Chemogenomic set

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

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

inactive at 1 µM for RORA, RORB, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

rem. activity(RORA) = 0.85, rem. activity(NR2C1) = 0.42, inactive at 10 µM for UL48, RXRA, HNF4A, NR2E1, NR4A1, NR5A1

inactive for VDR, NR1I2, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

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

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

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

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

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

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

fold-activation(NR1H2) = 5.01, inactive at 1 µM for NR1H3, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

rem. activity(NR5A1) = 0.47, inactive at 1 µM for NR1H2, NR1H3, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1

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

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

fold-activation(NR1H2) = 5.89, inactive at 1 µM for NR1H3, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

rem. activity(NR1H2) = 0.62, rem. activity(NR1H3) = 0.72, rem. activity(NR2E1) = 0.43, inactive for UL48, RXRA, HNF4A, NR2C1, NR4A1, NR5A1

Screened at 10 µM against 6 human serine proteases, closest target as % inhibition: CTSG (63%), estimated IC50 = 6 µM; Clean Eurofins-Cerep panel for non-serine proteases tested at 10 µM; Screened at 1 µM against 468 kinases (KinomeScan, DiscoverX), closest targets as % of control: STK38L (43%), MELK (44%); Screened at 10 µM against 45 GPCRs (PDSP panel), in-vitro potencies of closest targets: Ki(ADRA2C) = 3.29 µM, Ki(ADRB3) = 3.62 µM, Ki(ADRA2B) = 4.49 µM

Screened at 1 µM, S-Score(10) = 0.007 at 1 µM, closest targets as % of inhibition: STK17A (100%), DYRK2 (86%), PLK4 (77%), HIPK2 (72%), MEK5 (72%), HIPK1 (68%), HIPK3 (66%); In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(STK17A) >10000 nM, IC50(DYRK2) = 440 nM, IC50(PLK4) >10000 nM, IC50(HIPK2) = 3400 nM, IC50(MEK5) n.d., IC50(HIPK1) = 3700 nM, IC50(HIPK3) = 8100 nM; In-vitro follow-up of MEK5 in enzymatic assay: 0% inhibition at 1 µM (https://www.sciencedirect.com/science/article/pii/S2451945620305225?via%3Dihub);

Screened at 1 µM, S-Score(10) = 0.007 at 1 µM, closest targets as % of inhibition: STK17A (100%), DYRK2 (86%), PLK4 (77%), HIPK2 (72%), MEK5 (72%), HIPK1 (68%), HIPK3 (66%); In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(STK17A) >10000 nM, IC50(DYRK2) = 440 nM, IC50(PLK4) >10000 nM, IC50(HIPK2) = 3400 nM, IC50(MEK5) n.d., IC50(HIPK1) = 3700 nM, IC50(HIPK3) = 8100 nM; In-vitro follow-up of MEK5 in enzymatic assay: 0% inhibition at 1 µM (https://www.sciencedirect.com/science/article/pii/S2451945620305225?via%3Dihub);

Screened at 1 µM, closest targets as % of inhibition: TNIK (4.92%), ALK6 (27%), MAP4K4 (30%); In-vitro follow-up of closest targets and ALK family (biochemical assays, Reaction Biology, 10 mM ATP): IC50(ALK3) = 168 nM, IC50(ALK4) = 1660 nM, IC50(ALK5) 1950 nM, IC50(ALK6) = 88 nM, IC50(TNIK) = 41 nM; In-cellulo potency (NanoBRET assay in HEK293T cells): IC50(ALK3) = 536 nM, IC50(ALK4) = 8424 nM, IC50(ALK5) = 7932 nM, IC560(ALK6) = 1628 nM, https://www.thesgc.org/chemical-probes/m4k2234;

Screened at 1 µM, closest targets as % of inhibition: TNIK (4.92%), ALK6 (27%), MAP4K4 (30%); In-vitro follow-up of closest targets and ALK family (biochemical assays, Reaction Biology, 10 mM ATP): IC50(ALK3) = 168 nM, IC50(ALK4) = 1660 nM, IC50(ALK5) 1950 nM, IC50(ALK6) = 88 nM, IC50(TNIK) = 41 nM; In-cellulo potency (NanoBRET assay in HEK293T cells): IC50(ALK3) = 536 nM, IC50(ALK4) = 8424 nM, IC50(ALK5) = 7932 nM, IC560(ALK6) = 1628 nM, https://www.thesgc.org/chemical-probes/m4k2234;

Screened at 10 µM, closest target dTm(STK10) = 4.2K, all other targets dTm <4 K;

Screened at 10 µM, closest target dTm(STK10) = 4.2K, all other targets dTm <4 K;

Screened at 10 µM, closest target dTm(STK10) = 4.2K, all other targets dTm <4 K;

Screened at 1 µM, closest targets as % of inhibition: MAP4K4 (65%), CSNK1A1 (51%), MINK1 (42%), MAPK14 (37%), in-vitro potencies of closest targets: IC50(MAP4K4) = 873 nM, IC50(CSNK1A1) = 630 nM, IC50(MINK1) = 1573 nM, IC50(MAPK14) = 861 nM (https://pubs.acs.org/doi/10.1021/acschemneuro.7b00155);

Screened at 1 µM, closest targets as % of inhibition: MAP4K4 (65%), CSNK1A1 (51%), MINK1 (42%), MAPK14 (37%), in-vitro potencies of closest targets: IC50(MAP4K4) = 873 nM, IC50(CSNK1A1) = 630 nM, IC50(MINK1) = 1573 nM, IC50(MAPK14) = 861 nM (https://pubs.acs.org/doi/10.1021/acschemneuro.7b00155);

