Chemogenomic set

rel. activation(RXRA)=19.35% to bexarotene, inactive at 1 µM for UL48, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

Screened at 1 µM, closest targets as % of residual activity: RPS6KA3 (57%), CSF1R (74%), STK24 (74%), MELK (74%), compound also screened at 10 µM, https://pubmed.ncbi.nlm.nih.gov/23398362/, full-screening data available at Chembl;
Screened at 10 µM, against 63 kinases, radioenzymatic kinase assays (Upstate KinaseProfiler™), clean selectivity profile, https://www.nature.com/articles/nchembio760;

Screened at 1 µM, closest targets as % of residual activity: RPS6KA3 (57%), CSF1R (74%), STK24 (74%), MELK (74%), compound also screened at 10 µM, https://pubmed.ncbi.nlm.nih.gov/23398362/, full-screening data available at Chembl;
Screened at 10 µM, against 63 kinases, radioenzymatic kinase assays (Upstate KinaseProfiler™), clean selectivity profile, https://www.nature.com/articles/nchembio760;

Screened at 10 µM, IC50(PIK3CD) = 2.5 nM, IC50(PIK3CG) = 89 nM, 40-300-fold selective to other PI3K class I enzymes: IC50(PIK3CG) = 565 nM, IC50(PIK3CA) = 820 nM; 400- to 4000-fold selective against related kinases C2β, hVPS34, DNA-PK, and mTOR

Screened at 10 µM, IC50(PIK3CD) = 2.5 nM, IC50(PIK3CG) = 89 nM, 40-300-fold selective to other PI3K class I enzymes: IC50(PIK3CG) = 565 nM, IC50(PIK3CA) = 820 nM; 400- to 4000-fold selective against related kinases C2β, hVPS34, DNA-PK, and mTOR

Screened at 10 µM, closest targets as % of contr.: RPS6KA5 (76%); Screened against 50 related targets (GPCRs, ion channels, transporters): in-vitro potency of closest targets IC50(hPDE4D) = 4.7 µM, IC50(5HT2B) = 7.7 µM; No activity when tested against CYP isoforms (CYP3A3, CYP2D9, CYP2D6,CYP2C9)

Screened at 1 µM, closest targets as % of control: PIP5K1C (0%), MEK5 (0.95%), RIPK4 (4.5%), MLK3 (99%); In-vitro potency of closest targets (enzymatic assay, Reaction Biology): IC50(PIP5K1C) = 11 µM, IC50(MEK5) = 0.025 µM, IC50(RIPK4) = 5.69 µM, IC50(MLK3) = 2.75 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01803#; Screened at 10 µM in Eurofins Cerep-Panlabs Safety Screen 44 (GPCRS, Transporters, Ion Channels, Nuclear Receptors, other enzymes), closest targets as % of inhibition or stimulation: dopamine transporter (100%), hERG channel (89%), norepinephrine transporter (87%), M1 (84%), M2(70%), M3(74%), acetylcholinesterase (84%), https://www.thesgc.org/chemical-probes/cs-640;

Screened at 1 µM, closest targets as % of control: PIP5K1C (0%), MEK5 (0.95%), RIPK4 (4.5%), MLK3 (99%); In-vitro potency of closest targets (enzymatic assay, Reaction Biology): IC50(PIP5K1C) = 11 µM, IC50(MEK5) = 0.025 µM, IC50(RIPK4) = 5.69 µM, IC50(MLK3) = 2.75 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01803#; Screened at 10 µM in Eurofins Cerep-Panlabs Safety Screen 44 (GPCRS, Transporters, Ion Channels, Nuclear Receptors, other enzymes), closest targets as % of inhibition or stimulation: dopamine transporter (100%), hERG channel (89%), norepinephrine transporter (87%), M1 (84%), M2(70%), M3(74%), acetylcholinesterase (84%), https://www.thesgc.org/chemical-probes/cs-640;

Screened at 1 µM, closest targets as % of control: PIP5K1C (0%), MEK5 (0.95%), RIPK4 (4.5%), MLK3 (99%); In-vitro potency of closest targets (enzymatic assay, Reaction Biology): IC50(PIP5K1C) = 11 µM, IC50(MEK5) = 0.025 µM, IC50(RIPK4) = 5.69 µM, IC50(MLK3) = 2.75 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01803#; Screened at 10 µM in Eurofins Cerep-Panlabs Safety Screen 44 (GPCRS, Transporters, Ion Channels, Nuclear Receptors, other enzymes), closest targets as % of inhibition or stimulation: dopamine transporter (100%), hERG channel (89%), norepinephrine transporter (87%), M1 (84%), M2(70%), M3(74%), acetylcholinesterase (84%), https://www.thesgc.org/chemical-probes/cs-640;

