MK-4541 explained

Routes Of Administration:Oral
Class:Selective androgen receptor modulator
5α-Reductase inhibitor
Cas Number:796885-38-6
Pubchem:59691338
Drugbank:DB17016
Chemspiderid:88298114
Synonyms:MK4541
Iupac Name:2,2,2-trifluoroethyl N-[(1''S'',3''aS'',3''bS'',5''aR'',9''aR'',9''bS'',11''aS'')-6,9''a'',11''a''-trimethyl-7-oxo-2,3,3''a'',3''b'',4,5,5''a'',9''b'',10,11-decahydro-1''H''-indeno[5,4-f]quinolin-1-yl]carbamate
C:22
H:31
F:3
N:2
O:3
Smiles:C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2NC(=O)OCC(F)(F)F)CC[C@@H]4[C@@]3(C=CC(=O)N4C)C
Stdinchi:1S/C22H31F3N2O3/c1-20-10-8-15-13(4-7-17-21(15,2)11-9-18(28)27(17)3)14(20)5-6-16(20)26-19(29)30-12-22(23,24)25/h9,11,13-17H,4-8,10,12H2,1-3H3,(H,26,29)/t13-,14-,15-,16-,17+,20-,21+/m0/s1
Stdinchikey:OGBFNZPDLOPGEO-OCWMMRLVSA-N

MK-4541 is a dual selective androgen receptor modulator (SARM) and 5α-reductase inhibitor (5α-RI) which has been of interest for the potential treatment of prostate cancer but has not been marketed at this time.[1] [2] [3] [4] It is intended for use by mouth.

The drug is a steroidal androgen receptor (AR) modulator with mixed agonistic (androgenic) and antagonistic (antiandrogenic) effects. In preclinical research and animal studies, MK-4541 has been found to have androgenic or anabolic effects in muscle and bone, to strongly suppress testosterone levels (likely via androgenic antigonadotropic effects), and to have antiandrogenic effects in the prostate and in prostate cancer cells.[5] [6] Structurally, it is specifically a 4-azasteroid derivative.

MK-4541 was first described in the scientific literature by 2014.[7] [8] It was identified by screening of 3,000 compounds that were manually designed and predicted to have SARM activity.[9] The drug was developed by Merck. It might be being developed for potential medical use, but its developmental status has not been publicly disclosed. In any case, MK-4541 is not known to have advanced past preclinical studies as of 2020.

See also

Notes and References

  1. Web site: MK-4541: Uses, Interactions, Mechanism of Action . DrugBank Online . 26 September 2022 . 22 October 2024.
  2. Fonseca GW, Dworatzek E, Ebner N, Von Haehling S . Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials . Expert Opinion on Investigational Drugs . 29 . 8 . 881–891 . August 2020 . 32476495 . 10.1080/13543784.2020.1777275 .
  3. Christiansen AR, Lipshultz LI, Hotaling JM, Pastuszak AW . Selective androgen receptor modulators: the future of androgen therapy? . Translational Andrology and Urology . 9 . Suppl 2 . S135–S148 . March 2020 . 32257854 . 7108998 . 10.21037/tau.2019.11.02 . free .
  4. Lena A, Anker MS, Springer J . Muscle Wasting and Sarcopenia in Heart Failure-The Current State of Science . International Journal of Molecular Sciences . 21 . 18 . 6549 . September 2020 . 32911600 . 7555939 . 10.3390/ijms21186549 . MK-4541 [130], an androgen receptor agonist with 5α-reductase inhibitor function, exhibited anabolic effects and improvement of muscle function in castrated male mice. . free .
  5. Birudukota N, Mudgal MM, Shanbhag V . Discovery and development of azasteroids as anticancer agents . Steroids . 152 . 108505 . December 2019 . 31568765 . 10.1016/j.steroids.2019.108505 .
  6. Solomon ZJ, Mirabal JR, Mazur DJ, Kohn TP, Lipshultz LI, Pastuszak AW . Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications . Sexual Medicine Reviews . 7 . 1 . 84–94 . January 2019 . 30503797 . 6326857 . 10.1016/j.sxmr.2018.09.006 . Likewise, work by Schmidt et al. focused on MK-4541, which induces Caspase-3 activity and apoptosis in androgen independent AR positive prostate cancer cell lines while sparing AR- and AR + non-prostate cancer cells.[25] Chisamore et al. also demonstrated that administration of MK-4541 resulted in a decrease in plasma testosterone levels, likely through AR-mediated negative feedback signaling through the hypothalamic-pituitary-gonadal axis.[13] .
  7. Schmidt A, Meissner RS, Gentile MA, Chisamore MJ, Opas EE, Scafonas A, Cusick TE, Gambone C, Pennypacker B, Hodor P, Perkins JJ, Bai C, Ferraro D, Bettoun DJ, Wilkinson HA, Alves SE, Flores O, Ray WJ . Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells . The Journal of Steroid Biochemistry and Molecular Biology . 143 . 29–39 . September 2014 . 24565564 . 10.1016/j.jsbmb.2014.02.005 .
  8. Chisamore MJ, Gentile MA, Dillon GM, Baran M, Gambone C, Riley S, Schmidt A, Flores O, Wilkinson H, Alves SE . A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice . The Journal of Steroid Biochemistry and Molecular Biology . 163 . 88–97 . October 2016 . 27106747 . 10.1016/j.jsbmb.2016.04.007 .
  9. Li D, Zhou W, Pang J, Tang Q, Zhong B, Shen C, Xiao L, Hou T . A magic drug target: Androgen receptor . Medicinal Research Reviews . 39 . 5 . 1485–1514 . September 2019 . 30569509 . 10.1002/med.21558 . In literatures, a group of nonsteroidal SARMs (eg, RAD140 [36],153 MK‐4541 [37],154 and BA321 [38] 155) have been reported. [...] MK‐4541 was screened out from 3000 manually designed SARMs by biological experiments established to distinguish AR antagonists in PCa therapy, and then further verified by its anabolic activity.152,156 .

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