lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)n(C2CCCCC2)c1=O
InChIKey: NVTKJBXOBFRPLQ-UHFFFAOYSA-N
Target: Prolyl 4-hydroxylase (SINGLE PROTEIN), Paramecium bursaria Chlorella virus 1
UniProt: Q84406
Assay: Inhibition of N-terminal His6-tagged recombinant Paramecium bursaria chlorella virus 1 CPH expressed in Escherichia coli Rosetta 2 (DE3) cells pre-incubated for 5 mins before 2OG as substrate and Fe2 as co-factor addition in presence of L-ascorbate and measured after 5 mins MALDI TOF MS analysis
Measurement: Ki = 7650 nM (pChEMBL 5.119999885559082)
Descriptors: MW 393.44, ALogP 1.54, HBA 7, HBD 3, PSA 130.63, QED 0.7
Compound (SMILES): O=C(NC1CCCCCC1)c1c(-c2ccccc2)ccn(Cc2ccc(F)cc2)c1=O
InChIKey: XFCFHDRWNFQOJT-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using 2-OG containing [glycerol-1,2,3-3H]AEA as substrate preincubated for 30 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.51, ALogP 5.16, HBA 3, HBD 1, PSA 51.1, QED 0.58
Compound (SMILES): Cc1nc2c(c(Nc3c[nH]nc3C(=O)Nc3ccc(N4CCNCC4)cc3)n1)CCC2
InChIKey: DXUDRTZDTCQOLU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 D835Y mutant by Hotspot assay
Measurement: IC50 = 1.79 nM (pChEMBL 8.75)
Descriptors: MW 418.51, ALogP 2.4, HBA 7, HBD 4, PSA 110.86, QED 0.5
Compound (SMILES): COc1ccc2c(c1)c(C(=O)Nc1cc(C(=O)O)cc(-c3cnn(C)c3)c1)cn2C(C)=O
InChIKey: GMINUTRRQLVDKN-UHFFFAOYSA-N
Target: Bromodomain adjacent to zinc finger domain protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIF8
Assay: Inhibition of biotinylated-H4KAc4 binding to human His6-tagged BAZ2B (S1858 to S1972 residues) expressed in Escherichia coli BL21(DE3) after 2.5 hrs by luminescence-based AlphaScreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 432.44, ALogP 3.66, HBA 7, HBD 2, PSA 115.45, QED 0.5
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-MOVYNIQHSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin)
Measurement: IC50 = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): N#Cc1cc(F)cc(Oc2ccc3c(c2C(F)F)C(O)C(F)(F)S3(=O)=O)c1
InChIKey: HZDKYXAZAPXCKQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor A, long form (SINGLE PROTEIN), Homo sapiens
UniProt: P15692
Assay: ELISA Assay: About 7500 of 786-O cells in 180 μL of growth medium were seeded into each well of a 96 well plate with white clear bottom on the first day (07-200-566, Fisher Scientific) in the layout presented in FIG. 9.Four hours later, serial dilutions of 10× compound stocks were made in growth medium from 500×DMSO stocks, and 20 μL of those 10× stocks were added to each well to make final concentrations as follows (μM): 20, 6.7, 2.2, 0.74, 0.25, 0.082, 0.027, 0.009, 0.003, 0.001, 0. Each concentration had duplicated wells. About twenty hours later, the growth medium was removed by suction and each well was supplied with 180 μL of growth medium. About 20 μl freshly-made 10× compound stocks were added to each well. About twenty four hours later, cell culture medium was removed for the determination of VEGF concentration using an ELISA kit purchased from R&D systems by following the manufacturer's suggested method. The EC50 was calculated by GraphPad Prism using the dose-response-inhibition (four parameter) equation. The cell seeded plate was then subjected to CellTiter-Glo luminescence cell viability assay (Promega) by adding about 50 μL of Celltiter Glo reagent into each well and shaking the plate for 8 minutes at 550 rpm (Thermomixer R, Eppendorf). The luminescence signals were read in a plate reader (3 second delay, 0.5 second/well integration time, Synergy 2 multi Detection Microplate reader) immediately.
