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Lecture Notes in Computer Science, volume 11958 LNCS, pages 348-355
Large-Scale Prediction of the ARS Family Inhibitors of the Oncogenic KRASG12C Mutant
Publication type: Book Chapter
Publication date: 2020-02-13
Journal:
Lecture Notes in Computer Science
Quartile SCImago
Q3
Quartile WOS
—
Impact factor: —
ISSN: 03029743, 16113349, 18612075, 18612083
Abstract
The KRAS protein is a molecular switch that activates cellular processes, like cell growth and differentiation. The G12C point mutation of the KRAS is found in various cancer cells. It results in the accretion of the GTP-bound active form thus accelerating downstream signalling pathways. Recently ARS family of compounds was suggested as selective covalent inhibitors of the KRASG12C. The most prospective ARS-853 has IC
$$_{50}$$
= 1.6
$$\upmu $$
M that is too large for the medicinal applications. We demonstrate that calculated dissociation constants K
$$_\mathrm{d}$$
are proportional to the experimental IC
$$_{50}$$
values and can be utilized as a measure of the inhibitor potency. Using molecular modeling tools we suggest a set of novel compounds with the predicted IC
$$_{50}$$
values more than an order of magnitude lower than that of the ARS-853.
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Kulakova A. M. et al. Large-Scale Prediction of the ARS Family Inhibitors of the Oncogenic KRASG12C Mutant // Lecture Notes in Computer Science. 2020. Vol. 11958 LNCS. pp. 348-355.
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Kulakova A. M., Popinako A. V., Khrenova M. G. Large-Scale Prediction of the ARS Family Inhibitors of the Oncogenic KRASG12C Mutant // Lecture Notes in Computer Science. 2020. Vol. 11958 LNCS. pp. 348-355.
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TY - GENERIC
DO - 10.1007/978-3-030-41032-2_40
UR - https://doi.org/10.1007%2F978-3-030-41032-2_40
TI - Large-Scale Prediction of the ARS Family Inhibitors of the Oncogenic KRASG12C Mutant
T2 - Lecture Notes in Computer Science
AU - Kulakova, Anna M
AU - Popinako, Anna V
AU - Khrenova, Maria G.
PY - 2020
DA - 2020/02/13 00:00:00
PB - Springer Nature
SP - 348-355
VL - 11958 LNCS
SN - 0302-9743
SN - 1611-3349
SN - 1861-2075
SN - 1861-2083
ER -
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@incollection{2020_Kulakova,
author = {Anna M Kulakova and Anna V Popinako and Maria G. Khrenova},
title = {Large-Scale Prediction of the ARS Family Inhibitors of the Oncogenic KRASG12C Mutant},
publisher = {Springer Nature},
year = {2020},
volume = {11958 LNCS},
pages = {348--355},
month = {feb}
}
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