Chemogenomic set

Screened at 10 µM in DSF assays, dTm(BRD7) = 6.47 K, dTm(BRD9) = 9.21 K, closest target: dTm(CERC2) = 5.61 K, all other bromodomains <2 K; In vitro follow up of closest target: Kd(CERC2, ITC) = 200 nM; Screened against 32 bromodomains at 10 µM (Bromoscan and BromoMax

Screened at 10 µM in DSF assays, dTm(BRD7) = 6.47 K, dTm(BRD9) = 9.21 K, closest target: dTm(CERC2) = 5.61 K, all other bromodomains <2 K; In vitro follow up of closest target: Kd(CERC2, ITC) = 200 nM; Screened against 32 bromodomains at 10 µM (Bromoscan and BromoMax

Screened at 1 µM, in vitro activity of closest targets: Kd(CDK11) = 370 nM, Kd(EPHA8) = 550 nM, Kd(MUSK) = 530 nM

Screened at 1 µM, in vitro activity of closest targets: Kd(CDK11) = 370 nM, Kd(EPHA8) = 550 nM, Kd(MUSK) = 530 nM

Screened at 1 µM, in vitro activity of closest targets: Kd(CDK11) = 370 nM, Kd(EPHA8) = 550 nM, Kd(MUSK) = 530 nM

Screened at 1 µM, in vitro activity of closest targets: Kd(CDK11) = 370 nM, Kd(EPHA8) = 550 nM, Kd(MUSK) = 530 nM

Screened at 1 µM, in vitro activity of closest targets: Kd(CDK11) = 370 nM, Kd(EPHA8) = 550 nM, Kd(MUSK) = 530 nM

No targets with >70% inhibition at 100 nM and 500 nM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest targets as % of activity: HIPK2 (99%), HIPK3 (94%), GSK3A (90%); Eurofins binding assay: IC50(HIPK1) = 187 nM, IC50(HIPK2) = 23 nM, IC50(CLK3) >3 µM; In-cellular potency (NanoBRET assay in HEK293T cells): Ki(HIPK2) >10 µM, Ki(HIPK4) = 5.41 µM

Screened at 1 µM, closest target as % of contr. PIK3CB (9.8%); Selective over PI3P, PI4P, PI34P, PI45P at 800 nM (radiolabel incorporation assay in NIH3T3 cells)

Screened at 1 µM and 10 µM, highly selective within methyltransferase family; Selective over 9 reader proteins (UHRF1, BRPF1, WDR5, HGDF2, TDRD3, RBBP1, FXR1, EED, and SND1) in DSF assays: all enzymes dTm <2 K;

Screened at 1 µM and 10 µM, highly selective within methyltransferase family; Selective over 9 reader proteins (UHRF1, BRPF1, WDR5, HGDF2, TDRD3, RBBP1, FXR1, EED, and SND1) in DSF assays: all enzymes dTm <2 K;

Screened at 1 µM and 10 µM, highly selective within methyltransferase family; Selective over 9 reader proteins (UHRF1, BRPF1, WDR5, HGDF2, TDRD3, RBBP1, FXR1, EED, and SND1) in DSF assays: all enzymes dTm <2 K;

Screened at 1 µM and 10 µM, highly selective within methyltransferase family; Selective over 9 reader proteins (UHRF1, BRPF1, WDR5, HGDF2, TDRD3, RBBP1, FXR1, EED, and SND1) in DSF assays: all enzymes dTm <2 K;

Screened at 1 µM and 10 µM, highly selective within methyltransferase family; Selective over 9 reader proteins (UHRF1, BRPF1, WDR5, HGDF2, TDRD3, RBBP1, FXR1, EED, and SND1) in DSF assays: all enzymes dTm <2 K;

fold-activation(NR1H4) = 10.96, inactive at 1 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

fold-activation(NR1H4) = 10.96, inactive at 1 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

fold-activation(NR1H4) = 10.96, inactive at 1 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

fold-activation(NR1H4) = 10.96, inactive at 1 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

