Chemogenomic set

Screened at 100 nM, closest targets as % of contr.: LATS2 (0.7%), PRKACA (28%), PRKACB (36%), LATS1 (42%), PRKG1 (49%); Screened in Upstate kinase panel against 114 kinases at 10 µM, >250 fold selective, closest targets: IC50(NTRK1) = 252 nM, IC50(FLT3) = 303 nM, IC50(PKA) = 734 nM; Screened against 45 GPCR targets (PDSP screen), closest targets: Ki(OPRK1) = 187.33 nM, Ki(SIGMAR1) = 6765.5 nM; Screened in Eurofins-Panlabs radioligand binding assay against 63 targets at 10 µM, closest targets: Ki(SLC6A3) = 0.039 µM, Ki(DAT2) = 0.027 µM;

Screened at 1 µM, >1000-fold selective, off-targets with PoC <50%

Screened at 1 µM, >1000-fold selective, off-targets with PoC <50%

Screened at 1 µM off-targets with PoC <35%

Screened at 1 µM off-targets with PoC <35%

Highly selective; screen against 45 GPCR targets, closest target: Ki(GABA/PBR) = 374.92 nM; clean in Eurofins-Panlabs radioligand binding assay, screen against 68 targets, at 10 µM

Highly selective; Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets: Ki(GABA/PBR) = 346.58 nM, Ki(HTR2A) = 2071.02 nM, Ki(ADRA2A) = 2355.74 nM; Screened in Eurofins-Panlabs radioligand binding assay against 68 targets at 10 µM: closest target: HTR2B (63 % of contr.)

Screened at 1 µM; 8 additional targets: AURKC, ABL1, RPS6KA6, PIKFYVE, ERBB3, RPS6KA5, LRRK2 and STK38L, initially identified, but confirmed as false positive by NanoBRET: closest targets: IC50(TYRO3) = 3.8 µM (47-fold selective), IC50(ERBB3) = 18.2 µM (227-fold selective), other targets >20 µM in NanoBRET assays.

Screened at 1 µM, closest targets as % of contr.: MAPK15 (21%), HIPK1 (31%), HIPK2 (34%), NEK7 (40%), PIP5K2B (50%), STK16 (53%), S(35) = 0.02; Follow-up IC50s in cellular NanoBRET assays: IC50(HIPK1/2) >10 µM, IC50(STK16) = 167 nM (partial inhibition), others NA;

Screened at 1 µM, closest targets as % of contr.: MAPK15 (21%), HIPK1 (31%), HIPK2 (34%), NEK7 (40%), PIP5K2B (50%), STK16 (53%), S(35) = 0.02; Follow-up IC50s in cellular NanoBRET assays: IC50(HIPK1/2) >10 µM, IC50(STK16) = 167 nM (partial inhibition), others NA;

Screened at 1 µM, closest targets as % of contr.: MAPK15 (21%), HIPK1 (31%), HIPK2 (34%), NEK7 (40%), PIP5K2B (50%), STK16 (53%), S(35) = 0.02; Follow-up IC50s in cellular NanoBRET assays: IC50(HIPK1/2) >10 µM, IC50(STK16) = 167 nM (partial inhibition), others NA;

Screened at 10 µM against 68 enzymes, transporters, GPCRs, ion chanels, closest targets: IC50(MMP2) = 44 nM, IC50(MMP10) = 13 nM, IC50(MMP8) = 15 nM, IC50(MMP13) = 67 nM, IC50(MMP14) = 250 nM, IC50(MMP3) = 360 nM, IC50(MMP9) = 460 nM, IC50(MMP7) = 600 nM, IC50(MMP16) = 940 nM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: EGFR(S752-I759del) (40%), TYK2 (41%), PNCK (46%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest target as % inhibition: DRD2 (30%)

>2600-fold selective over other MMPs: IC50(MMP1) >10 µM, IC50(MMP2) = 18 nM, IC50(MMP3) = 600 nM, IC50(MMP7) >10 µM, IC50(MMP8) = 780 nM, IC50(MMP9) >10 µM, IC50(MMP10) = 160 nM, IC50(MMP14) >10 mM, IC50(ADAM17) >10 µM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: LRRK2 (43%), CDK4 (43.5%), FLT3(D835V) (44.2%), NTRK1 (46.7%); Screended against 45 GPCR targets (PDSP screen) at 10 µM, closest targets: Ki(HRH1) = 98 nM, Ki(TMEM97) = 4553 nM; Clean profile in MSD Pharma/Taiwan screen against 118 enzymes and receptors