Screened at 1 µM, closest targets as % of control: PIP5K1C (0%), MEK5 (0.95%), RIPK4 (4.5%), MLK3 (99%); In-vitro potency of closest targets (enzymatic assay, Reaction Biology): IC50(PIP5K1C) = 11 µM, IC50(MEK5) = 0.025 µM, IC50(RIPK4) = 5.69 µM, IC50(MLK3) = 2.75 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01803#; Screened at 10 µM in Eurofins Cerep-Panlabs Safety Screen 44 (GPCRS, Transporters, Ion Channels, Nuclear Receptors, other enzymes), closest targets as % of inhibition or stimulation: dopamine transporter (100%), hERG channel (89%), norepinephrine transporter (87%), M1 (84%), M2(70%), M3(74%), acetylcholinesterase (84%), https://www.thesgc.org/chemical-probes/cs-640;

Screened at 10 µM against a panel of GPCRs, kinases, and other enzymes, closest target as % of control: M1 (73%), full screening data available on OpenMe website, https://www.opnme.com/molecules/npy1r-bibo3304;
Screened at 10 µM against 44 GPCRs, hydrolases, and ion channels (SafetyScreen44™), closest targets as % of control: KAPPA(KOP, 30%), V1A (29%), full screening data available on OpenMe website, https://www.opnme.com/molecules/npy1r-bibo3304;

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 300 nM, closest targets as % of contr.: HIPK3(95.1%), YSK4 (97.5%), IRAK4 (94.8%), FLT3 D835H/Y (98.8%/98.3%), ERK8 (94.8);

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 500 nM, >90% inhibiton; in-vitro potency (Enzymatic inhibition assay, Thermo Fisher) of closest target: IC50(CLK1) = 239 nM, IC50(HIPK3) = 126 nM, https://www.sciencedirect.com/science/article/pii/S106345841930994X?via%3Dihub;

Screened at 10 µM, closest targets as % of control: CLK3 (2%), GSK3A (9.8%), HIPK1/3 (0.75%/ 3.8%), IRAK1 (2.8%), TAOK1 (8.8%), TYK2(JH1 domain-pseudokinase) (9.0%); Kd follow-up by DiscoverX: Kd(CLK3) = 1100 nM, Kd(GSK3A) = 550 nM, Kd(HIPK1/3) = 320 /230 nM, Kd(IRAK1) = 930 nM, Kd(TAOK1) = 1700 nM; Selective against 148 proteins from mouse brain (Competition Affinity Chromatography (KinAffinity, by Kinaxo Biotechnologies, Evotec)), closest targets: Kd,free(SLK) = 21 nM, Kd,free(DYRK1A) = 65 nM, Kd,free(CSNK2A1) = 326 nM, Kd,free(CSNK2N) = 382 nM, others > 500 nM

Screened at 10 µM, closest targets as % of control: CLK3 (2%), GSK3A (9.8%), HIPK1/3 (0.75%/ 3.8%), IRAK1 (2.8%), TAOK1 (8.8%), TYK2(JH1 domain-pseudokinase) (9.0%); Kd follow-up by DiscoverX: Kd(CLK3) = 1100 nM, Kd(GSK3A) = 550 nM, Kd(HIPK1/3) = 320 /230 nM, Kd(IRAK1) = 930 nM, Kd(TAOK1) = 1700 nM; Selective against 148 proteins from mouse brain (Competition Affinity Chromatography (KinAffinity, by Kinaxo Biotechnologies, Evotec)), closest targets: Kd,free(SLK) = 21 nM, Kd,free(DYRK1A) = 65 nM, Kd,free(CSNK2A1) = 326 nM, Kd,free(CSNK2N) = 382 nM, others > 500 nM

Screened at 10 µM, closest targets as % of control: CLK3 (2%), GSK3A (9.8%), HIPK1/3 (0.75%/ 3.8%), IRAK1 (2.8%), TAOK1 (8.8%), TYK2(JH1 domain-pseudokinase) (9.0%); Kd follow-up by DiscoverX: Kd(CLK3) = 1100 nM, Kd(GSK3A) = 550 nM, Kd(HIPK1/3) = 320 /230 nM, Kd(IRAK1) = 930 nM, Kd(TAOK1) = 1700 nM; Selective against 148 proteins from mouse brain (Competition Affinity Chromatography (KinAffinity, by Kinaxo Biotechnologies, Evotec)), closest targets: Kd,free(SLK) = 21 nM, Kd,free(DYRK1A) = 65 nM, Kd,free(CSNK2A1) = 326 nM, Kd,free(CSNK2N) = 382 nM, others > 500 nM

Screened at 10 µM, closest targets as % of control: CLK3 (2%), GSK3A (9.8%), HIPK1/3 (0.75%/ 3.8%), IRAK1 (2.8%), TAOK1 (8.8%), TYK2(JH1 domain-pseudokinase) (9.0%); Kd follow-up by DiscoverX: Kd(CLK3) = 1100 nM, Kd(GSK3A) = 550 nM, Kd(HIPK1/3) = 320 /230 nM, Kd(IRAK1) = 930 nM, Kd(TAOK1) = 1700 nM; Selective against 148 proteins from mouse brain (Competition Affinity Chromatography (KinAffinity, by Kinaxo Biotechnologies, Evotec)), closest targets: Kd,free(SLK) = 21 nM, Kd,free(DYRK1A) = 65 nM, Kd,free(CSNK2A1) = 326 nM, Kd,free(CSNK2N) = 382 nM, others > 500 nM