Screened at 1 µM, closest targets as % residual activity: RIPK2 (7%), VEGFR2 (11%), MINK1 (21%), VEGFR3 (28%), VEGFR1 (38%), MAP4K4 (41%), PDGFRA(V561D) (43%), PDGFRA (47%), TGFBR2 (47%); In-vitro follow-up of closest targets (radioisotopic protein kinase assay, 33PanQinase activity assay): IC50(RIPK2) = 54 nM, IC50(VEGFR2) = 97 nM (https://pubs.acs.org/doi/10.1021/jm500115w); Selectivity within ALK family (Radioisotopic protein kinase assay, HotSpot assay, Reaction Biology): IC50(ALK1) >10 µM, IC50(ALK2) >10 µM, IC50(ALK3) >10 µM, IC50(ALK4) = 0.013 µM, IC50(ALK5) = 0.011 µM, IC50(ALK6) >10 µM, IC50(ALK7) n.d. (https://pubs.acs.org/doi/10.1021/jm500115w);

Screened at 1 µM, closest targets as % residual activity: RIPK2 (7%), VEGFR2 (11%), MINK1 (21%), VEGFR3 (28%), VEGFR1 (38%), MAP4K4 (41%), PDGFRA(V561D) (43%), PDGFRA (47%), TGFBR2 (47%); In-vitro follow-up of closest targets (radioisotopic protein kinase assay, 33PanQinase activity assay): IC50(RIPK2) = 54 nM, IC50(VEGFR2) = 97 nM (https://pubs.acs.org/doi/10.1021/jm500115w); Selectivity within ALK family (Radioisotopic protein kinase assay, HotSpot assay, Reaction Biology): IC50(ALK1) >10 µM, IC50(ALK2) >10 µM, IC50(ALK3) >10 µM, IC50(ALK4) = 0.013 µM, IC50(ALK5) = 0.011 µM, IC50(ALK6) >10 µM, IC50(ALK7) n.d. (https://pubs.acs.org/doi/10.1021/jm500115w);

Screened at 1 µM, S(10) = 0.01, closest targets as % of contr.: JAK3 (6.6%), PIP3CG (2.8%), PIP5K2C (5.6%), SBK1 (4.6%);

Screened at 1 µM, S(10) = 0.01, closest targets as % of contr.: JAK3 (6.6%), PIP3CG (2.8%), PIP5K2C (5.6%), SBK1 (4.6%);

Screened at 10 µM, closest targets as % of contr.: CLK2 (25%), PIK3C2G (27%); Kd(mTOR) = 48 nM, Kd(PI3KC2b) = 40 nM (Kds by DiscoverX, PMID:28829592)

Screened at 10 µM, closest targets as % of contr.: CLK2 (25%), PIK3C2G (27%); Kd(mTOR) = 48 nM, Kd(PI3KC2b) = 40 nM (Kds by DiscoverX, PMID:28829592)

Screened at 10 µM, closest targets as % of contr.: CLK2 (25%), PIK3C2G (27%); Kd(mTOR) = 48 nM, Kd(PI3KC2b) = 40 nM (Kds by DiscoverX, PMID:28829592)

Screened at 10 µM, closest targets as % of contr.: CLK2 (25%), PIK3C2G (27%); Kd(mTOR) = 48 nM, Kd(PI3KC2b) = 40 nM (Kds by DiscoverX, PMID:28829592)

Screened at 1 µM, closest targets: IC50(AMPK) = 117 nM, IC50(BRSK1) = 187 nM, IC50(BRSK2) = 90 nM, IC50(CAMK2B) = 70 nM, IC50(DRAK1) = 71 nM, IC50(MNK2) = 148 nM, IC50(PHKG2) = 528 nM , IC50(PIM1) = 88 nM ,IC50(CDK1) = 354 nM, IC50(CDK5) = 902 nM, IC50(MAP3K5) = 60 nM, IC50(AXL) = 428 nM, IC50(MERTK) = 76 nM, IC50(RIPK2) = 590 nM;

