Xiangshu Xiao, Ph.D.

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Lab Phone:: 503 494-6249

Background

Our lab is focused on the development of novel cancer chemotherapeutic drugs targeting different biomolecular targets. To achieve these goals, we are utilizing the concepts and techniques in computer-assisted molecular modeling to design the molecules, organic chemistry to synthesize the molecules and biological assays to evaluate the molecules in cancer-relevant models. We recently discovered a small molecule inhibitor of CREB-mediated gene transcription by inhibiting the CREB-CBP interaction. This small molecule, naphthol AS-E, potently inhibits cancer cell proliferation and induce apoptosis in a variety of different cancer cells. Currently, we are investigating its mechanism of action and structure-activity relationships to design more potent derivatives as potential anticancer drugs. In addition, we are also interested in the development of novel nanotechnologies to deliver nucleic acids into the cells. This could potentially lead a new way for cancer gene therapy.

Selected Publications

"Structure-activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription," Bioorganic and Medicinal Chemistry (Vol: 20, Issue: 23, Page 6811-6820) - 2012

"Design, synthesis, and biological evaluation of conformationally constrained analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription," Journal of Medicinal Chemistry (Vol: 55, Issue: 8, Page 4020-4024) - 2012

"Targeting CREB for cancer therapy: Friend or foe," Current Cancer Drug Targets (Vol: 10, Issue: 4, Page 384-391) - 2010

"Discovery of a small-molecule inhibitor of the KIX-KID interaction," ChemBioChem (Vol: 10, Issue: 17, Page 2721-2724) - 2009

"Rapid identification of improved protein ligands using peptoid microarrays," Bioorganic and Medicinal Chemistry Letters (Vol: 19, Issue: 14, Page 3866-3869) - 2009

"Design and synthesis of a cell-permeable synthetic transcription factor mimic," Journal of Combinatorial Chemistry (Vol: 9, Issue: 4, Page 592-600) - 2007

"A general system for evaluating the efficiency of chromophore-assisted light inactivation (CALI) of proteins reveals Ru(ii) tris-bipyridyl as an unusually efficient "warhead"," Molecular BioSystems (Vol: 4, Issue: 1, Page 59-65) - 2007

"A cell-permeable synthetic transcription factor mimic," Angewandte Chemie - International Edition (Vol: 46, Issue: 16, Page 2865-2868) - 2007

"On the mechanism of conversion of 4-carboxy-3,4-dihydro-3-phenyl-1(2H)-isoquinolones to indeno[1,2-c]isoquinolines by thionyl chloride," Tetrahedron (Vol: 62, Issue: 41, Page 9705-9712) - 2006

"Total synthesis and biological evaluation of 22-hydroxyacuminatine," Journal of Medicinal Chemistry (Vol: 49, Issue: 4, Page 1408-1412) - 2006

"Isolation and characterization of coactivator-binding peptoids from a combinatorial library," Molecular BioSystems (Vol: 2, Issue: 11, Page 568-579) - 2006

"A convergent and stereoselective synthesis of a seco-precursor of macrolactin A," Tetrahedron (Vol: 61, Issue: 47, Page 11291-11298) - 2005

"Effect of E-ring modifications in camptothecin on topoisomerase I inhibition: A quantum mechanics treatment," Journal of Organic Chemistry (Vol: 70, Issue: 23, Page 9584-9587) - 2005

"A facile method to transform trans-4-carboxy-3,4-dihydro-3-phenyl-1(2H)- isoquinolones to indeno[1,2-c]isoquinolines," Journal of Organic Chemistry (Vol: 70, Issue: 16, Page 6496-6498) - 2005

"An ab initio quantum mechanics calculation that correlates with ligand orientation and DNA cleavage site selectivity in camptothecin-DNA-topoisomerase I ternary cleavage complexes," Journal of the American Chemical Society (Vol: 127, Issue: 28, Page 9960-9961) - 2005

"Synthesis of a sec-precursor and analogues of macrolactin A," Chemistry Letters (Vol: 34, Issue: 7, Page 906-907) - 2005

"Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines," Bioorganic and Medicinal Chemistry Letters (Vol: 15, Issue: 11, Page 2795-2798) - 2005

"On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage complex," Journal of Medicinal Chemistry (Vol: 48, Issue: 9, Page 3231-3238) - 2005

"Novel autoxidative cleavage reaction of 9-fluoredenes discovered during synthesis of a potential DNA-threading indenoisoquinoline," Journal of Organic Chemistry (Vol: 69, Issue: 22, Page 7495-7501) - 2004

"Design, synthesis, and biological evaluation of cytotoxic 11-aminoalkenylindenoisoquinoline and 11-diaminoalkenylindenoisoquinoline topoisomerase I inhibitors," Bioorganic and Medicinal Chemistry (Vol: 12, Issue: 19, Page 5147-5160) - 2004

"Synthesis, crystal structure, and conversion of the polycyclic tris-anhydrotetramer of O-aminobenzaldehyde to Cu(TAAB)²⁺," Synthetic Communications (Vol: 34, Issue: 21, Page 3901-3907) - 2004

"Design, Synthesis, and Biological Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Featuring Polyamine Side Chains on the Lactam Nitrogen," Journal of Medicinal Chemistry (Vol: 46, Issue: 26, Page 5712-5724) - 2003

"Design, synthesis, and biological evaluation of cytotoxic 11-alkenylindenoisoquinoline topoisomerase I inhibitors and indenoisoquinoline-camptothecin hybrids," Journal of Medicinal Chemistry (Vol: 46, Issue: 15, Page 3275-3282) - 2003

"The unexpected reductive products of Î´- alkoxyenal by sodium borohydride in methanol with a trace of magnesium methoxide," Chinese Chemical Letters (Vol: 13, Issue: 9, Page 809-810) - 2002

"An efficient and selective method for hydrolysis of acetonides," Synlett (Vol: , Issue: 4, Page 535-537) - 2001