 | |
| Clinical data | |
|---|---|
| Other names | JNJ26146900 |
| Drug class | Selective androgen receptor modulator |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C15H15F3N2O3S |
| Molar mass | 360.35 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
JNJ-26146900 is aselective androgen receptor modulator (SARM) which was developed byJohnson & Johnson for the potential treatment ofprostate cancer but was never marketed.[1][2][3][4][5][6]
The drug is anonsteroidalandrogen receptor (AR)modulator with mixedagonistic (androgenic) andantagonistic (antiandrogenic) effects.[2][6] In animals, it partially preventscastration-induced loss ofbody weight,lean body mass (LBM), and bone (osteopenia orosteoporosis) and reducesprostate weight and prostatetumor growth.[2][6] Thenonsteroidal antiandrogenbicalutamide was also effective in partially preventing castration-induced loss of body weight and lean body mass, suggesting thatit too may have some SARM-like activity in certaintissues.[6] However, neither JNJ-26146900 nor bicalutamide were as effective asdihydrotestosterone (DHT) in terms of these effects.[6] Based on the preceding findings, JNJ-26146900 shows a profile of androgenic andanabolic effects inmuscle and bone but antiandrogenic effects in the prostate.[2][3][4][5][6]The drug is a novelindolederivative SARM and isstructurally related toJNJ-37654032.[2][6]
JNJ-26146900 did not advance past thepreclinical research and was never tested in humans.[1] It was first described in thescientific literature by 2007.[2][3][6]
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).
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.
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.
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].