lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1NCc2nc(-c3c(F)cccc3F)cc(Nc3ccc(C(=O)N4CCOCC4)cc3)c21
InChIKey: XDTKWAGKBLDFOE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of Jak2 in human PBMC assessed as inhibition of GM-CSF-stimulated phosphorylation of STAT5
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 450.45, ALogP 3.49, HBA 5, HBD 2, PSA 83.56, QED 0.64
Compound (SMILES): O=c1c(/C=C/c2ccccc2Cl)nc2ccccc2n1Cc1ccccc1
InChIKey: ABBRXDCHEYVCBL-CCEZHUSRSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of PDGFR-beta (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 372.86, ALogP 5.27, HBA 3, HBD 0, PSA 34.89, QED 0.49
Compound (SMILES): O=C(N[C@@H]1CCCN(c2ncnc3[nH]ccc23)C1)[C@H](Nc1cc(Cl)cc(C(F)(F)F)c1)C1CC1
InChIKey: XSNVEELQPXGAPX-VQIMIIECSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Binding affinity to human partial length TXK (L238 to W527 residues ) expressed in bacterial expression system assessed dissociation constant by Kinomescan method
Measurement: Kd = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 492.93, ALogP 4.61, HBA 5, HBD 3, PSA 85.94, QED 0.47
Compound (SMILES): CC(C)NCc1ccccc1Cn1c(=S)[nH]c(=O)c2[nH]ccc21
InChIKey: JOVWUUZYWGSGRC-UHFFFAOYSA-N
Target: Thyroid peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P07202
Assay: Inhibitory Activity: To detect thyroid peroxidase (TPO) inhibitory activity, the production of hypoiodous acid (HOI) was quantified. HOI was detected by reacting it with methionine, which is converted to dehydro-methionine, which in turn is detected by reacting it with excess iodide at acidic pH. The reaction converts I− to I3 − that has absorbance at 353 nm. In brief, 0.6 μL compound serially diluted in DMSO was added to 25 μL 50 nM baculovirus-expressed recombinant human TPO (obtained from RSR Ltd, Cardiff, UK) in assay buffer (100 mM Na2HPO4/NaH2PO4, pH 7.4), after which absorbance at 353 nm was read to obtain a blank value. The enzyme reaction was initiated by the addition of 25 μL of a mix consisting of 2 mM methionine, 20 μM NaI and 100 μM H2O2 in assay buffer, and stopped by the addition of 10 μL catalase, 0.25 mg/mL. After an additional 5 min, 25 μL 600 mM sulphuric acid followed by 25 μL 100 mM KI were added, and absorbance at 353 nm was read 5 min after this addition. IC50 values of the compounds tested were obtained using standard procedures.In general, the compounds disclosed herein, which were tested, had a surprisingly high selectivity for the MPO enzyme over the TPO enzyme within the range of 220-1600 for the ratio IC50 (TPO)/IC50 (MPO).