Screened at 1 µM, closest targets: IC50(AMPK) = 117 nM, IC50(BRSK1) = 187 nM, IC50(BRSK2) = 90 nM, IC50(CAMK2B) = 70 nM, IC50(DRAK1) = 71 nM, IC50(MNK2) = 148 nM, IC50(PHKG2) = 528 nM , IC50(PIM1) = 88 nM ,IC50(CDK1) = 354 nM, IC50(CDK5) = 902 nM, IC50(MAP3K5) = 60 nM, IC50(AXL) = 428 nM, IC50(MERTK) = 76 nM, IC50(RIPK2) = 590 nM;

Screened at 1 µM, closest targets: IC50(AMPK) = 117 nM, IC50(BRSK1) = 187 nM, IC50(BRSK2) = 90 nM, IC50(CAMK2B) = 70 nM, IC50(DRAK1) = 71 nM, IC50(MNK2) = 148 nM, IC50(PHKG2) = 528 nM , IC50(PIM1) = 88 nM ,IC50(CDK1) = 354 nM, IC50(CDK5) = 902 nM, IC50(MAP3K5) = 60 nM, IC50(AXL) = 428 nM, IC50(MERTK) = 76 nM, IC50(RIPK2) = 590 nM;

inactive at 1 µM for NR1H3, NR1H2, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

fold-activation(NR1I2) = 2.24, fold-activation(NR2E1) = 1.84, inactive at 3 µM for NR1H4, UL48, RXRA, HNF4A, NR2C1, NR4A1, NR5A1

fold-activation(NR1I2) = 2.24, fold-activation(NR2E1) = 1.84, inactive at 3 µM for NR1H4, UL48, RXRA, HNF4A, NR2C1, NR4A1, NR5A1

Screened at 1 µM, closest targets AURKA (54%), PLK(53%), CLK1(43%), all IC50 >3.5 µM, In-vitro potency of closest target (Radiometric kinase assay ): Kd(CDK12) = 158 nM, https://www.nature.com/articles/nchembio.2166;

Screened at 100 µM in DSF assay, closest target: dTm(CEREBBP) = 1-3 K; Screened in CEREP panel against 50 GPCRs, ion channels and transporters at 10 µM, closest target as % inhibition: NK2 (48%)

Screened at 100 µM in DSF assay, closest target: dTm(CEREBBP) = 1-3 K; Screened in CEREP panel against 50 GPCRs, ion channels and transporters at 10 µM, closest target as % inhibition: NK2 (48%)

Screened at 100 µM in DSF assay, closest target: dTm(CEREBBP) = 1-3 K; Screened in CEREP panel against 50 GPCRs, ion channels and transporters at 10 µM, closest target as % inhibition: NK2 (48%)

Screened at 100 µM in DSF assay, closest target: dTm(CEREBBP) = 1-3 K; Screened in CEREP panel against 50 GPCRs, ion channels and transporters at 10 µM, closest target as % inhibition: NK2 (48%)

Screened at 10 µM and 50 µM: MS049 is highly selective and showed no inhibition of any enzyme in the panel; Screened in CEREP panel against 100 enzymes (GPCRs, ion channels, transporters, kinases) at 10 µM, clean profile; Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets (radioligand binding assays): Ki(H3) = 87 nM, Ki(Sigma 1) = 64 nM, Ki(Sigma 2) = 574 nM;

Screened at 10 µM and 50 µM: MS049 is highly selective and showed no inhibition of any enzyme in the panel; Screened in CEREP panel against 100 enzymes (GPCRs, ion channels, transporters, kinases) at 10 µM, clean profile; Screened against 45 GPCR targets (PDSP screen) at 10 µM, closest targets (radioligand binding assays): Ki(H3) = 87 nM, Ki(Sigma 1) = 64 nM, Ki(Sigma 2) = 574 nM;

No inhibition of AP-1 and CRE (IC50 >100 µM, TOPFLASH reporter assay); no interaction with the beta-catenin transcriptional coactivator p300.