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 405.3, ALogP 3.84, HBA 5, HBD 1, PSA 87.39, QED 0.78
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CO[Si](C)(C)C(C)(C)C)[C@H](O)CC[C@@]2(C)[C@@H]1C/C=C1/C(=O)OC[C@@H]1OC(C)=O
InChIKey: VJSLAEHMOUSVLS-IGVZYMBNSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of NF-kappaB stimulated STAT3 activation in human HeLa cells incubated with NF-kappaB for 16 hrs followed by compound addition measured after 4 hrs by luciferase reporter gene assay
Measurement: EC50 = 9960 nM (pChEMBL 5)
Descriptors: MW 506.76
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3c(C)[nH]c4ccccc34)c12
InChIKey: ONTCKBVHGQBHTF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 437.5, ALogP 6.16, HBA 5, HBD 2, PSA 92.62, QED 0.35
Compound (SMILES): COc1ccccc1CNc1nc(N)c2nc(-c3cccs3)sc2n1
InChIKey: VRCYNPYVXJBCSE-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human adenosine A1 receptor expressed in CHO cell membranes measured after 90 mins by scintillation counting method
Measurement: Ki = 17.3 nM (pChEMBL 7.760000228881836)
Descriptors: MW 369.48, ALogP 4.02, HBA 8, HBD 2, PSA 85.95, QED 0.55
Compound (SMILES): CCOCc1cn(-c2ccc(Cl)cc2)nn1
InChIKey: FJULFFCNBYKZJR-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at P2X7 receptor in LPS/IFNc-differentiated human THP-1 cells assessed as inhibition of ATP-induced IL-1beta release preincubated for 30 mins followed by LPS stimulation for 4 hrs using cells treated with ATP for 30 mins by ELISA
Measurement: IC50 = 67.46 nM (pChEMBL 7.170000076293945)
Descriptors: MW 237.69, ALogP 2.46, HBA 4, HBD 0, PSA 39.94, QED 0.82
Compound (SMILES): CC(=O)OCCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1Cl
InChIKey: ZYZYGWWRCWBUMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant N-terminal His6-tagged human carbonic anhydrase 5B (40 to 317 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 667 nM (pChEMBL 6.179999828338623)
Descriptors: MW 369.23, ALogP 1.32, HBA 5, HBD 2, PSA 115.56, QED 0.58
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIKDFTWWPULYOJ-FBYJCYDQSA-N
Target: Chymotrypsinogen A (SINGLE PROTEIN), Bos taurus
UniProt: P00766
Assay: Inhibition of bovine alpha-chymotrypsin using Suc-AAPF-MCA as substrate measured every 30 secs for 10 mins
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1457.7
Compound (SMILES): CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)c1c(N2CCCC2)c2ccccc2n(C)c1=O
InChIKey: MCDADOMPEINVRO-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 511.47, ALogP 5.45, HBA 4, HBD 0, PSA 45.55, QED 0.44
Compound (SMILES): COc1cc2ccn(CCOc3cccc(NC(=O)CCCCCCC(=O)NO)c3)c2c(OC)c1OC
InChIKey: SFICPVORFVXNPV-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of full length recombinant human HDAC5 preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.59, ALogP 4.53, HBA 8, HBD 3, PSA 120.28, QED 0.16
Compound (SMILES): COc1cc2c(NC3CCN(C(C)C)CC3)cc(C3CCCCC3)nc2cc1OCCCN1CCCC1
InChIKey: FQOJFAZVDGPADJ-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Non-competitive inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of 1 to 20 uM SAM by TR-FRET assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 508.75, ALogP 6.44, HBA 6, HBD 1, PSA 49.86, QED 0.37
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCc1cccc(NC(=O)c2ccccc2C(F)(F)F)c1)C(=O)O
InChIKey: RSBUOFNPLDYKRF-GJZGRUSLSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 85.11 nM (pChEMBL 7.070000171661377)
Descriptors: MW 426.35, ALogP 2.34, HBA 5, HBD 4, PSA 138.95, QED 0.51
Compound (SMILES): O=C1NC(SCc2ccc(Br)cc2)=N/C1=C\c1cccc(OCc2ccc(Cl)cc2)c1
InChIKey: YLXIWUKAIUBJCQ-XKZIYDEJSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in CHO cell membranes after 2 hrs by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 513.84, ALogP 6.44, HBA 4, HBD 1, PSA 50.69, QED 0.39
Compound (SMILES): COc1ccncc1-c1ccc(CN)o1.Cl.Cl
InChIKey: MQUODVTXNIMMFG-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using omeprazole as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 204.23, ALogP 1.81, HBA 4, HBD 1, PSA 61.28, QED 0.83
