Chemogenomic set

Screened at 10 µM, closest target: Ki(TMEM97) = 1107.9 nM; Screened against 122 enzymes, receptors, transporters and ion channels (Leadprofiling screen, Ricerca) at 10 µM, closest targets: IC50(MAPK3) = 4.87 µM, IC50(MAPK14) = 10.7 µM, IC50(CNR1) = 3.44 µM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % contr.: CDK5 (0%), CLK4 (0%), MAP3K13(0%), PRKAA1(39%)

Screened at 10 µM against 75 receptors, ion channels and other enzymes, closest targets as % inhibition: EDNRB (56%), OPRD1 (62 %); in vitro follow up: Ki(EDNRB) = 13000 nM; Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest target as % inhibition: HRH1(54%); In vitro follow up: Ki(HRH1) >10 µM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets: CDK5 (0%), CLK4 (0%), MAP3K13 (0%);

Screened at 1 µM, closest target: Ki(OPRD1) = 47.5 nM; Potency against NPFFR2 (GPR74) and NPFFR1 (GPR147) >30 fold;

Screened at 10 µM (binding assay), closest targets as % inhibition: EDNRA (97.1%), BZD peripheral (72.1%), CCK (63.1%), Cl- channel (77.4%); In vitro follow up of closest target: IC50(EDNRA) = 4.28 µM (>600-fold selective, EDNRB- dependent phosphatidylinositol hydrolysis assay in MMQ cells); Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets: FLT3(ITD,F691L) (13%), NEK5(29%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest target as % inhibition: HRH1 (36%); Screened in Eurofins-Cerep panel against 7 targets at 10 µM (enzymes and uptake assays): clean profile;

Screened at 10 µM, no target >50% of inhibition; F-04418948 displayed >2000-fold functional selectivity for the human EP2 receptor over antagonist activity against the human EP1, EP3, EP4, DP1 and CRTH2 receptors; Selectivity over human IP, FP, TP and LTB4 receptors; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: PRKAA2 (28%), TAOK3 (35%), PIK3CA (42%); Screened in CEREP ligand profiling (at 10 µM, against 125 targets), closest targets: IC50(NQO2) = 0.53 µM, IC50(PDE3) = 3.5 µM, IC50(LTB4R) = 9.7 µM

Screened at 10 µM, closest target: Ki(ADRB1) = 1.88 µM; Screened in CEREP panel of CCRs at 10 µM: >1000-fold selective over other CCRs (CCR10, CCR9, CCR6, CCR4, all >90% of control); Screened against 69 receptors (Eurofins-Panlabs screen) at 10 µM, closest target as % inhibition: DATRANS (71%); Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: NRD2 (34%), LRRK2 (43%)

Closest targets: Ki(DRD2) = 369.37 nM, Ki(TMEM97) = 489.44 nM, Ki(HTR6) = 748.23 nM; Screened against 45 GPCR targets (PDSD screen) at 10 µM, closest targets: Ki(D2) = 369.37 nM, Ki(5-HT6)= 748.23 nM, Ki(Sigma2) = 489.44 nM, Ki(DAT) = 1109 nM; Screened against 468 kinases (KINOMEscan DiscoverX) at 10 µM, closest targets: Kd(BTK) = 27 µM, Kd(MAPK8) = 19 µM, Kd(MAPK10) >30 µM, PMID: 28288109;

Highly selective in GPCR screen at 10 µM, clostest target: Ki(5-HT1A) = 849.9 nM