Screened at 10 µM, closest targets as % of control: CLK3 (2%), GSK3A (9.8%), HIPK1/3 (0.75%/ 3.8%), IRAK1 (2.8%), TAOK1 (8.8%), TYK2(JH1 domain-pseudokinase) (9.0%); Kd follow-up by DiscoverX: Kd(CLK3) = 1100 nM, Kd(GSK3A) = 550 nM, Kd(HIPK1/3) = 320 /230 nM, Kd(IRAK1) = 930 nM, Kd(TAOK1) = 1700 nM; Selective against 148 proteins from mouse brain (Competition Affinity Chromatography (KinAffinity, by Kinaxo Biotechnologies, Evotec)), closest targets: Kd,free(SLK) = 21 nM, Kd,free(DYRK1A) = 65 nM, Kd,free(CSNK2A1) = 326 nM, Kd,free(CSNK2N) = 382 nM, others > 500 nM

Screened at 1 µM, S(1) = 0.023, ~100-fold selective over DYRK2 (IC50 = 1890 nM); Screened at 1 µM against 124 kinases, Millipore kinase panel, closest targets as % of inhibition: AURAB (85%), DRAK1 (95%), DYRK2 (85%), FLT1(98%), FLT3(95%), KDR(88%), LOK(87%), MARK1(80%), MINK (87%), MLK1 (95%), MNK2 (90%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00098;

Screened at 1 µM, S(1) = 0.023, ~100-fold selective over DYRK2 (IC50 = 1890 nM); Screened at 1 µM against 124 kinases, Millipore kinase panel, closest targets as % of inhibition: AURAB (85%), DRAK1 (95%), DYRK2 (85%), FLT1(98%), FLT3(95%), KDR(88%), LOK(87%), MARK1(80%), MINK (87%), MLK1 (95%), MNK2 (90%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00098;

Screened at 1 µM, closest targets as % of control: STK2 (3.83%), SRPK1 (8.76%), SRPK2 (13.94%), PIM1 (54.68%), PKCe(55.07%), PKN1(55.56%); In-vitro potency of closest targets (Radioactive assay, Reaction Biology): IC50(CLK1) >10 µM, IC50(CLK2) >10 µM, IC50(CLK3) >10 µM, IC50(CLK4) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.2c01705#;

Screened at 1 µM, closest targets as % of control: STK2 (3.83%), SRPK1 (8.76%), SRPK2 (13.94%), PIM1 (54.68%), PKCe(55.07%), PKN1(55.56%); In-vitro potency of closest targets (Radioactive assay, Reaction Biology): IC50(CLK1) >10 µM, IC50(CLK2) >10 µM, IC50(CLK3) >10 µM, IC50(CLK4) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.2c01705#;

Screened at 1 µM, closest targets as % of control: STK2 (3.83%), SRPK1 (8.76%), SRPK2 (13.94%), PIM1 (54.68%), PKCe(55.07%), PKN1(55.56%); In-vitro potency of closest targets (Radioactive assay, Reaction Biology): IC50(CLK1) >10 µM, IC50(CLK2) >10 µM, IC50(CLK3) >10 µM, IC50(CLK4) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.2c01705#;

Screened at 1 µM, no kinases with <45% of control; In-vitro potency (Eurofins Enzymatic assay): IC50(CLK3) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, IC50(HIPK1) >10 µM, IC50(HIPK2) >10 µM, IC50(HIPK3) >10µM, IC50(HIPK4) >10 µM, IC50(PIM2) >10 µM, https://www.thesgc.org/chemical-probes/SGC-CLK-1;

Screened at 1 µM, no kinases with <45% of control; In-vitro potency (Eurofins Enzymatic assay): IC50(CLK3) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, IC50(HIPK1) >10 µM, IC50(HIPK2) >10 µM, IC50(HIPK3) >10µM, IC50(HIPK4) >10 µM, IC50(PIM2) >10 µM, https://www.thesgc.org/chemical-probes/SGC-CLK-1;

Screened at 1 µM, no kinases with <45% of control; In-vitro potency (Eurofins Enzymatic assay): IC50(CLK3) >10 µM, IC50(DYRK1A) >10 µM, IC50(DYRK1B) >10 µM, IC50(DYRK2) >10 µM, IC50(DYRK3) >10 µM, IC50(HIPK1) >10 µM, IC50(HIPK2) >10 µM, IC50(HIPK3) >10µM, IC50(HIPK4) >10 µM, IC50(PIM2) >10 µM, https://www.thesgc.org/chemical-probes/SGC-CLK-1;

Screened at 100 nM, closest targets as % of control: STK38L (24%), SRPK2 (34%), PIK3CA (44%), TNIK(45%), LRRK2(51%), NEK1(51%), RIOK1(54%), EIF2AK2 (55%), FYN (56%), STK32A (57%), RIPK2 (59%), FRK (60%), NIM1K (60%), PRPF4B (60%)

