Chemogenomic set

IC50 >20 µM for all targets tested

Screened at 1 µM, closest targets as % of contr.: MYLK4 (1.8%), MEK1 (4.5%), RIPK5 (5.2%), IRAK3 (9.2%), MEK2 (9.6%), DYRK1A (9.9%), YSK4 (9.9%), ULK3(11%), MEK4 (12%), HASPIN (13%), STK16 (14%), CLK2 (20%), CDK7 (20%), IRAK4 (21%), AURKB (23%), DYRK1B (26%), CLK1 (30%), RIOK2 (32%), CLK4 (34%), PIP4K2C (53%), MAP4K5 (96%); In-vitro follow-up of closest targets: IC50(MYLK4) = 66 nM, IC50(MEK1) >10000 nM, IC50(RIPK5) >10000 nM, IC50(MEK2) >10000 nM, IC50(DYRK1A) = 2040 nM, IC50(YSK4) = 4020 nM, IC50(ULK3) >10000 nM, IC50(MEK4) >10000 nM, IC50(HASPIN) = 1400 nM, IC50(STK16) = 560 nM, IC50(CLK2) = 290 nM, IC50(CDK7) >10000 nM, IC50(IRAK4) = 4500 nM, IC50(AURKB) = 1400 nM, IC50(DYRK1B) = 380 nM, IC50(CLK1) = 420 nM, IC50(CLK4) = 440 nM, IC50(PIP4K2C) = 1900 nM, IC50(MAP4K5) = 89 nM; In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(MYLK4) = 270 nM, IC50(PIP4K2C) >10000 nM, IC50(MAP4K5) >10000 nM (https://www.thesgc.org/chemical-probes/sgc-pikfyve-1)

Screened at 10 µM, in-vitro potencies of closest targets: Ki(TMEM97) = 226 nM, Ki(HRH4) = 3382 nM, Ki(HTR2C) >10000 nM, Ki(DRD2) >10000 nM; Selectivity within target family (competition fluorescence polarization binding assay): Kd(FKBP1A) = 116.4 nM, Kd(FKBP1B) = 38.9 nM, Kd(FKBP2) = 1053 nM, Kd(FKBP3) >10 µM, Kd(FKBP4) >50 µM; In-cellular follow up of closest targets within family (NanoBRET assay in HEK293T cells, FKBP51-NLuc): IC50(FKBP1A) = 771 nM, IC50(FKBP1B) = 80 nM, IC05(FKBP4) = 1409 nM

Screened at 10 µM, closest targets as % of inhibition: ALOX5 (85%), TBXAS1 (64%), EGFR (61%), MAPK14 (60%), TBXA2R (60%), others >10 µM

Screened at 10 µM, closest targets as % of inhibition: LYN (70%), MAPK14 (66%), PKC non-selective (-114%), others >10 µM

Screened in Ca2+ influx assay (using CHO cells expressing NMDA receptor subtype in the presence of glutamate at an EC30 concentration): EC50(GluN2A) = 0.51 µM, max potentiation at 30 µM = 350%; EC50(GluN2B) n.d., max potentiation at 30 µM <150%, EC50(GluN2C) >30 µM, max potentiation at 30 µM = 200%, EC50(GluN2D) = 9.6 µM, max potentiation at 30 µM = 260%; AMPA binding (scintillation proximity assay, SPA, with 100 µM glutamate): IC50 >30 µM; Screened at 10 µM against 47 targets (SAFETYscan assays, DiscoverX), in-vitro potencies of targets: IC50(PDE3A) = 7.9 µM (56% inhibition), others IC50 >10 µM

Screened in Ca2+ influx assay (using CHO cells expressing NMDA receptor subtype in the presence of glutamate at an EC30 concentration): EC50(GluN2A)>30 µM, max potentiation at 30 µM <150%; AMPA binding (scintillation proximity assay (SPA) with 100 µM glutamate): IC50 >30 µM