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 328.44, ALogP 2.93, HBA 4, HBD 3, PSA 65.61, QED 0.63
Compound (SMILES): CC(C)c1n[nH]c2c(NCc3ccc(-n4ccnc4)cc3)nc(SCCN)nc12
InChIKey: WBTZHHCDIMUWMI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13/Cyclin-K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of GST-tagged human CDK13/Cyclin K expressed in Sf9 cells using RBER-IRStide peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 408.54, ALogP 3.32, HBA 8, HBD 3, PSA 110.33, QED 0.3
Compound (SMILES): Fc1ccc(Cl)c(-c2ccc(NC[C@@H]3CC34CCN(CC3CCOCC3)CC4)nn2)c1
InChIKey: NORLOFDPLORONC-SFHVURJKSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using cocktail of isoform-specific probe substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.98, ALogP 4.88, HBA 5, HBD 1, PSA 50.28, QED 0.69
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(C)c1Cl
InChIKey: JGKXIESKLZBKHM-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 491.98, ALogP 3.57, HBA 7, HBD 1, PSA 91.04, QED 0.39
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2cccc3ccccc23)C(=O)c2ccc(-c3cssc3=S)cc2)cc1
InChIKey: LXJKCTXIMVDZAI-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 576.79, ALogP 6.89, HBA 6, HBD 1, PSA 80.47, QED 0.16
Compound (SMILES): CCCn1c(-c2ccncc2)cc2c1CCNC2=O
InChIKey: AUMWRYOMDFANOB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16513
Assay: Inhibition of NanoLuc-PKN2 (ser646-cys984)(unknown origin) expressed in HEK293 cells by cell-based NanoBRET target engagement assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 255.32, ALogP 2.25, HBA 3, HBD 1, PSA 46.92, QED 0.91
Compound (SMILES): COc1cc(OC)c(C2NCCc3c2[nH]c2ccc(F)cc32)cc1OC.Cl
InChIKey: LWHOEIHANZIFDG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 356.4, ALogP 3.57, HBA 4, HBD 2, PSA 55.51, QED 0.75
Compound (SMILES): Cc1nc(N)oc1CCCN/C(N)=N/C(=O)NCC(C)C1CCCCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CVWWNGBIVGCWNQ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 8317.64 nM (pChEMBL 5.079999923706055)
Descriptors: MW 364.49, ALogP 2.33, HBA 4, HBD 4, PSA 131.56, QED 0.33
Compound (SMILES): CC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C(F)(F)F)c2)ccn1
InChIKey: JRJSMTAUWDJJIH-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 0.36 nM (pChEMBL 9.4399995803833)
Descriptors: MW 409.45, ALogP 4.87, HBA 4, HBD 2, PSA 77.24, QED 0.68
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(N)=O)C(C)C
InChIKey: XHPNKAPWXFVQKQ-AEEVCGNZSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human recombinant MMP-8 (Phe21 to Gly467 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 729.18, ALogP 0.65, HBA 8, HBD 7, PSA 242.96, QED 0.11
Compound (SMILES): Clc1ccc(Nc2nc3ccccc3c3[nH]c(C4CCCCCCCC4)nc23)cc1Cl
InChIKey: VLFOIGWFHOKUEU-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 28.84 nM (pChEMBL 7.539999961853027)
Descriptors: MW 453.42, ALogP 8.38, HBA 3, HBD 2, PSA 53.6, QED 0.33
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1cnc(N)s1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RZWKIWSVEPQMPP-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 312.44, ALogP 1.46, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): Cc1nc(-c2cnc(NC3CC3)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: ZJIRIQBCHHNGDO-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R in CSF1-stimulated human THP-1 cells assessed as inhibition of CSF1R phosphorylation measured by ELISA assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 429.48, ALogP 3.31, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](OC(=O)c2cccc3ccccc23)[C@H]1OC(=O)c1cccc2ccccc12
InChIKey: PSBROSWEMLTASJ-BQOYKFDPSA-N
Target: P2X purinoceptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99571
Assay: Agonist activity at human P2X4R expressing HEK293 cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 815.52, ALogP 4.41, HBA 16, HBD 5, PSA 291.27, QED 0.08