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (-1%), CSNK1D (-6%), TNIK (12%), MAP4K4 (47%), MAP2K3 (43%), SAPK2a (41%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 539.9 nM, EC50(CSNK1D) = 12.9 nM, EC50(CSNK1E) = 51.8 nM, EC50(GAPVD1) = 137.7 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (-1%), CSNK1D (-6%), TNIK (12%), MAP4K4 (47%), MAP2K3 (43%), SAPK2a (41%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 539.9 nM, EC50(CSNK1D) = 12.9 nM, EC50(CSNK1E) = 51.8 nM, EC50(GAPVD1) = 137.7 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (-1%), CSNK1D (-6%), TNIK (12%), MAP4K4 (47%), MAP2K3 (43%), SAPK2a (41%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 539.9 nM, EC50(CSNK1D) = 12.9 nM, EC50(CSNK1E) = 51.8 nM, EC50(GAPVD1) = 137.7 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (3%), CSNK1D (-4%), MAP2K3 (44%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 24.2 nM, EC50(CSNK1D) = 7.6 nM, EC50(CSNK1E) = 10.2 nM, EC50(ACVR1B) = 2673.8 nM, EC50 (GAPVD1) = 11.4 nM, EC50(PRKD2) = 20027.9 nM, EC50(TGFBR1) = 759.7 nM, EC50(MAPK14) = 3163. 4 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (3%), CSNK1D (-4%), MAP2K3 (44%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 24.2 nM, EC50(CSNK1D) = 7.6 nM, EC50(CSNK1E) = 10.2 nM, EC50(ACVR1B) = 2673.8 nM, EC50 (GAPVD1) = 11.4 nM, EC50(PRKD2) = 20027.9 nM, EC50(TGFBR1) = 759.7 nM, EC50(MAPK14) = 3163. 4 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, using ATP conc. = Km, closest targets as % of activity: CSNK1A1 (7%), CSNK1E (3%), CSNK1D (-4%), MAP2K3 (44%), full screening data are available as supporting information, https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fanie.202217532&file=anie202217532-sup-0001-misc_information.pdf;
Screened at 1 µM, Kinobeads pulldown experiments (Kinobeads competition binding assays, using K-562, COLO-205, and MV-4-11 cells), EC50(CSNK1A) = 24.2 nM, EC50(CSNK1D) = 7.6 nM, EC50(CSNK1E) = 10.2 nM, EC50(ACVR1B) = 2673.8 nM, EC50 (GAPVD1) = 11.4 nM, EC50(PRKD2) = 20027.9 nM, EC50(TGFBR1) = 759.7 nM, EC50(MAPK14) = 3163. 4 nM, full screening data, with additional conc. are available as a supplemental table, https://pubmed.ncbi.nlm.nih.gov/36625768/;

Screened at 1 µM, closest targets as % of inhibition: CSNK1A1 (6%), CSNK1D (-6%), CSNK1E (0%), TNIK (43%), ZAP-70 (71%);

Screened at 1 µM, closest targets as % of inhibition: CSNK1A1 (6%), CSNK1D (-6%), CSNK1E (0%), TNIK (43%), ZAP-70 (71%);

Screened at 1 µM, closest targets as % of inhibition: CSNK1A1 (6%), CSNK1D (-6%), CSNK1E (0%), TNIK (43%), ZAP-70 (71%);

Screened at 1 µM, closest targets >80% of inhibition: CHEK1 (17%), RSK1 (4%), RSK2 (9%), AMPK (5%), BRSK1 (11%), IRAK1 (17%), NTRK1 (13%), full screening data are available as supporting information, https://pubmed.ncbi.nlm.nih.gov/23082860/;
Screened at 10 µM, against 121 kinases, closest targets as % of control: MAPK15 (11%), RSK1 (14%), STK33 (16%), AMPK (14%), BRSK2 (14%), NUAK1 (7%), PIM3 (17%), IRAK1 (9%), CHEK1 (6%), full screening data are available as supporting information, https://pubmed.ncbi.nlm.nih.gov/23082860/;

Screened at 10 µM (using 10 µM ATP), closest targets as % of inhibition: NEK1 (96.76%), MAP4K5(96.28%), MEKK2(94.29%), MER(92.85%), MAP3K10(9.2%), RPS6KA5(86.83%), full screening data are available as supporting information; In-vitro potency of closest targets (enzymatic assay): IC50(EIF2AK1) = 460 nM, IC50(BRK) = 822 nM, IC50(EIF2AK2) = 905 nM, IC50(MEKK2) = 954 nM, IC50(NEK1) = 9807 nM, IC50(MAP4K5) = 1764 nM, IC50(MEKK3) = 2847 nM, IC50(MER) = 3431 nM, IC50(MAP3K10) = 2796 nM, full screening data available in manuscript, https://pubmed.ncbi.nlm.nih.gov/23333938/;

Screened at 1 µM, closest targets as % of inhibition: ROCK1 (90.09%), ROCK2 (84.2%), PRKC (75.32%), AURKA (70.59%), RON (67.51%), RET (65.79%), full screening data available at Chembl, screened also at 100 nM, https://pubmed.ncbi.nlm.nih.gov/26501955/;
In-vitro potency (Scintillation Proximity Assay, SPA): IC50(RSK1) = 1100 nM, https://pubs.acs.org/doi/10.1021/jm0609014;
In-vitro potency (Scintillation Proximity Assay, SPA): IC50(RPS6KB1) = 1550 nM, https://pubs.acs.org/doi/10.1021/jm0609014;

