Title:

Assistant Professor (USC Campus)

Coker Life Science Building Room 509

Education

Description of Research Program
The McInnes laboratory at the University of South Carolina, Department of Pharmaceutical and Biomedical Sciences is engaged in the development of novel anti-cancer drugs based on inhibition of protein kinases involved in regulation of the cell cycle. Through advances in the understanding of the molecular differences between normal and cancer cells, we aim to exploit new information to design targeted therapeutics. The cell cycle is a series of events which a cell undergoes during the processes of growth and division. Deregulation of these events commonly leads to abnormal cell growth and uncontrolled division, the hallmarks of cancer. We are developing novel therapeutics based on restoring normal cell functions in cancer cells leading to arrest of cell growth and promotion of apoptosis (programmed cell death). Using computer screening, design and chemical synthesis, molecules will be constructed and tested for anti-cancer activity in model studies. This NIH funded research involves worldwide collaboration with leading scientists at Medical University of South Carolina, University of Nottingham, UK, University of Thessaly, Greece and at Dana Farber Cancer Institute, in Boston. Dr McInnes has 15 years of experience in cancer research, most recently working with Cyclacel Pharmaceuticals developing new cancer treatments through structure guided design.

Selected Publications

1.       Xia Z, Knaak C, Ma J, Beharry ZM, McInnes C, Wang W, Kraft AS and Smith CD  Synthesis and Evaluation of Novel Pim Protein Kinase Inhibitors. J. Med. Chem, 2009, 52, 74-82

2.       Nadkarni A, Furda A, McInnes C, Ruch R, & Douglas L. Pittman Functional Characterization of the RAD51D E233G Genetic Variant. Pharmacogenetics and Genomics, 2008, epub.

3.       McInnes C. Progress in the evaluation of CDK inhibitors as anti-tumor agents. Drug Discovery Today , 2008, 13, 875.

4.       McInnes C. Virtual Screening Strategies in Drug Discovery Current Opinion in Chemical Biology 2007, 11: 494-502

5.       McInnes C. Recent Advances in the Structure-Guided Design of Protein Kinase Inhibitors Frontiers in Drug Design and Discovery  2007, 3: 145-170

6.       McInnes C, Andrews MJ, Kontopidis G, Plater A, Innes L, Cowan A, Jewsbury P, Fischer PM. REPLACE: A Strategy for Iterative Design of Cyclin-Binding Groove Inhibitors Chembiochem. 2006  7, 1909  

7.       McInnes C, Mazumdar C, Mezna M, Meades C, Midgley C, Scaerou F, Carpenter C, Mackenzie M, Taylor P, Walkinshaw M, Fischer P and Glover D. Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance. 2006 Nature Chemical Biology 2(11):608-17.

8.       McInnes C, Mezna M and Kontopidis G. Catch the kinase conformer. 2006 Chem Biol. 13:693-4.

9.       McInnes C. Improved lead-finding for kinase targets using high-throughput docking. Curr Opin Drug Discov Devel. 2006 9(3), 339-47.

10.   McInnes C, Kontopidis G, Pandalaneni SR, McNae I, Gibson D, Mezna M, Thomas M, Wood G, Wang S, Walkinshaw MD, Fischer PM. Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design. Chem Biol. 2006 13(2), 201-11.

11.   Thomas MP, McInnes C, Fischer PM. Protein structures in virtual screening: a case study with CDK2.  J Med Chem. 2006 49(1), 92-104.

12.   Uhrinova, S, Uhrin, D, Powers, P, Watt, K, Zheleva, D, Fischer, P, McInnes, C and Paul Barlow, P; Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding. J. Mol. Biol. 2005, 350, 587-598

13.   McInnes C, Mezna M, Fischer PM; Progress in the Discovery of Polo-Like Kinase Inhibitors. Curr Topics Med Chem. 2005; 5, 181-197

14.   McInnes C, Fischer PM. Strategies for the design of potent and selective kinase inhibitors. Curr Pharm Des. 2005;  11(14), 1485-1863

15.   Kontopidis, G, Wu, SY, Zheleva, DI, Taylor, PR, McInnes, C, Lane, DP, Fischer, PM and Walkinshaw, M. From the Cover: Structural and biochemical studies of human proliferating cell nuclear antigen complexes provide a rationale for cyclin association and inhibitor design. Proc. Natl. Acad. Sci 2005; 102(6):1871-6.

16.   Andrews MJ, McInnes C, Kontopidis G, Innes L, Cowan A, Plater A, Fischer PM. Design, synthesis, biological activity and structural analysis of cyclic peptide inhibitors targeting the substrate recruitment site of cyclin-dependent kinase complexes. Org Biomol Chem. 2004; 2(19):2735-41.

17.   Wang S, Wood G, Meades C, Griffiths G, Midgley C, McNae I, McInnes C, Anderson S, Jackson W, Mezna M, Yuill R, Walkinshaw M, Fischer PM. Synthesis and biological activity of 2-anilino-4-(1H-pyrrol-3-yl) pyrimidine CDK inhibitors. Bioorg Med Chem Lett. 2004; 14(16):4237-40.

18.   McInnes C, Wang S, Anderson S, O'Boyle J, Jackson W, Kontopidis G, Meades C, Mezna M, Thomas M, Wood G, Lane DP, Fischer PM. Structural determinants of CDK4 inhibition and design of selective ATP competitive inhibitors. Chem Biol. 2004; 11(4):525-34.

19.   Wang S, Meades C, Wood G, Osnowski A, Anderson S, Yuill R, Thomas M, Mezna M, Jackson W, Midgley C, Griffiths G, Fleming I, Green S, McNae I, Wu SY, McInnes C, Zheleva D, Walkinshaw MD, Fischer PM. 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity. J Med Chem. 2004; 47(7):1662-75.

20.   Kontopidis G, Andrews MJ, McInnes C, Cowan A, Powers H, Innes L, Plater A,  Griffiths G, Paterson D, Zheleva DI, Lane DP, Green S, Walkinshaw MD, Fischer PM. Insights into cyclin groove recognition: complex crystal structures and inhibitor design through ligand exchange. Structure (Camb). 2003; 11(12):1537-46.

21.   Wu SY, McNae I, Kontopidis G, McClue SJ, McInnes C, Stewart KJ, Wang S, Zheleva DI, Marriage H, Lane DP, Taylor P, Fischer PM, Walkinshaw MD. Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Structure (Camb). 2003; 11(4):399-410.

22.   McInnes C, Andrews MJ, Zheleva DI, Lane DP, Fischer PM. Peptidomimetic design of CDK inhibitors targeting the recruitment site of the cyclin subunit. Curr Med Chem Anti-Canc Agents. 2003; 3(1):57-69.

23.   McInnes C, Zheleva DI, Gavine AL, Zhelev NZ, Fischer PM, Lane DP. Highly potent p21(WAF1)-derived peptide inhibitors of CDK-mediated pRb phosphorylation: delineation and structural insight into their interactions with cyclin A. J Pept Res. 2002; 60(5):257-70.