Compound (SMILES): Nc1nnc2c([nH]c3ccccc32)c1-c1ccccc1
InChIKey: DHDZFJQQXROKLC-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Binding affinity to His6/FLAG-tagged SMARCA4 (unknown origin) by isothermal titration calorimetric assay
Measurement: Kd = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 260.3, ALogP 3.36, HBA 3, HBD 2, PSA 67.59, QED 0.55
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(C(C)C)CC3)nc12
InChIKey: VBLIZEIXBKDACF-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, NMDA 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13224
Assay: Displacement of [3H]ifenprodil from recombinant human GluN2B NMDA receptor (unknown origin) expressed in dexamethasone-induced mouse L-M(TK-) cell after 120 mins by microbeta scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 346.5, ALogP 2.96, HBA 5, HBD 1, PSA 48.47, QED 0.9
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1OC
InChIKey: TZCPALNCOZRZIG-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 46.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 350.44, ALogP 1.68, HBA 5, HBD 2, PSA 90.65, QED 0.71
Compound (SMILES): C[C@H](c1c(Cl)ccc(C2CC2)c1Cl)n1cnc2cnc(-c3ccccc3[C@@H](C)C(=O)O)cc21
InChIKey: JPJWHCNGSBCZMI-HUUCEWRRSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO-K1 cells assessed as potentiation of GLP-1(9-36) induced beta-arrestin recruitment
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 480.4, ALogP 7.08, HBA 4, HBD 1, PSA 68.01, QED 0.32
Compound (SMILES): COC[C@H](Cc1ccccc1)NC[C@@H](O)c1cc(C(F)(F)F)nc2c(C(F)(F)F)cccc12
InChIKey: TZXAENYIJDOHQI-HNAYVOBHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as reduction in 6-beta-hydroxy-testosterone formation using testosterone as substrate preincubated for 20 mins in absence of NADPH followed by incubation with substrate for 10 mins by LC-MS/MS analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 472.43, ALogP 5.15, HBA 4, HBD 2, PSA 54.38, QED 0.45
Compound (SMILES): Cc1ccc(CNC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCC(=O)NC(C)(C)C)NC(=O)CCNC(=O)/C(C#N)=C/c2ccco2)cc1
InChIKey: VTKSMYDOQHZUPK-CNUXCAPHSA-N
Target: Proteasome subunit beta type-10 (SINGLE PROTEIN), Homo sapiens
UniProt: P40306
Assay: Inhibition of 20S proteasome subunit beta-2i (unknown origin) using Ac-KQL-AMC as substrate and measured after 30 mins
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 668.8, ALogP 3.22, HBA 7, HBD 5, PSA 182.43, QED 0.11
Compound (SMILES): O=C(Nc1nc2cccc(C3=CCC(NC(=O)C4CC4)CC3)n2n1)C1CC1
InChIKey: ZGAWRDQWSJYLKZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Activity Assay: JAK1 (h) was incubated with 20 mM Tris/HCl pH 7.5, 0.2 mM EDTA, 500 μM MGEEPLYWSFPAKKK, 10 mM magnesium acetate and [γ-33P]-ATP (activity and concentration were formulated as needed). Mg/ATP mixture was added to initiate the reaction. After incubating at room temperature for 40 minutes, the reaction mixture was added with 0.5% phosphoric acid to stop the reaction. Then 10 μL reaction solution was spotted on a P30 filter pad and washed with 0.425% phosphoric acid three times and methanol once over 4 minutes, dried, and counted scintillation.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 365.44, ALogP 2.54, HBA 5, HBD 2, PSA 88.39, QED 0.85
Compound (SMILES): Cc1ccccc1C1C(=O)N(C)c2cnc(Nc3ccc(S(N)(=O)=O)cc3)nc2N1C
InChIKey: FWEIAKDAIDQPRK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13188
Assay: Binding affinity to wild-type human partial length MST2 (D17 to E318 residues) expressed in bacterial expression system by Kinomescan method
Measurement: Kd = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 438.51, ALogP 2.33, HBA 7, HBD 2, PSA 121.52, QED 0.64
Compound (SMILES): CCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: CQXIEOVFWXPEIO-RXONAPBBSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: EC50 = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 3344.95
