3 / 4
E u r o p e a n C o n g r e s s o n
Advanced Chemistry
Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
Advanced Chemistry 2018
Page 22
M
alignant melanoma is the most aggressive form of skin cancer and it is
highly resistant to most existing therapies. Despite recent advances in both
targeted therapy and immunotherapy, acquired drug resistance often develops
quickly and the overall survival for malignant melanoma remains unsatisfactory.
Chemotherapeutic drugs including tubulin inhibitors (e.g., paclitaxel) are used in
treating malignant melanoma clinically, but their efficacy is often limited by the
ABC-transporter mediated drug efflux and non-specific tissue distribution, leading
to dose limiting toxicity. We have discovered several sets of novel tubulin inhibitors
that: 1) target the colchicine binding site in tubulin and have broad spectrum
of potent anticancer activity; 2) effectively circumvent major drug resistance
mechanisms that hinder the clinical efficacy with existing tubulin inhibitors; 3) are
orally bioavailable and have excellent drug-like properties; and 4) are efficacious
against both drug sensitive and drug resistant melanoma tumors in vivo. We have
solved the X-ray crystal structures for many of these compounds to confirm their
direct binding to tubulin (DJ-101 as an example shown in the figure). We have
also developed nanoparticle formulations for these agents and showed that these
targeted drug delivery approaches can improve the anticancer efficacy for these
tubulin inhibitors.
Biography
Wei Li has been working at the College of Pharmacy, the Univer-
sity of Tennessee Health Science Center (UTCoP) since he ob-
tained his PhD in chemistry from Columbia University in 1999.
Currently, he is a Professor and the Director of the UTCoP Drug
Discovery Center. His focus of research is Small Molecule Drug
Discovery, and currently his research is mainly funded by NIH/
NCI grants. He has published over 135 papers, 3 book chapters;
five issued US patents, and additional patents from other coun-
tries. He is a frequent grant Reviewer for NIH study sections,
and currently he is an Editorial Board Member for Current Me-
dicinal
Chemistry, Molecules
, and Acta
Pharmaceutica Sinica B
.
wli@uthsc.eduA new generation of orally available
tubulin inhibitors: the discovery and
development
Wei Li
UTHSC, Tennessee
Wei Li, J Org Inorg Chem 2018, Volume: 4
DOI: 10.21767/2472-1123-C2-004