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conferenceseries
.com
Volume 9
Journal of Biotechnology & Biomaterials
ISSN: 2155-952X
JOINT EVENT
February 28-March 02, 2019 | Berlin, Germany
5
th
International Conference on
Enzymology and Protein Chemistry
&
22
nd
Global Congress on
Biotechnology
Biotechnology 2019
Enzymology 2019
February 28-March 02, 2019
&
Cytochrome P450 enzymes as target for drug development
Klaus Pors
University of Bradford, UK
T
he cytochrome P450 (CYP) enzymes belong to a superfamily of mixed function oxidases that are unique in their ability
to oxidize xenobiotics, but under hypoxic conditions also can reduce certain chemical functionalities. There is now
growing evidence that CYP1A1 and 2W1 are overexpressed in many human tumor types. The presence of certain CYPs may
reflect a resistance mechanism by diminishing the pharmacological activity of anticancer drugs whilst specific CYPs can
also modulate cell proliferation by the formation or conversion of endogenous signaling molecules. The potential for CYP-
selective metabolism of xenobiotics coupled to their broad substrate specificity provides a unique opportunity to design drugs
whose activity is dependent on a critical functional group that can be unmasked or restored by CYP metabolism selectively
in tumor tissue. We have identified duocarmycin natural products which lend themselves to being great candidates for use in
prodrug strategies. The electronic distribution and lipophilicity of the embedded chloromethylindoline trigger fragment is a
key determinant in regioselective oxidation by specific CYP isoforms. We have synthesized and biologically evaluated several
libraries of duocarmycins and have shown them to be bioactivated by CYP1A1 and 2W1 in cell-free and cell-based assays. At
the meeting we will update on novel data from our drug discovery programme, which include single agent and combination
treatment with standard of care drugs using colorectal cancer xenograft models.
Biography
Klaus Pors is anAssociate Professor of Chemical Biology at The Institute of Cancer Therapeutics, University of Bradford, UK. His research group is involved with discovery
of novel biological and chemical tools to explore the importance of enzymes in different disease states. Particular focus is on exploiting abnormal cytochrome P450
(CYP), aldehyde dehydrogenase (ALDH) or aldo-keto reductase (AKR) expression in the tumour microenvironment as target for biomarker and drug discovery; he has
published 35 papers on these topics. He is a RSC Chemical Biology and Bioorganic Group committee member and the European Editor of Journal of Cancer Metastasis
and Treatment.
k.pors1@bradford.ac.ukKlaus Pors, J Biotechnol Biomater 2019, Volume 9
DOI: 10.4172/2155-952X-C2-115