Compound (SMILES): COCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1NC1CCCCC1
InChIKey: NKYZAALBVOKIMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant N-terminal His6-tagged human carbonic anhydrase 6 (21 to 290 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 10000 nM (pChEMBL 5)
Descriptors: MW 389.91, ALogP 2.11, HBA 5, HBD 3, PSA 110.52, QED 0.62
Compound (SMILES): Cn1ncc2c1Nc1ccccc1N(C(=O)Cc1cccc(N3CCN(Cc4cc(O)cc(O)c4)CC3)c1)C2
InChIKey: DJFQESWUILRMGI-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human vasopressin V1a receptor expressed in HEK293 cells assessed as inhibition of vasopressin-induced IP1 accumulation preincubated for 30 mins followed by vasopressin addition measured after 1 hr by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.63, ALogP 3.99, HBA 8, HBD 3, PSA 97.1, QED 0.36
Compound (SMILES): COc1cc(CN2CCN(c3cccc(CC(=O)N4Cc5cnn(C)c5Nc5ccccc54)c3)CC2)cc(OC)c1
InChIKey: RBRWJVWZCSSBLU-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human vasopressin V1a receptor expressed in HEK293 cells assessed as inhibition of vasopressin-induced IP1 accumulation preincubated for 30 mins followed by vasopressin addition measured after 1 hr by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 552.68, ALogP 4.59, HBA 8, HBD 1, PSA 75.1, QED 0.36
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(N(CC)c3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: PZPWWBWBYANFAR-UPRLRBBYSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/duck/Guangdong/674/2014(H5N6)) neuraminidase activity using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 to 60 mins by chemiluminescence assay
Measurement: IC50 = 24803.33 nM (pChEMBL 4.610000133514404)
Descriptors: MW 493.65, ALogP 4.8, HBA 5, HBD 3, PSA 90.9, QED 0.39
Compound (SMILES): CNCC(O)COc1ccc(S(=O)(=O)NCCc2ccccc2)cc1.Cl
InChIKey: YJUPYTQXWFAGCC-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]-CGP12177 from human beta2 ADR expressed in HEK293T cell membrane after 90 mins by scintillation counting
Measurement: Ki = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 364.47, ALogP 1.17, HBA 5, HBD 3, PSA 87.66, QED 0.59
Compound (SMILES): CC(C)[C@@H](NC(=O)c1ccc(-c2ccc(CSc3nc4c(c(=O)[nH]3)CCC4)c(F)c2)o1)C(=O)NC1CNC1
InChIKey: RCRISLYXLQPSRM-HSZRJFAPSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human MMP14 expressed in Escherichia coli using fTHP-15 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 539.63, ALogP 2.79, HBA 7, HBD 4, PSA 129.12, QED 0.24
Compound (SMILES): Nc1nc(NCCc2cccnc2)nc2sc(-c3ccco3)nc12
InChIKey: XFDJFLKGEUUOAG-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human adenosine A1 receptor expressed in CHO cell membranes measured after 90 mins by scintillation counting method
Measurement: Ki = 2.61 nM (pChEMBL 8.579999923706055)
Descriptors: MW 338.4, ALogP 2.98, HBA 8, HBD 2, PSA 102.75, QED 0.58
Compound (SMILES): O=C(O)CNC(=O)c1ncc(C#CCOc2ccc(Cl)cc2)cc1O
InChIKey: AIKDJELJHUPYNG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using phenacetin as substrate preincubated for 5 mins followed by addition of NADPH measured after 20 mins by LC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 360.75, ALogP 1.69, HBA 5, HBD 3, PSA 108.75, QED 0.7
Compound (SMILES): COc1ccc(F)c(-c2ccc(C3CCc4ccc([C@H](C5CC5)[C@H](C)C(=O)[O-])cc4O3)nc2)c1.[Na+]
InChIKey: URVJPHDSDQPGJZ-UCXMRBTASA-M
Target: Bile salt export pump (SINGLE PROTEIN), Homo sapiens
UniProt: O95342
Assay: Inhibition of human BSEP expressed in baculovirus infected Sf9 insect cell membrane vesicles assessed as reduction in ATP-dependent [3H]-taurocholic acid uptake
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 461.53, ALogP 6.18, HBA 4, HBD 1, PSA 68.65, QED 0.46
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Cl)s4)ccc3o2)cc1)c1ccc(Cl)s1
InChIKey: GIIMHZLVJHKFRO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 586.53, ALogP 6.53, HBA 8, HBD 2, PSA 118.37, QED 0.22
Compound (SMILES): Cc1nnn2c1-c1ccccc1N(c1ccc(Cl)cc1)CC2CCO