Highly selective (> 1000-fold) against other matrix metalloproteinases (FRET assays): IC50(MMP1) >22 µM, IC50(MMP2) = 18 µM, IC50(MMP3) >22 µM, IC50(MMP7) >22 µM, IC50(MMP8) >22 µM, IC50(MMP9) = 8.9 µM, IC50(MMP10) = 16 µM, IC50(MMP12) >22 µM, IC50(MMP14) = 8.3 µM; Screened against 468 kinases (KinomeScan DiscoverX) at 100 nM, closest targets as % of contr.: CDK19 (0%), CDKL3 (0%), CDK3 (43%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets: DRD5 (60% inhibition, Ki >10 µM); Screened against 56 targets (Invitrogen Panel) at 10 µM, closest targets: IC50(AURKA) = 1.3 µM, IC50(MAPKAPK2) = 1.1 µM, IC50(PRKAA1) = 1.9 µM, IC50(PRKACA) = 1.6 µM;

Selective in SGC bromodomain panel; Screened in Invitrogen kinase panel against 40 kinases at 10 µM, clean profile; No activity in a panel of 25 PDEs, ion channels and GPCRS, IC50 >50 µM; IC50(YEATS2/4) > 40 µM (HTRF assay);

Selective in SGC bromodomain panel; Screened in Invitrogen kinase panel against 40 kinases at 10 µM, clean profile; No activity in a panel of 25 PDEs, ion channels and GPCRS, IC50 >50 µM; IC50(YEATS2/4) > 40 µM (HTRF assay);

> 30-fold selective over 21 serine proteases (for all IC50 > 30 µM); Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: RPS6KA4 (33.5%), PRKG1 (45.5%), PRKACB (48.7%); Screened against 45 GPCR targets (PSDP screen) at 10 µM, closest target: Ki(HRH3) = 3.07 µM, Ki(DTR1A) = 4.98 µM, Ki(ADRB1) = 5.45 µM; Radioligand binding assays (Lead Profiling Screen, Eurofins) against 64 receptors and transporters at 10 µM: > 30-fold selective

No closely related mammalian protein known; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: ABL1(Q252H)-nonphosphorylated (0%), GRK7 (0%), CHUK (0%), PK5 (0%), JAK1 (33%), PRKCE (44%); Screened against 546 targets (Invitrogen kinase panel) at 3 µM: all kinases showed < 30% inhibition; Screened against 68 targets (Eurofins-Panlabs panel) at 10 µM: clean profile; Screened against 137 targets in CEREP screen at 20 µM, closest targets as % inhibition: FLT1 (64%), ABL1 (67%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest target as % of inhibition: SLC6A3 (61%);

No near family aspartyl proteases detected, closest target: IC50(SLC18A2) = 213 nM, 6 additional targets between 2-10 µM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: CIT (0%), EGFR (0%), IKBKE (0%), LATS2 (0%), AKT1 (5%), PIK3CA(C420R) (36%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest target: Ki(SLC6A3) = 3137 nM;

Targets tested in PDE activity assays, closest targets: Ki(PDE6) = 44 nM (44-fold selective), Ki(PDE5A) = 116 nM (116-fold selective), Ki(PDE298) = 298 nM (300-fold selective), others >1000-fold selective

Biochemical bovine OxPhos activity assay: >30 µM for Complex 2, 3, 4 and 5; Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets:Ki(HTR2B) = 558.19 nM, Ki(TMEM97) = 1118.32 nM, Ki(SIGMAR1) = 1179.84 nM, Ki(ADRA2C) = 3499.92 nM; Screened in Eurofins-CEREP, GPCR panel at 10 µM, closest target as % inhibition: HTR2B (73.5%); Selectivity > 500 fold against numerous kinases tested;

No near family aspartyl proteases, closest targets: IC50(SLC6A4) = 13 nM, IC50(SLC6A3) = 536 nM, IC50(Na channel site 2) = 1000 nM; Screened against 468 kinases (KinomeScan DiscoverX) at 1 µM, closest targets as % of contr.: ACVR2A (0%), EGFR (0%), MAP4K4 (0%), MAP4K5 (5.8%); Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets: Ki(SLC6A4) = 24 nM, Ki(SLC6A3) = 191 nM, Ki(SLC6A2) = 808 nM;

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

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

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, 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;