lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnn(C2(CC#N)CN(c3cc(F)c(C(=O)N[C@@H](C)C(F)(F)F)cc3F)C2)c1
InChIKey: MSGYSFWCPOBHEV-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 μL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hour and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a PHERA star plate reader (BMG, Cary, N.C.). The data for the JAK1 and/or JAK2 inhibitors were obtained by testing the compounds in the Example A assay at 1 mM ATP.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 507.47, ALogP 3.98, HBA 6, HBD 2, PSA 102.63, QED 0.49
Compound (SMILES): CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C
InChIKey: LLFOBMRPWNABCB-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using midazolam as substrate
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 446.53, ALogP 3.84, HBA 8, HBD 2, PSA 83.79, QED 0.48
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Kinesin-like protein KIF21A (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z4S6
Assay: Inhibition of Kir2.1 (unknown origin) by patch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of N-terminal GST-tagged human PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells assessed as increase in DNA trapping activity measured after 60 mins by fluorescence anisotropy binding assay
Measurement: EC50 = 415 nM (pChEMBL 6.380000114440918)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-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 = 38.77 nM (pChEMBL 7.409999847412109)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 1924.86 nM (pChEMBL 5.71999979019165)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnn(C2(CC#N)CN(c3cc(F)c(C(=O)N[C@@H](C)C(F)(F)F)cc3F)C2)c1
InChIKey: MSGYSFWCPOBHEV-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 μL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hour and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a PHERA star plate reader (BMG, Cary, N.C.).
Measurement: IC50 < 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 507.47, ALogP 3.98, HBA 6, HBD 2, PSA 102.63, QED 0.49
Compound (SMILES): CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C
InChIKey: LLFOBMRPWNABCB-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using midazolam as substrate
Measurement: IC50 = 9330 nM (pChEMBL 5.03000020980835)
Descriptors: MW 446.53, ALogP 3.84, HBA 8, HBD 2, PSA 83.79, QED 0.48
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL51
Assay: Inhibition of HCN2 (unknown origin) by patch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of c-Kit (unknown origin)
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Inhibition of N-terminal GST-tagged full-length recombinant human PARP3 (2 to 540 residues) expressed in Sf9 cells measured after 1 hr by fluorescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human beta-secretase 1 preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-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 = 10.4 nM (pChEMBL 7.980000019073486)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 1905.46 nM (pChEMBL 5.71999979019165)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by LC-MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnn(C2(CC#N)CN(c3cc(F)c(C(=O)N[C@@H](C)C(F)(F)F)cc3F)C2)c1
InChIKey: MSGYSFWCPOBHEV-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM 1050 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hour and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 507.47, ALogP 3.98, HBA 6, HBD 2, PSA 102.63, QED 0.49
Compound (SMILES): CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C
InChIKey: LLFOBMRPWNABCB-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using midazolam as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 446.53, ALogP 3.84, HBA 8, HBD 2, PSA 83.79, QED 0.48
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Ionotropic glutamate receptor NMDA 1/2C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14957
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2C receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by whole cell patch clamp method
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: CSF1R Kinase Assay: The activity of CSF1R kinase (CSF1R, SEQ ID NO: 1) was determined spectroscopically using a coupled pyruvate kinase/lactate dehydrogenase assay that continuously monitors the ATP hydrolysis-dependent oxidation of NADH (e.g., Schindler et al. Science (2000) 289: 1938-1942 Assays were conducted in 384-well plates (100 μL final volume) using 10 nM CSF1R (Eurofins), 1.5 units pyruvate kinase, 2.1 units lactate dehydrogenase, 1 mM phosphoenol pyruvate, 0.28 mM NADH, 0.7 mg/mL PolyEY and 1 mM ATP in assay buffer (100 mM Tris, pH 7.5, 15 mM MgCl2, 0.5 mM DTT, 0.1% octyl-glucoside, 0.002% (w/v) BSA, and 0.002% Triton X-100). Inhibition of CSF1R was measured by adding serial diluted test compound (final assay concentration of 1% DMSO). A decrease in absorption at 340 nm was monitored continuously for 4 hours at 30° C. on a multi-mode microplate reader (BioTek). The reaction rate was calculated using the 2-3 h time frame. The reaction rate at each concentration of compound was converted to percent inhibition using controls (i.e. reaction with no test compound and reaction with a known inhibitor) and IC50values were calculated by fitting a four-parameter sigmoidal curve to the data using Prism (GraphPad software).