Screened at 100 nM, closest targets as % of control: STK38L (24%), SRPK2 (34%), PIK3CA (44%), TNIK(45%), LRRK2(51%), NEK1(51%), RIOK1(54%), EIF2AK2 (55%), FYN (56%), STK32A (57%), RIPK2 (59%), FRK (60%), NIM1K (60%), PRPF4B (60%)

Screened at 100 nM, closest targets as % of control: STK38L (24%), SRPK2 (34%), PIK3CA (44%), TNIK(45%), LRRK2(51%), NEK1(51%), RIOK1(54%), EIF2AK2 (55%), FYN (56%), STK32A (57%), RIPK2 (59%), FRK (60%), NIM1K (60%), PRPF4B (60%)

Screened at 100 nM, closest targets as % of control: STK38L (24%), SRPK2 (34%), PIK3CA (44%), TNIK(45%), LRRK2(51%), NEK1(51%), RIOK1(54%), EIF2AK2 (55%), FYN (56%), STK32A (57%), RIPK2 (59%), FRK (60%), NIM1K (60%), PRPF4B (60%)

Screened at 1 µM against NR2A1, NR2B1, NR2C1, NR2E1, NR4A1, NR5A1 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): fold-activation = 25.62 (NR2B1); Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM against NR2A1, NR2B1, NR2C1, NR2E1, NR4A1, NR5A1 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): fold-activation = 25.62 (NR2B1); Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM against NR2A1, NR2B1, NR2C1, NR2E1, NR4A1, NR5A1 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): fold-activation = 25.62 (NR2B1); Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM, closest targets as % of contr.: PIM2 (0%), VRK2 (29%), KIT(V55D,V654A) (41%), NLK (41%); Screened at 10 µM against 45 GPCRs (PDPS screen), closest targets as % of inhibition: HTR1E (31.76%), HTR2C (31.08%), ADRA1B (30.19%);

Screened at 10 µM (KINOMEscan, DiscoverX), off-target with >90% PoC; IC50(CDK4/7) = 220/200 nM (Radiometric kinase assay,https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049);
In-vitro potency (radiometric kinase assay, using ATP = Km): IC50(CDK1/cyclinB) = 26 nM, IC50(CDK2/cyclinE) = 3 nM, IC50(CDK2/cyclinA) = 4 nM, IC50(CDK4/cyclinD) = 216 nM, IC50(CDK5/p25) = 10 nM, IC50(CDK7/cyclinH) = 200 nM, IC50(CDK9/cyclinT)= 13 nM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049;

Screened at 10 µM (KINOMEscan, DiscoverX), off-target with >90% PoC; IC50(CDK4/7) = 220/200 nM (Radiometric kinase assay,https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049);
In-vitro potency (radiometric kinase assay, using ATP = Km): IC50(CDK1/cyclinB) = 26 nM, IC50(CDK2/cyclinE) = 3 nM, IC50(CDK2/cyclinA) = 4 nM, IC50(CDK4/cyclinD) = 216 nM, IC50(CDK5/p25) = 10 nM, IC50(CDK7/cyclinH) = 200 nM, IC50(CDK9/cyclinT)= 13 nM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049;

Screened at 10 µM (KINOMEscan, DiscoverX), off-target with >90% PoC; IC50(CDK4/7) = 220/200 nM (Radiometric kinase assay,https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049);
In-vitro potency (radiometric kinase assay, using ATP = Km): IC50(CDK1/cyclinB) = 26 nM, IC50(CDK2/cyclinE) = 3 nM, IC50(CDK2/cyclinA) = 4 nM, IC50(CDK4/cyclinD) = 216 nM, IC50(CDK5/p25) = 10 nM, IC50(CDK7/cyclinH) = 200 nM, IC50(CDK9/cyclinT)= 13 nM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049;

Screened at 10 µM (KINOMEscan, DiscoverX), off-target with >90% PoC; IC50(CDK4/7) = 220/200 nM (Radiometric kinase assay,https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049);
In-vitro potency (radiometric kinase assay, using ATP = Km): IC50(CDK1/cyclinB) = 26 nM, IC50(CDK2/cyclinE) = 3 nM, IC50(CDK2/cyclinA) = 4 nM, IC50(CDK4/cyclinD) = 216 nM, IC50(CDK5/p25) = 10 nM, IC50(CDK7/cyclinH) = 200 nM, IC50(CDK9/cyclinT)= 13 nM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049;

Screened at 1 µM, closest targets as % of control: NEK1(45%), STK38L (47%), BMX(50%)

Screened at 1 µM, closest targets as % of control: NEK1(45%), STK38L (47%), BMX(50%)

Various assays types used, i.e. TR-FRET, Luminescence assay, FLINT, Electrophysiological assay, LEADseeker SPA; No activation across HDACs 1–11 at 100 μM; Selective for PADI4 over PADI1-3 (tested with recombinant enzymes and cell lysates).