Screened at 1 µM, closest targets as % of inhibition: FLT3 (90.8%), MAP4K4 (86.3%), MINK1 (80.5%), NTRK1 (71%), NTRK2 (86%), JAK1 (83.5%), JAK2 (80.5%), LRRK2 (91.4%), TAK-TAB (74.5%); In-vitro potency of closest targets (Z'-Lyte kinase biochemical assay, conc. ATP = Km(app), Thermo Fisher Scientific): IC50(FLT3) = 177 nM, IC50(MAP4K4) = 680 nM, IC50(MINK1) = 879 nM, IC50(NTRK1) = 313 nM, IC50(NTRK2) = 259 nM, IC50(JAK1) = 282 nM, IC50(JAK2) = 486 nM, IC50(LRRK2) = 198 nM, IC50(TAK-TAB) = 966 nM (https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00380); In-cellulo follow-up of closest targets (NanoBRET assay, HEK293T cells): EC50(LRRK2) = 5.2 µM, EC50(NTRK2) = 5.6 µM, EC50(NTRK1) = 11 µM, EC50(FLT3) >50 µM, EC50(JAK1) >50 µM, EC50(JAK2) >50 µM (https://www.sgc-ffm.uni-frankfurt.de/chemProbes#!specificprobeoverview/GNE-2256);

Screened at 10 µM, closest targets as % of inhibition: OPRK1 (78%), rat ADORA2A (69%), human OPRM1 (55%); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(OPRK1) = 773.3 nM

Screened at 10 µM, in-vitro potencies of closest targets: Ki(SIGMAR1) = 63.33 nM, Ki(TMEM97) = 1399.16 nM, Ki(SLC6A4) = 2614.09 nM, Ki(ADRA2B) = 3691.26 nM, Ki(SLC6A3) = 5284.45 nM

Screened at 1 µM, clean selectivity profile with no kinase inhibited >60%; Screened at 10 µM against 77 targets outside the target family (Eurofins safety panel), closest targets as % of inhibition: TBXAS1 (98%), HTR2B (98%), MAOB (81%), PDE3 (74%), PDE5A (62%);

Screened at 10 µM, in-vitro potencies of closest targets: IC50(HTR6) = 4.6 µM, IC50(AVPR1A, human) = 7.1 µM, IC50(PTGER1) >30 µM, IC50(PTGER2) >30 µM; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(HTR1E) >10 µM, Ki(HTR5A) = 1.625 µM

Screened at 10 µM, in-vitro potencies of closest targets: Ki(OPRD1) = 597.96 nM, Ki(GABA/PBR) = 733.68 nM, Ki(HTR6) = 1523.62 nM, Ki(SLC6A3) = 9585.29 nM

Screened at 3 µM against PPARa/d/g, LXRa/b, CAR, FXR, GR, Era/b, Tra/b, VDR, PXR, RXRa: clean selectivity profile with no significant agonism/antagonism detected; Screened at 1 µM and 10 µM in CEREP panel against 50 receptors and other enzymes: clean selectivity profile with no target inhibited >50%; Screened at 10 µM against 50 kinases (DiscoverX), clean selectivity profile with no target inhibited >50%; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(TMEM97) = 636.99 nM, Ki(SIGMAR1) = 3125.58 nM, Ki(ADRA2B) = 9223.59 nM

Selective versus other PDE family members (>250 fold in Scintillation proximity assays): Ki(hPDE1B1) = 3.4 µM, Ki(hPDE2A) = 32 µM, Ki(hPDE3A) = 49 µM, Ki(hPDE4D3) = 15 µM, Ki(hPDE5A3) = 8.5 µM, Ki(hPDE6AB) = 85 µM, Ki(hPDE7A1) = 23 µM, Ki(hPDE8A1) = 41 µM, Ki(hPDE9A) >33 µM, Ki(hPDE10A2) = 0.013 µM, Ki(hPDE11A4) = 46 µM; Screened at 10 µM in CEREP panel against 50 receptors and other enzymes: clean selectivity profile; Screened at 10 µM against 230 kinases (Millipore panel): clean selectivity profile with no inhibition of kinases <50%; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(ADRA2B) >10 µM, Ki(HTR2C) = 2.197 µM, Ki(HTR2B) = 2.293 µM, Ki(HTR7) = 8.745 µM

Screened at 10 µM, in-vitro potencies of closest targets: Ki(GABAA) = 1.822 µM, Ki(SLC6A3) = 4.132 µM