Screened at 1 µM, closest targets as % of inhibition: ROCK1 (91.85%), ROCK2 (89.92%), AURKA (70.15%), PRKX (59.21%), full screening data available at Chembl, screened also at 100 nM, https://pubmed.ncbi.nlm.nih.gov/26501955/;
In-vitro potency (Scintillation Proximity Assay, SPA): IC50(RSK1) = 620 nM, https://pubs.acs.org/doi/10.1021/jm0609014;
In-vitro potency (Scintillation Proximity Assay, SPA): IC50(RPS6KB1) = 560 nM, https://pubs.acs.org/doi/10.1021/jm0609014;

Screened at 1 µM, closest targets as % of control: LCK (13%), FLT3(16%), BRK (31%), full screening data available as supporting information

Screened at 1 µM nd 10 µM, closest targets as % of control at 1 µM: MAP3K7 (16%), MST2 (17%), BRSK1 (18%), MAP2K2 (17%), ERK1 (16%), full screening data available as supplemental information; Screened at 1 µM against 451 kinases (KinomeScan, DiscoverX), closest targets as % of control: KIT (L576P, 9.4%), LRRK2 (G2019S, 2.1%), others >10%, full screening data available as supporting information,https://pubmed.ncbi.nlm.nih.gov/23066449/; Screened in KiNativ Profiling in tissue from inhibitor-treated animals, closest targets JNK1/2/3 and TBK1 potential dose-related inhibition (∼35–40% at 50 and 100 mg/kg), full screening data available as supporting information,https://pubmed.ncbi.nlm.nih.gov/23066449/;

Screened at 1 µM, S(1) = 0.005, closest targets as % of control: CDK9 (0.35%), DYRK1B (0.6%), TAOK3 (2.3%), HIPK4 (4.4%), CDC2L5 (5.5%), IRAK1 (6.5%), DYRK1A (9.2%), CDK7 (9.2%), full screening data are available as supporting information; https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Adapta Eu kinase assay, CDK7/CycH/MNAT1, conc. ATP = Km): IC50(CDK7) >10 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Z-Lyte kinase assay, conc. ATP = Km): IC50(DYRK1B) = 350 nM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Z'LYTE kinase assays, CDK1/CyclinB, conc. ATP = Km): IC50(CDK1) = 0.584 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Z'LYTE kinase assays, CDK2/CyclinA, conc. ATP = Km): IC50(CDK2) = 0.706 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Z'LYTE kinase assays, CDK5/p25, conc. ATP = Km): IC50(CDK5) = 1.05 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Lanthascreen Eu kinase binding assays, CDK8/CyclinC, conc. ATP = Km): IC50(CDK8) >10 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Lanthascreen Eu kinase binding assays, CDK14/CyclinY, conc. ATP = Km): IC50(CDK14) = 3.45 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Lanthascreen Eu kinase binding assays, CDK16/CyclinY, conc. ATP = Km): IC50(CDK16) = 0.605 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Lanthascreen Eu kinase binding assays, CDK17/CyclinY, conc. ATP = Km): IC50(CDK17) = 1.5 µM, https://www.nature.com/articles/nchembio.2538;
In-vitro potency (Lanthascreen Eu kinase binding assays, CDK18/CyclinY, conc. ATP = Km): IC50(CDK18) = 4.9 µM, https://www.nature.com/articles/nchembio.2538;
In-cellular potency (Immunoblot assay, Bio-AT7519 pulldown using MOLT4 wt cells): IC50(CDK7) >1 µM, https://www.nature.com/articles/nchembio.2538;
In-cellular potency (Immunoblot assay, Bio-AT7519 pulldown using MOLT4 wt cells): IC50(CDK2) >1 µM, https://www.nature.com/articles/nchembio.2538;
In-cellular potency (Immunoblot assay, Bio-AT7519 pulldown using MOLT4 CRBN-/- cells): IC50(CDK7) >1 µM, https://www.nature.com/articles/nchembio.2538;
In-cellular potency (Immunoblot assay, Bio-AT7519 pulldown using MOLT4 CRBN-/- cells): IC50(CDK2) >1 µM, https://www.nature.com/articles/nchembio.2538;
In-cellular potency (Immunoblot assay, Bio-AT7519 pulldown using MOLT4 CRBN-/- cells): IC50(CDK9) <250 nM, https://www.nature.com/articles/nchembio.2538;
Screened at 1 µM in Kinativ chemical proteomics, using MOLT4 cell lysates, closest targets as % of inhibition: CDK9 (99%), CDK10 (99%), CRK7 (50.1%), full screening data are available as supporting information, https://www.nature.com/articles/nchembio.2538;

Screened at 2 µM, closest targets as % of inhibition: HER3 (75.9%), LYN (79.8%), FYN (65.7%), HER2 (69.8%), full screening data are available as supporting information, https://pubmed.ncbi.nlm.nih.gov/25326665/;
In-vitro potency (Z'-LYTETM Kinase Assay, Invitrogen,): IC50(EGFR) = 5.6 µM, https://pubmed.ncbi.nlm.nih.gov/25326665/;
In-vitro potency (Z'-LYTETM Kinase Assay, Invitrogen,): IC50(HER2) = 2.63 µM, https://pubmed.ncbi.nlm.nih.gov/25326665/;

Screened at 1 µM, closest targets as % of control: GSK3A (>80%), GSK3B (>80%), LCK (>80%), PKG1B (>80%), full screening data available as supporting information, In-vitro potency (enzymatic assay): IC50(TNKS1) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(GSK3A) = 0.462 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(GSK3B) = 0.690 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(LCK) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(PKG1B) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
Screened at 10 µM against a panel of 55 receptors, ion channels, and enzymes (CEREP panel), closest targets as % of control: KOP (72%), 5HT Transporter (70%), full screening data available as supporting information, https://pubs.acs.org/doi/10.1021/jm501436m;