Screened at 1 µM, closest target as % of inhibition: CHRM2 (40.7%)

Screened at 1 µM againstNR1A1, NR1B1, NR1C3, NR1F3, NR1H3, NR1I1, NR1I2, NR1I3, NR2A1, NR2B1, NR4A1, NR5A2 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): clean selectivty profile with no significant agonism/antagonism detected; Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM againstNR1A1, NR1B1, NR1C3, NR1F3, NR1H3, NR1I1, NR1I2, NR1I3, NR2A1, NR2B1, NR4A1, NR5A2 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): clean selectivty profile with no significant agonism/antagonism detected; Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM againstNR1A1, NR1B1, NR1C3, NR1F3, NR1H3, NR1I1, NR1I2, NR1I3, NR2A1, NR2B1, NR4A1, NR5A2 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): clean selectivty profile with no significant agonism/antagonism detected; Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 1 µM againstNR1A1, NR1B1, NR1C3, NR1F3, NR1H3, NR1I1, NR1I2, NR1I3, NR2A1, NR2B1, NR4A1, NR5A2 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): clean selectivty profile with no significant agonism/antagonism detected; Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

Screened at 10 µM against NR1A1, NR2A1, NR2B1, NR2C1, NR2E1, NR4A1, NR5A1 and VP16 in a Gal4 hybrid reporter gene assay (HEK293T cells were cotransfected with pFR-Luc reporter, pRL-SV40 control reporter and pFA-CMV containing the Gal4-DBD fused with human NR-LBD of interest or pECE-SV40-Gal4-VP16): clean selectivty profile with no significant agonism/antagonism detected; Screened at 20 µM in a bromodomain and kinase panel against ABL1, AURKA, BRD4, BRPF1, CDK2, CSNK1D, FGFR3, GSK3B, MAPK1, TRIM24 in DSF assays: clean selectivity profile with no significant binding (?Tm < 2 K)

inactive at 10 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

Screened at 3 µM, in-vitro potency of closest target: Kd(CSF1R) = 2716 nM (90.1% inhibition), S-score(10) = 0.005 at 3 µM; In-vitro potencies of other FGFR family members (enzyme activity assays): IC50(FGFR1) = 591 nM, IC50(FGFR2) = 493 nM, IC50(FGFR3) = 150 nM; IC50(p70S6Kb) > 10 μM (https://aacr.silverchair-cdn.com/aacr/content_public/journal/cancerdiscovery/5/4/10.1158_2159-8290.cd-14-1029/4/21598290cd141029-sup-137537_2_supp_0_njmz90.pdf?Expires=1675264845&Signature=C7J4HfbPNEkAbAqzPJ39H9yL-DM-ZriAd8q9~z8YUG1gWwYiv~YY3KnIOiETJu6s6ant4xiTBoYwoCLgll18xYBmbGpqFihOfhV-o13a7i6vEvF1O1eaowwAMUXKijlCNqDlMeXH0BaQ1JGUfaWJ-rcaUZdvfAS~UHg~9yVyE3t7x2JTKWLV3T1OQ0xNVih6dxAH~ACl87xwuIVD4NVAlkEcGUWPGXNzCUzk8-SlPnWgBxnUZLP6R8NhMbrjeOlLoYg0TNe9HVYyYuOCI6bAajPrnqSaYv1qC1eoQq-HWafjwJ7N3T5waFSlCi~COA3D0QYQ~UdoNRFASuZZzqG1Lg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)

Screened at 20 µM, closest targets in the screen: dTm FLT1 = 7.6 K, STK10 = 4.8K, clean profile;
Screened in enzymatic assays: IC50(PDGFR) >50 µM, IC50(EGFR) >50 µM, IC50(SRC) >50 µM, IC50(MAPK1) >50 µM, IC50(PRKCA) >50 µM, IC50(INSR) >50 µM, IC50(CDK4) >50 µM; In-cellulo follow-up of closest targets (autophosphorylation of PDGFR in rat aortic smooth muscle cells, EGF receptors in A431 cells, and INSR in NIHIR cells): IC50(EGFR) >1 µM, IC50(INSR) >1 µM, IC50(PDGF) >30 µM (https://jpet.aspetjournals.org/content/286/1/569.long);

Screened at 1 μM, closest targets as % of inhibition: FLT3 (96%), GSG2 (93%), TYK2 (93%), CSNK2A (66%), KIT(A829) = 79%), KIT(D816) = 86%), MINK (77%), PDGFRA (79%), PDGFRB (57%), MELK (86%); In-vitro follow-up of closest targets (biochemical assays): IC50(FLT3) = 180 nM, IC50(GSG2) = 190 nM, IC50(KIT, A829) > 10 µM, IC50(PDGFRA) = 420 nM, IC50(MELK) = 2 nM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00052);