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)N5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: UTHRHKGJHFUFBP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 461.52, ALogP 3.23, HBA 6, HBD 2, PSA 105.36, QED 0.44
Compound (SMILES): NC(=O)c1ccc(OCC2CCC2)cc1F
InChIKey: VLOWWMKTNSPEAY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human PARP2 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 223.25, ALogP 2.1, HBA 2, HBD 1, PSA 52.32, QED 0.85
Compound (SMILES): COC(=O)C1CCN(C(=O)Cc2ccc(NCc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: NQLDZGLJAMJTPQ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 450.5, ALogP 1.15, HBA 10, HBD 3, PSA 162.24, QED 0.46
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCNCC4)c3)n2)c1Cl
InChIKey: YYCRQWMDRNTZLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 V564F mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 727.4 nM (pChEMBL 6.139999866485596)
Descriptors: MW 542.43, ALogP 4.87, HBA 11, HBD 3, PSA 123.93, QED 0.28
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc3sc4ccccc4c3c2)[C@H]1NC(C)=O
InChIKey: HLHDCHXBXBBXLH-PPJWLVRDSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4M in human liver microsomes incubated for 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 480.63, ALogP 5.01, HBA 5, HBD 3, PSA 87.66, QED 0.4
Compound (SMILES): COC(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN(C)CC5)c(F)c4)c3n2)[C@@H](C)C1
InChIKey: CXZJXVJPISUKMR-IYBDPMFKSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 482.56, ALogP 2.58, HBA 8, HBD 1, PSA 93.72, QED 0.61
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1ccccc1
InChIKey: CFSRLUGJCGONGU-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Ile414Met mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 353 nM (pChEMBL 6.449999809265137)
Descriptors: MW 244.25, ALogP 2.81, HBA 3, HBD 2, PSA 66.76, QED 0.87
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCCC3)ccc12
InChIKey: PCAWJIMDNGAMRA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human PARP2 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 274.32, ALogP 2.18, HBA 3, HBD 2, PSA 74.95, QED 0.9
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2cccnc21
InChIKey: UXPONYQLKCUMSK-CQSZACIVSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in mouse AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 330.43, ALogP 2.47, HBA 4, HBD 2, PSA 90.01, QED 0.85
Compound (SMILES): N.O=C(O)c1cc(-c2ccc(CNc3ccc(Br)cc3)o2)ccc1O
InChIKey: MVHXINROGSSELN-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Non-competitive inhibition of human recombinant LDHA assessed as inhibition constant using varying concentration of pyruvate as substrate preincubated for 10 mins followed by substrate addition and measured every 60 sec for 10 mins in the presence of NADH by fluorescence assay
Measurement: Ki = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 388.22, ALogP 4.73, HBA 4, HBD 3, PSA 82.7, QED 0.59
Compound (SMILES): COc1ccc(NC(=O)N2CCc3c(sc(NC(=O)c4cnn(C)c4)c3C#N)C2)cc1
InChIKey: WVYHDFDOBCBKGI-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of Src (unknown origin)
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 436.5, ALogP 3.2, HBA 7, HBD 2, PSA 112.28, QED 0.65
Compound (SMILES): COc1ccc(CN2CCC[C@H](OCc3ccc(F)c(C)c3)C2)cc1F
InChIKey: DICPGMOKBHQFRK-SFHVURJKSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 361.43, ALogP 4.46, HBA 3, HBD 0, PSA 21.7, QED 0.76
Compound (SMILES): CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1CC(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1
InChIKey: HUAZIQKZKFNJLA-YSEMLTDISA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of recombinant human MMP7 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 = 2097 nM (pChEMBL 5.679999828338623)
Descriptors: MW 986.16, ALogP 0.63, HBA 12, HBD 8, PSA 335.9, QED 0.05
Compound (SMILES): OC[C@H]1O[C@H](Sc2cncc(Br)c2)[C@H](O)[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@H]1O
