher affinity for the AR have been derived from DIMP and thalidomide.^{[10] [11]}

See also

• AA560
• BOMT

Notes and References

1. Hashimoto Y, Tanatani A, Nagasawa K, Miyachi H . Thalidomide as a multitarget drug and its application as a template for drug design. Drugs of the Future. 29. 4. 2004. 383. 0377-8282. 10.1358/dof.2004.029.04.792298.
2. Liu B, Su L, Geng J, Liu J, Zhao G . Developments in nonsteroidal antiandrogens targeting the androgen receptor . ChemMedChem . 5 . 10 . 1651–1661 . October 2010 . 20853390 . 10.1002/cmdc.201000259 . 23228778 .
3. Hashimoto Y . Structural development of synthetic retinoids and thalidomide-related molecules . Cancer Chemotherapy and Pharmacology . 52 . Suppl 1 . S16–S23 . July 2003 . 12819930 . 10.1007/s00280-003-0590-3 . 22663471 .
4. Boris A, Scott JW, DeMartino L, Cox DC . Endocrine profile of a nonsteroidal antiandrogen N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide (DIMP) . Acta Endocrinologica . 72 . 3 . 604–614 . March 1973 . 4739363 . 10.1530/acta.0.0720604 .
5. Book: Singhal RL, Thomas JA . Cellular Mechanisms Modulating Gonadal Action. 1 January 1976. University Park Press. 978-0-8391-0776-7. 239.
6. Ahlin K, Forsberg JG, Jacobsohn D, Thore-Berger B . The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy . Archives d'Anatomie Microscopique et de Morphologie Expérimentale . 64 . 1 . 27–44 . 1975 . 1217898 .
7. Heyns W, Verhoeven G, De Moor P . Androgen binding in rat uterus cytosol. Study of the specificity . Journal of Steroid Biochemistry . 7 . 5 . 335–343 . May 1976 . 180344 . 10.1016/0022-4731(76)90092-3 .
8. Book: Rasmusson GH . Chemical control of androgen action. . January 1986 . 21 . 179-188 (182) . Daily PM, Pawsen PA . Annual Reports in Medicinal Chemistry. https://books.google.com/books?id=qsFCGskRHZQC&pg=PA182 . Academic Press . 978-0-08-058365-5 .
9. Wakeling AE, Furr BJ, Glen AT, Hughes LR . Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens . Journal of Steroid Biochemistry . 15 . 355–359 . December 1981 . 7339263 . 10.1016/0022-4731(81)90297-1 .
10. Gao W, Bohl CE, Dalton JT . Chemistry and structural biology of androgen receptor . Chemical Reviews . 105 . 9 . 3352–3370 . September 2005 . 16159155 . 2096617 . 10.1021/cr020456u .
11. Kaur P, Khatik GL . Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer . Mini Reviews in Medicinal Chemistry . 16 . 7 . 531–546 . 2016 . 26776222 . 10.2174/1389557516666160118112448 .