Screened at 1 μM inhibition, closest targets as % of residual activity: MAP4K5 (8%), PAK3 (9%), PAK2 (10%), NLK (13%), PKN3 (35%), PAK1 (36%), MAP2K4 (37%), TIE2 (39%), MST4 (45%), MELK (48%); In-vitro follow-up of closest targets (33PanQinase assay, Reaction Biology): IC50(MAP4K5) = 210 nM, IC50(PAK3) = 140 nM, IC50(PAK2) = 41 nM, IC50(NLK) = 13 nM, IC50(PKN3) = 1400 nM, IC50(PAK1) = 580 nM, IC50(MAP2K4) = 830 nM, IC50(TIE2) = 3100 nM, IC50(MST4) = 1600 nM, IC50(MELK) = 2200 nM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144); In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(MAP4K5) = 13 µM, IC50(NLK) = 0.25 µM, IC50(PKN3) = 6.7 µM, IC50(TIE2) = 6 µM, IC50(MST4) = 34 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144;

Screened at 1 μM inhibition, closest targets as % of residual activity: MAP4K5 (8%), PAK3 (9%), PAK2 (10%), NLK (13%), PKN3 (35%), PAK1 (36%), MAP2K4 (37%), TIE2 (39%), MST4 (45%), MELK (48%); In-vitro follow-up of closest targets (33PanQinase assay, Reaction Biology): IC50(MAP4K5) = 210 nM, IC50(PAK3) = 140 nM, IC50(PAK2) = 41 nM, IC50(NLK) = 13 nM, IC50(PKN3) = 1400 nM, IC50(PAK1) = 580 nM, IC50(MAP2K4) = 830 nM, IC50(TIE2) = 3100 nM, IC50(MST4) = 1600 nM, IC50(MELK) = 2200 nM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144); In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(MAP4K5) = 13 µM, IC50(NLK) = 0.25 µM, IC50(PKN3) = 6.7 µM, IC50(TIE2) = 6 µM, IC50(MST4) = 34 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144;

Screened at 1 μM inhibition, closest targets as % of residual activity: MAP4K5 (8%), PAK3 (9%), PAK2 (10%), NLK (13%), PKN3 (35%), PAK1 (36%), MAP2K4 (37%), TIE2 (39%), MST4 (45%), MELK (48%); In-vitro follow-up of closest targets (33PanQinase assay, Reaction Biology): IC50(MAP4K5) = 210 nM, IC50(PAK3) = 140 nM, IC50(PAK2) = 41 nM, IC50(NLK) = 13 nM, IC50(PKN3) = 1400 nM, IC50(PAK1) = 580 nM, IC50(MAP2K4) = 830 nM, IC50(TIE2) = 3100 nM, IC50(MST4) = 1600 nM, IC50(MELK) = 2200 nM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144); In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(MAP4K5) = 13 µM, IC50(NLK) = 0.25 µM, IC50(PKN3) = 6.7 µM, IC50(TIE2) = 6 µM, IC50(MST4) = 34 µM, https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02144;

Clean selectivity profile with no target activity >50%; Screened in enzymatic assays against other transaminases: IC50(GOT1/2) >50 µM; Screened at 6 µM against 30 proteases, all targets IC50 >10 µM; Screened at 2 µM against 45 kinases (enzymatic assays), clean selectivity profile with all kinases IC50 >7 µM

Clean selectivity profile with no target activity >50%; Screened in enzymatic assays against other transaminases: IC50(GOT1/2) >50 µM; Screened at 6 µM against 30 proteases, all targets IC50 >10 µM; Screened at 2 µM against 45 kinases (enzymatic assays), clean selectivity profile with all kinases IC50 >7 µM

Screened at 10 µM, in vitro-potencies of closest targets: Ki(SLC6A3) = 1377.15 nM, Ki(HTR2A) = 2576.32 nM; Selectivity against family members in biochemical assays, all >30 fold: IC50(hTRPV1) >25 µM, IC50(hTRPV4) >25 µM, IC50(hTRPC3) >25 µM, IC50(hTRPC5) = 5.6 µM, IC50(hTRPC6) >25 µM, IC50(hKCNK9, TASK-3) >30 µM, IC50(hCACNA1H, Cav3.2) >25 µM; Selectivity screen in Eurofins Lead Profiling Screen, GPCR Profiling Screen and Bayer Kinase Panel was performed, in-vitro potencies of closest targets: Ki (SLC6A3, human) = 0.9 μM, Ki(PGR, human) = 4 μM, EC50(ESR1) = 2.1 μM

Screened at 10 µM, closest target as % of inhibition: HTR3A (38%); Screened against other human prostanoid receptor (binding assay, Eurofins/Panlabs): IC50(PTGFR) = 22 nM, IC50(EP1) >10 µM, IC50(EP2) >10 µM, IC50(EP3) >10 µM, IC50(EP4) >10 µM, IC50(IP) >10 µM, IC50(DP) >10 µM, IC50(CRTH2) >10 µM, >420-fold selective; Screened in cell-based assay (Eurofins/Panlabs): IC50(TBXA2R) = 2.2 µM, 200-fold selective; Screened at 10 µM against 77 other targets (Leadprofiling Screen, Panlabs), closest target as % of inhibition: TBXAS1 (33%); Screened at 10 µM against 8 ion channels (Ion channel profiler, Eurofins): IC20(Nav1.5) >10 μM, IC20(Kv4.3/KChIP2) >10 μM, IC20(Cav1.2) >10 μM, IC20(Kv1.5) >10 μM, IC20(KCNQ/minK) >10 μM, IC20(herG) >10 μM, IC20(HCN4) >10 μM, IC20(Kir2.1) >10 μM

