PhD Scientific Days 2018

Poster presentations: Pathology

Computer aided design of new selective inhibitors against KRAS G12C

Előadó neve

Orgován, Zoltán

Az előadás címe

Computer aided design of new selective inhibitors against KRAS G12C

Szerző(k) neve és munkahelye

Zoltán Orgován, György M. Keserű
RCNS-HAS, Medicinal Chemistry Research Group

Bemutatás módja

Poszter

Szekció

Poster presentations: Pathology

Language of the presentation

English

Összefoglaló szövege

KRAS is one of the most interesting oncogenic targets, as its mutations play a role in high percentage of oncological indications such as lung cancer and colorectal cancer. Despite of the 30 years of research, selective inhibitors against KRAS mutants are rare. The extreme affinity of its native GTP/GDP ligand and the limited structural differences between the apo and mutated protein suggest covalent inhibitors as a promising approach. The design of covalent inhibitors for KRAS is challenging, because the active site of the protein is accommodated near to a highly flexible loop. Since all of the known covalent docking programs treat the protein rigid, the predictive power of these tools is limited. We used induced fit docking simulations combined with covalent docking in order to render the binding pocket suitable for the ligand and to form the covalent bound. With this methodology most of the experimental ligand binding conformations were reproducible, therefore this method could be useful in designing new covalent KRAS inhibitors. This work is supported by NVKP-16-1-2016-0020.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2981

Authors (legacy)

Zoltán Orgován, György M. Keserű
RCNS-HAS, Medicinal Chemistry Research Group