lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: SUBYPZBREZXPCW-GJZGRUSLSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μL of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 455.47, ALogP 2.58, HBA 7, HBD 3, PSA 113.6, QED 0.52
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(Cl)c2)c2cc(C)[nH]c2c1=O
InChIKey: IHZXYEFDJOXHGJ-ONEGZZNKSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: IC50 measurements for inhibitors using BRD9 AlphaLisa Binding Assay: His/Flag epitope tagged BRD9134-239 was cloned, expressed, and purified to homogeneity. BRD9 binding and inhibition was assessed by monitoring the engagement of biotinylated H4-tetraacetyl peptide (New England Peptide, NEP2069-11/13) with the target using the AlphaLisa technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate BRD9 (50 nM final) was combined with peptide (3 nM final) in 50 mM HEPES (pH 7.5), 150 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.8% DMSO) or compound dilution series in DMSO. After 20 minutes incubation at room temperature AlphaLisa Streptavidin Acceptor Beads (Perkin-AL125C) and AlphaLisa Nickel donor beads (Perkin AS 10 ID) were added to a final concentration of 15 ug/mL each. After ninety minutes of equilibration in the dark, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 425.92, ALogP 4.01, HBA 4, HBD 1, PSA 67.33, QED 0.64
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CCO)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YWQFJBMWXOICTC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of XO44 binding to CDK1 in human KURAMOCHI cells preincubated with compound by Western blot analysis
Measurement: EC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 435.55, ALogP 1.28, HBA 8, HBD 2, PSA 117.42, QED 0.7
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3S(C)(=O)=O)c2)n1
InChIKey: VAOLRFKJTAEDTE-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human ALK2 by NanoBERT assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.54, ALogP 4.36, HBA 7, HBD 2, PSA 105.56, QED 0.38
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cccnc3C)cc2N2C[C@@H]3C[C@H]2CN3)n1
InChIKey: VCZPJHYQIPIKSV-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μL of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 510.57, ALogP 4.46, HBA 7, HBD 2, PSA 92.27, QED 0.4
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Binding affinity to human muscarinic M3 receptor expressed in human HEK293T cells cells co-expressing beta-arrestin2 assessed as inhibition of carbachol-induced beta-arrestin recruitment preincubated for 30 mins followed by carbachol stimulation and measured after 90 mins by PathHunter assay
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 1053.66
Compound (SMILES): C[C@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)c1ccc(Cl)cc1
InChIKey: FIUCLBJMUGCQTF-NSHDSACASA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Affinity Biochemical interaction: (inhibition of enzyme activity with [3H]cGMP or [3H]cAMP as the substrate) EUB0002477a PDE8A
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 357.85, ALogP 4.06, HBA 5, HBD 2, PSA 75.6, QED 0.74
Compound (SMILES): COCCCO[C@H]1CN(c2ccc(O[C@@H]3CCN(c4cc(OC)ncc4Cl)C[C@H]3C)cc2)[C@@H](CC(=O)O)[C@@H]1C
InChIKey: CEBGUURUAFCIGS-UAVGYUILSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 562.11, ALogP 4.76, HBA 8, HBD 1, PSA 93.59, QED 0.37
Compound (SMILES): CC(C)(O)c1ccc(NC(=O)c2cc(C(=O)NCc3ccc(F)c(F)c3)c(F)cc2Cl)cc1
InChIKey: UBFZZQYNCOPFNS-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Inverse agonist activity at human FXR expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 476.88, ALogP 5.17, HBA 3, HBD 3, PSA 78.43, QED 0.46
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(C)(C)O)cc2)c2cc[nH]c2c1=O
InChIKey: HCKOJNDQXGXWSS-SNAWJCMRSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: IC50 measurements for inhibitors using BRD9 AlphaLisa Binding Assay: His/Flag epitope tagged BRD9134-239 was cloned, expressed, and purified to homogeneity. BRD9 binding and inhibition was assessed by monitoring the engagement of biotinylated H4-tetraacetyl peptide (New England Peptide, NEP2069-11/13) with the target using the AlphaLisa technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate BRD9 (50 nM final) was combined with peptide (3 nM final) in 50 mM HEPES (pH 7.5), 150 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.8% DMSO) or compound dilution series in DMSO. After 20 minutes incubation at room temperature AlphaLisa Streptavidin Acceptor Beads (Perkin-AL125C) and AlphaLisa Nickel donor beads (Perkin AS 10 ID) were added to a final concentration of 15 ug/mL each. After ninety minutes of equilibration in the dark, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 322.41, ALogP 3.8, HBA 3, HBD 2, PSA 58.02, QED 0.72
