This is an exciting time for small molecule drug discovery and soon for patients, who have been underserved by current treatment approaches. In the past year alone, we’ve seen the emergence of a number of new companies and investments like Arvinas, Kymera Therapeutics and C4 Therapeutics, companies that are pioneering a new field called targeted protein degradation (PROTAC). And companies like HotSpot Therapeutics, Relay Therapeutics, Revolution Medicine and Black Diamond Therapeutics, are pursuing novel discovery platforms to target allosteric sites that expand our ability to treat disease.

Allosteric drug discovery is not new. Anyone involved in central nervous system (CNS) or GPCR-related research exclusively inhabits an allosteric world. What’s striking today is the number of new and different approaches that promise to greatly extend the scope of allostery to new target classes and disease areas. At the same time, the medical benefits of allosteric drug discovery are becoming clear, especially in the field of oncology. The potential for clinical cures with Novartis’ BCR-ABL targeted asciminib is exciting while firsocostat, developed by Gilead / Nimbus Therapeutics, has overcome challenges associated with the active site approaches to targeting Acetyl CoA Carboxylase (ACC).

We announced the founding and Series A financing of HotSpot Therapeutics in July 2018 to pursue the systematic identification and discovery of allosteric mechanisms used by Nature to control proteins. The response has been incredible. The resulting discussions with the pharma community and press have made it clear that there is a lot of pent up demand for small molecule innovation. Beyond the obvious questions such as “what is allosteric drug discovery?”, many are interested in the approaches used to discover these molecules; which disease biology might now be accessible; and why the molecules are superior to active site inhibitors.

In response, HotSpot is launching a new blog called Allokraft, showcasing the most compelling innovations in allosteric small molecule drug discovery.

Allokraft will go well beyond HotSpot’s programs and approach. As such, we will be hosting a series of leaders in the field of allostery to share their thoughts on the future of allosteric drug discovery. In each post we aim to highlight the big-picture relevance of how allostery is changing the way drug discovery is conducted and the impact that these medicines are expected to have on patients. The name Allokraft was chosen to convey the allosteric topic matter while emphasizing the fact that small molecule drug discovery remains a highly tailored, bespoke exercise that even today relies upon the insights of experienced drug hunters.

We hope that you enjoy our posts and welcome any feedback and topic suggestions in the blog’s comments section below.