Screened at 10 µM, ATP-site competition binding assay, S(10) = 0.012, closest targets: Kd(BMK1) = 80 nM, Kd(DCAMKL2) = 190 nM, Kd(TNK1) = 890 nM, Kd(PLK4) = 600 nM; Cellular selectivity profiling using KiNativ method against 181 kinases in HeLa cells, closest targets: IC50(TNK1/2) = 10/ 18 µM, IC50(RSK1/2) = 29/ 47 µM, IC50(FAK) = 39 µM, IC50(PIK4CA/L) = 36 µM, others >50 µM;

Screened at 10 µM, closest targets as % of contr.: NTRK1 (59%); Screened against 300 proteins in Kinobeads assays, in-vitro potencies of closest targets: Kdapp(BRD4) = 1915 nM, Kdapp(MAP2K1) = 62 nM, Kdapp(MAP2K2) = 9 nM (https://www.science.org/doi/10.1126/science.aan4368)

Screened at 10 µM, closest targets as % of contr.: NTRK1 (59%); Screened against 300 proteins in Kinobeads assays, in-vitro potencies of closest targets: Kdapp(BRD4) = 1915 nM, Kdapp(MAP2K1) = 62 nM, Kdapp(MAP2K2) = 9 nM (https://www.science.org/doi/10.1126/science.aan4368)

Screened at 20 µM, closest targets with dTm >3K: dTm(AURKB) = 13.8 K, dTm(STK6) = 9.08 K, dTm(FLT1) = 4.33 K;

Kinases screened via competition binding assays: S(Kd < 300 nM) = 0.0026, S(Kd < 3µM) = 0.0052

Kinases screened via competition binding assays: S(Kd < 300 nM) = 0.0026, S(Kd < 3µM) = 0.0052

Screened at 1 µM, highly selective allosteric inhibitor

Screened at 1 µM, highly selective allosteric inhibitor

Screened at 1 µM, highly selective allosteric inhibitor

Screened at 1 µM, closest targets in the screen: DDR1, DDR2, KIT, ZAK, RSK, MYLK4, but confirmed by NanoBRET as false positive (IC50s of 910-140000 nM)

Screened at 1 µM, closest targets in the screen: DDR1, DDR2, KIT, ZAK, RSK, MYLK4, but confirmed by NanoBRET as false positive (IC50s of 910-140000 nM)

Screened at 1 µM, closest targets as % of inhibition: BLK (92%), CAMK2A (95%), EPHA2 (100%), EPHA4 (94%), FGFR2 (90%), FGR (97%), MAPKAPK3 (91%), NTRK3 (91%); Proteomics (Kinobeads assays), in-vitro potencies of closest targets: Kdapp(AURKA) = 5 nM, Kdapp(ACAD10) = 78 nM, Kdapp(AURKB) = 195 nM, Kdapp(PDPK1) = 289 nM, Kdapp(EPHA2) = 309 nM, Kdapp(EPHA4) = 455 nM, Kdapp(DNAJA1) = 962 nM, Kd(ABL2) = 1009 nM, Kdapp(GNAI2) = 184 nM, Kdapp(PSMA7) = 405 nM, Kdapp(MCM4) = 629 nM, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542668/;

Screened at 10 µM, closest targets as % contr.: JAK3(JH1 catalytic domain) (3.2%), PRKACA (4.2%), PRKACB (6.4%); Additionally screened against 85 kinase targets at 1 µM, closest target as % of contr.: RPS6KA2 (20%), PMID: 19740074;

Screened at 10 µM, closest targets as % contr.: JAK3(JH1 catalytic domain) (3.2%), PRKACA (4.2%), PRKACB (6.4%); Additionally screened against 85 kinase targets at 1 µM, closest target as % of contr.: RPS6KA2 (20%), PMID: 19740074;