Compound (SMILES): O=C(O)c1ccnc(C(=O)NS(=O)(=O)c2ccccc2)c1
InChIKey: JQDWPQLTUCCHOR-UHFFFAOYSA-N
Target: RNA demethylase ALKBH5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P6C2
Assay: Inhibition of ALKBH5 (66 to 292 residues) (unknown origin) extracted from Escherichia coli BL21 (DE3) cells using m6A ssDNA as substrate measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 52060 nM (pChEMBL 4.28000020980835)
Descriptors: MW 306.3, ALogP 0.9, HBA 5, HBD 2, PSA 113.43, QED 0.87
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 1842 nM (pChEMBL 5.739999771118164)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): CC(C)C(C(=O)O)C(C)NC(=O)Nc1ccc(Br)cc1
InChIKey: GYDLWCFVSYYOGO-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at FPR2 (unknown origin) expressed in CHO/Galpha16 cells assessed as increase in calcium flux by FLIPR assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 343.22, ALogP 3.32, HBA 2, HBD 3, PSA 78.43, QED 0.77
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CCO)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YWQFJBMWXOICTC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 1.41 nM (pChEMBL 8.850000381469727)
Descriptors: MW 435.55, ALogP 1.28, HBA 8, HBD 2, PSA 117.42, QED 0.7
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 10.1 nM (pChEMBL 8)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Binding affinity to saturated human muscarinic M3 expressed in CHO cells assessed as dissociation constant incubated for 2 hrs by flow cytometry
Measurement: Kd = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 1053.66
Compound (SMILES): C[C@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)c1ccc(Cl)cc1
InChIKey: FIUCLBJMUGCQTF-NSHDSACASA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Affinity Biochemical interaction: (inhibition of enzyme activity with [3H]cGMP or [3H]cAMP as the substrate) EUB0002477a PDE9A
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 357.85, ALogP 4.06, HBA 5, HBD 2, PSA 75.6, QED 0.74
Compound (SMILES): COCCCO[C@H]1CN(c2ccc(O[C@@H]3CCN(c4cc(OC)ncc4Cl)C[C@H]3C)cc2)[C@@H](CC(=O)O)[C@@H]1C
InChIKey: CEBGUURUAFCIGS-UAVGYUILSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 562.11, ALogP 4.76, HBA 8, HBD 1, PSA 93.59, QED 0.37
Compound (SMILES): CC(C)(O)c1ccc(NC(=O)c2cc(C(=O)NCc3ccc(F)c(F)c3)c(F)cc2Cl)cc1
InChIKey: UBFZZQYNCOPFNS-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Inverse agonist activity at human THRA expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 476.88, ALogP 5.17, HBA 3, HBD 3, PSA 78.43, QED 0.46
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): O=C(O)c1ccnc(C(=O)NS(=O)(=O)c2ccccc2)c1
InChIKey: JQDWPQLTUCCHOR-UHFFFAOYSA-N
Target: RNA demethylase ALKBH5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P6C2
Assay: Inhibition of ALKBH5 (66 to 292 residues) (unknown origin) extracted from Escherichia coli BL21 (DE3) cells using m6A ssDNA as substrate measured immediately by fluorescence polarization assay
Measurement: IC50 = 64910 nM (pChEMBL 4.190000057220459)
Descriptors: MW 306.3, ALogP 0.9, HBA 5, HBD 2, PSA 113.43, QED 0.87
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 1335 nM (pChEMBL 5.880000114440918)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CCO)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YWQFJBMWXOICTC-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 435.55, ALogP 1.28, HBA 8, HBD 2, PSA 117.42, QED 0.7
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 37.2 nM (pChEMBL 7.429999828338623)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Binding affinity to saturated human muscarinic M3 expressed in CHO cells assessed as dissociation constant incubated for 2 hrs in presence of atropine by flow cytometry
Measurement: Kd = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 1053.66
Compound (SMILES): C[C@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)c1ccc(Cl)cc1
InChIKey: FIUCLBJMUGCQTF-NSHDSACASA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Affinity Biochemical interaction: (inhibition of enzyme activity with [3H]cGMP or [3H]cAMP as the substrate) EUB0002477a PDE4D
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 357.85, ALogP 4.06, HBA 5, HBD 2, PSA 75.6, QED 0.74
Compound (SMILES): COCCCO[C@H]1CN(c2ccc(O[C@@H]3CCN(c4cc(OC)ncc4Cl)C[C@H]3C)cc2)[C@@H](CC(=O)O)[C@@H]1C
InChIKey: CEBGUURUAFCIGS-UAVGYUILSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 562.11, ALogP 4.76, HBA 8, HBD 1, PSA 93.59, QED 0.37
Compound (SMILES): CC(C)(O)c1ccc(NC(=O)c2cc(C(=O)NCc3ccc(F)c(F)c3)c(F)cc2Cl)cc1
InChIKey: UBFZZQYNCOPFNS-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Inverse agonist activity at human THRB expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 476.88, ALogP 5.17, HBA 3, HBD 3, PSA 78.43, QED 0.46
