Research And Grants

Leveraging Open Science and Collaboration to Identify Clinical Quality ALK2 Inhibitors for DIPG

Diffuse intrinsic pontine glioma (DIPG) is a rare, fatal brain cancer for which there are no good treatments.  Part of the problem is that, doing business as business is currently done, there are no financial incentives for discovering medicines for DIPG. Traditional companies see that potential for return on investment is low due to the high failure rate of medicines in the clinic, the low patient population, and the added difficulties of treating children.  Financial incentives should not be the barrier that stops the identification of life saving medicines: the need for effective treatments for these children is paramount. Since current business models do not support DIPG drug discovery, new business models are clearly needed, and this is a key to our approach. We are part of a global team, working under the umbrella of M4K pharma, using open science and collaboration to revolutionize the way affordable new medicines are discovered and developed. Kinases are important and attractive drug targets, and over 80 kinase inhibitors have been approved by the FDA for clinical use. Evidence suggests that the kinase ALK2 is an excellent target for DIPG drug discovery. Our goal is to advance an ALK2 inhibitor into clinical trials.

Our M4K team has identified a selection of high quality ALK2 inhibitors and are triaging them to determine whether we have a suitable clinical candidate that meets our high standards. These include excellent ALK2 inhibitory potency in cells, high selectivity over other kinases, and chemical properties that will allow for oral dosing, safety, and delivery of high concentration to the region of the brain where the tumor is located.  In parallel to our ongoing analysis of current compounds, we are designing and making new inhibitors of ALK2 in case no current compound meets our high standards, and to provide a backup compound if we determine that we already have a compound that is suitable for advancement. This application, “Leveraging open science and collaboration to identify clinical quality ALK2 inhibitors for DIPG” seeks funding to help us with our goal of discovering effective, safe, and affordable medicines for DIPG patients. The Drewry lab seeks funding for two specific aims. In aim 1 we will screen ALK2 inhibitors from all M4K partners in our state-of-the-art NanoBRET cellular assays, for both our primary target ALK2, and off target kinases that we need to have selectivity over. The data generated in this assay is critical to our overall mission. In aim 2 we will design, synthesize, and evaluate new compounds designed to be address issues and potential issues in our current compounds.