InChIKey: FNCLKJPMEFPXOR-QFACEVIFSA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Binding affinity to recombinant human Galectin-3 expressed in Escherichia coli assessed as dissociation constant by fluorescence polarization
Measurement: Kd = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 533.33, ALogP 2.29, HBA 9, HBD 3, PSA 113.52, QED 0.43
Compound (SMILES): CN(C1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1)c1ccccc1
InChIKey: NAYXGFSGXGZZCZ-ZROIWOOFSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of GST-fused human recombinant DYRK1B expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 321.34, ALogP 2.38, HBA 5, HBD 1, PSA 63.16, QED 0.86
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](NC(C)=O)CCSSCC[C@H](C(N)=O)NC1=O
InChIKey: MWUXCBIVLGSGOO-INFFCAIZSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 47.86 nM (pChEMBL 7.320000171661377)
Descriptors: MW 1243.53
Compound (SMILES): Cn1c(CN2CCC(c3cccc(OCc4ccc(Cl)cc4F)n3)CC2)nc2ccc(C(=O)O)nc21
InChIKey: ZFDHZDONBOMVLZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by patch-clamp method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 509.97, ALogP 4.81, HBA 7, HBD 1, PSA 93.37, QED 0.38
Compound (SMILES): CC(C)n1c(=O)n(C)c2cnc3ccc(-c4ccc(OCCCN(C)C)nc4)cc3c21
InChIKey: FBYDIXCPNMJMEZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells incubated for 2 hrs by Alexa Fluor 488/Hoeschst staining based plate reader assay
Measurement: IC50 > 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 419.53, ALogP 3.86, HBA 7, HBD 0, PSA 65.18, QED 0.43
Compound (SMILES): COc1cc(-c2cn(C)c(=O)c3cnccc23)cc(OC)c1CN1CCN(CCCCCOc2cc(-c3scnc3C)ccc2CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)CC1
InChIKey: ZAGCLFXBHOXXEN-JPTLTNPLSA-N
Target: von Hippel-Lindau disease tumor suppressor (SINGLE PROTEIN), Homo sapiens
UniProt: P40337
Assay: ITC (VHL:VZ185) (ITC binary complex (VHL:VZ185))
Measurement: Kd = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 995.23, ALogP 6.03, HBA 14, HBD 3, PSA 180.69, QED 0.08
Compound (SMILES): C[C@@H]1CC(=O)Nc2ncnc(N3CCN(C(=O)[C@H](CNC4CC4)c4ccc(Cl)cc4)[C@@H]4C[C@@H]43)c21
InChIKey: DOJSODPNZWPNBR-PPRPKMEESA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes at 0.01 to 30 uM using phenacetin as substrate in presence of NADPH by UPLC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 481, ALogP 2.9, HBA 6, HBD 2, PSA 90.46, QED 0.66
Compound (SMILES): C=CC(=O)N1CCC(C(=O)O)(c2ccc(OC)cc2)CC1
InChIKey: WZFZVGUXQHXMTJ-UHFFFAOYSA-N
Target: CXXC-type zinc finger protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2H0
Assay: Inhibition of GST-tagged human IDAX (130 to 181 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 289.33, ALogP 1.83, HBA 3, HBD 1, PSA 66.84, QED 0.86
Compound (SMILES): CC(C)(O)c1ccc(-c2cccc(N(CC34CCC(c5noc(C(C)(C)F)n5)(CC3)CC4)C(=O)[C@H]3C[C@](O)(C(F)(F)F)C3)c2)cc1
InChIKey: AEMZJBZKICOPPC-RNMMDBENSA-N
Target: RNA-binding protein FXR2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51116
Assay: Agonist activity at human FXR2 expressed in HEK293 cells coexpressing IBABP
Measurement: EC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 643.72, ALogP 7.5, HBA 6, HBD 2, PSA 99.69, QED 0.25
Compound (SMILES): C=CC(=O)Nc1ccc2ncnc(Nc3ccc4[nH]cc(Br)c4c3)c2c1
InChIKey: ATUXFPJRTSKHFB-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of SRC (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.26, ALogP 4.74, HBA 4, HBD 3, PSA 82.7, QED 0.43
Compound (SMILES): Cc1cc(NC(=O)COc2ccc(Cl)cc2Cl)n(C2CCS(=O)(=O)C2)n1
InChIKey: NVBSEMQBJVQXCV-UHFFFAOYSA-N
Target: G protein-activated inward rectifier potassium channel 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P48051
Assay: Activation of Kir3.2 channel (unknown origin) by thallium flux assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 418.3, ALogP 2.88, HBA 6, HBD 1, PSA 90.29, QED 0.81
Compound (SMILES): FC(F)(F)c1cccc(COC2CCN(Cc3ccc4[nH]cnc4c3)CC2)c1
