RAR Antagonists

Alternative Name: Retinoic acid receptor (RAR) antagonists

Description: Vitamin A (dietary retinol) is essential for normal spermatogenesis. Defects in spermatogenesis (as a result of RARa knock-out) include failure of spermatids to align and be released into the lumen, and presumably reflecting aberrant orientation to the Sertoli cells. However, the molecular mechanisms underlying retinol regulation of spermatogenesis remain to be elucidated.

Target

Product Details

User: Male

Hormonal: No

Duration Type: Short-acting

Role in reproduction: Spermatogenesis

Multipurpose Preventive Technology (MPT): No

Status Details

Developer: NICHD, Columbia University, University of Washington, University of Minnesota

Project Phase: Discovery and Early Development

Development Stage: Target Validation

Active Development: Yes

Status Details:
  • Target has been validated in knock-out mice models. RAR knockout model exhibited male sterility and aberrant spermatogenesis. Potential lead compounds specific to the individual receptors have been identified and synthesized. Testing of a potential lead compound induced sterility in vivo in a time dependent manner.
  • BMS-189453 is a synthetic retinoid that acts as a panantagonist for all three RARs.

Additional Information

References:
  • Chung SS, et al. (2011) Oral administration of a retinoic acid receptor antagonist reversibly inhibits spermatogenesis in mice. Endocrinology. 152(6): 2492-2502.

  • Chung SS, et al. (2009) Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis. Development. 136(12): 2091-100.

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