Screened at 1 µM, closest targets as % of control: GSK3A (>80%), GSK3B (>80%), LCK (>80%), PKG1B (>80%), full screening data available as supporting information, In-vitro potency (enzymatic assay): IC50(TNKS1) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(GSK3A) = 0.462 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(GSK3B) = 0.690 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(LCK) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
In-vitro potency (enzymatic assay, Millipore): IC50(PKG1B) >10 µM, https://pubs.acs.org/doi/10.1021/jm501436m;
Screened at 10 µM against a panel of 55 receptors, ion channels, and enzymes (CEREP panel), closest targets as % of control: KOP (72%), 5HT Transporter (70%), full screening data available as supporting information, https://pubs.acs.org/doi/10.1021/jm501436m;

Screened at 1 µM, Caliper assay (microfluidics capillary electrophoresis technology), using conc. ATP=Km, closest targets as % of inhibition: STK10 (95.26%), BRK (84.98%), TEK (78.74%), KDR (47.78%), ERBB4 (44.38%), also screened at 0.1 µM, closest targets as % of inhibition: TEK (75%), STK10 (43.93%), BRK (29.02%), ERBB4 (15.02%), full screening data are available at Chembl., https://pubmed.ncbi.nlm.nih.gov/26501955/

Screened at 1 µM, Caliper assay (microfluidics capillary electrophoresis technology), using conc. ATP=Km, closest targets as % of inhibition: STK10 (95.26%), BRK (84.98%), TEK (78.74%), KDR (47.78%), ERBB4 (44.38%), also screened at 0.1 µM, closest targets as % of inhibition: TEK (75%), STK10 (43.93%), BRK (29.02%), ERBB4 (15.02%), full screening data are available at Chembl., https://pubmed.ncbi.nlm.nih.gov/26501955/

Screened at 10 µM, using conc. ATP = Km, closest targets as % of control: DDR2 (0.08%), MAP3K9 (1.20%), MAP4K5 (3.22%), BRK (4.25%), MER(4.34%), MAP3K11 (4.40%), MYLK2 (4.41%), RET (4.80%), MAP3K10 (5.86%), NTRK1 (5.92%), NTRK3 (6.85%), IKBKE (8.81%), LCK (10.19%), full screening data available as supporting information, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro follow-up of closest targets in the screen (enzymatic assay, ReactionBiology): IC50(KIT) = 154 nM, IC50(AURKB) = 407 nM, IC50(BRK) = 412 nM, IC50(MAP3K10) = 452 nM, IC50(MER) = 474 nM, IC50(DDR2) = 524 nM, IC50(MYLK2) = 701 nM, IC50(IKBKE) = 1064 nM, IC50(MAP3K11) = 1140 nM, IC500(RET) = 1215 nM, IC50(LCK) = 1250 nM, IC50(NEK4) = 1402 nM, IC50(MAP4K5) = 1569 nM, IC50(MAp3K9) = 1578 nM, IC50(NTRK1) = 1756 nM, IC50(AXL) = 2705 nM, IC50(YES1) = 3195 nM, IC50(WNK2) = 3892 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (HTRF assay): IC50(EIF2AK1) = 420 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (HTRF assay): IC50(EIF2AK2) = 696 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (ADP-Glo assay): IC50(RIPK1) = 18.2 nM, https://www.nature.com/articles/cdd201758;

Screened at 10 µM, using conc. ATP = Km, closest targets as % of control: DDR2 (0.08%), MAP3K9 (1.20%), MAP4K5 (3.22%), BRK (4.25%), MER(4.34%), MAP3K11 (4.40%), MYLK2 (4.41%), RET (4.80%), MAP3K10 (5.86%), NTRK1 (5.92%), NTRK3 (6.85%), IKBKE (8.81%), LCK (10.19%), full screening data available as supporting information, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro follow-up of closest targets in the screen (enzymatic assay, ReactionBiology): IC50(KIT) = 154 nM, IC50(AURKB) = 407 nM, IC50(BRK) = 412 nM, IC50(MAP3K10) = 452 nM, IC50(MER) = 474 nM, IC50(DDR2) = 524 nM, IC50(MYLK2) = 701 nM, IC50(IKBKE) = 1064 nM, IC50(MAP3K11) = 1140 nM, IC500(RET) = 1215 nM, IC50(LCK) = 1250 nM, IC50(NEK4) = 1402 nM, IC50(MAP4K5) = 1569 nM, IC50(MAp3K9) = 1578 nM, IC50(NTRK1) = 1756 nM, IC50(AXL) = 2705 nM, IC50(YES1) = 3195 nM, IC50(WNK2) = 3892 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (HTRF assay): IC50(EIF2AK1) = 420 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (HTRF assay): IC50(EIF2AK2) = 696 nM, https://pubmed.ncbi.nlm.nih.gov/22827572/;
In-vitro potency (ADP-Glo assay): IC50(RIPK1) = 18.2 nM, https://www.nature.com/articles/cdd201758;

