Kinase 2023: 10th SCI / RSC Symposium on Kinase Inhibitor Design

Dr. Amit Choudhary is an Assistant Professor of Medicine at Harvard Medical School, an Associate Biologist at Brigham and Women’s Hospital, and an Associate Member at the Broad Institute. He performed his pre-doctoral studies in Chemistry at Indian Institute of Science‒Bangalore and doctoral studies in Biophysics, where he elucidated a new force akin to the hydrogen bond in its quantum mechanical origin. Subsequently, he was appointed a Junior Fellow of the Harvard Society of Fellows. The efforts of Choudhary laboratory have been recognized by Burroughs Wellcome Fund’s Career Award at the Scientific Interface, NIH Director’s Transformative Research Award, DARPA’s Safe Genes and HEALR awards, Vilcek Prize for Creative Promise, ICBS Young Chemical Biologist Award, and Juvenile Diabetes Research Foundation’s Innovation Award. Dr. Choudhary is a scientific founder of Photys Therapeutics that leverages the group’s findings on bifunctional molecules that induce or remove post-translational modifications.

Dr. Ana Martinez is Research Professor at the Biological Research Center (CIB) of Spanish National Council for Research (CSIC). Her interest is focused on neurodegenerative disorders, leading numerous research projects on the medicinal chemistry and rational drug design of new drugs for Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, spinal cord trauma and multiple sclerosis. Her research is in close contact with biopharmaceutical companies for technology transfer. Since February 2002 till January 2008, she was R&D Director of NeuroPharma, after called NOSCIRA. During this period, two of her research projects reached clinical trials as disease modifying agents for Alzheimer's disease. In 2008, she returned to her academic laboratory where several projects have been developed in a private-public environment. She is author of more than a three hundred scientific publications, more than fourty active patents in the field and editor of several books. She acts as scientific advisory board for several SMEs in the biotech field and recently she is founder of ANKAR PHARMA, which goal is full the gap between basic drug discovery research and clinical trials for neurodegenerative diseases.

Andreas Blum is an Associate Director in Medicinal Chemistry at Merck KGaA in Darmstadt (Germany). He graduated from the Philipps-University Marburg (Germany) in 2007 obtaining his Ph.D. Medicinal Chemistry, followed by a postdoc at Imperial College in London with Prof. Barrett. In 2009, he joined Boehringer Ingelheim in Biberach (Germany) as a lab leader in Medicinal Chemistry, where he worked as team member and project leader for several research projects in cardio-metabolics. At the end of 2016, he moved to Merck KGaA changing his focus to oncology research and was appointed to group leader last year.

Anne Valade is a Director in Medicinal Chemistry at UCB BioPharma in Braine-L’Alleud (Belgium). She graduated from the University of Paris XI (Orsay, France) and obtained her Ph.D. in Organic Chemistry in 2004 with Professor Beau. She joined the UCB Medicinal Chemistry team in 2006 as a Senior Scientist, after a postdoctoral fellowship with Prof. Hodgson at the University of Oxford. At UCB, she has been involved in multiple projects targeting central nervous system (CNS) diseases. She contributed to the identification of several preclinical candidates, including the first clinical SV2A PET ligand, for which she received the EFMC runner-up Prize for a Young Medicinal Chemist in 2016.

Antonio Ricci is a Principal Scientist and Group Leader in the Medicinal Chemistry department at F. Hoffmann- La Roche in Basel (CH). He joined the Medicinal Chemistry department in 2003 as research associate and moved through different ranks up to the position of a research scientist. Antonio is a passionate drug hunter with major contributions to late stage projects, e.g. the discovery of Basimglurant, a promising novel medicine for psychiatric diseases. His recent research is focusing on oncology, in particular cancer cell targeted therapies.

Bryan is a Principal Scientist in the Discovery Chemistry department at Genentech (US). He obtained his M.Sc. in organic chemistry at the University of British Columbia (Canada). Since joining Genentech in 2009, Bryan has been involved in multiple kinase programs such as LRRK2 (for neurodegenerative diseases), EGFR (for oncology) and HPK1 (for cancer immunology). He is currently supporting small molecule drug discovery programs as a project team or chemistry team leader. For his contributions to the field of organic and medicinal chemistry, Bryan was a recipient of the 2022 American Chemical Society Technical Achievements Award in Organic Chemistry.