InChIKey: YFPRVZQGLGSZKO-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from D3 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 948 nM (pChEMBL 6.019999980926514)
Descriptors: MW 389.42, ALogP 4.76, HBA 3, HBD 1, PSA 41.15, QED 0.68
Compound (SMILES): O=C(NO)C(Cc1ccccc1)NS(=O)(=O)c1ccc(-c2cn(-c3ccc(-c4ccccc4)cc3)nn2)cc1
InChIKey: OTCQKJMDFJEBFM-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 539.62, ALogP 4, HBA 7, HBD 3, PSA 126.21, QED 0.19
Compound (SMILES): O=C1NCc2nc(-c3c(F)cccc3F)cc(Nc3ccc(C(=O)N4CCOCC4)cc3)c21
InChIKey: XDTKWAGKBLDFOE-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of Jak1/Jak3 in human PBMC assessed as inhibition of IL2-stimulated phosphorylation of STAT5
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 450.45, ALogP 3.49, HBA 5, HBD 2, PSA 83.56, QED 0.64
Compound (SMILES): O=c1c(/C=C/c2ccccc2Cl)nc2ccccc2n1Cc1ccccc1
InChIKey: ABBRXDCHEYVCBL-CCEZHUSRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 372.86, ALogP 5.27, HBA 3, HBD 0, PSA 34.89, QED 0.49
Compound (SMILES): O=C(N[C@@H]1CCCN(c2ncnc3[nH]ccc23)C1)[C@H](Nc1cc(Cl)cc(C(F)(F)F)c1)C1CC1
InChIKey: XSNVEELQPXGAPX-VQIMIIECSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Binding affinity to human full length BMX (M1 to H675 residues ) expressed in bacterial expression system assessed dissociation constant by Kinomescan method
Measurement: Kd = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 492.93, ALogP 4.61, HBA 5, HBD 3, PSA 85.94, QED 0.47
Compound (SMILES): Fc1ccc(Cl)c(-c2ccc(NC[C@@H]3CC34CCN(CC3CCOCC3)CC4)nn2)c1
InChIKey: NORLOFDPLORONC-SFHVURJKSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using cocktail of isoform-specific probe substrate
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 444.98, ALogP 4.88, HBA 5, HBD 1, PSA 50.28, QED 0.69
Compound (SMILES): COc1cc(OC)c(C2NCCc3c2[nH]c2ccc(F)cc32)cc1OC.Cl
InChIKey: LWHOEIHANZIFDG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 356.4, ALogP 3.57, HBA 4, HBD 2, PSA 55.51, QED 0.75
Compound (SMILES): Cc1nc(N)oc1CCCN/C(N)=N/C(=O)NCC(C)C1CCCCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CVWWNGBIVGCWNQ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 364.49, ALogP 2.33, HBA 4, HBD 4, PSA 131.56, QED 0.33
Compound (SMILES): CC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C(F)(F)F)c2)ccn1
InChIKey: JRJSMTAUWDJJIH-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 0.74 nM (pChEMBL 9.130000114440918)
Descriptors: MW 409.45, ALogP 4.87, HBA 4, HBD 2, PSA 77.24, QED 0.68
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(N)=O)C(C)C
InChIKey: XHPNKAPWXFVQKQ-AEEVCGNZSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 (Ala20 to Asp707 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 729.18, ALogP 0.65, HBA 8, HBD 7, PSA 242.96, QED 0.11
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1cnc(N)s1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RZWKIWSVEPQMPP-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 312.44, ALogP 1.46, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](OC(=O)c2cccc3ccccc23)[C@H]1OC(=O)c1cccc2ccccc12
InChIKey: PSBROSWEMLTASJ-BQOYKFDPSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Agonist activity at human P2X7R expressing HEK293 cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: EC50 = 16595.87 nM (pChEMBL 4.78000020980835)
Descriptors: MW 815.52, ALogP 4.41, HBA 16, HBD 5, PSA 291.27, QED 0.08
Compound (SMILES): Nc1nnc2c([nH]c3ccccc32)c1-c1ccccc1
InChIKey: DHDZFJQQXROKLC-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Binding affinity to human SMARCA4 (A1448 to S1575 residues) expressed in bacterial expression system by bromoscan assay
Measurement: Kd = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 260.3, ALogP 3.36, HBA 3, HBD 2, PSA 67.59, QED 0.55
Compound (SMILES): C[C@H](c1c(Cl)ccc(C2CC2)c1Cl)n1cnc2cnc(-c3ccccc3[C@@H](C)C(=O)O)cc21