Screened at 1 µM using Km =ATP, closest targets as % of inhibition: CDK4(cyclinD3, 102.4%), CDK6(cyclinD3, 101.7%), CLK1 (100.3%), HIPK2(88.9%), MAP2K5 (84.8%), FLT3(84.5%), ERK5(77.9%), NTRK1(72.7%), CLK2(72.5%), PKD3(72.1%), PKD2(71.9%), PKR(71.4%), DYRK1B(70.5%), PKD1(69.1%), PEK(68.8%), HIPK3(63.4%), HIPK4(62.5%), NUAK2(61.9%), CDK9(cyclinT1, 59.8%), HIPK1(57.4%), CAMK2D(54%), TSSK1(53.5%), DYRK3(52.3%), MER(52.2%); In-vitro potency of closest targets (biochemical dose-responce assay using ATP = Km, Carna Biosciences): Ki(CLK1) = 16 nM, Ki(FLT3) = 53 nM, Ki(HIPK2) = 70 nM, Ki(MAP2K5) = 90 nM, Ki(ERK5) = 129 nM, Ki(DYRK1B) = 162 nM, Ki(CLK2) = 176 nM, Ki(PKD3) = 204 nM, Ki(PKR) = 241 nM, Ki(PKD2) = 277 nM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened against 17 non-kinase proteins (CEREP ligand displacement assays), in-vitro potency of closest targets: EC50(Adren Alpha 1a) >10 µM, EC50(Dopamine 1) >10 µM, EC50(Histamine 1) >10 µM, EC50(Muscarinic 1) >10 µM, EC50(5HT2b) >10 µM, EC50(Adren Beta 2) >10 µM, EC50(Cannabinoid 1) >10 µM, EC50(Mu Opioid) >10 µM, EC50(SERT) >10 µM, EC50(DAT) >10 µM, EC50(NET) >10 µM, EC50(PDE3A1) >180 µM, EC50(PDE4D3) = 3.4 µM, EC50(PDE5A1) = 2.9 µM, EC50(L-Type Calcium) >20 µM, EC50(Sodium, Nav1.5) >10 µM, EC50(BRD4) >25 µM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened at 1 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (2%), PKD1 (44%), ERK8 (47%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened at 10 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (8%), DYRK1A (9%), ERK8 (13%), CK2 (13%), MELK (14%), GCK(15%), DYRK3 (16%), PKD1 (18%), PLK1 (18%), NTRK1(18%), TAK1(21%), PHK (22%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened against 520 kinases (competition-binding assay), closest targets: Kd(CDK6) = 76 nM, Kd(PIP4K2A) = 208 nM, Kd(CLK1) = 276 nM, Kd(CSNK2B) = 448 nM, Kd(CSNK2A2) = 488 nM, Kd(CDK4) = 572 nM, Kd(EIF3J) = 701 nM, Kd(CSNK2A1/A3) = 760 nM, Kd(MAP2K4) = 1251 nM, Kd(CDK17) = 1272 nM, Kd(CCNT2) = 1665 nM, Kd(PIP4K2C) = 1721 nM, Kd(CCNT1) = 2676 nM, Kd(CDK16) = 2778 nM, Kd(MAPK9) = 2856 nM, Kd(MED23) = 2998 nM, Kd(AAK1) = 4216 nM, Kd(PRKD2) = 5623 nM, Kd(CDK9) = 9492 nM, Kd(STK16) = 9969 nM, Kd(TAOK3) = 15852 nM, Kd(PRKD3) = 16296 nM, Kd(BMP2K) = 26466 nM, Kd(Q6ZSR9) = 27334 nM, Kd(TAOK2) = 27973 nM, https://pubmed.ncbi.nlm.nih.gov/29191878/;

Screened at 1 µM using Km =ATP, closest targets as % of inhibition: CDK4(cyclinD3, 102.4%), CDK6(cyclinD3, 101.7%), CLK1 (100.3%), HIPK2(88.9%), MAP2K5 (84.8%), FLT3(84.5%), ERK5(77.9%), NTRK1(72.7%), CLK2(72.5%), PKD3(72.1%), PKD2(71.9%), PKR(71.4%), DYRK1B(70.5%), PKD1(69.1%), PEK(68.8%), HIPK3(63.4%), HIPK4(62.5%), NUAK2(61.9%), CDK9(cyclinT1, 59.8%), HIPK1(57.4%), CAMK2D(54%), TSSK1(53.5%), DYRK3(52.3%), MER(52.2%); In-vitro potency of closest targets (biochemical dose-responce assay using ATP = Km, Carna Biosciences): Ki(CLK1) = 16 nM, Ki(FLT3) = 53 nM, Ki(HIPK2) = 70 nM, Ki(MAP2K5) = 90 nM, Ki(ERK5) = 129 nM, Ki(DYRK1B) = 162 nM, Ki(CLK2) = 176 nM, Ki(PKD3) = 204 nM, Ki(PKR) = 241 nM, Ki(PKD2) = 277 nM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened against 17 non-kinase proteins (CEREP ligand displacement assays), in-vitro potency of closest targets: EC50(Adren Alpha 1a) >10 µM, EC50(Dopamine 1) >10 µM, EC50(Histamine 1) >10 µM, EC50(Muscarinic 1) >10 µM, EC50(5HT2b) >10 µM, EC50(Adren Beta 2) >10 µM, EC50(Cannabinoid 1) >10 µM, EC50(Mu Opioid) >10 µM, EC50(SERT) >10 µM, EC50(DAT) >10 µM, EC50(NET) >10 µM, EC50(PDE3A1) >180 µM, EC50(PDE4D3) = 3.4 µM, EC50(PDE5A1) = 2.9 µM, EC50(L-Type Calcium) >20 µM, EC50(Sodium, Nav1.5) >10 µM, EC50(BRD4) >25 µM, https://pubmed.ncbi.nlm.nih.gov/27496135/; Screened at 1 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (2%), PKD1 (44%), ERK8 (47%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened at 10 µM against 140 kinases (Dundee kinase profiling), closest targets as % of contr.: HIPK2 (8%), DYRK1A (9%), ERK8 (13%), CK2 (13%), MELK (14%), GCK(15%), DYRK3 (16%), PKD1 (18%), PLK1 (18%), NTRK1(18%), TAK1(21%), PHK (22%), https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00049; Screened against 520 kinases (competition-binding assay), closest targets: Kd(CDK6) = 76 nM, Kd(PIP4K2A) = 208 nM, Kd(CLK1) = 276 nM, Kd(CSNK2B) = 448 nM, Kd(CSNK2A2) = 488 nM, Kd(CDK4) = 572 nM, Kd(EIF3J) = 701 nM, Kd(CSNK2A1/A3) = 760 nM, Kd(MAP2K4) = 1251 nM, Kd(CDK17) = 1272 nM, Kd(CCNT2) = 1665 nM, Kd(PIP4K2C) = 1721 nM, Kd(CCNT1) = 2676 nM, Kd(CDK16) = 2778 nM, Kd(MAPK9) = 2856 nM, Kd(MED23) = 2998 nM, Kd(AAK1) = 4216 nM, Kd(PRKD2) = 5623 nM, Kd(CDK9) = 9492 nM, Kd(STK16) = 9969 nM, Kd(TAOK3) = 15852 nM, Kd(PRKD3) = 16296 nM, Kd(BMP2K) = 26466 nM, Kd(Q6ZSR9) = 27334 nM, Kd(TAOK2) = 27973 nM, https://pubmed.ncbi.nlm.nih.gov/29191878/;