Generative AI design has established itself as a tool to efficiently perform drug discovery. Two major questions still remain. One, how broadly can AI design methods be applied across target space. Two, how complex can the desired profile of AI designed molecules be. Recent work has shown the use of AI design for targets using 2D data driven approaches and for relatively simple property optimisation. In this work we show how AI can be applied and scaled using 3D structures to deliver complex property profiles. First, we show that our target tractability platform can scale to proteome wide analysis in a few hours and for less than the cost of an iPhone. We show the analysis on the human kinome - and highlight the need for improved structural models including flexibility. Second, we demonstrate that this system, coupled with our generative design capability, can scalably produce highly-potent (<100 nM) and novel starting points, which we show across 3 kinase targets. We show areas of the approach that could be further enhanced such as for protein structure quality and highlight new avenues for developing improved selectivity in molecules. Finally, we showcase our capability on the design of our clinical candidate for CDK7, GTAEXS617, designed in <12 months and in 136 experimental compounds. We talk through the design of the molecule and the differentiated biological response to other CDK7 inhibitors.

Daniel Lietha is a structural biologist interested in kinase structure and regulation. He did his postdoctoral work with Prof. M.J. Eck at the Dana-Faber Cancer Institute, Harvard Medical School (USA). In 2009 he started his independent research, first at the Spanish National Cancer Research Centre (CNIO, Madrid) and since 2019 at the Margarita Salas Center for Biological Research (CIB-CSIC, Madrid). His research focuses on understanding the structure and mechanisms of signalling complexes involved in cell migration and cancer invasion. He further utilizes structural and mechanistic insights for allosteric drug discovery aiming to target native regulatory sites with high specificity.

Rehan Aqil is a Principal Scientist in Medicinal Chemistry at Domainex. He graduated from King’s College London and obtained his PhD in organic chemistry with Professor William B. Motherwell at University College London (2002). Rehan has worked on a number of kinase programmes over his career including IKKε/TBK1 dual inhibitors for oncology and was the lead chemist in developing MAP4K4 kinase inhibitors for cardioprotection, following myocardial infarction. In addition, he led the back-up series team on the Tankyrase inhibitor programme which was successfully licensed to Merck Soreno, by Domainex’s client, ICR. His recent work has focused on covalent inhibitors targeting cardiac fibrosis.

Ryan joined Bristol Myers Squibb (BMS) in 2010 where he was given an ambitious side project looking at inhibiting TYK2 via the pseudokinase by his supervisor and eventual mentor David Weinstein. Said project culminated in their invention of the first ever clinical agent to target a pseudokinase domain (deucravacitinib). For this invention Ryan and the TYK2 pseudokinase chemistry team were recognized with the 2019 Thomas A. Edison Patent award. Ryan was also recognized as a 2020 ACS Young (Industrial) Investigator and has served as a researcher advocate for PhRMA (GoBoldly) and as a patient (psoriasis) advocate within BMS.

Sam joined the University of Manchester as a Senior Lecturer in Medicinal Chemistry in November 2016. Prior to this he worked at the University of Birmingham from 2013 and at AstraZeneca from 2005-2013. During this time he has been accountable for chemistry strategy and delivery for all phases of drug discovery projects from target review and hit generation, through to lead optimisation and pre-clinical development. His work at AstraZeneca led to the development of a targeted anti-cancer agent osimertinib that was approved by the FDA in November 2015, and along with his colleagues Sam has been recognised for this work through the 2017 RSC Malcolm Campbell Award and the 2018 ACS Heroes of Chemistry award.

Simon has completed his Degree & PhD at the University of Sheffield and then joined GlaxoWellcome in 1998. He is now Scientific Director (Medicinal Chemistry) at GlaxoSmithkline, Stevenage with roles including project leader and subject matter expert. He has over 18 years experience working with SCI, organising events and helping to develop the scientific community.

Sophie is a team leader in the Medicinal Chemistry department in Stevenage (UK). She joined GSK in 2006, following her graduation from CPE Lyon in France with a Masters degree in Chemical Sciences and Engineering. In 2011, she entered the GSK/Strathclyde PhD programme under the supervision of Dr Craig Jamieson, from which she graduated in 2015. For the past 17 years, Sophie has worked on a variety of targets across multiple disease areas, from fragment-based drug discovery approaches all the way to late lead optimisation. She led the PI4KB medicinal chemistry team that delivered a first in class inhaled clinical candidate for the prevention of rhinoviral-driven exacerbations in respiratory diseases.

Bill received his D.Phil in organic chemistry working in lab of Prof. Sir Jack Baldwin at the University of Oxford in 1996. After postdoctoral research with Prof. Jeff Winkler and Prof. Franklin Davis in Philadelphia he returned to the UK and joined AstraZeneca in 2000. He worked first at the Alderley Park, Macclesfield site before moving to Cambridge, UK in 2015 where he is currently a Director in Oncology chemistry. Bill has worked in several therapy areas, across various drug modalities in all stages of drug discovery and is the author of over than 30 patents and publications.