JNJ-26146900 is a selective androgen receptor modulator (SARM) which was developed by Johnson & Johnson for the potential treatment of prostate cancer but was never marketed.[1][2][3][4][5][6]
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| Other names | JNJ26146900 |
| Drug class | Selective androgen receptor modulator |
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| Formula | C15H15F3N2O3S |
| Molar mass | 360.35 g·mol−1 |
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Description
editThe drug is a nonsteroidal androgen receptor (AR) modulator with mixed agonistic (androgenic) and antagonistic (antiandrogenic) effects.[2][6] In animals, it partially prevents castration-induced loss of body weight, lean body mass (LBM), and bone and reduces prostate weight and prostate tumor growth.[2][6] The nonsteroidal antiandrogen bicalutamide was also effective in partially preventing castration-induced loss of body weight and lean body mass, suggesting that it too may have some SARM-like activity in certain tissues.[6] However, neither JNJ-26146900 nor bicalutamide were as effective as dihydrotestosterone (DHT) in terms of these effects.[6] Based on the preceding findings, JNJ-26146900 shows a profile of androgenic and anabolic effects in muscle and bone but antiandrogenic effects in the prostate.[2][3][4][5][6] The drug is a novel indole derivative SARM and is structurally related to JNJ-37654032.[2][6]
JNJ-26146900 did not advance past the preclinical research and was never tested in humans.[1] It was first described in the scientific literature by 2007.[2][3][6]
See also
editReferences
edit- ^ a b "Delving into the Latest Updates on JNJ-26146900 with Synapse". Synapse. 12 October 2024. Retrieved 22 October 2024.
- ^ a b c d e f Mohler ML, Bohl CE, Narayanan R, He Y, Hwang DJ, Dalton JT, et al. (20 August 2008), Nonsteroidal Tissue-Selective Androgen Receptor Modulators, Methods and Principles in Medicinal Chemistry, Wiley, pp. 249–304, doi:10.1002/9783527623297.ch8, ISBN 978-3-527-31872-8, ISSN 1865-0562,
Several articles characterizing compounds of Template 3 (Figure 8.13), the indoles were recently published with only JNJ26146900 (78) demonstrating tissue-selective activity [178]. JNJ26146900 (78) retains LA weight, but reduces prostate weight in intact animals, and partially offsets castration-induced losses in BMD and LBM. JNJ26146900 blocked testosterone-induced prostate cancer growth and demonstrated favorable activity in a prostate cancer xenograft model using CWR22-LD1 prostate cancer cells (Figure 8.13, top right).
- ^ a b c Bai C, Flores O, Schmidt A (May 2007). "Opportunities for development of novel therapies targeting steroid hormone receptors". Expert Opinion on Drug Discovery. 2 (5): 725–737. doi:10.1517/17460441.2.5.725. PMID 23488961.
Furthermore, SARMs such as JNJ-26146900 that have been shown to antagonize the growth of prostate tumors in animal models while maintaining anabolic effects on bone and muscle may provide an alternative to current therapies in the management of PCa.
- ^ a b Fan P, Jordan VC (24 June 2013). "An Emerging Principle: Selective Nuclear Receptor Modulators". Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health. Imperial College Press. pp. 431–456. doi:10.1142/9781848169586_0016. ISBN 978-1-84816-957-9.
The recently developed compound JNJ-26146900 (Johnson & Johnson Pharmaceutical Research and Development) acts as a pure androgen antagonist of prostate cancer while maintaining anabolic effects on bone and muscle in rats.12 Its profile makes it a strong candidate for consideration as the future antiandrogen SARMs in the treatment of advanced prostate cancer.
- ^ a b Tabbal M, Fuleihan EH (2010). "Future Therapies". Osteoporosis in Men. Elsevier. pp. 713–732. doi:10.1016/b978-0-12-374602-3.00057-2. ISBN 978-0-12-374602-3.
In an intact animal model, an indole SARM, JNJ-26146900, was shown to reduce prostate weight, similarly to the androgen antagonist bicalutamide and, in a mouse xenograft model of prostate cancer, it reduced testosterone-induced prostate growth. The compound also prevented orchidectomy-induced loss of muscle and bone mass and improved material properties of bone as assessed by BV, trabecular connectivity and number [68].
- ^ a b c d e f g h Allan G, Lai MT, Sbriscia T, Linton O, Haynes-Johnson D, Bhattacharjee S, et al. (January 2007). "A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats". The Journal of Steroid Biochemistry and Molecular Biology. 103 (1): 76–83. doi:10.1016/j.jsbmb.2006.07.006. PMID 17049844.