Screened at 1 µM, clean selectivity profile with no kinase inhibited >50%; Screened at 10 µM against 45 GPCRs (PDSP screen), in vitro-potencies of closest targets: Ki(HTR2C) = 373.79 nM, Ki(GABAA/BZP) = 511.7 nM, Ki(HTR1D) = 417.5 nM, Ki(HTR2B) = 699.39 nM, Ki(SLC6A2) = 1935.54 nM, Ki(ADRA2B) = 2570.64 nM, Ki(ADRA2C) = 3432.79 nM

Screened at 10 µM, in-vitro potencies of closest targets: Ki(HRH3) = 92.76 nM, Ki(SIGMAR1) = 125.1 nM, Ki(HRH2) = 148.82, Ki(HTR2C) = 266.79 nM, Ki(HTR2B) = 290.75 nM, Ki(HTR7) = 334.53 nM, Ki(ADRA2C) = 414.29 nM, Ki(ADRA2B) = 475.35 nM, Ki(HTR6) = 606.4 nM, Ki(HTR2A) = 757.58 nM, Ki(HRH4) = 711.87 nM, Ki(SLC6A3) = 864.98 nM, Ki(TMEM97) = 1463.21 nM, Ki(HTR1D) = 2037.31, Ki(SLC6A2) = 3112.25 nM, Ki(HTR5A) = 6131.61 nM

Screened at 10 µM, in-vitro potency of closest target: Ki(SIGMAR1) = 3.429 µM; No inhibition of other deubiquitylating enzymes in activity-based protein profiling assay (ABPP) experiment; Selectivity outside target family (2‐step labeling Pull‐down proteomics experiment): off-target PARK7 (has cysteine in active site) identified

Screened at 10 µM, in-vitro potency of closest target: Ki(SLC6A3) >10 µM, Ki(ADRA2A) >10 µM

Screened at 10 µM, in-vitro potencies of closest targets: Ki(SLC6A3) = 4270.11 nM, Ki(TMEM97) = 7307.71 nM

Screened at 10 µM, closest targets as % of contr.: CCKA/H (12%), DELTA2/H (47%)

Screened at 10 µM, clean selectivity profile with no target <80% of contrl.

Screened at 1 µM, closest targets as % of control: MAPK15 (2.5%), others >20%;

Screened at 1 µM, closest targets as % of control: MAPK15 (2.5%), others >20%;

Screened at 1 µM, closest targets as % of control: MAPK15 (2.5%), others >20%;

Screened at 1 µM, closest targets as % of contr: MAP3K3(8.2%), MAP4K2(3.4%), JAK3(2.7%), MST2(1.8%), MAP4K3(4.8%), RIOK3(4.8%), RSK4(9.8%), MST4(7%), PRKCE(12%), MEK1(13%), EGFR(L747-E749del, 14%), EGFR(L747-S752del,14%), MEK5(14%), MEST1(18%), MEK2(19%), PIP5K1A(20%); In-vitro potency of closest targets (Z-Lyte assay assay, Invitrogen, using 7.75 µM ATP): IC50(MST4) = 178 nM, https://pubs.acs.org/doi/10.1021/jm5014055;

Screened at 1 µM, closest targets as % of contr: MAP3K3(8.2%), MAP4K2(3.4%), JAK3(2.7%), MST2(1.8%), MAP4K3(4.8%), RIOK3(4.8%), RSK4(9.8%), MST4(7%), PRKCE(12%), MEK1(13%), EGFR(L747-E749del, 14%), EGFR(L747-S752del,14%), MEK5(14%), MEST1(18%), MEK2(19%), PIP5K1A(20%); In-vitro potency of closest targets (Z-Lyte assay assay, Invitrogen, using 7.75 µM ATP): IC50(MST4) = 178 nM, https://pubs.acs.org/doi/10.1021/jm5014055;

Screened at 200 nM, clean proteome-wide degradation selectivity, only target found CSNK1A1;

