lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)CN(CCCNC(=N)N)C(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: FGTXJLSBIKUVQB-NETOACFBSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse MC5R by alphascreen cAMP assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 949.13, ALogP -1.19, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(c3ccccc3)c3ccccc34)cc2)cc1
InChIKey: YPPVVNXEJUDPRL-YTTGMZPUSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in inositol phosphate accumulation in presence of terbium cryptate-labeled anti IP1/d2-labelled IP1 measured after 120 mins by HTRF assay
Measurement: EC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 570.73, ALogP 7.53, HBA 4, HBD 1, PSA 53.01, QED 0.21
Compound (SMILES): Cc1nc(NC(=O)NCCc2cn(CC(F)F)cn2)sc1C#Cc1cccnc1
InChIKey: FUKVQYDAJUEJHW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 416.46, ALogP 3.07, HBA 6, HBD 2, PSA 84.73, QED 0.61
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(Br)cc23)cc1
InChIKey: PESSDQDERPAVNH-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human C-terminal 6His-tagged AChE (Glu32 to Leu614 residues) expressed in CHO cells using acetylthiocholine iodide as substrate preincubated for 5 mins measured after 15 mins by DTNB reagent based assay
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 408.26, ALogP 5.01, HBA 4, HBD 3, PSA 74.25, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)c2sc(NC(=O)c3ccco3)nc2-c2ccccc2)cc1
InChIKey: NSGJWVVFFNBRGB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 42.2 nM (pChEMBL 7.380000114440918)
Descriptors: MW 388.45, ALogP 5.19, HBA 5, HBD 1, PSA 72.2, QED 0.48
Compound (SMILES): O=C(N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12)C1CCS(=O)(=O)CC1
InChIKey: LOOWXSUDJJEUCC-JBRSBNLGSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 673.64, ALogP 5.45, HBA 5, HBD 1, PSA 97.38, QED 0.34
Compound (SMILES): CNc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: PHEGDBVVFIATGX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 437.92, ALogP 4.13, HBA 4, HBD 2, PSA 53.6, QED 0.61
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(Cl)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YEMOJJTZJLWRNY-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 53.2 nM (pChEMBL 7.269999980926514)
Descriptors: MW 425.94, ALogP 2.4, HBA 7, HBD 1, PSA 97.19, QED 0.81
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of N-terminal FLAG-tagged human recombinant mTOR (1362 to end residues) using ULight-4E-BP1 (Thr37/46) peptide as substrate incubated for 1 hr in presence of ATP by Lance Ultra assay
Measurement: IC50 = 1802 nM (pChEMBL 5.739999771118164)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 973.4 nM (pChEMBL 6.010000228881836)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of recombinant rat DYRK1A kinase domain (1 to 499 residues) expressed in bacterial expression system using KKISGRLSPIMTEQ as substrate by ADP-glo assay
Measurement: IC50 = 2210 nM (pChEMBL 5.659999847412109)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC.Cl
InChIKey: KMKKFZCVBRAWNX-GSAMTNRBSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000289bCl SIGMAR1
Measurement: Ki = 289 nM (pChEMBL 6.539999961853027)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(OC)cc4n3)C2)cc1
InChIKey: ADHABGMDGASWTO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): C[C@H](CO)n1cnnc1-c1cccc(NC(=O)Nc2cc3ccccn3n2)n1
InChIKey: GSYUZRLLPWNNAL-GFCCVEGCSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human recombinant TYK2 (875 to end residues) using GGMEDIYFEFMGG as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting analysis
Measurement: IC50 = 1689 nM (pChEMBL 5.769999980926514)
Descriptors: MW 378.4, ALogP 2.19, HBA 8, HBD 3, PSA 122.26, QED 0.49
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 MPro using Dabcyl-KTSAVLQSGFRKME-Edans as substrate assessed as inhibition constant measured for 10 mins by FRET assay
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ZYILDTWBSDDXCD-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 501.53, ALogP 2.03, HBA 9, HBD 3, PSA 167.47, QED 0.33
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using midazolam as substrate preincubated for 15 mins followed by NADPH addition and measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(C)cc3)s2)cc1
InChIKey: QWYBNZBBHWLLPB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 428.51, ALogP 5.61, HBA 5, HBD 1, PSA 68.29, QED 0.41
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(Cl)c2)CC1
InChIKey: NPVINTHTFSBGKQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 0.043 nM (pChEMBL 10.369999885559082)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): CN1COc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2C1=O
InChIKey: KDMVVQOQEKIXTC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Receptor Binding Assay: 5-HT7: (1) The prepared membrane was applied with buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of (��)-pindolol (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-5-CT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each of the reaction tubes was incubated at 25° C. for 120 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 11.2 nM (pChEMBL 7.949999809265137)
