Hollings Home  
 
Campbell McInnes, PhD
Associate Professor of Drug Discovery & Biomedical Sciences
College of Pharmacy
USC

Email: mcinnes@cop.sc.edu
 
       Print This Page
       
 
 


 

Campbell McInnes, PhD

Return to Search Page  

Research Interest:

The major goals of my current research are to discover novel chemical entities based on inhibiting deregulated cell cycle protein kinases and which can be developed as anti-tumor therapeutics. I have extensive experience and a consistent track record both in the pharmaceutical industry and in academia in anti-cancer drug development. My primary expertise is in structure-guided drug design employing the techniques of computational chemistry, structural biology, and synthetic organic chemistry towards the generation of enzyme and protein-protein interaction inhibitors. I am principal investigator of a research project that is NIH-funded and involves collaborations to demonstrate that novel non-Adenosine-5’-triphosphate (ATP) competitive compounds are mechanistically distinct from conventional kinase inhibitors that are based on blocking ATP binding and which are non-selective in nature. Promising compounds will be further developed by medicinal chemistry, cellular phenotypic characterization, and testing in preclinical tumor models.

Selected Publications:

1.Craig SN, Wyatt MD, McInnes C. Current assessment of polo-like kinases as anti-tumor drug targets. Expert Opin Drug Discov. .9(7):773-89, 2014.
View in: PubMed

2.Premnath PN, Liu S, Perkins T, Abbott J, Anderson E, McInnes C. Fragment based discovery of arginine isosteres through REPLACE: towards non-ATP competitive CDK inhibitors. Bioorg Med Chem. .22(1):616-22, 2013. PMCID: PMC3917480
View in: PubMed

3.Liu S, Premnath PN, Bolger JK, Perkins TL, Kirkland LO, Kontopidis G, McInnes C. Optimization of non-ATP competitive CDK/cyclin groove inhibitors through REPLACE-mediated fragment assembly. J Med Chem. .56(4):1573-82, 2013. PMCID: PMC3692612
View in: PubMed

4.McInnes C, Estes K, Baxter M, Yang Z, Farag DB, Johnston P, Lazo JS, Wang J, Wyatt MD. Targeting subcellular localization through the polo-box domain: non-ATP competitive inhibitors recapitulate a PLK1 phenotype. Mol Cancer Ther. .11(8):1683-92, 2012. PMCID: PMC3711794
View in: PubMed

5.Smith MA, McInnes C, Whitaker RM, Lindsey CC, Comer RF, Beeson CC, Schnellmann RG. Calpain 10 homology modeling with CYGAK and increased lipophilicity leads to greater potency and efficacy in cells. ACS Chem Biol. .7(8):1410-9, 2012.
View in: PubMed

6.McInnes C, Wyatt MD. PLK1 as an oncology target: current status and future potential. Drug Discov Today. .16(13-14):619-25, 2011.
View in: PubMed

7.Wang S, Griffiths G, Midgley CA, Barnett AL, Cooper M, Grabarek J, Ingram L, Jackson W, Kontopidis G, McClue SJ, McInnes C, McLachlan J, Meades C, Mezna M, Stuart I, Thomas MP, Zheleva DI, Lane DP, Jackson RC, Glover DM, Blake DG, Fischer PM. Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents. Chem Biol. .17(10):1111-21, 2010.
View in: PubMed

8.Liu S, Bolger JK, Kirkland LO, Premnath PN, McInnes C. Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements. ACS Chem Biol. .5(12):1169-82, 2010. PMCID: PMC3425359
View in: PubMed

9.Wang S, Midgley CA, Scaërou F, Grabarek JB, Griffiths G, Jackson W, Kontopidis G, McClue SJ, McInnes C, Meades C, Mezna M, Plater A, Stuart I, Thomas MP, Wood G, Clarke RG, Blake DG, Zheleva DI, Lane DP, Jackson RC, Glover DM, Fischer PM. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem. .53(11):4367-78, 2010.
View in: PubMed

10.McIntyre NA, McInnes C, Griffiths G, Barnett AL, Kontopidis G, Slawin AM, Jackson W, Thomas M, Zheleva DI, Wang S, Blake DG, Westwood NJ, Fischer PM. Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. J Med Chem. .53(5):2136-45, 2010.
View in: PubMed

11.Kontopidis G, Andrews MJ, McInnes C, Plater A, Innes L, Renachowski S, Cowan A, Fischer PM. Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin a through structure-guided design. ChemMedChem. .4(7):1120-8, 2009.
View in: PubMed

12.Gruver AM, Yard BD, McInnes C, Rajesh C, Pittman DL. Functional characterization and identification of mouse Rad51d splice variants. BMC Mol Biol. .10:27, 2009. PMCID: PMC2667185
View in: PubMed

13.Nadkarni A, Furda A, Rajesh C, McInnes C, Ruch RJ, Pittman DL. Functional characterization of the RAD51D E233G genetic variant. Pharmacogenet Genomics. .19(2):153-60, 2009.
View in: PubMed

14.Kirkland LO, McInnes C. Non-ATP competitive protein kinase inhibitors as anti-tumor therapeutics. Biochem Pharmacol. .77(10):1561-71, 2009.
View in: PubMed

15.Xia Z, Knaak C, Ma J, Beharry ZM, McInnes C, Wang W, Kraft AS, Smith CD. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. .52(1):74-86, 2009.
View in: PubMed

16.McInnes C. Progress in the evaluation of CDK inhibitors as anti-tumor agents. Drug Discov Today. .13(19-20):875-81, 2008.
View in: PubMed

17.McInnes C. Virtual screening strategies in drug discovery. Curr Opin Chem Biol. .11(5):494-502, 2007.
View in: PubMed

