Over the past few years, Waverley Pharma has developed a strong PARP-1 inhibitor program, considering the recent concerns highlighted by the FDA. Since PARP-1 selective inhibition is critical, Waverley Pharma’s PARP-1 program focuses on discovering novel potent and selective compound towards PARP-1 inhibition. We have successfully identified several highly potent and selective PARP-1 lead compounds after screening more than 450 compounds synthesized within the project. Many of these compounds have sub-nanomolar or single digit nanomolar IC50 for PARP-1 inhibition as measured by PARP-1 enzymatic assay kits.
Our most promising lead compound,CAWP-1322, features a sub-nanomolar PARP-1 inhibition activity (IC500.03 nM) and 1000-fold selectivity against PARP-2. Preliminary results show good microsomal stability (in both mouse and human liver), high Caco2 bidirectional permeability with low efflux ratio and a suitable selectivity against hERG channel inhibition (IC50 > 11 µM). In addition, CAWP-1322 was also found to inhibit cancer cell colony formation inhibition in adeno lung cancer PDX model LXFA 2184 (IC50 = 1.08 µM). Similarly, two other lead compounds CAWP-1446 and CAWP-1477 also showed promising results in selective PARP-1 inhibition over PARP-2. Structure-activity relationships studies have been carried out as are bio-profiling assays, and PK studies for selected compounds. Herein, we envisioned an opportunity to develop a highly selective and potent PARP-1 inhibitor with desirable pharmacokinetics and safety pharmacology. Waverley Pharma is also actively working to protect the intellectual property space surrounding the compounds of interest from its portfolio and is open to discussion with potential new partners to further develop the lead candidates.
Waverley Pharma is open to collaborations and partnerships for the commercialization of our pipeline. We invite you to learn more about our current pipeline of oncology medications and our future plans.
connect with our team