Screened at 1 µM, closest targets as % of inhibition: P70S6K (47%), SGK (39%), CDK1 (cyclinB, 2%), CDK2 (cyclinA, -7%), CDK2 (cyclinE, 18%), CDK3 (cyclinE, 2%), CDK5(p25, -1%), CDK5 (p35, -1%), CDK6 (cyclinD3, 12%), CDK7 (cyclinH/MAT1, 7%), CDK9 (cyclinT1, 13%); In-vitro potency of closest targets (enzymatic assays): IC50(GSK3A) = 691 nM, IC50(FLT3) >30 µM, IC50(NTRK3) >30 µM; Screened at 10 µM against 59 receptors and ion channels (CEREP panel, binding assay), closest targets as % of inhibition: A1 (48%), D2 (54%); In-vitro potency of closest targets (CEREP binding assay): IC50(D2) = 8.5 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00597#;

Screened at 1 µM, closest targets as % of inhibition: CSNK1G1 (43%), MAPK10 (51%), TAOK3 (n.d.); Screened at 1 µM (Select Screen profiling, Lantha screen, 143 kinases), closest targets as % of displacement: DYRK2 (80%), STK39 (82%), TAOK3 (94%), https://pubmed.ncbi.nlm.nih.gov/30067358/; Screened at 1 µM (Select Screen profiling, Adapta assay, https://pubmed.ncbi.nlm.nih.gov/30067358/;
In-vitro potency : IC50(CDK2) >100 µM (CDK2/CCNA2 radiometric assay), IC50(CDK9) = 16 µM (Enzyme Inhibition Assay using the LANCE System), IC50(CDK8) >10 µM (TR-FRET assay), IC50(CDK7)>10 µM (TR-FRET assay), IC50(CDK13) = 10 nM (Enzyme Inhibition Assay using the LANCE System), https://pubmed.ncbi.nlm.nih.gov/30067358/;

Screened at 10 µM, closest targets as % of contr.: GSK3B (3%), GSK3A (4%), KIT (6%), CDK3 (cyclinE, 10%), EPHB1 (11%), CAMK2B (13%), CDK2 (cyclinE, 13%), CDK1 (cyclinE, 14%), YES (14%), ARG (16%), CDK5(p35, 20%), EPHA1 (20%), NTRK1(20%), CAMK2G (21%), CAMK2D (22%), LYN(23%), FYN(24%), MLK1(24%), IRAK1(27%), SRC(28%), FGR(29%), FLT4(30%); In-vitro potency of closest targets (Merck Millipore kinase assay using 10 µM ATP): IC50(ARG) = 2843 nM, IC50(CAMK2B) = 1650 nM, IC50(CAMK2G) = 2081 nM, IC50(CAMK2D) = 3340 nM, IC50(SRC) = 5293 nM, IC50(EPHA1) = 1737 nM, IC50(EPHB1) = 2032 nM, IC50(FGR) = 7754 nM, IC50(GSK3A) = 45 nM, IC50(GSK3B) = 87 nM, IC50(IRAK1) = 5454 nM, IC50(LYN) = 3514 nM, IC50(MLK1) = 3010 nM, IC50(YES) = 1495 nM;

Screened at 10 µM, closest targets as % of inhibition (using ATP = Km app): GSK3B (89%), GSK3A (82.2%), CSNK1E(48.9%); Screened at 10 µM against 31 kinases (Adapta Assay using ATP = Km app), closest targets as % of inhibition: LRRK2(I2020T, 100%), LRRK2 (100%), LRRK2(R1441C, 96.1%), LRRK2 (G2019S, 95%), SPHK2(67.7%), PIK3CD/PIK3R1 (p110 delta/p85 alpha, 66%), PIK3C2B (PI3K-C2 beta, 64.1%), CDK9/cyclin T1 (63.9%), SPHK1 (53.7%), GSG2 (45%), https://pubmed.ncbi.nlm.nih.gov/31668947/; In-vitro potency (enzymatic assay on full-lenght LRRK2): IC50(LRRK2) >10 µM, https://pubmed.ncbi.nlm.nih.gov/31668947/; Screened at 10 µM against 162 kinases (LanthaScreen Eu Kinase Binding Assay), closest targets as % of inhibition: TAOK1 (31.8%), CDK8/cyclinC (17%), CDK16(PCTK1)/cyclinY (15%), NLK(13.4%), CLK4(12.3%), SIK3(12.2%), https://pubmed.ncbi.nlm.nih.gov/31668947/; Screened at 10 µM against 20 kinases (Rxn Biology kinase assay using 10 µM ATP), targets as % of inhibition: GSK3B (96.5%), GSK3A (90.6%), CDK6/cyclin D1 (83.4%), CDK6/cyclin D3 (52.7%), CDK4/cyclin D1(46.7%), CDK4/cyclin D3(46.3%), MEK2(8.7%), AKT3(6.7%), MAPK1(5.8%), MEK1(4.5%), AXL(4.1%), EGFR(3.4%), ERBB2(2.6%), AKT2(1.6%), AKT1(0.2%), ERK1(-5.8%), MAPK15 (-25.6%), MAPK7(-29.8%), MET(-31.5%), MAPK7(-42.4%), https://pubmed.ncbi.nlm.nih.gov/31668947/;