18.McInnes C, Mazumdar A, Mezna M, Meades C, Midgley C, Scaerou F, Carpenter L, Mackenzie M, Taylor P, Walkinshaw M, Fischer PM, Glover D. Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance. Nat Chem Biol. .2(11):608-17, 2006.
View in: PubMed

19.McInnes C, Mezna M, Kontopidis G. Catch the kinase conformer. Chem Biol. .13(7):693-4, 2006.
View in: PubMed

20.Okram B, Nagle A, Adrián FJ, Lee C, Ren P, Wang X, Sim T, Xie Y, Wang X, Xia G, Spraggon G, Warmuth M, Liu Y, Gray NS. A general strategy for creating "inactive-conformation" abl inhibitors. Chem Biol. .13(7):779-86, 2006.
View in: PubMed

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

22.Thomas MP, McInnes C. Structure-based discovery and optimization of potential cancer therapeutics targeting the cell cycle. IDrugs. .9(4):273-8, 2006.
View in: PubMed

23.Kontopidis G, McInnes C, 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. .13(2):201-11, 2006.
View in: PubMed

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

25.Uhrinova S, Uhrin D, Powers H, Watt K, Zheleva D, Fischer P, McInnes C, Barlow PN. Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding. J Mol Biol. .350(3):587-98, 2005.
View in: PubMed

26.Kontopidis G, Wu SY, Zheleva DI, Taylor P, McInnes C, Lane DP, Fischer PM, Walkinshaw MD. Structural and biochemical studies of human proliferating cell nuclear antigen complexes provide a rationale for cyclin association and inhibitor design. Proc Natl Acad Sci U S A. .102(6):1871-6, 2005. PMCID: PMC548533
View in: PubMed

27.McInnes C, Mezna M, Fischer PM. Progress in the discovery of polo-like kinase inhibitors. Curr Top Med Chem. .5(2):181-97, 2005.
View in: PubMed

28.McInnes C, Fischer PM. Strategies for the design of potent and selective kinase inhibitors. Curr Pharm Des. .11(14):1845-63, 2005.
View in: PubMed

29.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. .2(19):2735-41, 2004.
View in: PubMed

30.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. .14(16):4237-40, 2004.
View in: PubMed

31.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. .11(4):525-34, 2004.
View in: PubMed

32.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. .47(7):1662-75, 2004.
View in: PubMed

33.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. .11(12):1537-46, 2003.
View in: PubMed

34.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. .11(4):399-410, 2003.
View in: PubMed

35.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 Anticancer Agents. .3(1):57-69, 2003.
View in: PubMed

36.Atkinson GE, Cowan A, McInnes C, Zheleva DI, Fischer PM, Chan WC. Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: structural variants of the C-terminal Phe. Bioorg Med Chem Lett. .12(18):2501-5, 2002.
View in: PubMed

37.McInnes C, Wang J, Al Moustafa AE, Yansouni C, O'Connor-McCourt M, Sykes BD. Structure-based minimization of transforming growth factor-alpha (TGF-alpha) through NMR analysis of the receptor-bound ligand. Design, solution structure, and activity of TGF-alpha 8-50. J Biol Chem. .273(42):27357-63, 1998.
View in: PubMed

38.McInnes C, Sykes BD. Growth factor receptors: structure, mechanism, and drug discovery. Biopolymers. .43(5):339-66, 1997.
View in: PubMed

39.McInnes C, Hoyt DW, Harkins RN, Pagila RN, Debanne MT, O'Connor-McCourt M, Sykes BD. NMR study of the transforming growth factor-alpha (TGF-alpha)-epidermal growth factor receptor complex. Visualization of human TGF-alpha binding determinants through nuclear Overhauser enhancement analysis. J Biol Chem. .271(50):32204-11, 1996.
View in: PubMed

40.Leone-Bay A, Ho KK, Agarwal R, Baughman RA, Chaudhary K, DeMorin F, Genoble L, McInnes C, Lercara C, Milstein S, O'Toole D, Sarubbi D, Variano B, Paton DR. 4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone. J Med Chem. .39(13):2571-8, 1996.
View in: PubMed

41.Campbell AP, McInnes C, Hodges RS, Sykes BD. Comparison of NMR solution structures of the receptor binding domains of Pseudomonas aeruginosa pili strains PAO, KB7, and PAK: implications for receptor binding and synthetic vaccine design. Biochemistry. .34(50):16255-68, 1995.
View in: PubMed

42.Leone-Bay A, McInnes C, Wang N, DeMorin F, Achan D, Lercara C, Sarubbi D, Haas S, Press J, Barantsevich E, et al. Microsphere formation in a series of derivatized alpha-amino acids: properties, molecular modeling, and oral delivery of salmon calcitonin. J Med Chem. .38(21):4257-62, 1995.
View in: PubMed

43.Wong WY, Campbell AP, McInnes C, Sykes BD, Paranchych W, Irvin RT, Hodges RS. Structure-function analysis of the adherence-binding domain on the pilin of Pseudomonas aeruginosa strains PAK and KB7. Biochemistry. .34(40):12963-72, 1995.
View in: PubMed

44.McInnes C, Kay CM, Hodges RS, Sykes BD. Conformational differences between cis and trans proline isomers of a peptide antigen representing the receptor binding domain of Pseudomonas aeruginosa as studied by 1H-NMR. Biopolymers. .34(9):1221-30, 1994.
View in: PubMed

45.McInnes C, Sönnichsen FD, Kay CM, Hodges RS, Sykes BD. NMR solution structure and flexibility of a peptide antigen representing the receptor binding domain of Pseudomonas aeruginosa. Biochemistry. .32(49):13432-40, 1993.
View in: PubMed