Dr. Cosford’s laboratory uses medicinal chemistry, chemical biology, rational drug design and microfluidic approaches.
Dr. Cosford joined Sanford-Burnham faculty in January 2008.
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Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).
Sidique S, Ardecky R, Su Y, Narisawa S, Brown B, Millán JL, Sergienko E, Cosford ND
Bioorg Med Chem Lett. 2009 Jan 1;19(1):222-5
Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1.
Kim I, Shu CW, Xu W, Shiau CW, Grant D, Vasile S, Cosford ND, Reed JC
J Biol Chem. 2009 Jan 16;284(3):1593-603
Pharmacological characterization of (S)-(2)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine HCl (SIB-1508Y, Altinicline), a novel nicotinic acetylcholine receptor agonist.
Rao TS, Adams PB, Correa LD, Santori EM, Sacaan AI, Reid RT, Cosford ND
Brain Res. 2008 Oct 9;1234:16-24
Rapid multistep synthesis of 1,2,4-oxadiazoles in a single continuous microreactor sequence.
Grant D, Dahl R, Cosford ND
J Org Chem. 2008 Sep 19;73(18):7219-23
HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus.
Johnston PA, Phillips J, Shun TY, Shinde S, Lazo JS, Huryn DM, Myers MC, Ratnikov BI, Smith JW, Su Y, Dahl R, Cosford ND, Shiryaev SA, Strongin AY
Assay Drug Dev Technol. 2007 Dec;5(6):737-50
Preclinical studies of celastrol and acetyl isogambogic acid in melanoma.
Abbas S, Bhoumik A, Dahl R, Vasile S, Krajewski S, Cosford ND, Ronai ZA
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6769-78
Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity.
Smith ND, Poon SF, Huang D, Green M, King C, Tehrani L, Roppe JR, Chung J, Chapman DP, Cramer M, Cosford ND
Bioorg Med Chem Lett. 2004 Nov 15;14(22):5481-4
Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity.
Roppe J, Smith ND, Huang D, Tehrani L, Wang B, Anderson J, Brodkin J, Chung J, Jiang X, King C, Munoz B, Varney MA, Prasit P, Cosford ND
J Med Chem. 2004 Sep 9;47(19):4645-8
One-step synthesis of 3-aryl- and 3,4-diaryl-(1H)-pyrroles using tosylmethyl isocyanide (TOSMIC).
Smith ND, Huang D, Cosford ND
Org Lett. 2002 Oct 3;4(20):3537-9
SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5.
Varney MA, Cosford ND, Jachec C, Rao SP, Sacaan A, Lin FF, Bleicher L, Santori EM, Flor PJ, Allgeier H, Gasparini F, Kuhn R, Hess SD, Veliçelebi G, Johnson EC
J Pharmacol Exp Ther. 1999 Jul;290(1):170-81
Nicholas Cosford's Research Focus
Bone Mineralization Disorders, Cancer, Neurodegenerative and Neuromuscular Diseases, Neurological and Psychiatric Disorders
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.
About Nicholas Cosford
Dr. Cosford joined Sanford-Burnham faculty in January 2008. Prior to that he was Project Manager for the Conrad Prebys Center for Chemical Genomics from 2005 to 2008 and has been Director of Medicinal Chemistry at Sanford-Burnham La Jolla site since 2006. Dr. Cosford has over 15 years experience leading small-molecule drug discovery projects in the pharmaceutical industry, and more recently at Sanford-Burnham. 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 (Altinicline, SIB-1508Y) from initiation of research through to Phase II clinical; taking mGluR5 negative allosteric modulators from HTS hits through in vivo proof-of-concept to IND status; and design, synthesis and optimization of an mGluR5 PET tracer clinical candidate. Dr. Cosford’s research in the areas of medicinal chemistry and small molecule synthesis has resulted in more than 50 peer reviewed scientific publications, 21 issued patents, and more than 25 additional patent applications pending. In 2006 Dr. Cosford received the FRAXA Research Foundation Award for Outstanding Contributions to Fragile X Research.