Screened at 10 µM, closest targets as % of inhibition (using ATP = Km app): GSK3B (89%), GSK3A (82.2%), CSNK1E(48.9%); Screened at 10 µM against 31 kinases (Adapta Assay using ATP = Km app), closest targets as % of inhibition: LRRK2(I2020T, 100%), LRRK2 (100%), LRRK2(R1441C, 96.1%), LRRK2 (G2019S, 95%), SPHK2(67.7%), PIK3CD/PIK3R1 (p110 delta/p85 alpha, 66%), PIK3C2B (PI3K-C2 beta, 64.1%), CDK9/cyclin T1 (63.9%), SPHK1 (53.7%), GSG2 (45%), https://pubmed.ncbi.nlm.nih.gov/31668947/; In-vitro potency (enzymatic assay on full-lenght LRRK2): IC50(LRRK2) >10 µM, https://pubmed.ncbi.nlm.nih.gov/31668947/; Screened at 10 µM against 162 kinases (LanthaScreen Eu Kinase Binding Assay), closest targets as % of inhibition: TAOK1 (31.8%), CDK8/cyclinC (17%), CDK16(PCTK1)/cyclinY (15%), NLK(13.4%), CLK4(12.3%), SIK3(12.2%), https://pubmed.ncbi.nlm.nih.gov/31668947/; Screened at 10 µM against 20 kinases (Rxn Biology kinase assay using 10 µM ATP), targets as % of inhibition: GSK3B (96.5%), GSK3A (90.6%), CDK6/cyclin D1 (83.4%), CDK6/cyclin D3 (52.7%), CDK4/cyclin D1(46.7%), CDK4/cyclin D3(46.3%), MEK2(8.7%), AKT3(6.7%), MAPK1(5.8%), MEK1(4.5%), AXL(4.1%), EGFR(3.4%), ERBB2(2.6%), AKT2(1.6%), AKT1(0.2%), ERK1(-5.8%), MAPK15 (-25.6%), MAPK7(-29.8%), MET(-31.5%), MAPK7(-42.4%), https://pubmed.ncbi.nlm.nih.gov/31668947/;

Screened at 1 µM, closest targets as % of engagement: CDK7 (95.5%), MARK4(93.3%), AMPK1 (54.4%), AMPK2(53.5%), MST3(41.8%), CAMK2G (35.8%), CAMK2D(34.1%), TBK1(32.4%), SNRK(30.4%)

Screened at 1 µM, closest targets as % of control: PRKDC (-1%), PIK3C2G (-12%), MTOR (41%), full screening data are available as supporting information, https://pubmed.ncbi.nlm.nih.gov/34428039/;
In-cellular potency (Immunoblot assay, ATR dependent inhibition of histone H2AX -Ser139 phosphorylation (G-H2AX) in HT-144 cells): IC50(ATR) = 2360 nM, https://pubmed.ncbi.nlm.nih.gov/34428039/;

Screened at 1 µM, closest targets as % of control: PRKDC (-1%), PIK3C2G (-12%), MTOR (41%), full screening data are available as supporting information, https://pubmed.ncbi.nlm.nih.gov/34428039/;
In-cellular potency (Immunoblot assay, ATR dependent inhibition of histone H2AX -Ser139 phosphorylation (G-H2AX) in HT-144 cells): IC50(ATR) = 2360 nM, https://pubmed.ncbi.nlm.nih.gov/34428039/;

