Investigation of novel anti-tubulin agents.

Ongoing research projects include investigation of novel antitubulin agents that interact with tubulin at all classes of drug sites; characterization of drug binding sites by peptide sequencing following photoactivation or chemical reaction with appropriately designed analogs; characterization of total tubulin content, beta-tubulin isotype distribution and gamma-tubulin content of the cell lines in the NCI drug screen; characterization of biochemical and cytological properties of a marine peptide that enhances actin assembly; and an active search for and characterization of compounds that cause mitotic arrest by new mechanisms.

Interactive possibilities and available reagents include: Collaboration and/or advice on documenting drug interactions with tubulin and actin, with particular interest in details of molecular interactions with tubulin. Advice on preparation of microtubule proteins.

Credentials

Dr. Ernest Hamel received his B.A. in 1965 from Harvard University and his M.D. and Ph.D. in Biochemistry in 1972 from the University of Chicago. After a postdoctoral fellowship at National Institute of Child Health and Human Development (1972-1975), Dr. Hamel returned to the University of Chicago for postgraduate medical education in Pediatrics (1975-1977). Following training in pediatric hematology-oncology at the National Cancer Institute (1977-1978), Dr. Hamel began working in the area of rnicrotubule biochemistry and pharmacology in the Developmental Therapeutics Program of the NCI, initially in the Laboratory of Biochemical Pharmacology, and, now, in the Screening Technologies Branch. His areas of research interest are protein-protein interactions in microtubules, interactions of small ligands, particularly compounds of potential clinical utility, with tubulin and mechanisms of mitosis and cytokinesis.

Recent Publications

NCBI PubMed listing of publications by Ernest Hamel.

Mu F, Lee DJ, Pryor DE, Hamel E, Cushman M. Synthesis and Investigation of Conformationally Restricted Analogues of Lavendustin A as Cytotoxic Inhibitors of Tubulin Polymerization. J Med Chem. 2002 Oct 10;45(21):4774-4785.

Cushman M, Mohanakrishnan AK, Hollingshead M, Hamel E. The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization. J Med Chem. 2002 Oct 10;45(21): 4748-4754.

Han S, Hamel E, Bastow K, McPhail A, Brossi A, Lee K. Antitumor agents. Part 215: Antitubulin effects of cytotoxic B-Ring modified allocolchicinoids. Bioorg Med Chem Lett. 2002 Oct 21;12(20):2851.

Ojo-Amaize EA, Nchekwube EJ, Cottam HB, Bai R, Verdier-Pinard P, Kakkanaiah VN, Varner JA, Leoni L, Okogun JI, Adesomoju AA, Oyemade OA, Hamel E. Hypoestoxide, a natural nonmutagenic diterpenoid with antiangiogenic and antitumor activity: possible mechanisms of action. Cancer Res. 2002 Jul 15;62(14):4007-14.

Pryor DE, O'Brate A, Bilcer G, Diaz JF, Wang Y, Wang Y, Kabaki M, Jung MK, Andreu JM, Ghosh AK, Giannakakou P, Hamel E. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 2002 Jul 23;41(29):9109-15.

Smith AB, Corbett RM, Pettit GR, Chapuis JC, Schmidt JM, Hamel E, Jung MK. Synthesis and biological evaluation of a spongistatin AB-spiroketal analogue. Bioorg Med Chem Lett. 2002 Aug 5;12(15):2039-42.

Marquez BL, Watts KS, Yokochi A, Roberts MA, Verdier-Pinard P, Jimenez JI, Hamel E, Scheuer PJ, Gerwick WH. Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J Nat Prod. 2002 Jun;65(6):866-71.

Bai R, Covell DG, Liu C, Ghosh AK, Hamel E. (-)-Doliculide, a new macrocyclic depsipeptide enhancer of actin assembly. J Biol Chem. 2002 Jun 20

Flynn BL, Hamel E, Jung MK. One-pot synthesis of benzo[b]furan and indole inhibitors of tubulin polymerization. J Med Chem. 2002 Jun 6;45(12):2670-3.

Pettit GR, Grealish MP, Jung MK, Hamel E, Pettit RK, Chapuis JC, Schmidt JM. Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate. J Med Chem. 2002 Jun 6;45(12):2534-42.

Pettit RK, Hamel E, Verdier-Pinard P, Roberson RW, Hazen KC, Pettit GR, Crews LC. Antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene. Mycoses. 2002 Apr;45(3-4):65-74.

Flynn, B.L., Flynn, G.P., Hamel, E., Jung, M.K. The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4. Bioorg Med Chem Lett. 2001 Sep 3;11(17):2341-3.