Identification of Anabolic Selective Androgen Receptor Modulators with Reduced Activities in Reproductive Tissues and Sebaceous Glands

    October 2009 in “ Journal of biological chemistry/˜The œJournal of biological chemistry ”
    Azriel Schmidt, Shun Ichi Harada, Donald B. Kimmel, Chang Bai, Fang Chen, Su Jane Rutledge, Robert L. Vogel, Angela Scafonas, Michael A. Gentile, Pascale V. Nantermet, Sheila McElwee-Witmer, Brenda L Pennypacker, P. Masarachia, Soumya P. Sahoo, Yun-Tae Kim, Robert Meißner, George D. Hartman, Mark E. Duggan, Gideon A. Rodan, Dwight A. Towler, William J. Ray
    TLDR Two new compounds were found to build bone and muscle without affecting reproductive organs and skin oil glands.
    The study identified and characterized selective androgen receptor modulators (SARMs), specifically TFM-4AS-1 and FTBU-1, which promoted bone and muscle growth while minimizing effects on reproductive organs and sebaceous glands. TFM-4AS-1 acted as a partial agonist, increasing bone and muscle mass in ovariectomized rats without promoting prostate growth, and showed partial antagonism in prostate and seminal vesicle growth. FTBU-1, a non-steroidal SARM, exhibited similar gene selectivity with improved solubility and no 5α-reductase inhibition, demonstrating anabolic effects on bone with minimal impact on the uterus. These findings suggested that SARMs like TFM-4AS-1 and FTBU-1 could provide safer therapeutic options for conditions like muscle wasting and osteoporosis, avoiding the side effects of traditional androgen therapy.
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