Descriptors: MW 439.49, ALogP 4.04, HBA 6, HBD 0, PSA 68.04, QED 0.54
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(C(=O)c2ccc(F)cc2F)s1)c1ccco1
InChIKey: RVXUCDYZOPPLSL-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki = 124 nM (pChEMBL 6.909999847412109)
Descriptors: MW 410.4, ALogP 5.16, HBA 5, HBD 1, PSA 72.2, QED 0.46
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: GQODKPDOYBQBRL-GJOOVXBSSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Displacement of [125I]-1-DMe-NPFF from human NPFF1 receptor
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 898.08, ALogP -0.95, HBA 10, HBD 13, PSA 349.85, QED 0.03
Compound (SMILES): Cc1c(N2CCC3(CC2)Cc2ccccc2[C@H]3N)nc(C)n(-c2cccc(Cl)c2Cl)c1=O
InChIKey: MFHWVKLJXFEKJX-JOCHJYFZSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Biochemical Assay: The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2,E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 469.42, ALogP 5, HBA 5, HBD 1, PSA 64.15, QED 0.57
Compound (SMILES): Cn1cc(-c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)cn1
InChIKey: XQQYRDDJENLAME-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of human full length recombinant DYRK2 using casein substrate by radiometric scintillation assay
Measurement: IC50 = 771 nM (pChEMBL 6.110000133514404)
Descriptors: MW 355.4, ALogP 4.3, HBA 6, HBD 0, PSA 61.67, QED 0.48
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNCc3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: YKNBYIQXICDOOY-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 558.62, ALogP 1.9, HBA 10, HBD 4, PSA 179.5, QED 0.2
Compound (SMILES): CNc1nc(NCc2ncccn2)c2c(-c3ccc4ncccc4c3)c[nH]c2n1
InChIKey: PMWVYONICYRLNY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Binding affinity to CLK4 (unknown origin) assessed as dissociation constant
Measurement: Kd = 0.61 nM (pChEMBL 9.210000038146973)
Descriptors: MW 382.43, ALogP 3.62, HBA 7, HBD 3, PSA 104.3, QED 0.43
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccc(Cl)cc2)CC1
InChIKey: HDFGGNSQPFXQRL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Receptor Binding Assay: 5-HT1A: Radioligand binding was performed using membranes from CHO-K1 cells stably transfected with the human 5-HT1A receptor. All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-8-OH-DPAT (final concentration 1 nM, Kd 0.8 nM) and 150 μL diluted membranes (10 μg protein per well) prepared in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl2, 0.1 mM EDTA, 0.1% ascorbic acid) were transferred to polypropylene 96-well microplate using 96-wells pipetting station Rainin Liquidator (MettlerToledo). Serotonin (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 60 minutes at 27° C. The reaction was terminated by rapid filtration through GF/C filter mate presoaked with 0.3% polyethyleneimine for 30 minutes. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.4) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and then solid scintillator MeltiLex was melted on filter mates at 90° C. for 5 minutes. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (GraphPad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): NCc1ccc(NC(=O)N2C(=O)CC2CC(=O)NCCC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: WNJSILFLYVIFJS-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Agonist activity at alphaVbeta6 in human HT-29 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 348.36, ALogP 0.26, HBA 5, HBD 4, PSA 141.83, QED 0.52
Compound (SMILES): Cc1nc(NC(=O)NCCc2cn(CC(F)F)cn2)sc1C#Cc1cccnc1
InChIKey: FUKVQYDAJUEJHW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 416.46, ALogP 3.07, HBA 6, HBD 2, PSA 84.73, QED 0.61
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(Br)cc23)cc1
InChIKey: PESSDQDERPAVNH-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human C-terminal FLAG/His-tagged HDAC1 (1 to 482 residues) expressed in Sf9 insect cells using fluor de lys SIRT1 as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 408.26, ALogP 5.01, HBA 4, HBD 3, PSA 74.25, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)c2sc(NC(=O)c3ccco3)nc2-c2ccccc2)cc1
InChIKey: NSGJWVVFFNBRGB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]DPCPX from rat brain cortical membrane A1AR in absence of GTP by scintillation counting analysis
Measurement: IC50 = 0.067 nM (pChEMBL 10.170000076293945)
Descriptors: MW 388.45, ALogP 5.19, HBA 5, HBD 1, PSA 72.2, QED 0.48
Compound (SMILES): CNc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: PHEGDBVVFIATGX-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 437.92, ALogP 4.13, HBA 4, HBD 2, PSA 53.6, QED 0.61
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 977.24 nM (pChEMBL 6.010000228881836)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of recombinant human HASPIN kinase domain (470 to 798 residues) expressed in bacterial expression system using histone H3(1-21) peptide as substrate by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC.Cl