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of N-terminal GST-tagged recombinant human PARP5A (1001 to 1327 residues) expressed in Sf9 cells measured after 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human Cathepsin D preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-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 = 2705.19 nM (pChEMBL 5.570000171661377)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: GPCRScan assay: inhibition of 5-HT1B
Measurement: Ki = 477.93 nM (pChEMBL 6.320000171661377)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by LC-MS analysis
Measurement: IC50 = 3130 nM (pChEMBL 5.5)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C
InChIKey: LLFOBMRPWNABCB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using midazolam as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 446.53, ALogP 3.84, HBA 8, HBD 2, PSA 83.79, QED 0.48
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Ionotropic glutamate receptor NMDA 1/2D (PROTEIN COMPLEX), Homo sapiens
UniProt: O15399
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2D receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by whole cell patch clamp method
Measurement: EC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: c-Kit Kinase Assay: The activity of unphosphorylated c-KIT kinase (c-KIT, SEQ ID NO: 2) was determined spectroscopically using a coupled pyruvate kinase/lactate dehydrogenase assay that continuously monitors the ATP hydrolysis-dependent oxidation of NADH (e.g., Schindler et al. Science (2000) 289: 1938-1942). Assays were conducted in 384-well plates (100 μL final volume) using 16 nM c-KIT (DeCode Biostructures), 1.5 units pyruvate kinase, 2.1 units lactate dehydrogenase, 1 mM phosphoenol pyruvate, 0.28 mM NADH, 0.7 mg/mL PolyEY and 1 mM ATP in assay buffer (100 mM Tris, pH 7.5, 15 mM MgCl2, 0.5 mM DTT, 0.1% octyl-glucoside, 0.002% (w/v) BSA, and 0.002% Triton X-100). Inhibition of c-KIT was measured by adding serial diluted test compound (final assay concentration of 1% DMSO). A decrease in absorption at 340 nm was monitored continuously for 6 hours at 30° C. on a multi-mode microplate reader (BioTek). The reaction rate was calculated using the 2-3 h time frame. The reaction rate at each concentration of compound was converted to percent inhibition using controls (i.e. reaction with no test compound and reaction with a known inhibitor) and IC50 values were calculated by fitting a four-parameter sigmoidal curve to the data using Prism (GraphPad software). as implemented in the GraphPad Prism software package.
Measurement: IC50 = 864 nM (pChEMBL 6.059999942779541)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Inhibition of N-terminal FLAG-tagged recombinant human PARP7 (400 to 657 residues) expressed in Sf9 cells measured after 1 hr by fluorescence assay
Measurement: IC50 = 41.7 nM (pChEMBL 7.380000114440918)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Cathepsin G (SINGLE PROTEIN), Homo sapiens
UniProt: P08311
Assay: Inhibition of human Cathepsin G preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin) extracted from Escherichia coli BL21 (DE3) cells measured for 60 mins by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: GPCRScan assay: inhibition of 5-HT1B
Measurement: Ki = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using mephenytoin as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by LC-MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnn(C2(CC#N)CN(c3cc(F)c(C(=O)N[C@@H](C)C(F)(F)F)cc3F)C2)c1
InChIKey: MSGYSFWCPOBHEV-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Scintillation Proximity Assay: PI3Kδ:The kinase reaction was conducted in polystyrene 384-well matrix white plate from Thermo Fisher Scientific in a final volume of 25 μL. Inhibitors were first diluted serially in DMSO and added to the plate wells before the addition of other reaction components. The final concentration of DMSO in the assay was 0.5%. The PI3K assays were carried out at room temperature in 20 mM MOPS, pH 6.7, 10 mM MgCl2, 5 mM DTT and CHAPS 0.03%. Reactions were initiated by the addition of ATP, the final reaction mixture consisted of 20 μM PIP2, 20 μM ATP, 0.2 μCi [γ-33P] ATP, 4 nM PI3Kδ. Reactions were incubated for 210 min and terminated by the addition of 40 μL SPA beads suspended in quench buffer: 150 mM potassium phosphate pH 8.0, 20% glycerol. 25 mM EDTA, 400 μM ATP. The final concentration of SPA beads was 1.0 mg/mL. After the plate sealing, plates were shaken overnight at room temperature and centrifuged at 1800 rpm for 10 minutes, the radioactivity of the product was determined by scintillation counting on Topcount (Perkin-Elmer).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 507.47, ALogP 3.98, HBA 6, HBD 2, PSA 102.63, QED 0.49
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Glutamate receptor ionotropic, NMDA 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q12879
Assay: Positive allosteric modulation of GluN2A receptor (unknown origin)
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: PDGFRα Kinase Assay: The activity of unphosphorylated PDGFRα kinase was determined spectroscopically using a coupled pyruvate kinase/lactate dehydrogenase assay that continuously monitors the ATP hydrolysis-dependent oxidation of NADH (e.g., Schindler et al. Science (2000) 289: 1938-1942). Assays were conducted in 384-well plates (100 μL final volume) using 11.7 nM PDGFRα (DeCode Biostructures), 1.5 units pyruvate kinase, 2.1 units lactate dehydrogenase, 1 mM phosphoenol pyruvate, 0.28 mM NADH, 0.7 mg/mL PolyEY and 1 mM ATP in assay buffer (100 mM Tris, pH 7.5, 15 mM MgCl2, 0.5 mM DTT, 0.1% octyl-glucoside, 0.002% (w/v) BSA, and 0.002% Triton X-100). Inhibition of PDGFRα was measured by adding serial diluted test compound (final assay concentration of 1% DMSO). A decrease in absorption at 340 nm was monitored continuously for 6 hours at 30° C. on a multi-mode microplate reader (BioTek). The reaction rate was calculated using the 2-3 h time frame. The reaction rate at each concentration of compound was converted to percent inhibition using controls (i.e. reaction with no test compound and reaction with a known inhibitor) and IC50values were calculated by fitting a four-parameter sigmoidal curve to the data using Prism (GraphPad software).