Screened at 1 µM, closest targets as % of inhibition: TNK2 (85%), PDGFRB (84%), ZAK (86%), full screening data available as supporting information

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 1 µM, in-vitro potency of closest targets (binding assay, Ambit): Kd(ALK) = 230 nM, Kd(CAMKK1) = 1100 nM, Kd(CAMKK2) = 87 nM, Kd(DAPK1) = 100 nM, Kd(DAPK3) = 70 nM, Kd(FER) = 53 nM, Kd(GAK) = 87 nM, Kd(MYLK) = 170 nM, Kd(PTK2) = 84 nM, Kd(PTK2B) = 130 nM, Kd(RPS6KA6) = 560 nM, Kd(TTK) = 51 nM, Kd(PLK1) = 0.09 nM, https://pubmed.ncbi.nlm.nih.gov/22172702/;

Screened at 20 µM, clean profile, no target with dTm >2 K, in-house data;
Screened against 25 kinases in enzymatic assays, in-vitro potency of closest targets: IC50(GSK3A) = 260 nM, IC50(GSK3B) = 330 nM, others >10 µM, but targets not named in the literature, https://pubmed.ncbi.nlm.nih.gov/23021994/;

Screened at 20 µM, clean profile, no target with dTm >2 K, in-house data;
Screened against 25 kinases in enzymatic assays, in-vitro potency of closest targets: IC50(GSK3A) = 260 nM, IC50(GSK3B) = 330 nM, others >10 µM, but targets not named in the literature, https://pubmed.ncbi.nlm.nih.gov/23021994/;

Screened at 20 µM, clean profile, no target with dTm >2 K, in-house data;
Screened against 25 kinases in enzymatic assays, in-vitro potency of closest targets: IC50(GSK3A) = 260 nM, IC50(GSK3B) = 330 nM, others >10 µM, but targets not named in the literature, https://pubmed.ncbi.nlm.nih.gov/23021994/;

Screened at 20 µM, clean profile, no target with dTm >2 K, in-house data;
Screened against 25 kinases in enzymatic assays, in-vitro potency of closest targets: IC50(GSK3A) = 260 nM, IC50(GSK3B) = 330 nM, others >10 µM, but targets not named in the literature, https://pubmed.ncbi.nlm.nih.gov/23021994/;

Screened at 1 µM, closest targets as % of control: MET (0%), NEK6 (0%), PIM2 (0%), WEE1 (0%), STK17B (0.9%), CAMKK2 (7.8%), AURKA (14%), CAMKK1 (14%), STK38L (29%), CDKL1 (40%), HIPK1 (41%), HIPK4 (41%), HIPK2 (53%), STK17A (73%), STK16 (77%), https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(MET) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(NEK6) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(WEE1) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(STK17B) = 34 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(CAMKK2) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(AURKB) = 8947 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(CAMKK1) = 5183 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(STK38L) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(CDKL1) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(HIPK1) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(HIPK4) = 4352 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(HIPK2) = 8612 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(STK17A) = 4666 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-vitro potency (enzymatic assay): Kd(STK16) = 648 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(AURKB) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(STK38L) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(HIPK1) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(HIPK4) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(HIPK2) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;
In-cellular potency (NanoBRET assay, HEK293T cells): IC50(STK16) >10000 nM, https://www.thesgc.org/chemical-probes/SGC-STK17B-1;

Screened at 1 µM, closest targets as % of control: DCAMKL2(1.9%), DCAMKL1(5.9%), HIPK4 (44%), ABL1 (44%), full screening data available as supporting information; Screened at 2.5 µM, in activity-based proteomic profiling against 250 kinases using KiNativ assay profiling in PATU-8988T cell lysates, closest targets as % of inhibition: DCAMKL1 (52.3%), TBK1 (43.6%), DCAMKL1 (40.1%), MAPK15(36%), full screening data available as supporting informatio, https://pubmed.ncbi.nlm.nih.gov/32251410/;