Screened at 1 µM, closest targets as % of control: ZAP70 (0.875%), MAP2K5 (1.3%), LRRK3(G2019S) = 1.3%), SYK(2.4%), NEK10(3.45%), LRRK2(4%), JAK1(JH2, 5%), TTK (5.75%), STK33(9.8%), Screened also at 10 µM, full screening data available at OpenMe website, https://www.opnme.com/molecules/syk-bi1002494; Screened at 10 µM and 1 µM against 383 kinases (Kinase panel, Invitrogen), closest targets at 1 µM as % of control: FER (2%), FES (5%), LRRK2 (3%), MAP3K9 (-3%), RET (V804L, 2%), STK22D (1%), SYK (-7%), full screening data available at OpenMe website, https://www.opnme.com/molecules/syk-bi1002494; Screened at 10 µM against 64 other enzymes (GPCRs, ion channels, SafetyScreen44™), closest targets as % of control: D2 (agonist, 3%), full screening data available at OpenMe website, https://www.opnme.com/molecules/syk-bi1002494;

Screened at 10 µM against panel of GPRCs, ion channels, and hydrolases, clean selectivity profile

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of contr.: COX-2 (80%), full screening data available on OpenMe website, https://www.opnme.com/molecules/slc13a5-bi01383298;

Screened at 10 µM against GPCRs, ion channels, and hydrolases, closest target as % of control: NA+/SITE2 (voltage-gated, 21%), full screening data available on OpenMe website, https://www.opnme.com/molecules/sos1-kras-inhibitor-bi-3406;

Screened at 1 µM, closest targets as % of control: LRRK2 (4%), LRRK2 (fl, 3%), PTK2 (-0.5%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ptk2-protac-bi-0319; Screened at 1 µM against 397 kinases (Kinase selectivity panels, Thermo Fischer SelectScreen Kinase Profiling Services), closest target >90 % of control: LRRK2, https://pubmed.ncbi.nlm.nih.gov/30739444/; Proteomics at 3 µM, using A549 cells treated for 18h, closest target (protein capillary electrophoresis): EC50 (PDE6D) >1 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01826; Screened at 10 µM against 44 other enzymes (SafetyScreen44™, GPCRS, ion channels, hydrolases), closest targets as % of control: CA+/DHPSI/R (Voltage-gated ion channel, 32%), DELTA2/H (GPCR, 35%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ptk2-protac-bi-0319;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: SLC6A4 (31%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: SLC6A4 (31%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: SLC6A4 (31%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest targets as % of control: Gcorticoid (43%), full screening data available on Open Me website, https://www.opnme.com/molecules/gpr40-agonist-bi-2081;

Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases, closest targets as % of control: COX-2 (86%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ncini-bi-224436;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of contr.: DELTA2 (38%), full screening data available on OpenMe website, https://www.opnme.com/search-results/BI-9307;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of contr.: DELTA2 (33%), full screening data available on OpenMe website, https://www.opnme.com/search-results/BI-9307;

Screened at 10 µM, closest targets as % of control: CCKA/H (75%), full screening data available on OPENme website;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of contr.: PDE4D2 (53%), full screening data available on OpenMe website, https://www.opnme.com/molecules/hcv-protease-bi-1388;

Screened at 10 µM against a panel of GPRCs, ion channels, and hydrolases, closest target as % of control: 5HT2B (72.3%), clean selectivity profile;

Screened at 10 µM against 121 GPCRs, ion channels, and kinases, closest target: M1 (13%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cathepsin-c-inhibitor-bi-9740;

Screened at 10 µM against a panel of GPCRS, ion channels, and other enzymes, closest targets as % of control: 5HT1A (54%), full screening data available on OPENMe website, https://www.opnme.com/molecules/chymase-bi-1942

Screened at 10 µM against 44 GPCRs, ion channels, and kinases, closest target as % of control: OPRM1 (81%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cathepsin-s-inhibitor-bi-1915;

Screened at 10 µM against 44 GPCRs, ion channels, and kinases, closest target as % of control: 5HT1B (61%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cathepsin-s-inhibitor-bi-1915;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest targets as % of control: PDE2A (1%), MAOB (51%), full screening data available on OpenMe website, https://www.opnme.com/molecules/pde2-inhibitor-bi-1960;