Screened at 1 µM, closest target as % of contr.: RAF1 (8%)

Screened at 0.1 µM, closest targets as % of contr.: CLK2 (0%), FLT3(N841I) (0%), FLT3(D835V) (0.2%), YSK4 (1.7%), JAK2 (4.8%), FLT3(D835Y) (5.9%), STK16 (7.7%), JAK3 (8.2), TTK (8.3%), FLT3(ITD,F691L) (9%), FLT3(D835H) (9.8%); Screened in Invitrogen panel at 10 µM, closest targets: IC50(NTRK1) = 56 nM, IC50(MAP3K9) = 75.3 nM; Screened in CEREP panel against 122 human receptors, ion channels, enzymes, closest target: Ki(ADORA3) = 27 nM; Screened in GPCR screen against 45 targets at 10 µM, clean profile;

Screened at 0.1 µM, closest targets as % of contr.: CLK2 (0%), FLT3(N841I) (0%), FLT3(D835V) (0.2%), YSK4 (1.7%), JAK2 (4.8%), FLT3(D835Y) (5.9%), STK16 (7.7%), JAK3 (8.2), TTK (8.3%), FLT3(ITD,F691L) (9%), FLT3(D835H) (9.8%); Screened in Invitrogen panel at 10 µM, closest targets: IC50(NTRK1) = 56 nM, IC50(MAP3K9) = 75.3 nM; Screened in CEREP panel against 122 human receptors, ion channels, enzymes, closest target: Ki(ADORA3) = 27 nM; Screened in GPCR screen against 45 targets at 10 µM, clean profile;

Closest targets: Kd(EPHA5) = 37.9 nM, other targets with low Kd values determined, however targets areof low- to no confidence; Cellular potency of closely related targets (NanoBRET assay in HEK293T cells): IC50(EPHA1) = 330 nM, IC50(EPHA3) = 1000 nM, IC50(EPHA4) = 100 nM, IC50(EPHA5) = 37 nM, IC50(EPHA6) = 2000 nM, IC50(EPHA7) = 2000 nM, IC50(EPHA8) = 12 nM, IC50(EPHB1) = 1000 nM, IC50(EPHB2) = 37 nM, IC50(EPHB3) = 330 nM, IC50(EPHB6) = 330 nM;Screened against 40 kinases in TR-FRET-based LanthaScreen™ and Caliper mobility shift assays, closest targets: IC50(RAF1) = 395 nM, IC50(c-Sarc) = 1266 nM, IC50(c-ABL) = 1667 nM, others >10 µM (PMID: 20803239)

Closest targets: Kd(EPHA5) = 37.9 nM, other targets with low Kd values determined, however targets areof low- to no confidence; Cellular potency of closely related targets (NanoBRET assay in HEK293T cells): IC50(EPHA1) = 330 nM, IC50(EPHA3) = 1000 nM, IC50(EPHA4) = 100 nM, IC50(EPHA5) = 37 nM, IC50(EPHA6) = 2000 nM, IC50(EPHA7) = 2000 nM, IC50(EPHA8) = 12 nM, IC50(EPHB1) = 1000 nM, IC50(EPHB2) = 37 nM, IC50(EPHB3) = 330 nM, IC50(EPHB6) = 330 nM;Screened against 40 kinases in TR-FRET-based LanthaScreen™ and Caliper mobility shift assays, closest targets: IC50(RAF1) = 395 nM, IC50(c-Sarc) = 1266 nM, IC50(c-ABL) = 1667 nM, others >10 µM (PMID: 20803239)

Screened at 1 µM, closest targets with <10% of contr.: ABL1, BLK, DDR1, FLT3, KIT, LCK, STK10, MAP2K5, MET, HIPK4, AURKB/C, FER, HCK, MST1R, CDK19, FRK, SRC, TIE1, CHEK2, MUSK, CDK8, CSF1R, EPHB6, PDGFRB, ROS1, NRTK1/3, MAP4K5, and mutants; Cellular selectivity (quantitative chemical proteomics, cell-based phosphorylation and proliferation assays in Hs578t cells), closest targets: Kd(cMET) = 13 nM,Kd(FER) = 107 nM, Kd(MAP2K5) = 124 nM, Kd(ABL1) = 154 nM, Kd(SRC) = 217 nM;