Screened at 10 µM, in-vitro potency of closest target: IC50(CTSG, cathepsin G) = 110 nM, >100-fold selective; Screened at 10 µM against 44 targets outside target family (Eurofins Safety Screen44TM), clean selectivity profile; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(HTR1D) = 1130.61 nM, Ki(OPRK1) = 4948.48 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 6.4, pKd(TAF1L, BD2) = 5.7, pKd(BRD9) = 5.7, pKd(CECR2) = 5.5, pKd(BAZ2A) = 5.5, pKd(BAZ2B) = 5.1; Selective for the BD2 domain of BET proteins; Clean in selectivity screen against 48 targets (GPCRs, ion-channels, other targets); Chemoproteomics data (3 vectors) showed excellent non BCPs selectivity; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 257.47 nM, Ki(DRD4) = 982.65 nM, Ki(DRD2) = 964.05 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 6.4, pKd(TAF1L, BD2) = 5.7, pKd(BRD9) = 5.7, pKd(CECR2) = 5.5, pKd(BAZ2A) = 5.5, pKd(BAZ2B) = 5.1; Selective for the BD2 domain of BET proteins; Clean in selectivity screen against 48 targets (GPCRs, ion-channels, other targets); Chemoproteomics data (3 vectors) showed excellent non BCPs selectivity; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 257.47 nM, Ki(DRD4) = 982.65 nM, Ki(DRD2) = 964.05 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 6.4, pKd(TAF1L, BD2) = 5.7, pKd(BRD9) = 5.7, pKd(CECR2) = 5.5, pKd(BAZ2A) = 5.5, pKd(BAZ2B) = 5.1; Selective for the BD2 domain of BET proteins; Clean in selectivity screen against 48 targets (GPCRs, ion-channels, other targets); Chemoproteomics data (3 vectors) showed excellent non BCPs selectivity; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 257.47 nM, Ki(DRD4) = 982.65 nM, Ki(DRD2) = 964.05 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 6.4, pKd(TAF1L, BD2) = 5.7, pKd(BRD9) = 5.7, pKd(CECR2) = 5.5, pKd(BAZ2A) = 5.5, pKd(BAZ2B) = 5.1; Selective for the BD2 domain of BET proteins; Clean in selectivity screen against 48 targets (GPCRs, ion-channels, other targets); Chemoproteomics data (3 vectors) showed excellent non BCPs selectivity; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 257.47 nM, Ki(DRD4) = 982.65 nM, Ki(DRD2) = 964.05 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 1621 nM, Kd(BRD2, BD2) = 35 nM (64-fold selective), Kd(BRD3, BD1) = 2082 nM, Kd(BRD3, BD2) = 32 nM (63-fold selective), Kd(BRD4, BD1) = 769 nM, Kd(BRD4, BD2) = 9 nM (85-fold selective), Kd(BRDT, BD1) = 2454 nM, Kd(BRDT, BD2) = 15 nM (164-fold selective); In-vitro potencies (SPR measurements): Kd(BRD4, BD1) >10 µM, Kd(BRD4, BD2) = 30 nM, excellent selectivity against other BCPs, Kd >30 µM for TAF1(BD2), BRD9, TAF1L(BD2), BAZ2A, CECR2, BAZ2B; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(HTR1D) = 3438.75 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 1621 nM, Kd(BRD2, BD2) = 35 nM (64-fold selective), Kd(BRD3, BD1) = 2082 nM, Kd(BRD3, BD2) = 32 nM (63-fold selective), Kd(BRD4, BD1) = 769 nM, Kd(BRD4, BD2) = 9 nM (85-fold selective), Kd(BRDT, BD1) = 2454 nM, Kd(BRDT, BD2) = 15 nM (164-fold selective); In-vitro potencies (SPR measurements): Kd(BRD4, BD1) >10 µM, Kd(BRD4, BD2) = 30 nM, excellent selectivity against other BCPs, Kd >30 µM for TAF1(BD2), BRD9, TAF1L(BD2), BAZ2A, CECR2, BAZ2B; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(HTR1D) = 3438.75 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 1621 nM, Kd(BRD2, BD2) = 35 nM (64-fold selective), Kd(BRD3, BD1) = 2082 nM, Kd(BRD3, BD2) = 32 nM (63-fold selective), Kd(BRD4, BD1) = 769 nM, Kd(BRD4, BD2) = 9 nM (85-fold selective), Kd(BRDT, BD1) = 2454 nM, Kd(BRDT, BD2) = 15 nM (164-fold selective); In-vitro potencies (SPR measurements): Kd(BRD4, BD1) >10 µM, Kd(BRD4, BD2) = 30 nM, excellent selectivity against other BCPs, Kd >30 µM for TAF1(BD2), BRD9, TAF1L(BD2), BAZ2A, CECR2, BAZ2B; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(HTR1D) = 3438.75 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 