Screened at 10 µM against 121 GPCRs, ion channels, and kinases, closest target as % of control: KAPPA(KOP, 73%), full screening data available on OpenMe website, https://www.opnme.com/molecules/dpap1-inhibitor-bi-2051;

Screened at 10 µM against 121 GPCRs, ion channels, and kinases, closest target as % of control: NA+/SITE2(65%), full screening data available on OpenMe website, https://www.opnme.com/molecules/dpap1-inhibitor-bi-2051;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest targets as % of control: ALPHA2 (5.5%), PPARG (8%), ALPHA2C (23%), full screening data available on Open Me website, https://www.opnme.com/molecules/gpr40-agonist-bi-2081;

Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases, closest target as % of control: KAPPA(KOP) (67%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ncini-bi-224436;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of control: COX-1 (20%), full screening data available on OpenMe website, https://www.opnme.com/molecules/hiv-bi-2540;

Screened at 10 µM, closest targets as % of control: A2A (antagonist, 44%), M1 (45%), PDE4D2 (32%), full screening data available at OpenMe website, https://www.opnme.com/molecules/syk-bi1002494; Screened at 1 µM against 239 kinases (Invitrogen Kinase panel) identifying 23 kinases with >50% of control, clean selectivity profile, https://www.opnme.com/molecules/syk-bi1002494;

Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases, closest targets as % of control: 5HT2B (14%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cai-inhibitor-bi-3257;

Screened at 1 µM, closest targets as % of control: BMPR2 (41%), PLK4 (38%), full screening data available on OpenMe website, https://www.opnme.com/molecules/sos1-kras-inhibitor-bi-3406;
Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases (SafetyScreen44™), closest targets as % of control: ALPHA1A (antagonist, 7%), NA+/SITE2 (voltage-gated, 4%), full screening data available on OpenMe website, https://www.opnme.com/molecules/sos1-kras-inhibitor-bi-3406;

Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases, closest targets as % of control: PDE4D2 (5%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cai-inhibitor-bi-3257;

Screened at 10 µM against a panel of GPCRS, ion channels, and other enzymes, closest targets as % of control: 5HT2B (12%), full screening data available on OPENMe website, https://www.opnme.com/molecules/bcl6-bi-3802;
Screened at 10 µM against a panel of 54 kinases (Invitrogen Lab), closest target as % of control: MAP2K1 (71%), full screening data available on OPENMe website, https://www.opnme.com/molecules/bcl6-bi-3802;

Screened at 10 µM against a panel of GPCRS, ion channels, and other enzymes, closest target as % of control: M2 (13%), full screening data available on OPENMe website, https://www.opnme.com/molecules/bcl6-bi-3812;
Screened at 10 µM against a panel of 54 kinases (Invitrogen Lab), closest target as % of control: RAF1 (79%), full screening data available on OPENMe website, https://www.opnme.com/molecules/bcl6-bi-3802;

Screened at 10 µM, clean selectivity profile

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of control: 5HT2B (53%), full screening data available on OpenMe website, https://www.opnme.com/molecules/phgdh-inhibitor-bi-4916;

Screened at 10 µM against 44 GPCRs, ion channels, and hydrolases, closest targets as % of control: PDE3A (14%), full screening data available on OpenMe website, https://www.opnme.com/molecules/phgdh-inhibitor-bi-4924;

Screened at 10 µM against a panel of GPCRS, ion channels, and other enzymes, closest targets as % of control: MU (44%), full screening data available on OPENMe website, https://www.opnme.com/molecules/bcl6-bi-3802:

Screened at 10 µM against GPCRs, ion channels, and hydrolases, closest target as % of control: KAPPA (65%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ne-inhibitor-bi-5524;

Screened at 10 µM against GPCRs, ion channels, and hydrolases, closest target as % of control: 5HT3 (81%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ne-inhibitor-bi-5524;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of control: LCK (84%), full screening data available on OpenMe website, https://www.opnme.com/molecules/phgdh-inhibitor-bi-4916;

Screened at 10 µM against panel of GPCRs, ion channels, and other enzymes, closest targets as % of control: CANNABINOID2 (-13%), CB1 (4.5%), PEP4 (13%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cetp-inhibitor-bi-5756;

