Christopher Hulme, PhD
Christopher Hulme completed his D.Phil at Oxford University. Subsequently, he spent 15 years in big pharma, holding positions as head of High-throughput Medicinal Chemistry and Global Head of Platform Library Sciences, spanning RPR, Amgen & Eli Lilly. As such, he established targeted and diversity-oriented screening collections, engaging in over 60 hit-lead and multiple lead optimization campaigns. He joined the University of Arizona in 2007 and has garnered in excess of $20 million during this tenure from public and private sources. Currently, his lab is focused on small molecule and targeted protein degradation discovery paradigms. In particular, the development of small molecule kinase inhibitors is of interest. In 2018 he co-founded Iluminos Therapeutics, currently pushing forward Dyr533 into IND enabling studies for the treatment of Down Syndrome and Alzheimer's Disease through selective inhibition of the kinase Dyrk1a. More recently, with a significant venture capital investment, Dr Hulme co-founded the start-up Branch Therapeutics LLC, whose primary mission is the development of multi-targeted kinase inhibitors towards colo-rectal cancer. The Hulme group trains bona fide student drug hunters in the art of medicinal chemistry and efforts span hit generation through SAR/SPR optimization, in vivo studies and latterly extensive interactions with CDMOs for GLP drug substance manufacturing on a kilo scale. We are always actively looking for students with a strong background in organic chemistry.
Cancer Focus
The group has inhibitors (advanced lead optimization) and degraders of Dyrk1a (pancreatic cancer, neuroblastoma, Collab: Prof. Walter Becker UAachen, Prof. Bill Montfort, UArizona) and Dyrk1b (CRPC, Collab: Prof. Ed Gelmann). Moreover, we have multi-targeted kinase inhibitors of the two major cancer stemness pathways, WNT and PI3K-AKT-mTOR. The WNT activity has been benchmarked versus industry standards, with advanced leads exhibiting superior efficacy and lower toxicity. Noteworthy the PI3K activity of these molecules is alpha-selective. Despite being multi-targeted in nature, key molecules are significantly more kinome selective than other WNT inhibitors, notably abemaciclib and cirtuvivint. (Collab: Prof. Curtis Thorne & Aaron Scott, UArizona, Prof. Sourav Banerjee U. Dundee). The profiles of these molecules afford opportunities toward colorectal, GBM (& DIPG) (Collab: Sourav Banerjee, UDundee, Artak Tovmasyan, Barrow Institute), breast cancer, and liver cancer (Collab: Paul Monga, UPitt). An additional multi-targeted project toward AML has surpassed the cellular activity exhibited by Gilteritinib and due to their unique multi-targeted nature, are expected to be active in gilteritinib resistant cell lines (Collab: Prof J. Carew). The lab has a CMGC kinase chemotype franchise (DYRKs, CLKs, CDKs, HIPKs) established over 13 years with additional composition of matter for inhibitors of cancer-related kinases such as Haspin, FLT3 (+ gain of function mutants), PGFRA/B (+ gain of function mutants), c-KIT, b-RAF (+V600E), IRAK1/3 and PI4kIIIbeta. The group has also discovered novel potent inhibitors of the LBD of AR, which appear to behave as inhibitors of the splice variant Arv7.