InChIKey: JPJWHCNGSBCZMI-HUUCEWRRSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Positive allosteric modulator activity at human GLP-1R transfected in rat INS-1 832/13 cells assessed as potentiation of GLP-1(9-36) induced cAMP accumulation
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 480.4, ALogP 7.08, HBA 4, HBD 1, PSA 68.01, QED 0.32
Compound (SMILES): Cc1ccc(CNC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCC(=O)NC(C)(C)C)NC(=O)CCNC(=O)/C(C#N)=C/c2ccco2)cc1
InChIKey: VTKSMYDOQHZUPK-CNUXCAPHSA-N
Target: Proteasome subunit beta type-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P28070
Assay: Inhibition of 20S proteasome subunit beta-2c (unknown origin) using Ac-KQL-AMC as substrate and measured after 30 mins
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 668.8, ALogP 3.22, HBA 7, HBD 5, PSA 182.43, QED 0.11
Compound (SMILES): O=C(Nc1nc2cccc(C3=CCC(NC(=O)C4CC4)CC3)n2n1)C1CC1
InChIKey: ZGAWRDQWSJYLKZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Activity Assay: JAK2 (h) and 8 mM MOPS pH 7.0, 0.2 mM EDTA, 100M KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC, 10 mM magnesium acetate and [γ-33P]-ATP (activity and concentration were formulated as needed) were incubated together. Mg/ATP mixture was added to initiate the reaction. After incubating at room temperature for 40 minutes, the reaction mixture was added with 0.5% phosphoric acid to stop the reaction. Then 10 L reaction solution was spotted on a P30 filter pad and washed with 0.425% phosphoric acid three times and methanol once over 4 minutes, dried, and counted scintillation.
Measurement: IC50 = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 365.44, ALogP 2.54, HBA 5, HBD 2, PSA 88.39, QED 0.85
Compound (SMILES): NC(=O)c1ccc(OCC2CCC2)cc1F
InChIKey: VLOWWMKTNSPEAY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human N-terminal 6His-tagged TNKS2 (1030 to 1317 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 223.25, ALogP 2.1, HBA 2, HBD 1, PSA 52.32, QED 0.85
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCNCC4)c3)n2)c1Cl
InChIKey: YYCRQWMDRNTZLT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 V555M mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 268.4 nM (pChEMBL 6.570000171661377)
Descriptors: MW 542.43, ALogP 4.87, HBA 11, HBD 3, PSA 123.93, QED 0.28
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc3sc4ccccc4c3c2)[C@H]1NC(C)=O
InChIKey: HLHDCHXBXBBXLH-PPJWLVRDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated for 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 60800 nM (pChEMBL 4.21999979019165)
Descriptors: MW 480.63, ALogP 5.01, HBA 5, HBD 3, PSA 87.66, QED 0.4
Compound (SMILES): COC(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN(C)CC5)c(F)c4)c3n2)[C@@H](C)C1
InChIKey: CXZJXVJPISUKMR-IYBDPMFKSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human recombinant N-terminal GST tagged ALK2 (147 to end residues) expressed in baculovirus infected in Sf9 cells assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 3 hrs by HTRF assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 482.56, ALogP 2.58, HBA 8, HBD 1, PSA 93.72, QED 0.61
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Oc1ccccc1
InChIKey: CFSRLUGJCGONGU-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Binding affinity to recombinant human CaMK2alpha Ile464His mutant expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 353 nM (pChEMBL 6.449999809265137)
Descriptors: MW 244.25, ALogP 2.81, HBA 3, HBD 2, PSA 66.76, QED 0.87
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCCC3)ccc12
InChIKey: PCAWJIMDNGAMRA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human N-terminal 6His-tagged TNKS2 (1030 to 1317 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 274.32, ALogP 2.18, HBA 3, HBD 2, PSA 74.95, QED 0.9
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2cccnc21
