EUB0001326b_CDK6

Screened at 1 µM using Km =ATP, closest targets as % of inhibition: CDK4(cyclinD3, 102.4%), CDK6(cyclinD3, 101.7%), CLK1 (100.3%), HIPK2(88.9%), MAP2K5 (84.8%), FLT3(84.5%), ERK5(77.9%), NTRK1(72.7%), CLK2(72.5%), PKD3(72.1%), PKD2(71.9%), PKR(71.4%), DYRK1B(70.5%), PKD1(69.1%), PEK(68.8%), HIPK3(63.4%), HIPK4(62.5%), NUAK2(61.9%), CDK9(cyclinT1, 59.8%), HIPK1(57.4%), CAMK2D(54%), TSSK1(53.5%), DYRK3(52.3%), MER(52.2%); In-vitro potency of closest targets (biochemical dose-responce assay using ATP = Km, Carna Biosciences): Ki(CLK1) = 16 nM, Ki(FLT3) = 53 nM, Ki(HIPK2) = 70 nM, Ki(MAP2K5) = 90 nM, Ki(ERK5) = 129 nM, Ki(DYRK1B) = 162 nM, Ki(CLK2) = 176 nM, Ki(PKD3) = 204 nM, Ki(PKR) = 241 nM, Ki(PKD2) = 277 nM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened against 17 non-kinase proteins (CEREP ligand displacement assays), in-vitro potency of closest targets: EC50(Adren Alpha 1a) >10 µM, EC50(Dopamine 1) >10 µM, EC50(Histamine 1) >10 µM, EC50(Muscarinic 1) >10 µM, EC50(5HT2b) >10 µM, EC50(Adren Beta 2) >10 µM, EC50(Cannabinoid 1) >10 µM, EC50(Mu Opioid) >10 µM, EC50(SERT) >10 µM, EC50(DAT) >10 µM, EC50(NET) >10 µM, EC50(PDE3A1) >180 µM, EC50(PDE4D3) = 3.4 µM, EC50(PDE5A1) = 2.9 µM, EC50(L-Type Calcium) >20 µM, EC50(Sodium, Nav1.5) >10 µM, EC50(BRD4) >25 µM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened at 1 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (2%), PKD1 (44%), ERK8 (47%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened at 10 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (8%), DYRK1A (9%), ERK8 (13%), CK2 (13%), MELK (14%), GCK(15%), DYRK3 (16%), PKD1 (18%), PLK1 (18%), NTRK1(18%), TAK1(21%), PHK (22%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened against 520 kinases (competition-binding assay), closest targets: Kd(CDK6) = 76 nM, Kd(PIP4K2A) = 208 nM, Kd(CLK1) = 276 nM, Kd(CSNK2B) = 448 nM, Kd(CSNK2A2) = 488 nM, Kd(CDK4) = 572 nM, Kd(EIF3J) = 701 nM, Kd(CSNK2A1/A3) = 760 nM, Kd(MAP2K4) = 1251 nM, Kd(CDK17) = 1272 nM, Kd(CCNT2) = 1665 nM, Kd(PIP4K2C) = 1721 nM, Kd(CCNT1) = 2676 nM, Kd(CDK16) = 2778 nM, Kd(MAPK9) = 2856 nM, Kd(MED23) = 2998 nM, Kd(AAK1) = 4216 nM, Kd(PRKD2) = 5623 nM, Kd(CDK9) = 9492 nM, Kd(STK16) = 9969 nM, Kd(TAOK3) = 15852 nM, Kd(PRKD3) = 16296 nM, Kd(BMP2K) = 26466 nM, Kd(Q6ZSR9) = 27334 nM, Kd(TAOK2) = 27973 nM, https://pubmed.ncbi.nlm.nih.gov/29191878/;