PDE 3, 5, 9 inhibitors

Product Overview

Alternative Name: Phosphodiesterase (PDE) 3, 5, 9 inhibitors, PDE3A

Development Status: Active Development

Target: Female

Mode: Non-hormonal

Delivery Type: TBD

Duration Type: TBD

Description: Phosphodiesterases (PDE) decrease cyclic AMP and GMP levels, and are important regulators of many biologic systems. There are 11 families. Compartmentalization of PDE isoforms exists, such that type 3A is predominant in the oocyte but not in the somatic cells of the follicle. Selectively blocking PDE3 prevents the final maturation of the oocyte without affecting ovulation or menstrual cyclicity. PDE5 (granulosa cells of the developing follicle) and PDE9 (oocyte) participate indirectly preventing the breakdown of cGMP, an endogeneous regulator of PDE3.

Updated date: May 30, 2018

Vertical Tabs

Status

Project Phase: Discovery

Project Stage: Target ID/Validation

Began discovery in: 1999

Status Details:
  • Selective inhibitors of PDE3 have been tested in rodents and in macaques and block oocyte maturation in vitro and in vivo without affecting menstrual cycles or sexual behavior.
  • A contraceptive study has been completed in macaques; no pregnancies occurred with serum levels of the selective PDE3 inhibitor ORG9935 above 300 nmol/L. Dosing was daily oral or once/week depot injection.
  • Poor absorption of the ORG9935 compound led to widely varying serum levels. ORG 9935 is no longer available. A search for new selective inhibitors is currently underway.

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