Nicholas Cosford, Ph.D.
Research Assistant Professor(s)
Nicholas Cosford's Research Focus
We are interested in investigating the interactions of small molecule compounds with therapeutically important proteins and cellular signaling pathways. One aspect of our research emphasizes the use of medicinal chemistry and chemical biology approaches to probe intracellular pathways that regulate cell survival and cell growth. Another area of active research is the development of synthetic chemistry methodology using microfluidic technology for the rapid synthesis of biologically active small molecules. Therapeutically, we are primarily focused on the discovery and optimization of compounds that have the potential to treat cancer, CNS diseases and infectious diseases.
Nicholas Cosford's Bio
Dr. Cosford obtained his B.Sc. in chemistry from the University of Bath in England and his Ph.D. in organic chemistry from Emory University in Atlanta. As a medicinal chemist with more than 25 years of experience leading small-molecule drug discovery and hit-to-lead optimization projects, he worked in both biotech and big pharma prior to joining SBP in 2005.
At Sibia Neurosciences and at Merck Research Laboratories, he directed multidisciplinary research teams focused on small-molecule hit-to-lead optimization and was responsible for moving several lead compounds through to the clinical phase. Examples include taking a nicotinic receptor agonist from initiation of research through to Phase II clinical; taking mGlu5 negative allosteric modulators (NAMs) from HTS hits through in vivo proof-of-concept to Phase I/II (ongoing); design, synthesis and optimization of an mGlu5 PET tracer clinical candidate; and design, synthesis and optimization of an Akt allosteric inhibitor preclinical candidate that led to MK2206. To date, Dr. Cosford’s research has resulted in more than 90 peer-reviewed scientific publications, more than 40 issued patents, and more than 40 additional patent applications pending.
In 2006, he received the FRAXA Foundation Award for Outstanding Contributions to Fragile X Research. His ongoing industry alliances include serving as a scientific advisor to CalAsia Pharmaceuticals, which seeks to accelerate academic discoveries into treatments for unmet medical needs, and to TumorGen MDx, where he has helped design a microchip to detect the presence of cancer stem cells.
Publications
Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates.
Egan DF, Chun MG, Vamos M, Zou H, Rong J, Miller CJ, Lou HJ, Raveendra-Panickar D, Yang CC, Sheffler DJ, Teriete P, Asara JM, Turk BE, Cosford ND, Shaw RJ
Mol Cell 2015 Jul 16 ;59(2):285-97
Characterization of Potent SMAC Mimetics that Sensitize Cancer Cells to TNF Family-Induced Apoptosis.
Welsh K, Milutinovic S, Ardecky RJ, Gonzalez-Lopez M, Ganji SR, Teriete P, Finlay D, Riedl S, Matsuzawa S, Pinilla C, Houghten R, Vuori K, Reed JC, Cosford ND
PLoS One 2016 ;11(9):e0161952
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.
Dhanya RP, Sheffler DJ, Dahl R, Davis M, Lee PS, Yang L, Nickols HH, Cho HP, Smith LH, D'Souza MS, Conn PJ, Der-Avakian A, Markou A, Cosford ND
J Med Chem 2014 May 22 ;57(10):4154-72
Targeting Unc51-like Autophagy Activating Kinase 1 (ULK1) overcomes adaptive drug resistance in acute myelogenous leukemia.
Bhattacharya S, Piya S, Ma H, Sharma P, Zhang Q, Baran N, Ruvolo VR, McQueen T, Davis RE, Pourebrahim R, Konopleva M, Kantarjian H, Cosford NDP, Andreeff M, Borthakur G
Mol Cancer Res 2023 Feb 14 ;
Protein Tyrosine Phosphatase Biochemical Inhibition Assays.
Baranowski MR, Wu J, Han YN, Lambert LJ, Cosford NDP, Tautz L
Bio Protoc 2022 Sep 20 ;12(18)
Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.
Haass-Koffler CL, Francis TC, Gandhi P, Patel R, Naemuddin M, Nielsen CK, Bartlett SE, Bonci A, Vasile S, Hood BL, Suyama E, Hedrick MP, Smith LH, Limpert AS, Roberto M, Cosford NDP, Sheffler DJ
SLAS Discov 2022 Dec ;27(8):448-459
Novel potent azetidine-based compounds irreversibly inhibit Stat3 activation and induce antitumor response against human breast tumor growth in vivo.
Yue P, Zhu Y, Brotherton-Pleiss C, Fu W, Verma N, Chen J, Nakamura K, Chen W, Chen Y, Alonso-Valenteen F, Mikhael S, Medina-Kauwe L, Kershaw KM, Celeridad M, Pan S, Limpert AS, Sheffler DJ, Cosford NDP, Shiao SL, Tius MA, Lopez-Tapia F, Turkson J
Cancer Lett 2022 May 28 ;534:215613
Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.
Bata N, Cosford NDP
ACS Pharmacol Transl Sci 2021 Dec 10 ;4(6):1728-1746
Discovery of novel furanylbenzamide inhibitors that target oncogenic tyrosine phosphatase SHP2 in leukemia cells.
Raveendra-Panickar D, Finlay D, Layng FI, Lambert LJ, Celeridad M, Zhao M, Barbosa K, De Backer LJS, Kwong E, Gosalia P, Rodiles S, Holleran J, Ardecky R, Grotegut S, Olson S, Hutchinson JH, Pasquale EB, Vuori K, Deshpande AJ, Cosford NDP, Tautz L
J Biol Chem 2022 Jan ;298(1):101477
