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.
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
Chaikuad A, Koschade SE, Stolz A, Zivkovic K, Pohl C, Shaid S, Ren H, Lambert LJ, Cosford NDP, Brandts CH, Knapp S
Biochem J 2019 Mar 12 ;476(5):875-887
A Combination of Flow and Batch Mode Processes for the Efficient Preparation of mGlu<sub>2/3</sub> Receptor Negative Allosteric Modulators (NAMs).
Dhanya RP, Herath A, Sheffler DJ, Cosford NDP
Tetrahedron 2018 Jun 21 ;74(25):3165-3170
Limpert AS, Lambert LJ, Bakas NA, Bata N, Brun SN, Shaw RJ, Cosford NDP
Trends Pharmacol Sci 2018 Dec ;39(12):1021-1032
Metabotropic Glutamate Receptor 5 as a Target for the Treatment of Depression and Smoking: Robust Preclinical Data but Inconclusive Clinical Efficacy.
Barnes SA, Sheffler DJ, Semenova S, Cosford NDP, Bespalov A
Biol Psychiatry 2018 Jun 1 ;83(11):955-962
Discovery of 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a potent and orally bioavailable tissue-nonspecific alkaline phosphatase (TNAP) inhibitor.
Pinkerton AB, Sergienko E, Bravo Y, Dahl R, Ma CT, Sun Q, Jackson MR, Cosford NDP, Millán JL
Bioorg Med Chem Lett 2018 Jan 1 ;28(1):31-34
Synthesis and Preliminary Studies of a Novel Negative Allosteric Modulator, 7-((2,5-Dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[<sup>11</sup>C]methoxyphenyl) quinoline-2-carboxamide, for Imaging of Metabotropic Glutamate Receptor 2.
Zhang X, Kumata K, Yamasaki T, Cheng R, Hatori A, Ma L, Zhang Y, Xie L, Wang L, Kang HJ, Sheffler DJ, Cosford NDP, Zhang MR, Liang SH
ACS Chem Neurosci 2017 Sep 20 ;8(9):1937-1948