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 40.3 nM (pChEMBL 7.389999866485596)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43781
Assay: Inhibition of recombinant human DYRK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 208.9 nM (pChEMBL 6.679999828338623)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Inhibition of CDK13 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 = 4550 nM (pChEMBL 5.340000152587891)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Binding affinity to saturated human muscarinic M1 expressed in CHO cells assessed as dissociation constant incubated for 2 hrs in presence of atropine by flow cytometry
Measurement: Kd = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 1053.66
Compound (SMILES): CC(C)(O)c1ccc(NC(=O)c2cc(C(=O)NCc3ccc(F)c(F)c3)c(F)cc2Cl)cc1
InChIKey: UBFZZQYNCOPFNS-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Inverse agonist activity at PPARgamma in mouse 3T3-L1 adipocytes assessed as inhibition of adipogenesis by measuring lipid droplet staining by BODIPY 495 incubated for 6 days by fluorescence based assay
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 476.88, ALogP 5.17, HBA 3, HBD 3, PSA 78.43, QED 0.46
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43781
Assay: Inhibition of recombinant human DYRK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43781
Assay: Inhibition of recombinant human DYRK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 111.8 nM (pChEMBL 6.949999809265137)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR20
Assay: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 611.7 nM (pChEMBL 6.210000038146973)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: O94921
Assay: Inhibition of CDK14 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Binding affinity to saturated human muscarinic M1 expressed in CHO cells assessed as dissociation constant incubated for 2 hrs by flow cytometry
Measurement: Kd = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 1053.66
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR20
Assay: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR20
Assay: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 1931 nM (pChEMBL 5.710000038146973)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 197.2 nM (pChEMBL 6.710000038146973)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00536
Assay: Inhibition of CDK16 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of atropine from human muscarinic M3 receptor expressed in CHO cells incubated for 2 hrs by flow cytometric competition binding assay
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 1053.66
Compound (SMILES): CCOc1ccc2nc(N3CCCN(C(=S)Nc4ccccc4F)CC3)c(C#N)cc2c1
InChIKey: RQXUPDSAFGWKMO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.56, ALogP 4.55, HBA 5, HBD 1, PSA 64.42, QED 0.59
Compound (SMILES): COc1ccc2nc3c(CO)cc(OC)cc3c(SC[C@H]3CCNC3)c2c1
InChIKey: PBGPFWACZLCJFH-ZDUSSCGKSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.5, ALogP 3.6, HBA 6, HBD 2, PSA 63.61, QED 0.5
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells using myelin basic protein as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 20.6 nM (pChEMBL 7.690000057220459)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 17 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00537
Assay: Inhibition of CDK17 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of atropine from human muscarinic M3 receptor expressed in CHO cells incubated for 2 hrs by flow cytometric competition binding assay
Measurement: Ki = 2.188 nM (pChEMBL 8.65999984741211)
Descriptors: MW 1053.66
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Escherichia coli using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 18 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07002
Assay: Inhibition of CDK18 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of tiotropium bromide from human muscarinic M3 receptor expressed in CHO cells incubated for 4 hrs by flow cytometric competition binding assay
Measurement: Ki = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 1053.66
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CCCc1cc(N[C@@H]2CC[C@@H](N)C2)n2nccc2n1
InChIKey: JTBZUSIDMCXPIU-ZYHUDNBSSA-N
Target: Cyclin-dependent kinase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BWU1
Assay: Inhibition of CDK19 (unknown origin) incubated for 120 mins in presence of ATP by HotSpot kinase assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 259.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.24, QED 0.88
