Kirk R. Gustafson, Ph.D.
Molecular Targets Laboratory
Building 562, Room 201
Frederick, MD 21702-1201
The NCI maintains a repository of natural product extracts that is the largest and most diverse in the world. These extracts, derived from terrestrial, marine and microbial organisms, constitute a unique source of chemical diversity for the discovery of compounds that can interact with specific molecular targets associated with human cancer. We are utilizing high throughput screening technologies to help identify compounds and extracts that can specifically interact with or modulate the function of selected biochemical targets or processes. Bioassay-guided chemical fractionation of natural products extracts is employed to isolate and purify the individual bioactive compounds. Identification and structural characterization of these compounds provides new structural classes or molecular scaffolds for the development of potential drug leads or biological probes which can interact with the desired molecular target. In addition to extensive spectroscopic analyses, our efforts include rigorous evaluation of a new compound's potency, molecular target specificity, and mode of action.
Blees JS, Bokesch HR, Rübsamen D, Schulz K, Milke L, Bajer MM, Gustafson KR, Henrich CJ, McMahon JB, Colburn NH, Schmid T, Brüne B. Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1. PLoS One. 2012;7(10):e46567.
Diyabalanage T, Ratnayake R, Wilson JA, Henrich CJ, Beutler JA, Colburn NH, McMahon JB, Gustafson KR. Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian plant Nothospondias staudtii. Bioorg Med Chem Lett. 2011;21(15):4397-9.
Versiani MA, Diyabalanage T, Ratnayake R, Henrich CJ, Bates SE, McMahon JB, Gustafson KR. Flavonoids from eight tropical plant species that inhibit the multidrug resistance transporter ABCG2. J Nat Prod. 2011;74(2):262-6.
Oku N, Takada K, Fuller RW, Wilson JA, Peach ML, Pannell LK, McMahon JB, Gustafson KR. Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica. J Am Chem Soc. 2010;132(30):10278-85.
Grkovic T, Blees JS, Colburn NH, Schmid T, Thomas CL, Henrich CJ, McMahon JB, Gustafson KR. Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4. J Nat Prod. 2011;74(5):1015-20.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on October 5th, 2017