. 2023 Oct 16;13(43):30118–30128. doi: 10.1039/d3ra04874h

Kinases–ligand interactions recorded during docking. The recorded interactions during kinase–ligand docking are as follows: hydro I. represents hydrophobic interactions, HB refers to hydrogen bond interactions, WM denotes water-mediated interactions, and π–π signifies π-stacking interactions. Ref. ligand refers to the ligand that co-crystallizes with each respective kinase.

Kinase	Compound 4a dock score (kcal mol⁻¹)	Compound 4b dock score (kcal mol⁻¹)	Ref. ligand dock score (kcal mol⁻¹)	Compound 4a interactions	Compound 4b interactions	Ref. ligand interactions
CSFR1	−7.60	−8.27	−11.18	Hydro. I: Met637, Cys774, Asp796, Ile646, Phe797, Val647, Leu640	Hydro. I: Met637, Ile636, Thr663, Asp796, Ile646, Ile794, Val647	Hydro. I: Phe797, Glu664, Val596, Val647, Cys666, Tyr665
CSFR1	−7.60	−8.27	−11.18	HB: Glu633, Gly795	HB: Asp796	HB: Asp796, Cys666
AKT2	−6.05	−4.27	−10.42	Hydro. I: Met229, Asp293, Glu236, Met282, Gly161, Phe439, Thr213	Hydro. I: Lys160, Val166, Thr292, lys181, Gly161	Hydro. I: lys181, Val166, Tyr231, Gly164, Met229, Met282, Ala232, Thr292, Phe439
AKT2	−6.05	−4.27	−10.42	HB: Tyr231, Arg6, Glu230	HB: Asp293, Glu236, Arg6, π-cation Arg6	HB: Glu230, Ala232, Asp293
HER2	−8.81	−5.52	−10.74	Hydro. I: Met801, Leu800, Lys753, Asp863, Met801, Leu852, Thr733	Hydro. I: Met801, Lys753, Thr862, Cys805, Gly727, Leu852	Hydro. I: Leu796, Met774, Phe864, Gln799, Leu852
HER2	−8.81	−5.52	−10.74	HB: Asp863, Ile752	HB: Phe864, Arg849	HB: Leu796, Asp863, Lys753, Met801, Cys805
PDGFRA	−6.94	−6.10	−9.37	Hydro. I: Cys677, Leu599, Ala625, Ala840,Val607, Arg841	Hydro. I: Phe678, Tyr679, Leu599, Ala840, Cys677	Hydro. I: Tyr679, Asn684, Phe679, Leu599, Ala840, R841, K627
PDGFRA	−6.94	−6.10	−9.37	HB: Aromatic HB Glu675	HB: Asp681, Arg841, Cys677	HB: Asp681, Cys677, salt bridge Asp681
BRAF	−7.70	−7.83	−11.0	Hydro. I: Trp531, Asp594, Gly466, Thr526	Hydro. I: Gly466, Leu514, Asp594, Ile527, Asn581, Gly593	Hydro. I: Trp531, Ile527, Phe583, Gly466, Lys483
BRAF	−7.70	−7.83	−11.0	HB: Phe583 (π–π), Cys532, Ser536 (WM) Trp531(WM)	HB: Cys532, Asp594	HB: Glu501, Cys532, Asn580 (WM)
MEK2	−6.24	−4.70	−9.60	Hydro. I: Arg193, Lys196, Leu119, Leu219, Cys211, Phe213, Lys101	Hydro. I: Met234, Arg193, Lys196, Leu119, Leu219, Cys211	Hydro. I: Lys196, Arg193, Leu119, Leu219, Met141
MEK2	−6.24	−4.70	−9.60	HB: Ser216	HB: Lys101	HB: Asp194, Lys101, Phe213 (π–π), Val131
JAK	−9.25	<3.0	−10.9	Hydro. I: Met929, Tyr931, Gly993, Leu855	Hydro. I: —	Hydro. I: Met929, Tyr931, Gly993, Leu855, Arg980, Asn981, Gly935
JAK	−9.25	<3.0	−10.9	HB: Glu930, Leu932, Leu983 (WM)	HB: —	HB: Glu930, Leu932
AKT1	−6.90	<3.0	−11.2	Hydro. I: Asp292, Lys158, Lys276, Asn279, Thr291	Hydro. I: —	Hydro. I: Asn279, Phe438, Lys279, Asp292, Ala230, Met281
AKT1	−6.90	<3.0	−11.2	HB: Ala230	HB: —	HB: Ala230,Glu228, Met281, Glu234, Asn279