Screened at 1 µM, closest targets with <10% of contr.: ABL1, BLK, DDR1, FLT3, KIT, LCK, STK10, MAP2K5, MET, HIPK4, AURKB/C, FER, HCK, MST1R, CDK19, FRK, SRC, TIE1, CHEK2, MUSK, CDK8, CSF1R, EPHB6, PDGFRB, ROS1, NRTK1/3, MAP4K5, and mutants; Cellular selectivity (quantitative chemical proteomics, cell-based phosphorylation and proliferation assays in Hs578t cells), closest targets: Kd(cMET) = 13 nM,Kd(FER) = 107 nM, Kd(MAP2K5) = 124 nM, Kd(ABL1) = 154 nM, Kd(SRC) = 217 nM;

Screened at 1 µM, closest targets with <10% of contr.: ABL1, BLK, DDR1, FLT3, KIT, LCK, STK10, MAP2K5, MET, HIPK4, AURKB/C, FER, HCK, MST1R, CDK19, FRK, SRC, TIE1, CHEK2, MUSK, CDK8, CSF1R, EPHB6, PDGFRB, ROS1, NRTK1/3, MAP4K5, and mutants; Cellular selectivity (quantitative chemical proteomics, cell-based phosphorylation and proliferation assays in Hs578t cells), closest targets: Kd(cMET) = 13 nM,Kd(FER) = 107 nM, Kd(MAP2K5) = 124 nM, Kd(ABL1) = 154 nM, Kd(SRC) = 217 nM;

Screened at 10 µM, closest targets as % of contr.: SGK2 (0%), PRKX (4%), RSK4 (12%), SGK (13%), RSK3 (14%), NUAK1 (16%), ROCK2 (17%); Screened against panel of 13 kinases (PDK, AKT1, ALK5, ASK1, AURA, AURB, EGFR, GSK3B, IKK1, PIK3CG, ROCK1, SYK, VEGFR2): IC50(ODK) = 2.5 nM, IC50(AURB) = 3162 nM, IC50(ROCK1) = 7943 nM, others >10 µM;

Screened at 1 µM, follow-up Kds for closest targets: Kd(GSK3B) = 8.3 nM, Kd(PRKCD) = 25 nM, Kd(RSK4) = 25 nM, Kd(PRKCQ) = 36 nM, Kd(FLT3(D835Y)) = 40 nM, Kd(PRKCH) = 46 nM, Kd(FLT3(D835H)) = 49 nM, Kd(FLT3(ITD)) = 72 nM, Kd(MAPK15) = 76 nM, Kd(RSK2Kd) = 87 nM, 18 other targets with Kd 0.1-1 µM;

Screened at 1 µM, follow-up Kds for closest targets: Kd(GSK3B) = 8.3 nM, Kd(PRKCD) = 25 nM, Kd(RSK4) = 25 nM, Kd(PRKCQ) = 36 nM, Kd(FLT3(D835Y)) = 40 nM, Kd(PRKCH) = 46 nM, Kd(FLT3(D835H)) = 49 nM, Kd(FLT3(ITD)) = 72 nM, Kd(MAPK15) = 76 nM, Kd(RSK2Kd) = 87 nM, 18 other targets with Kd 0.1-1 µM;

Screened at 1 µM, follow-up Kds for closest targets: Kd(GSK3B) = 8.3 nM, Kd(PRKCD) = 25 nM, Kd(RSK4) = 25 nM, Kd(PRKCQ) = 36 nM, Kd(FLT3(D835Y)) = 40 nM, Kd(PRKCH) = 46 nM, Kd(FLT3(D835H)) = 49 nM, Kd(FLT3(ITD)) = 72 nM, Kd(MAPK15) = 76 nM, Kd(RSK2Kd) = 87 nM, 18 other targets with Kd 0.1-1 µM;