InChIKey: KMKKFZCVBRAWNX-GSAMTNRBSA-N
Target: Alpha-2B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18089
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000289bCl ADRA2B
Measurement: Ki = 4643 nM (pChEMBL 5.329999923706055)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(OC)cc4n3)C2)cc1
InChIKey: ADHABGMDGASWTO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 Main Protease
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ZYILDTWBSDDXCD-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 501.53, ALogP 2.03, HBA 9, HBD 3, PSA 167.47, QED 0.33
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-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 15 mins followed by NADPH addition and measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(C)cc3)s2)cc1
InChIKey: QWYBNZBBHWLLPB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28647
Assay: Displacement of [3H]NECA from rat adenosine receptor A3 expressed in CHO cell membranes incubated for 60 mins by radioligand competition assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 428.51, ALogP 5.61, HBA 5, HBD 1, PSA 68.29, QED 0.41
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(Cl)c2)CC1
InChIKey: NPVINTHTFSBGKQ-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): CN1COc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2C1=O
InChIKey: KDMVVQOQEKIXTC-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31390
Assay: Receptor Binding Assay: Histamine H1: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer (potassium dihydrogen phosphate 1.36 g, 0.1 mol/L sodium hydroxide 79 ml, metered to 200 ml with double-distilled water) was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 uL of membrane preparation was added into each reaction tube. (3) 100 uL of buffer was added into the total binding tube (TB), 100 uL of promethazine (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 uL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 uL of radioactive ligand 3H-pyrilamine was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each of the reaction tubes was incubated at 30° C. for 60 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and the ice-chilled assay buffer was used for adequate washing. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation solution was added and blended. 2* Isotope ligand [3H]-5-CT (85.4 Ci/mmol) was purchased from PerkinElmer Company; (+-)-pindolol was purchased from RBI Company; GF/C glass fiber filter paper was purchased from Whatman Company; Tris was imported and divided into aliquots; PPO and POPOP were purchased from Shanghai No. 1 Reagent Factory; liposoluble scintillation cocktail was purchased from Shanghai Reagent Factory. Beckman LS-6500 Multi-function Liquid Scintillation Counter was used.
Measurement: Ki > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 439.49, ALogP 4.04, HBA 6, HBD 0, PSA 68.04, QED 0.54
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: GQODKPDOYBQBRL-GJOOVXBSSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Displacement of [125I]-1-DMe-NPFF from human NPFF2 receptor
Measurement: Ki = 0.077 nM (pChEMBL 10.109999656677246)
Descriptors: MW 898.08, ALogP -0.95, HBA 10, HBD 13, PSA 349.85, QED 0.03
Compound (SMILES): Cc1c(N2CCC3(CC2)Cc2ccccc2[C@H]3N)nc(C)n(-c2cccc(Cl)c2Cl)c1=O
InChIKey: MFHWVKLJXFEKJX-JOCHJYFZSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Biochemical Assay (with IRSI_2pY): The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2,E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min with activating IRSI_2pY. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 469.42, ALogP 5, HBA 5, HBD 1, PSA 64.15, QED 0.57
Compound (SMILES): Cn1cc(-c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)cn1
InChIKey: XQQYRDDJENLAME-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86Z02
Assay: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 209 nM (pChEMBL 6.679999828338623)
Descriptors: MW 355.4, ALogP 4.3, HBA 6, HBD 0, PSA 61.67, QED 0.48
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNCc3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: YKNBYIQXICDOOY-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 558.62, ALogP 1.9, HBA 10, HBD 4, PSA 179.5, QED 0.2
Compound (SMILES): CNc1nc(NCc2ncccn2)c2c(-c3ccc4ncccc4c3)c[nH]c2n1
InChIKey: PMWVYONICYRLNY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 administered orally
Measurement: IC50 = 0.096 nM (pChEMBL 10.020000457763672)
Descriptors: MW 382.43, ALogP 3.62, HBA 7, HBD 3, PSA 104.3, QED 0.43
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccc(Cl)cc2)CC1
InChIKey: HDFGGNSQPFXQRL-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): NCc1ccc(NC(=O)N2C(=O)CC2CC(=O)NCCC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: WNJSILFLYVIFJS-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta6 in human HT-29 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 348.36, ALogP 0.26, HBA 5, HBD 4, PSA 141.83, QED 0.52
