Science
High levels of prostaglandin F2 alpha (PGF2α) are underlying causes of multiple diseases in the uterus, lung, and other organs.The rationale of selective antagonism of the PGF2α pathway as precision therapies for these conditions has been well established; they will work better and are also safer. However, despite three decades of discovery efforts by pharmaceutical companies, there is no approved drug to date that specifically targets the PGF2α pathway. In this backdrop, we have created potent small molecule antagonists of this pathway that have exquisite selectivity, without affecting other essential prostaglandin functions.
Chemistry
The Medical Chemistry team overcame the perennial challenges of insufficient selectivity among a highly similar family of G protein-coupled receptors (GPCR). As a result, we have succeeded in creating a potent and highly selective drug candidate, and backup compounds, ready to be developed into first-in-class medicines for multiple indications.
Pharmacology
Our small molecule selective antagonists of the PGF2α pathway have been comprehensively characterized using the standard battery of pharmacological tools, as well disease relevant studies specific to the PGF2α pathway. Their superior profiles include:
- High potency in inhibiting PGF2α pathway in rodents and humans, at sub-nanomolar range,
- Over 100x selectivity for the PGF2α pathway over other prostaglandin pathways,
- Excellent pharmacokinetics (PK) profile amenable for oral administration,
- Clean safety profile based on extensive in vitro assessments,
- Preclinical efficacy and differentiation potential demonstrated in in vitro, ex vivo (human), and in vivo (animal) models.