Screened at 1 µM, follow-up Kds for closest targets: Kd(GSK3B) = 8.3 nM, Kd(PRKCD) = 25 nM, Kd(RSK4) = 25 nM, Kd(PRKCQ) = 36 nM, Kd(FLT3(D835Y)) = 40 nM, Kd(PRKCH) = 46 nM, Kd(FLT3(D835H)) = 49 nM, Kd(FLT3(ITD)) = 72 nM, Kd(MAPK15) = 76 nM, Kd(RSK2Kd) = 87 nM, 18 other targets with Kd 0.1-1 µM;

In-vitro potency of closest target: IC50(CDK11) = 1.7 nM

Screened at 10 µM, S(10) = 0.003, closest target: IC50(PAK2) = 72 nM; Screened against 27 receptors (Novartis panel) at 10 µM, closest target: IC50(H1) = 13 µM, IC50(M1) = 13 µM; Screened against panel of 48 bromodomains at 10 µM in DSF-assay, all targets dTm < 1 K clean profile

Screened at 1 µM, S(10) = 0.02, follow-up Kds for closest targets: Kd(PIP5K1C) = 260 nM, Kd(RIOK1) = 72 nM, Kd(RIOK3) = 290 nM; Kd(RIOK3) = 290 nM, Kd(CDKL2) = 880 nM, Kd(MYLK2) = 960 nM;

Screened at 1 µM, S(10) = 0.02, follow-up Kds for closest targets: Kd(PIP5K1C) = 260 nM, Kd(RIOK1) = 72 nM, Kd(RIOK3) = 290 nM; Kd(RIOK3) = 290 nM, Kd(CDKL2) = 880 nM, Kd(MYLK2) = 960 nM;

Screened at 1 µM, off-target PoC of 12%

Screened at 1 µM, closest targets as % of contrl.: ALK(C1156Y) (0.3%), CAMKK1/2 (3.7/ 3.4%), PIP5K2C (4.2%), PLK2/3 (1.2/ 0.5%), RPS6KA4(KD2-C) (0.3%); follow-up IC50s of closest targets: IC50(PLK2) = 3.5 nM, IC50(PLK3) = 9 nM; Screened in Dundee panel against 30 kinases at 10 µM, clean profile; Screened in SafetyScreen44™ (Eurofins) against 64 targets (GPCRS, ion channels, transporters) at 10 µM, closest target as % of contr. ALPHA1A/R (13%);

Screened at 1 µM, closest targets as % of contrl.: ALK(C1156Y) (0.3%), CAMKK1/2 (3.7/ 3.4%), PIP5K2C (4.2%), PLK2/3 (1.2/ 0.5%), RPS6KA4(KD2-C) (0.3%), follow-up IC50s of closest targets: IC50(PLK2) = 3.5 nM, IC50(PLK3) = 9 nM; Screened in Dundee panel against 30 kinases at 10 µM, clean profile; Screened in SafetyScreen44™ (Eurofins) against 64 targets (GPCRS, ion channels, transporters) at 10 µM, closest target as % of contr. ALPHA1A/R (13%);