Screened at 1 µM, closest targets as % of control: DCAMKL2(1.9%), DCAMKL1(5.9%), HIPK4 (44%), ABL1 (44%), full screening data available as supporting information; Screened at 2.5 µM, in activity-based proteomic profiling against 250 kinases using KiNativ assay profiling in PATU-8988T cell lysates, closest targets as % of inhibition: DCAMKL1 (52.3%), TBK1 (43.6%), DCAMKL1 (40.1%), MAPK15(36%), full screening data available as supporting informatio, https://pubmed.ncbi.nlm.nih.gov/32251410/;

In-cellulo follow-up (NanoBRET assays in HEK293T cells): IC50(ALK3) >10 µM, IC50(ALK4) >10 µM, IC50(ALK5) >10 µM, IC560(ALK6) = >10 µM; https://www.thesgc.org/chemical-probes/m4k2234

In-cellulo follow-up (NanoBRET assays in HEK293T cells): IC50(ALK3) >10 µM, IC50(ALK4) >10 µM, IC50(ALK5) >10 µM, IC560(ALK6) = >10 µM; https://www.thesgc.org/chemical-probes/m4k2234

inactive at 1 µM for VDR, NR1I2, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

inactive at 1 µM for NR1I2, NR1I3, UL48, RXRA, HNF4A, NR2C1, NR2E1, NR4A1, NR5A1

Screened at 20 µM, clean selectivity profile, dTm(MST3) = 0.2 K, dTm(MST4) = 0.8 K, dTM(PAK1) = 0.9 K

Screened at 20 µM, clean selectivity profile, dTm(MST3) = 0.2 K, dTm(MST4) = 0.8 K, dTM(PAK1) = 0.9 K

Screened at 20 µM, clean selectivity profile, dTm(MST3) = 0.2 K, dTm(MST4) = 0.8 K, dTM(PAK1) = 0.9 K

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

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

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

Screened at 1 µM, highly selective with all targets >55% remaining activity, PRMT5 (55%), other targets >90%

Screened at 1 µM, closest targets as % of contr.: CAMK2D (60%), CAMK2G (59%), MKNK2 (55%), MYLK (54%); In-vitro follow-up (enzymatic assays, Milipore): IC50(CAMK2D) = 810 nM, IC50(MKNK2) = 760 nM, IC50(CAMK2G) = 1000 nM, IC50(MYLK) = 1000 nM;

Screened at 1 µM, closest targets as % of contr.: CAMK2D (60%), CAMK2G (59%), MKNK2 (55%), MYLK (54%); In-vitro follow-up (enzymatic assays, Milipore): IC50(CAMK2D) = 810 nM, IC50(MKNK2) = 760 nM, IC50(CAMK2G) = 1000 nM, IC50(MYLK) = 1000 nM;

Selectivity within target family (GLS2 enzyme activity assay): IC50 >30 µM (>1000 fold)

In-vitro potency of closest targets: Kd(EGFR) = 2.4 nM, Kd(EGFR, E746-A750del) = 8.6 nM, Kd(EGFR, G719C) = 0.92 nM, Kd(EGFR, G719S) = 2.1 nM, Kd(EGFR, L747-E749del, A750P) = 2.2 nM, Kd(EGFR, L747-T751del, Sins) = 3.5 nM, Kd(EGFR, L747-S752del, P753S) = 3.9 nM, Kd(EGFR, L858R) = 2.8 nM, Kd(EGFR, L861Q) = 1.2 nM, Kd(EGFR, S752-I759del) = 4.2 nM, Kd(ERBB2) = 7 nM, Kd(ERBB4) = 54 nM, Kd(RIPK2) = 3600 nM, Kd(STK10) = 4400 nM; In-vitro potencies of closest targets (Radiometric kinase assay (10 µM ATP)): IC50(ERBB4) = 367 nM, IC50(SRC) = 3500 nM, IC50(RAF1) >10000 nM, IC50(MAP2K1) >10000 nM, IC50(MAPK1) >10000 nM, IC50(CSF1R) >10000 nM, IC50(CDK1) >10000 nM, IC50(CDK2) >10000 nM, IC50(MAPK14) >10000 nM, IC50(TEK) >10000 nM, IC50(KDR) >10000 nM (https://aacrjournals.org/mct/article/1/2/85/233686/The-Effects-of-the-Novel-Reversible-Epidermal)

In-vitro potency of closest targets: Kd(EGFR) = 2.4 nM, Kd(EGFR, E746-A750del) = 8.6 nM, Kd(EGFR, G719C) = 0.92 nM, Kd(EGFR, G719S) = 2.1 nM, Kd(EGFR, L747-E749del, A750P) = 2.2 nM, Kd(EGFR, L747-T751del, Sins) = 3.5 nM, Kd(EGFR, L747-S752del, P753S) = 3.9 nM, Kd(EGFR, L858R) = 2.8 nM, Kd(EGFR, L861Q) = 1.2 nM, Kd(EGFR, S752-I759del) = 4.2 nM, Kd(ERBB2) = 7 nM, Kd(ERBB4) = 54 nM, Kd(RIPK2) = 3600 nM, Kd(STK10) = 4400 nM; In-vitro potencies of closest targets (Radiometric kinase assay (10 µM ATP)): IC50(ERBB4) = 367 nM, IC50(SRC) = 3500 nM, IC50(RAF1) >10000 nM, IC50(MAP2K1) >10000 nM, IC50(MAPK1) >10000 nM, IC50(CSF1R) >10000 nM, IC50(CDK1) >10000 nM, IC50(CDK2) >10000 nM, IC50(MAPK14) >10000 nM, IC50(TEK) >10000 nM, IC50(KDR) >10000 nM (https://aacrjournals.org/mct/article/1/2/85/233686/The-Effects-of-the-Novel-Reversible-Epidermal)