Compound (SMILES): Cc1nc(NC(=O)NCCc2cn(CC(F)F)cn2)sc1C#Cc1cccnc1
InChIKey: FUKVQYDAJUEJHW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3B (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 416.46, ALogP 3.07, HBA 6, HBD 2, PSA 84.73, QED 0.61
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(Br)cc23)cc1
InChIKey: PESSDQDERPAVNH-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC2 (1 to 488 residues) expressed in Sf9 insect cells using fluor de lys SIRT1 as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 408.26, ALogP 5.01, HBA 4, HBD 3, PSA 74.25, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)c2sc(NC(=O)c3ccco3)nc2-c2ccccc2)cc1
InChIKey: NSGJWVVFFNBRGB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]DPCPX from rat brain cortical membrane A1AR in presence of 100 uM of GTP by scintillation counting analysis
Measurement: IC50 = 0.084 nM (pChEMBL 10.079999923706055)
Descriptors: MW 388.45, ALogP 5.19, HBA 5, HBD 1, PSA 72.2, QED 0.48
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: Ki = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 310.8 nM (pChEMBL 6.510000228881836)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of recombinant human PIM1 expressed in bacterial expression system using histone H1 as substrate by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC.Cl
InChIKey: KMKKFZCVBRAWNX-GSAMTNRBSA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000289bCl ADRA2C
Measurement: Ki = 5766 nM (pChEMBL 5.239999771118164)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Covalent inhibition of SARS-CoV-2 main protease
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ZYILDTWBSDDXCD-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at human A2A receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 = 90.8 nM (pChEMBL 7.039999961853027)
Descriptors: MW 501.53, ALogP 2.03, HBA 9, HBD 3, PSA 167.47, QED 0.33
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Binding affinity to MAO-B (unknown origin)
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(C)cc3)s2)cc1
InChIKey: QWYBNZBBHWLLPB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]DPCPX from rat brain cortical membrane A1AR in absence of GTP by scintillation counting analysis
Measurement: IC50 = 0.0756 nM (pChEMBL 10.119999885559082)
Descriptors: MW 428.51, ALogP 5.61, HBA 5, HBD 1, PSA 68.29, QED 0.41
Compound (SMILES): Cn1cc(-c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)cn1
InChIKey: XQQYRDDJENLAME-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2X6
Assay: Inhibition of human recombinant HIPK2 using myelin substrate by radiometric scintillation assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 355.4, ALogP 4.3, HBA 6, HBD 0, PSA 61.67, QED 0.48
Compound (SMILES): CNc1nc(NCc2ncccn2)c2c(-c3ccc4ncccc4c3)c[nH]c2n1
InChIKey: PMWVYONICYRLNY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of human CLK1 administered orally
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 382.43, ALogP 3.62, HBA 7, HBD 3, PSA 104.3, QED 0.43
Compound (SMILES): NCc1ccc(NC(=O)N2C(=O)CC2CC(=O)NCCC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: WNJSILFLYVIFJS-UHFFFAOYSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha5beta1 in human K562 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 348.36, ALogP 0.26, HBA 5, HBD 4, PSA 141.83, QED 0.52
Compound (SMILES): Cc1nc(NC(=O)NCCc2cn(CC(F)F)cn2)sc1C#Cc1cccnc1
InChIKey: FUKVQYDAJUEJHW-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin)
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 416.46, ALogP 3.07, HBA 6, HBD 2, PSA 84.73, QED 0.61
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(Br)cc23)cc1
InChIKey: PESSDQDERPAVNH-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residus) expressed in baculovirus infected Sf9 insect cells using fluor de lys SIRT1 as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 408.26, ALogP 5.01, HBA 4, HBD 3, PSA 74.25, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)c2sc(NC(=O)c3ccco3)nc2-c2ccccc2)cc1
InChIKey: NSGJWVVFFNBRGB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]DPCPX from rat brain cortical membrane A1AR assessed as GTP shift
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 388.45, ALogP 5.19, HBA 5, HBD 1, PSA 72.2, QED 0.48
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells assessed as inhibition of channel tail current at holding potential of -80 mV by Qpatch assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human CK1epsilon expressed in baculovirus infected Sf9 insect cells using RRKHAAIGSpAYSITA as substrate by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of eGFP-fused SARS-CoV-2 main protease transfected in HEK293T/17 cells incubated for 3 days by flow cytometry analysis
Measurement: EC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Binding affinity to MAO-A (unknown origin)
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58