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Fluorescence Anisotropy Binding Assay: PARP1: Recombinant full length 6HIS tagged PARP1 protein was diluted to 6 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 2 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Inhibition of human renin preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: GPCRScan assay: inhibition of 5-HT1D
Measurement: Ki = 219.42 nM (pChEMBL 6.659999847412109)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by LC-MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13224
Assay: Positive allosteric modulation of GluN2B receptor (unknown origin)
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: FLT3 Kinase Assay: The activity of FLT3 kinase was determined spectroscopically using a coupled pyruvate kinase/lactate dehydrogenase assay that continuously monitors the ATP hydrolysis-dependent oxidation of NADH (e.g., Schindler et al. Science (2000) 289: 1938-1942). Assays were conducted in 384-well plates (100 μL final volume) using 1.6 nM FLT3 (Invitrogen), 1.5 units pyruvate kinase, 2.1 units lactate dehydrogenase, 1 mM phosphoenol pyruvate, 0.28 mM NADH, 0.7 mg/mL PolyEY and 1 mM ATP in assay buffer (100 mM Tris, pH 7.5, 15 mM MgCl2, 0.5 mM DTT, 0.1% octyl-glucoside, 0.002% (w/v) BSA, and 0.002% Triton X-100). Inhibition of FLT3 was measured by adding serial diluted test compound (final assay concentration of 1% DMSO). A decrease in absorption at 340 nm was monitored continuously for 6 hours at 30° C. on a multi-mode microplate reader (BioTek). The reaction rate was calculated using the 3-4 h time frame. The reaction rate at each concentration of compound was converted to percent inhibition using controls (i.e. reaction with no test compound and reaction with a known inhibitor) and IC50 values were calculated by fitting a four-parameter sigmoidal curve to the data using Prism (GraphPad software).
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Fluorescence Anisotropy Binding Assay: PARP2: Recombinant full length PARP2 protein was diluted to 6 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 2 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 > 1500 nM (pChEMBL 5.823999881744385)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of human tissue plasminogen activator preincubated for 5 mins followed by substrate addition by fluorometer analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: GPCRScan assay: inhibition of 5-HT1D
Measurement: Ki = 194.98 nM (pChEMBL 6.710000038146973)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by LC-MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Glutamate receptor ionotropic, NMDA 2C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14957
Assay: Positive allosteric modulation of GluN2C receptor (unknown origin)
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Fluorescence Anisotropy Binding Assay: PARP3: Recombinant full length PARP3 protein was diluted to 100 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 6 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Reversible inhibition of human plasma kallikrein assessed as inhibition constant
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Displacement of fluorescent labeled RBN011198 from human NanoLuc-tagged full-length PARP7 expressed in HEK293T cells using NanoGlo substrate incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Glutamate receptor ionotropic, NMDA 2D (SINGLE PROTEIN), Homo sapiens
UniProt: O15399
Assay: Positive allosteric modulation of GluN2D receptor (unknown origin)
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Fluorescence Anisotropy Binding Assay: PARP5a: Recombinant PARP5a binding domain was diluted to 160 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 6 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibitory Activity In Vitro Assay : Plasma kallikrein inhibitory activity in vitro was determined using standard published methods. Human plasma kallikrein (Protogen) was incubated at 25° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of PARP10 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2NL67
Assay: Fluorescence Anisotropy Binding Assay: PARP6: Recombinant full length GST tagged PARP6 protein was diluted to 160 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 6 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibitory Activity In Vitro Assay: KLK1 inhibitory activity in vitro was determined using standard published methods. Human KLK1 (Callbiochem) was incubated at 25° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Inhibition of PARP14 (unknown origin)
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Determination of the % Inhibition for FXIa: FXIa inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Sturzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human FXIa (Enzyme Research Laboratories) was incubated at 25° C. with the fluorogenic substrate Z-Gly-Pro-Arg-AFC and 40 μM of the test compound (or alternatively at various concentrations of the test compound in order to determine IC50). Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of PARP11 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Determination of the % Inhibition for FXIIa: Factor XIIa inhibitory activity in vitro was determined using standard published methods (see e.g. Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Baeriswyl et al., ACS Chem. Biol., 2015, 10 (8) 1861; Bouckaert et al., European Journal of Medicinal Chemistry 110 (2016) 181). Human Factor XIIa (Enzyme Research Laboratories) was incubated at 25° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin)