Screened at 10 µM against panel of GPCRs, ion channels, and other enzymes, closest target as % of control: MUSCARIN (78%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ccr10-bi-6901;

Screened at 10 µM against panel of GPCRs, ion channels, and other enzymes, closest target as % of control: M2 (8%), GCORTICOID (18%), full screening data available on OpenMe website, https://www.opnme.com/molecules/ccr10-bi-6901;

Screened at 10 µM against a panel of ion channels, GPCRs, hydrolases, and other enzymes, closest target as % of control: CCKA (57%), full screening data available on OpenMe website, https://www.opnme.com/molecules/hcv-polymerase-1-bi207127;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: M3 (20%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: M3 (20%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: M3 (20%), full screening data available on OpenMe website;

Screened at 10 µM against a panel of GPCRs, ion channels, and other enzymes, closest target as % of control: PDE4D2 (29%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cetp-inhibitor-bi-5756;

Screened at 10 µM against 121 GPCRs, ion channels, kinases, closest targets as % of control: KAPPA(5%), KAPPA(KOP, 16.8%), M1 (10%), 5HTUP (14%), full screening data available on OpenMe website, https://www.opnme.com/molecules/cathepsin-c-inhibitor-bi-9740;

Screened at 10 µM against panel of GPCRs, ion channels, and other enzymes, closest targets as % of control: MU (4%), DATRANS (17%), full screening data available on OpenMe website, https://www.opnme.com/molecules/npy1r-bibo3304;

Screened at 10 µM, closest targets as % of control: Cathepsin D (43%), full screening data available in supplement info, https://pubmed.ncbi.nlm.nih.gov/20823284/;
In-vitro potency (enzymatic assay): IC50(Cathepsin D) = 30 µM, https://pubmed.ncbi.nlm.nih.gov/20823284/;
Screened at 10 µM, against a panel of 50 other enzymes (GPCRs, transporters) closest targets as % of control: Acyl CoA-cholesterol acetyltransferase, hepatic (78%), PP2B (50%), full screening data available in supplement info, https://pubmed.ncbi.nlm.nih.gov/20823284/;
In-vitro potency (enzymatic assay): IC50(Acyl CoA-cholesterol acetyltransferase) = 2.4 µM, https://pubmed.ncbi.nlm.nih.gov/20823284/;
In-vitro potency (enzymatic assay): IC50(PP2B) = 9 µM, https://pubmed.ncbi.nlm.nih.gov/20823284/;
Screened at 10 µM against a panel of 44 ion channels, GPCRs, hydrolases, and other enzymes (SafetyScreen44™) closest target as % of contr.: PDE4D2 (42%), full screening data available on OpenMe website, https://www.opnme.com/molecules/hcv-protease-bi-201335;

Screened at 1 µM, closest target with >50% of inhibtion:PIK3KA, PIK3KD, PIK3G; In-vitro follow-up of cloestes targets in biochemical assays: IC50(PIK3KA) >60 nM, IC50(PIK3KD) >60 nM, IC50(PIK3G) = 37.8 nM, https://pubmed.ncbi.nlm.nih.gov/31699977/;

Screened at 1 µM, (MS experiment, 298 protein and lipid kinase peptides, corresponding to 203 unique protein and lipid kinase), closest targets as % of inhibition: PIK3C3 (>96%), PIK3CB (67.7%), PIK3CD (62.5%), SMG(52%)

Screened at 20 µM, closest target: dTm(STK17B) = 2.5 K, clean profile;
Screened against 67 kinases, enzymatic assays: In-vitro potency, all targets IC50 >10 µM, https://www.nature.com/articles/nature21702; Screened against 61 non-kinase targets in enzymatic assays, in-vitro potency of closest targets: IC50(5HT2B, antagonism) = 5.9 µM, others IC50 >10 µM, https://www.nature.com/articles/nature21702/tables/1;

Screened at 1 µM, closest targets as % of inhibition: DYRK2 (47%9, IKBKB(34%), PIK3CA(24%), PIK3CA(E545A, 19%), PIK3CA(Q546K, 21%), PIK3CA(E542K, 21%);