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

October 2009 in “ Journal of biological chemistry/The Journal 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

selective androgen receptor modulators SARMs TFM-4AS-1 FTBU-1 androgen receptor partial agonist non-steroidal SARM 5α-reductase inhibition anabolic effects bone growth muscle growth prostate growth seminal vesicle growth ovariectomized rats reproductive organs sebaceous glands 5-alpha-reductase inhibition

Studysummary This study reports that TFM-4AS-1, a selective androgen receptor modulator, promoted bone and muscle growth with reduced effects on reproductive organs in ovariectomized rats.

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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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