Screened at 20 µM, dTm values of closest targets: dTm(BMP2K) = 6.8 K, dTm(AAK1) = 4.2 K, dTm(STK6) = 4.2 K, dTm(PLK4) = 4.0 K, dTm(STK3) = 3.4 K, dTm(MAP3K5) = 3.32 K, dTm(FLT1) = 2.9 K, dTm(CLK1) = 2.9 K, dTm(STK10) = 2.3 K, dTm(PIM3) = 2.1 K, dTm(STK17A) = 1.5K;

Screened at 10 µM, in-vitro potencies of closest targets (enzymatic assays): IC50(AAK1) = 188 nM, IC50(GAK) = 272 nM, IC50(IRAK3) = 921 nM; In-cellulo follow-up of closest targets (NanoBRET assay in HEK293T cells): IC50(AAK1) = 7 µM, IC50(GAK) = 6.5 µM, IC50(IRAK3) >20 µM (https://www.sgc-ffm.uni-frankfurt.de/chemProbes#!specificprobeoverview/BI%20605906); Screened at 10 µM in Panlabs panel, closest targets as % of contr.: PDE3A (31%), all other targets >50% (https://www.sgc-ffm.uni-frankfurt.de/chemProbes#!specificprobeoverview/BI%20605906); Screened at 10 µM against 45 GPCRs (PDSP screen), in-vitro potencies of closest targets: Ki(DRD3) = 428.07 nM, Ki(DRD2) = 341.44 nM, Ki(GABA/PBR) = 2622.51 nM (https://www.sgc-ffm.uni-frankfurt.de/chemProbes#!specificprobeoverview/BI%20605906);

Screened at 1 µM, conc. ATP = Km, closest targets >90% of inhibition: AURKA/TPX2 (97%), TNK1 (94%), JAK3(92%), QIK(91%); Screened at 10 µM against a broad panel of receptors, ion channels, and transporters (CEREP Wide Ligand Profile screen), in-vitro potency of closest target: IC50(KDR) = 1600 nM, others <50% inhibition, IC50 follow-up in cell-based assay (NovaScreen): IC50(KDR) >30 µM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00917);

Screened at 1 µM, conc. ATP = Km, closest targets >90% of inhibition: AURKA/TPX2 (97%), TNK1 (94%), JAK3(92%), QIK(91%); Screened at 10 µM against a broad panel of receptors, ion channels, and transporters (CEREP Wide Ligand Profile screen), in-vitro potency of closest target: IC50(KDR) = 1600 nM, others <50% inhibition, IC50 follow-up in cell-based assay (NovaScreen): IC50(KDR) >30 µM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00917);

Screened at 1 µM, conc. ATP = Km, closest targets >90% of inhibition: AURKA/TPX2 (97%), TNK1 (94%), JAK3(92%), QIK(91%); Screened at 10 µM against a broad panel of receptors, ion channels, and transporters (CEREP Wide Ligand Profile screen), in-vitro potency of closest target: IC50(KDR) = 1600 nM, others <50% inhibition, IC50 follow-up in cell-based assay (NovaScreen): IC50(KDR) >30 µM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00917);

All >1000-fold selective except BMPR2 (IC50 = 193 nM, ~960-fold selective); Selective within JAK family (HTRF assay, 1 mM ATP): IC50(JAK1) >10 µM, IC50(JAK2) >10 µM, IC50(JAK3) >10 µM, IC50(TYK2, JH1 domain) >10 µM, IC50(TYK2, JH2 domain) = 0.2 nM (https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b00444);

Screened at 0.5 µM, in-vitro potency of closest target: Ki(CDK9) = 110 nM, others >50-fold selective for TYK2

Screened at 0.5 µM, in-vitro potency of closest target: Ki(CDK9) = 110 nM, others >50-fold selective for TYK2

Screened at 0.5 µM, in-vitro potency of closest target: Ki(CDK9) = 110 nM, others >50-fold selective for TYK2

Screened at 1 µM, 16 kinases with >50% inhibition, in-vitro follow-up of closest targets: Kd(CDK7) = 38 nM, Kd(MAPK15) = 53 nM, others Kd(CAMK4) = 360 nM, Kd(DAPK1) = 420 nM, Kd(HIPK3) = 480 nM, Kd(STK17B) = 930 nM;

Screened at 1 µM, 16 kinases with >50% inhibition, in-vitro follow-up of closest targets: Kd(CDK7) = 38 nM, Kd(MAPK15) = 53 nM, others Kd(CAMK4) = 360 nM, Kd(DAPK1) = 420 nM, Kd(HIPK3) = 480 nM, Kd(STK17B) = 930 nM;

Screened at 1 µM, 16 kinases with >50% inhibition, in-vitro follow-up of closest targets: Kd(CDK7) = 38 nM, Kd(MAPK15) = 53 nM, others Kd(CAMK4) = 360 nM, Kd(DAPK1) = 420 nM, Kd(HIPK3) = 480 nM, Kd(STK17B) = 930 nM;

Screened at 1 µM, closest targets as % of control: STK10 (0.6%), DYRK1B (6.7%); In-vitro potency of closest targets (Competition-binding assay, DiscoverX): Kd(STK10) = 57 nM, Kd(DYRK1B) >30 µM; Screened at 10 µM against 89 targets (Eurofins-Panlabs Screen), closest targets as % of inhibition: human Adenosine transporter (71%), ADORA2A (67%), GABAA chloride channel TBOB receptor (60%), PTGS1 (54%), sodium channel site 2 (53%), PDE4 (52%); In-vitro potency of closest target: IC50(human Adenosin transporter) = 370 nM (https://www.sgc-ffm.uni-frankfurt.de/#!specificprobeoverview/BAY%201816032);