个人简介

B.S., 1992, Jacksonville Univ. Ph.D., 1997, Univ. of Virginia Postdoctoral Research, 1998-2000, Colorado State Univ. AwardOrganizationDivisionLevel CodeType CodeStart DateEnd Date Brian D. Novis Senior Award from the International Myeloma FoundationProfessionalHonors2012 Multiple Myeloma Senior Research AwardMultiple Myeloma Research FoundationProfessionalHonors20102010 Multiple Myeloma Senior Research AwardMultiple Myeloma Research FoundationProfessionalHonors20082008 Teacher-Scholar AwardMichigan State UniversityProfessionalHonors20052005 Research Scholar AwardAmerican Cancer SocietyProfessionalHonors2003 Alfred Burger Fellowship, Senior Thesis FellowshipUniversity of VirginiaGraduateFellowship1997 Ph.D.University of VirginiaGraduateDegree1997 Dean’s Reserve FellowshipUniversity of VirginiaGraduateFellowship1994 Bachelor of ScienceJacksonville UniversityUndergraduateDegree1992

研究领域

Biological Organic

(Research Description PDF - 884 kb) Our research program provides an interdisciplinary blend of synthetic and bioorganic chemistry that includes the total synthesis of natural products, the discovery of new reactions, as well as the evaluation for their cellular mechanism and medicinal properties. Natural products are still the primary source for medicines, and marine sponge metabolites represent a highly diverse and complex class of natural products with remarkable biological activities. Our laboratory is focused on the total synthesis of marine sponge alkaloids, to examine their potent anti-cancer and anti-inflammatory properties. The Oroidins: The oroidin family of alkaloids is a highly diverse and complex class of biologically active secondary marine sponge metabolites containing characteristic pyrrole-2-carboxamide and 2-aminoimidazoline (or derivatives thereof) moieties. Members of this group include the highly publicized palau’amine as well as the structurally related phakellins and phakellstatins. Our group recently developed a novel NBS mediated addition of guanidines to olefins, which was used in the total synthesis of dibromophakellin and many of its analogues. Cellular studies in our lab subsequently identified the human proteasome as a possible target responsible for the exiting biological properties these compounds elicit. Others: Natural Product Inspired Scaffold Design: Our scaffold design program aims at the development of small molecular weight scaffolds containing a high degree of diversity. The skeletal diversity of our scaffolds is inspired by natural products, but unlike their natural counterparts these scaffolds are readily optimized for their pharmacokinetic and pharmacodynamic properties. Examples include: (left below) our imidazolone-based Chk2 inhibitors, which protect normal cells from ionizing radiation (IR) without interfering with IR induced killing of tumor cells and our imidazoline based, TCH-compounds, which elicit remarkable in vivo efficacy towards diseases such as cancer (right below) and rheumatoid arthritis. Studies to elucidate their cellular mechanism of action are currently on-going in our labs.

近期论文

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Inhibition of the human proteasome by imidazoline scaffolds, Azevedo, L.; Lansdell, A.T.; Ludwig, J.; Mosey, R.; Woloch, D.; Cogan, D.; Patten, G.; Kuszpit, M.; Fisk, J. and Tepe, J.J., Journal of Medicinal Chemistry, 2013, 56, 5974-5978. Noncompetitive modulation of the proteasome by imidazoline scaffolds overcomes bortezomib resistance and delays MM tumor growth in vivo Lansdell, T.A.; Hurchla, M.A.; Xiang, J.; Hovde, S.; Weilbaecher, K.N.; Henry, R.W.; Tepe, J.J., ACS Chemical Biology, 2013, 8, 578-587. Non-competitive inhibition of the human proteasome attenuates collagen-induced arthritis, Lansdell, T.A.; O’Reilly, S.; Woolliscroft, T.; Kahlon, D. K.; Hovde, S.; McCormick, J.J.; Henry, R.W.; Cornicelli, J.A. ; Tepe, J.J., Bioorganic & Medicinal Chemistry Letters 2012, 22, 4816-4819. Palau’amine and Related Oroidin-alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome, Lansdell, T.A.; Hewlett, N.M.; Skoumbourdis, A.P.; Fodor, M.D.; Seiple, I.B. Su, S.; Baran, P.S.; Feldman, K.S.; Tepe, J.J., Journal of Natural Products 2012, 75, 980-985. Synthesis and evaluation of debromohymenialdisine-derived Chk2 inhibitors, Saleem, R.S.Z.; Lansdell, T.A.; Tepe, J.J., Bioorganic & Medicinal Chemistry 2012, 20, 1475-1481. Radioprotection by hymenialdisine-derived checkpoint kinase 2 inhibitors, Nguyen, T.N.T.; Saleem, R.S.Z.; Luderer, M.J.; Tepe, J.J., ACS Chemical Biology 2012, 7, 172-184. Total synthesis of the natural product (±)-dibromophakellin and analogues, Hewlett, N.M.; Tepe, J.J., Org. Lett. 2011, 13, 4550-4553.