Screened at 1 µM, S(10) = 0.05, closest targets as % of contr.: ABL (M351T phosph.) (5.5%), ABL (Q252H phosph.) (6.8%), ABL (T315I phosph.) (1.6%), AURKA (0.05%), AURKB (3.4%), DCAMKL1 (8.3%), MAP3K2 (2.6%), MAP3K3 (2%), JAK1 (JH2 pseudokinase domain) (4.3%), STK24 (0.9%), STK26 (0.6%), PIK3CG (0.15%), PIP5K1C (10%), PIP5K2C (8%), RIPK4 (9.5%), TAOK1 (2.6%), TAOK2 (3.4%), TAOK3 (4.5%), TYK2 (JH1 catalytic domain, 2.7%), ULK2 (4.8%); Follow-up Kds and IC50s: Kd/IC50(ABL, M351T phosph.) = 42/ 17.6 nM, KD/IC50(ABL (Q252H phosph.) = 24/ 11.6 nM, Kd/IC50(ABL, T315I phosph.) = 14/ 16.6 nM, Kd/IC50 (AURKA) = 13/ 19.4 nM, Kd/IC50(AURKB) = 40/ 19.4 nM, Kd/IC50(DCAMKL1) = 25/ 27.9 nM, Kd/IC50(MAP3K2) = 19/ 79.6 nM, Kd/IC50(MAP3K3) = 27/ 38.4 nM, Kd/IC50(JAK1, JH2 pseudokinase domain) = 22/ 38.7 nM, Kd/IC50(STK24) = 18/ 44.8 nM, Kd/IC50(STK26) = 16/ 27.3 nM, Kd/IC50(PIK3CG) = 4.8/ 38.4 nM, Kd/IC50(PIP5K1C) = 77/ 436 nM, Kd(PIP5K2C) = 34 nM, Kd(RIPK4) = 140 nM, Kd/IC50(TAOK1) = 180/ 165 nM, Kd/IC50(TAOK2) = 100/ 134 nM, Kd/IC50(TAOK3) = 610/ 254 nM, Kd/IC50(TYK2, JH1 catalytic domain) = 610/ 254 nM, Kd/IC50(ULK2) = 35/ 41.5 nM;

Screened at 1 µM, S(10) = 0.05, closest targets as % of contr.: ABL (M351T phosph.) (5.5%), ABL (Q252H phosph.) (6.8%), ABL (T315I phosph.) (1.6%), AURKA (0.05%), AURKB (3.4%), DCAMKL1 (8.3%), MAP3K2 (2.6%), MAP3K3 (2%), JAK1 (JH2 pseudokinase domain) (4.3%), STK24 (0.9%), STK26 (0.6%), PIK3CG (0.15%), PIP5K1C (10%), PIP5K2C (8%), RIPK4 (9.5%), TAOK1 (2.6%), TAOK2 (3.4%), TAOK3 (4.5%), TYK2 (JH1 catalytic domain, 2.7%), ULK2 (4.8%); Follow-up Kds and IC50s: Kd/IC50(ABL, M351T phosph.) = 42/ 17.6 nM, KD/IC50(ABL (Q252H phosph.) = 24/ 11.6 nM, Kd/IC50(ABL, T315I phosph.) = 14/ 16.6 nM, Kd/IC50 (AURKA) = 13/ 19.4 nM, Kd/IC50(AURKB) = 40/ 19.4 nM, Kd/IC50(DCAMKL1) = 25/ 27.9 nM, Kd/IC50(MAP3K2) = 19/ 79.6 nM, Kd/IC50(MAP3K3) = 27/ 38.4 nM, Kd/IC50(JAK1, JH2 pseudokinase domain) = 22/ 38.7 nM, Kd/IC50(STK24) = 18/ 44.8 nM, Kd/IC50(STK26) = 16/ 27.3 nM, Kd/IC50(PIK3CG) = 4.8/ 38.4 nM, Kd/IC50(PIP5K1C) = 77/ 436 nM, Kd(PIP5K2C) = 34 nM, Kd(RIPK4) = 140 nM, Kd/IC50(TAOK1) = 180/ 165 nM, Kd/IC50(TAOK2) = 100/ 134 nM, Kd/IC50(TAOK3) = 610/ 254 nM, Kd/IC50(TYK2, JH1 catalytic domain) = 610/ 254 nM, Kd/IC50(ULK2) = 35/ 41.5 nM;

inactive at 1 µM for NR1H3, NR1H2, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

inactive at 3 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

inactive at 3 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

inactive at 1 µM for NR1H3, NR1H2, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

fold-activation(PPARD) = 19.05, inactive at 1 µM for UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1