InChIKey: UXPONYQLKCUMSK-CQSZACIVSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in mouse AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 20.89 nM (pChEMBL 7.679999828338623)
Descriptors: MW 330.43, ALogP 2.47, HBA 4, HBD 2, PSA 90.01, QED 0.85
Compound (SMILES): N.O=C(O)c1cc(-c2ccc(CNc3ccc(Br)cc3)o2)ccc1O
InChIKey: MVHXINROGSSELN-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate measured every 60 sec for 10 mins by fluorescence based assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 388.22, ALogP 4.73, HBA 4, HBD 3, PSA 82.7, QED 0.59
Compound (SMILES): COc1ccc(NC(=O)N2CCc3c(sc(NC(=O)c4cnn(C)c4)c3C#N)C2)cc1
InChIKey: WVYHDFDOBCBKGI-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Binding affinity to His tagged N-terminal full length recombinant human STAT3 extracted from Baculovirus infected Sf9 cells assessed as dissociation constant measured upto 360 secs by SPR analysis
Measurement: Kd = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 436.5, ALogP 3.2, HBA 7, HBD 2, PSA 112.28, QED 0.65
Compound (SMILES): CC[C@H](C)[C@@H](C(=O)N1CCC[C@H]1CC(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1
InChIKey: HUAZIQKZKFNJLA-YSEMLTDISA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrate preincubated for 15 mins followed by substrate addition by fluroscence based assay
Measurement: IC50 = 261 nM (pChEMBL 6.579999923706055)
Descriptors: MW 986.16, ALogP 0.63, HBA 12, HBD 8, PSA 335.9, QED 0.05
Compound (SMILES): OC[C@H]1O[C@H](Sc2cncc(Br)c2)[C@H](O)[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@H]1O
InChIKey: FNCLKJPMEFPXOR-QFACEVIFSA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Binding affinity to human galectin-3 assessed as dissociation constant by competitive fluorescence polarization assay
Measurement: Kd = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 533.33, ALogP 2.29, HBA 9, HBD 3, PSA 113.52, QED 0.43
Compound (SMILES): CN(C1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1)c1ccccc1
InChIKey: NAYXGFSGXGZZCZ-ZROIWOOFSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 321.34, ALogP 2.38, HBA 5, HBD 1, PSA 63.16, QED 0.86
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](NC(C)=O)CCSSCC[C@H](C(N)=O)NC1=O
InChIKey: MWUXCBIVLGSGOO-INFFCAIZSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human MC5R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: IC50 = 4168.69 nM (pChEMBL 5.380000114440918)
Descriptors: MW 1243.53
Compound (SMILES): COc1cc(-c2cn(C)c(=O)c3cnccc23)cc(OC)c1CN1CCN(CCCCCOc2cc(-c3scnc3C)ccc2CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)CC1
InChIKey: ZAGCLFXBHOXXEN-JPTLTNPLSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: ITC (VZ185:BRD9-BD)
Measurement: Kd = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 995.23, ALogP 6.03, HBA 14, HBD 3, PSA 180.69, QED 0.08
Compound (SMILES): C[C@@H]1CC(=O)Nc2ncnc(N3CCN(C(=O)[C@H](CNC4CC4)c4ccc(Cl)cc4)[C@@H]4C[C@@H]43)c21
InChIKey: DOJSODPNZWPNBR-PPRPKMEESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes at 0.01 to 30 uM using diclofenac as substrate in presence of NADPH by UPLC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 481, ALogP 2.9, HBA 6, HBD 2, PSA 90.46, QED 0.66
Compound (SMILES): C=CC(=O)N1CCC(C(=O)O)(c2ccc(OC)cc2)CC1
InChIKey: WZFZVGUXQHXMTJ-UHFFFAOYSA-N
Target: F-box/LRR-repeat protein 19 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PCT2
Assay: Inhibition of GST-tagged human FBXL19 (31 to 86 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 289.33, ALogP 1.83, HBA 3, HBD 1, PSA 66.84, QED 0.86
Compound (SMILES): CC(C)(O)c1ccc(-c2cccc(N(CC34CCC(c5noc(C(C)(C)F)n5)(CC3)CC4)C(=O)[C@H]3C[C@](O)(C(F)(F)F)C3)c2)cc1
InChIKey: AEMZJBZKICOPPC-RNMMDBENSA-N
Target: RNA-binding protein FXR2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51116
Assay: Agonist activity at human FXR2 expressed in Huh-7 cells coexpressing BSEP
Measurement: EC50 = 389 nM (pChEMBL 6.409999847412109)
Descriptors: MW 643.72, ALogP 7.5, HBA 6, HBD 2, PSA 99.69, QED 0.25