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibitory Activity Assay: Example compounds were evaluated for inhibition of the human activated kallikrein enzyme in two formats of an assay employing a fluorogenic peptide substrate. In one assay format, the concentrations of reagents were as follows: 20 mM Tris pH 7.5, 1 mM EDTA, 150 mM sodium chloride, 0.1% PEG-400, 0.1% Triton X-100, 500 pM activated kallikrein enzyme, 300 uM Pro-Phe-Arg-7-amido-4-methylcoumarin substrate. Prior to reaction initiation with substrate, enzyme and inhibitors were preincubated for 30 min at RT. After initiation with substrate, reactions were incubated for 10 min at RT and fluorescence emission at 460 nm from 380 nm excitation measured with a microplate reader. In another assay format, the concentrations of reagents were as follows: 20 mM Tris pH 7.5, 1 mM EDTA, 150 mM sodium chloride, 0.1% PEG-400, 0.1% Triton X-100, 5 pM activated kallikrein enzyme, 300 uM Pro-Phe-Arg-7-amido-4-methylcoumarin substrate. Prior to reaction initiation with substrate, enzyme and inhibitors were preincubated for 30 min at RT. After initiation with substrate, reactions were incubated for 18 h at RT and fluorescence emission at 460 nm from 380 nm excitation measured with a microplate reader.
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of PARP2 (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Inhibition of PARP3 (unknown origin)
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of TNKS1 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKK3
Assay: Inhibition of PARP4 (unknown origin)
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of TNKS2 (unknown origin)
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2NL67
Assay: Inhibition of PARP6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Inhibition of PARP7 (unknown origin)
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N3A8
Assay: Inhibition of PARP8 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0J9
Assay: Inhibition of PARP12 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXQ6
Assay: Inhibition of PARP9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase PARP16 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5Y8
Assay: Inhibition of PARP16 (unknown origin)
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Binding affinity to PARP7 (unknown origin) assessed as dissociation constant
Measurement: Kd = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Enzymatic Assay for Inhibition of PARP7: Displacement of Probe A, a biotinylated probe binding to the TIPARP active site, was measured using a time-resolved fluorescence energy transfer (TR-FRET) assay. 20 nL of a dose response curve of each test compound was spotted in black 384-well polystyrene proxiplates (Perkin Elmer) using a Mosquito (TTP Labtech). Reactions were performed in a 8 μL volume by adding 6 μL of TIPARP and Probe A in assay buffer (20 mM HEPES pH=8, 100 mM NaCl, 0.1% bovine serum albumin, 2 mM DTT and 0.002% Tween20), incubating with test compound at 25° C. for 30 min, then adding 2 μL of ULight-anti 6×His and LANCE Eu-W1024 labeled streptavidin (Perkin Elmer). The final concentrations of TIPARP and Probe A were 6 nM and 2 nM, respectively. The final concentration of ULight-anti 6xHis and LANCE Eu-W1024 labeled streptavidin were 4 nM and 0.25 nM, respectively. Reactions were incubated at 25° C. for an additional 30 min, then read on an Envision platereader equipped with a LANCE/DELFIA top mirror (Perkin Elmer) using excitation of 320 nm and emission of 615 nm and 665 nM with a 90 μs delay. The ratio of the 665/615 nm emission were calculated for each well to determine the amount of complex of TIPARP and Probe A in each well. Control wells containing a negative control of 0.25% DMSO vehicle or a positive control of 100 μM Example 190 were used to calculate the % inhibition as described below:% ⁢ ⁢ inhibition = 100 × TRF cmpd - TRF min TRF max - TRF minwhere TRFcmpd is the TR-FRET ratio from the compound treated well, TRFmin is the TR-FRET ratio from the Example 190-treated positive control well and TRFmax is the TR-FRET ratio from the DMSO-treated negative control well.The % inhibition values were plotted as a function of compound concentration and the following 4-parameter fit was applied to derive the IC50 the values:Y = Bottom + ( Top - Bottom ) ( 1 + ( X IC 50 ) Hill ⁢ ⁢ Coefficientwhere top and bottom are normally allowed to float, but may be fixed at 100 or 0 respectively in a 3-parameter fit. The Hill Coefficient is normally allowed to float but may also be fixed at 1 in a 3-parameter fit. Y is the % inhibition and x is the compound concentration.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4