1621 nM, Kd(BRD2, BD2) = 35 nM (64-fold selective), Kd(BRD3, BD1) = 2082 nM, Kd(BRD3, BD2) = 32 nM (63-fold selective), Kd(BRD4, BD1) = 769 nM, Kd(BRD4, BD2) = 9 nM (85-fold selective), Kd(BRDT, BD1) = 2454 nM, Kd(BRDT, BD2) = 15 nM (164-fold selective); In-vitro potencies (SPR measurements): Kd(BRD4, BD1) >10 µM, Kd(BRD4, BD2) = 30 nM, excellent selectivity against other BCPs, Kd >30 µM for TAF1(BD2), BRD9, TAF1L(BD2), BAZ2A, CECR2, BAZ2B; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(HTR1D) = 3438.75 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 13 nM, Kd(BRD3, BD1) = 5 nM, Kd(BRD4, BD1) = 5.9 nM, Kd(BRDT, BD1) = 18 nM; Selectivity screen against 50 targets (GPCRs, ion-channels, other targets), in-vitro potencies of closest targets: pIC50(CHRNA1) = 6, pIC50(CYP3A4) = 6; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 485.92 nM, Ki(DRD4) = 856.99 nM, Ki(GABAA) = 1595.89 nM, Ki(GABAA/BZP) = 1970.29 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 13 nM, Kd(BRD3, BD1) = 5 nM, Kd(BRD4, BD1) = 5.9 nM, Kd(BRDT, BD1) = 18 nM; Selectivity screen against 50 targets (GPCRs, ion-channels, other targets), in-vitro potencies of closest targets: pIC50(CHRNA1) = 6, pIC50(CYP3A4) = 6; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 485.92 nM, Ki(DRD4) = 856.99 nM, Ki(GABAA) = 1595.89 nM, Ki(GABAA/BZP) = 1970.29 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 13 nM, Kd(BRD3, BD1) = 5 nM, Kd(BRD4, BD1) = 5.9 nM, Kd(BRDT, BD1) = 18 nM; Selectivity screen against 50 targets (GPCRs, ion-channels, other targets), in-vitro potencies of closest targets: pIC50(CHRNA1) = 6, pIC50(CYP3A4) = 6; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 485.92 nM, Ki(DRD4) = 856.99 nM, Ki(GABAA) = 1595.89 nM, Ki(GABAA/BZP) = 1970.29 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): Kd(BRD2, BD1) = 13 nM, Kd(BRD3, BD1) = 5 nM, Kd(BRD4, BD1) = 5.9 nM, Kd(BRDT, BD1) = 18 nM; Selectivity screen against 50 targets (GPCRs, ion-channels, other targets), in-vitro potencies of closest targets: pIC50(CHRNA1) = 6, pIC50(CYP3A4) = 6; Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 485.92 nM, Ki(DRD4) = 856.99 nM, Ki(GABAA) = 1595.89 nM, Ki(GABAA/BZP) = 1970.29 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 7.3, pKd(TAF1L, BD2) = 6.4, selective for the BD1 domain of BET proteins; Follow-up of closest targets (FRET assay): pIC50(TAF1, BD1) = 5.0 ± 0.1, n = 3 (BRD4, BD1 selectivity = 500-fold); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(DRD4) = 1013.12 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 7.3, pKd(TAF1L, BD2) = 6.4, selective for the BD1 domain of BET proteins; Follow-up of closest targets (FRET assay): pIC50(TAF1, BD1) = 5.0 ± 0.1, n = 3 (BRD4, BD1 selectivity = 500-fold); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(DRD4) = 1013.12 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 7.3, pKd(TAF1L, BD2) = 6.4, selective for the BD1 domain of BET proteins; Follow-up of closest targets (FRET assay): pIC50(TAF1, BD1) = 5.0 ± 0.1, n = 3 (BRD4, BD1 selectivity = 500-fold); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(DRD4) = 1013.12 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 7.3, pKd(TAF1L, BD2) = 6.4, selective for the BD1 domain of BET proteins; Follow-up of closest targets (FRET assay): pIC50(TAF1, BD1) = 5.0 ± 0.1, n = 3 (BRD4, BD1 selectivity = 500-fold); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potency of closest target: Ki(DRD4) = 1013.12 nM

In-vitro potencies of closest targets in BROMOScan (DiscoverX): pKd(TAF1, BD2) = 5.4, pKd(EP300) = 5.1, pKd(CREBBP) = 5.0, pKd(EP300) = 5.1; Cross screening in liability panel against 48 targets (GPCRs, transporter, ion-channels, and other targets), closest target: pEC50(CB2 receptor) <5; Selective for BD2 domain of BET proteins; Screened at 10 µM against 45 GPCRs (PDSP screen), closest target as % inhibition: OPRK1(40%);