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: IPPGGAXXAKWHHQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of tiotropium bromide from human muscarinic M3 receptor expressed in CHO cells incubated for 4 hrs by flow cytometric competition binding assay
Measurement: Ki = 0.1318 nM (pChEMBL 9.880000114440918)
Descriptors: MW 1053.66
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 0.101 nM (pChEMBL 10)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Binding affinity to human CLK1 assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 0.62 nM (pChEMBL 9.210000038146973)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Binding affinity to human GSK-3beta assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 3.745 nM (pChEMBL 8.430000305175781)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 449 nM (pChEMBL 6.349999904632568)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): Cn1cc(-c2ccc3cnc(NC(=O)C4CCN(S(C)(=O)=O)CC4)cc3c2)cn1
InChIKey: GXCOUFPTCZUTEE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The screening assay for DYRK1A kinase activity: Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission.Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).The Emission ratio (Em) was calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation was then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves were generated and inhibitory concentration (IC50) values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 413.5, ALogP 2.25, HBA 6, HBD 1, PSA 97.19, QED 0.71
Compound (SMILES): CN(C)CCC(=O)Nc1cccc(Nc2ncc(F)c(Nc3c(F)cccc3F)n2)c1
InChIKey: DQTGZYHNKSMMIB-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) incubated for 90 mins using Ulight-CFFKNIVTPRTPPPSQGK-amide as substrate in presence of ATP by microplate reader analysis
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 430.43, ALogP 4.27, HBA 6, HBD 3, PSA 82.18, QED 0.5
Compound (SMILES): O=C(N[C@H]1C[C@@H]1c1ccccc1)[C@@H]1CN(C(=O)c2cc(Cl)c(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2Cl)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: NJHIKCKHBGSNMX-ABSGTHFKSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60603
Assay: Agonist activity at TLR2/TLR1 in human THP-1 cells
Measurement: EC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 977.99, ALogP 7.06, HBA 6, HBD 4, PSA 157.02, QED 0.09
Compound (SMILES): Cn1c(=O)c2c(ncn2Cc2ccc(C(C)(C)C)cc2)n(C)c1=O
InChIKey: ZFZAIHKQJBMYLO-UHFFFAOYSA-N
Target: Sulfonylurea receptor 1, Kir6.2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14654
Assay: Activation of Kir6.2/SUR1 (unknown origin) channel opening expressed in human T-REx-293 cells by thallium flux assay
Measurement: EC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 326.4, ALogP 1.78, HBA 6, HBD 0, PSA 61.82, QED 0.72
Compound (SMILES): COc1cccc(-c2cccc(NC(=O)c3nc4c(n3C)CCNC4)c2C)c1F
InChIKey: WHRNKVAUZKJEMF-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD-1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 394.45, ALogP 3.44, HBA 5, HBD 2, PSA 68.18, QED 0.71
Compound (SMILES): Oc1cccc(-n2nc(-c3cc(O)c(O)c(O)c3)c3nc(-c4ccc(Cl)cc4)nnc32)c1
InChIKey: BCPHVNNXROQIHU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) expressed in Sf9 cells
Measurement: IC50 = 17300 nM (pChEMBL 4.760000228881836)
Descriptors: MW 447.84, ALogP 4.02, HBA 9, HBD 4, PSA 137.41, QED 0.3
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CCO)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YWQFJBMWXOICTC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 435.55, ALogP 1.28, HBA 8, HBD 2, PSA 117.42, QED 0.7
Compound (SMILES): O=C(NCCc1ccc(F)cc1)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)NCCc4ccc(F)cc4)[C@H](C(=O)NCCc4ccc(F)cc4)C3)cc2)C[C@H]1C(=O)NCCc1ccc(F)cc1
InChIKey: FCJBZKNUWYKSJO-AXRJLGSNSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60603
Assay: Agonist activity at TLR2/TLR1 in human THP-1 cells
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 933.02, ALogP 5.06, HBA 6, HBD 4, PSA 157.02, QED 0.09
Compound (SMILES): Cn1cc(-c2nc(NC3CCN(S(C)(=O)=O)CC3)ncc2Cl)cn1
InChIKey: CGKJOISVQXEPSG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysis
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 370.87, ALogP 1.37, HBA 7, HBD 1, PSA 93.01, QED 0.87
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(N4CCOC[C@@H]4C)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: BYYFORUHJRHMMU-QMMMGPOBSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 469.35, ALogP 4.42, HBA 6, HBD 3, PSA 107.55, QED 0.52
Compound (SMILES): Cc1cccc(-n2cc(C)c3cc(C(=O)NS(C)(=O)=O)ccc32)c1
InChIKey: QLRCVALQRZFUQM-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07699
Assay: Inhibition of human Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 342.42, ALogP 2.94, HBA 4, HBD 1, PSA 68.17, QED 0.8