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- W4292169364 abstract "Abstract Activity cliffs (ACs) are defined as pairs of structurally similar compounds with large difference in their potencies against certain biotarget. We recently proposed that potent AC members induce significant entropically‐driven conformational modifications of the target that unveil additional binding interactions, while their weakly‐potent counterparts are enthalpically‐driven binders with little influence on the protein target. We herein propose to extract pharmacophores for ACs‐infested target(s) from molecular dynamics (MD) frames of purely “enthalpic” potent binder(s) complexed within the particular target. Genetic function algorithm/machine learning (GFA/ML) can then be employed to search for the best possible combination of MD pharmacophore(s) capable of explaining bioactivity variations within a list of inhibitors. We compared the performance of this approach with established ligand‐based and structure‐based methods. Kinase inserts domain receptor (KDR) was used as a case study. KDR plays a crucial role in angiogenic signalling and its inhibitors have been approved in cancer treatment. Interestingly, GFA/ML selected, MD‐based, pharmacophores were of comparable performances to ligand‐based and structure‐based pharmacophores. The resulting pharmacophores and QSAR models were used to capture hits from the national cancer institute list of compounds. The most active hit showed anti‐KDR IC 50 of 2.76 μM." @default.
- W4292169364 created "2022-08-18" @default.
- W4292169364 creator A5021040056 @default.
- W4292169364 creator A5039196671 @default.
- W4292169364 creator A5059351261 @default.
- W4292169364 creator A5079521314 @default.
- W4292169364 date "2022-09-01" @default.
- W4292169364 modified "2023-10-18" @default.
- W4292169364 title "Pharmacophore Modeling of Targets Infested with Activity Cliffs <i>via</i> Molecular Dynamics Simulation Coupled with QSAR and Comparison with other Pharmacophore Generation Methods: KDR as Case Study" @default.
- W4292169364 cites W1565103836 @default.
- W4292169364 cites W1608885177 @default.
- W4292169364 cites W1839471912 @default.
- W4292169364 cites W1964321215 @default.
- W4292169364 cites W1964605826 @default.
- W4292169364 cites W1964869969 @default.
- W4292169364 cites W1965364481 @default.
- W4292169364 cites W1969855058 @default.
- W4292169364 cites W1976262446 @default.
- W4292169364 cites W1977903211 @default.
- W4292169364 cites W1978483047 @default.
- W4292169364 cites W1978506033 @default.
- W4292169364 cites W1980264281 @default.
- W4292169364 cites W1981737096 @default.
- W4292169364 cites W1990627326 @default.
- W4292169364 cites W1992610234 @default.
- W4292169364 cites W1993746685 @default.
- W4292169364 cites W1997295815 @default.
- W4292169364 cites W1998025025 @default.
- W4292169364 cites W2000292756 @default.
- W4292169364 cites W2002359419 @default.
- W4292169364 cites W2002503643 @default.
- W4292169364 cites W2005377760 @default.
- W4292169364 cites W2005518172 @default.
- W4292169364 cites W2007986629 @default.
- W4292169364 cites W2008061399 @default.
- W4292169364 cites W2010933199 @default.
- W4292169364 cites W2014060139 @default.
- W4292169364 cites W2014276094 @default.
- W4292169364 cites W2015080758 @default.
- W4292169364 cites W2017975014 @default.
- W4292169364 cites W2019096305 @default.
- W4292169364 cites W2019980219 @default.
- W4292169364 cites W2020160932 @default.
- W4292169364 cites W2030004217 @default.
- W4292169364 cites W2032347891 @default.
- W4292169364 cites W2032395997 @default.
- W4292169364 cites W2034541070 @default.
- W4292169364 cites W2035387891 @default.
- W4292169364 cites W2035992044 @default.
- W4292169364 cites W2041662325 @default.
- W4292169364 cites W2043757581 @default.
- W4292169364 cites W2047603685 @default.
- W4292169364 cites W2047709056 @default.
- W4292169364 cites W2048543398 @default.
- W4292169364 cites W2052922662 @default.
- W4292169364 cites W2054198001 @default.
- W4292169364 cites W2055701360 @default.
- W4292169364 cites W2058698413 @default.
- W4292169364 cites W2059228661 @default.
- W4292169364 cites W2060803687 @default.
- W4292169364 cites W2061669497 @default.
- W4292169364 cites W2062594120 @default.
- W4292169364 cites W2063544208 @default.
- W4292169364 cites W2066171949 @default.
- W4292169364 cites W2067484324 @default.
- W4292169364 cites W2069258346 @default.
- W4292169364 cites W2070753604 @default.
- W4292169364 cites W2071659281 @default.
- W4292169364 cites W2075216460 @default.
- W4292169364 cites W2076200054 @default.
- W4292169364 cites W2078877418 @default.
- W4292169364 cites W2079967481 @default.
- W4292169364 cites W2081065649 @default.
- W4292169364 cites W2081285751 @default.
- W4292169364 cites W2083497194 @default.
- W4292169364 cites W2084588841 @default.
- W4292169364 cites W2084630618 @default.
- W4292169364 cites W2085526045 @default.
- W4292169364 cites W2086190523 @default.
- W4292169364 cites W2086979769 @default.
- W4292169364 cites W2087300213 @default.
- W4292169364 cites W2089756110 @default.
- W4292169364 cites W2092174614 @default.
- W4292169364 cites W2094966898 @default.
- W4292169364 cites W2099783548 @default.
- W4292169364 cites W2103293485 @default.
- W4292169364 cites W2105380402 @default.
- W4292169364 cites W2108508060 @default.
- W4292169364 cites W2110477693 @default.
- W4292169364 cites W2110872379 @default.
- W4292169364 cites W2113788015 @default.
- W4292169364 cites W2114796829 @default.
- W4292169364 cites W2116480660 @default.
- W4292169364 cites W2116773587 @default.
- W4292169364 cites W2117620409 @default.
- W4292169364 cites W2118405368 @default.
- W4292169364 cites W2119395197 @default.
- W4292169364 cites W2122932522 @default.
- W4292169364 cites W2134473756 @default.
- W4292169364 cites W2136362490 @default.