This page uses content from Wikipedia and is licensed under CC BY-SA.

RU-58841

RU-58841
RU-58841 structure.svg
Clinical data
Other namesPSK-3841; HMR-3841
Drug classNonsteroidal antiandrogen
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H18F3N3O3
Molar mass369.344 g·mol−1
3D model (JSmol)

RU-58841, also known as PSK-3841 or HMR-3841, is a nonsteroidal antiandrogen (NSAA) which was formerly under investigation by ProStrakan (previously ProSkelia and Strakan) for potential use as a topical treatment for androgen-dependent conditions including acne, pattern hair loss[1], and excessive hair growth.[2][3][4] The compound is similar in structure to the NSAA RU-58642 but contains a different side-chain.[5] These compounds are similar in chemical structure to nilutamide,[6] which is related to flutamide, bicalutamide, and enzalutamide, all of which are NSAAs similarly.[7] RU-58841 can be synthesized either by building the hydantoin moiety or by aryl coupling to 5,5-dimethylhydantoin.[8]

RU-58841 produces cyanonilutamide (RU-56279) and RU-59416 as metabolites in animals.[9] Cyanonilutamide has relatively low affinity for the androgen receptor but shows significant antiandrogenic activity in animals.[9] RU-59416 has very low affinity for the androgen receptor.[9]

Affinities of a selection of androgen receptor
ligands at steroid hormone receptors

Compound AR ER PR GR MR
Metribolone 290 < 0.1 190 4 38
Dihydrotestosterone 180 ? ? ? ?
Testosterone 100 ? ? ? ?
Cyproterone acetate 10 ? ? ? ?
Bicalutamide 1.8 ? ? ? ?
Nilutamide 0.8 ? ? ? ?
Hydroxyflutamide 0.8 ? ? ? ?
RU-59063 300 <0.1 <0.1 <0.1 <0.1
RU-58841 150 ? ? ? ?
RU-58642 46 <0.1 <0.1 <0.1 <0.1
RU-57073 163 <0.1 <0.1 <0.1 <0.1
RU-56187 92 <0.1 <0.1 <0.1 <0.1
Notes: Values are RBAs (%). Reference ligands (100%) were testosterone for the AR, estradiol for the ERα and ERβ, progesterone for the PR, dexamethasone for the GR, and aldosterone for the MR. Sources: See template.

See also

References

  1. ^ "RU58841 studies and information". Anagen.
  2. ^ PSK-3841 (HMR-3841, RU-58841) - AdisInsight
  3. ^ Battmann T, Bonfils A, Branche C, Humbert J, Goubet F, Teutsch G, Philibert D (January 1994). "RU 58841, a new specific topical antiandrogen: a candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism". J. Steroid Biochem. Mol. Biol. 48 (1): 55–60. doi:10.1016/0960-0760(94)90250-X. PMID 8136306.
  4. ^ Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis C, Blume-Peytavi U, Schäfer-Korting M (January 2005). "RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia". Pharmazie. 60 (1): 8–12. PMID 15700772.
  5. ^ Van Dort ME, Jung YW (April 2001). "Synthesis and structure-activity studies of side-chain derivatized arylhydantoins for investigation as androgen receptor radioligands". Bioorg. Med. Chem. Lett. 11 (8): 1045–7. doi:10.1016/s0960-894x(01)00146-9. PMID 11327585.
  6. ^ Poulos GA, Mirmirani P (February 2005). "Investigational medications in the treatment of alopecia". Expert Opin Investig Drugs. 14 (2): 177–84. doi:10.1517/13543784.14.2.177. PMID 15757393.
  7. ^ Elancheran, R.; Maruthanila, V. L.; Ramanathan, M.; Kabilan, S.; Devi, R.; Kunnumakara, A.; Kotoky, Jibon (2015). "Recent discoveries and developments of androgen receptor based therapy for prostate cancer". MedChemComm. 6 (5): 746–768. doi:10.1039/C4MD00416G. ISSN 2040-2503.
  8. ^ Leonard, Matthew J.; Lingham, Anthony R.; Niere, Julie O.; Jackson, Neale R. C.; McKay, Peter G.; Hügel, Helmut M. (2014). "Alternative synthesis of the anti-baldness compound RU58841". RSC Adv. 4 (27): 14143–14148. doi:10.1039/C4RA00332B. ISSN 2046-2069.
  9. ^ a b c Cousty-Berlin D, Bergaud B, Bruyant MC, Battmann T, Branche C, Philibert D (October 1994). "Preliminary pharmacokinetics and metabolism of novel non-steroidal antiandrogens in the rat: relation of their systemic activity to the formation of a common metabolite". J. Steroid Biochem. Mol. Biol. 51 (1–2): 47–55. doi:10.1016/0960-0760(94)90114-7. PMID 7947350.

Further reading