InChIKey: PBZMPCXVZAPRES-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding Assay: BRD binding and inhibition was assessed by measuring the interaction of biotinylated acetyl-histone H4 peptide (Anaspec #64989) with the BRD target protein utilising AlphaScreen® technology (Perkin Elmer). In a white 384-well low volume plate (Greiner #784076), 100 nL of compound series in DMSO (0.5% final concentration) was added to the BRD target protein (80 nM final). After 30 min incubation at RT, H4 peptide was added to a final concentration of 2.5 nM. AlphaScreen streptavidin donor beads and AlphaScreen nickel chelate acceptor beads were added to a final concentration of 10 ug/mL each and allowed to incubate in a darkened environment for 1 h at RT. Plates were read on an EnVision plate reader (Perkin Elmer) and IC50's calculated using a four parameter non-linear curve fit.These conditions are identical for all BRDs screened except BRD2D2 which uses 160 nM protein and 1.25 nM peptide.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 354.84, ALogP 3.98, HBA 5, HBD 1, PSA 54.18, QED 0.77
Compound (SMILES): Cc1nnn2c1-c1ccc(C(=O)N[C@@H](C)c3ccccc3)cc1N(c1ccc(Cl)cc1)CC2
InChIKey: FBYKSRDDFYPNNO-KRWDZBQOSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding Assay: BRD binding and inhibition was assessed by measuring the interaction of biotinylated acetyl-histone H4 peptide (Anaspec #64989) with the BRD target protein utilising AlphaScreen® technology (Perkin Elmer). In a white 384-well low volume plate (Greiner #784076), 100 nL of compound series in DMSO (0.5% final concentration) was added to the BRD target protein (80 nM final). After 30 min incubation at RT, H4 peptide was added to a final concentration of 2.5 nM. AlphaScreen streptavidin donor beads and AlphaScreen nickel chelate acceptor beads were added to a final concentration of 10 ug/mL each and allowed to incubate in a darkened environment for 1 h at RT. Plates were read on an EnVision plate reader (Perkin Elmer) and IC50's calculated using a four parameter non-linear curve fit.These conditions are identical for all BRDs screened except BRD2D2 which uses 160 nM protein and 1.25 nM peptide.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 457.97, ALogP 5.55, HBA 5, HBD 1, PSA 63.05, QED 0.44
Compound (SMILES): CCC(C)NCC(O)COc1ccc(C(=O)NCCc2ccc(S(N)(=O)=O)cc2)cc1.Cl
InChIKey: HCFVUMHBJGFRDI-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]-CGP12177 from human beta2 ADR expressed in HEK293T cell membrane after 90 mins by scintillation counting
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 449.57, ALogP 1.43, HBA 6, HBD 4, PSA 130.75, QED 0.39
Compound (SMILES): CN(C)c1ccc([C@H]2C[C@@]3(C)[C@@H](CC[C@@]3(O)C#CC(C)(C)C)[C@@H]3CCC4=CC(=O)CCC4=C32)cc1
InChIKey: MKYOYWSMPLRHDW-SSKMXYOESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using midazolam as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 471.69, ALogP 6.43, HBA 3, HBD 1, PSA 40.54, QED 0.51
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)OC(=O)[C@H](Cc1ccccc1)N(C)C)C(=O)N[C@@H](C)C(=O)N(C)[C@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OC
InChIKey: FVCUETVFTFPUEO-CHLGYZHBSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of cathepsin D in human MDA-MB-231 cells using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 4 hrs followed by compound washout and subsequent 10 mins trypsinization prior to substrate addition measured at 30 secs interval for 30 mins by fluorescence assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 1134.43
Compound (SMILES): O=C1/C(=C/c2cccc(OCCCCCCOc3ccccc3Cl)c2)N=C2SCCCN12
InChIKey: RERCLTVAGBXAHI-PYCFMQQDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in CHO cell membranes after 2 hrs by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 471.02, ALogP 6.03, HBA 5, HBD 0, PSA 51.13, QED 0.31
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCc1cccs1)C(=O)O
InChIKey: JMKFNKYDQCSAJT-BQBZGAKWSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 776.25 nM (pChEMBL 6.110000133514404)
Descriptors: MW 245.26, ALogP 0.13, HBA 5, HBD 3, PSA 109.85, QED 0.66
Compound (SMILES): O=C(O)c1nc2ccccc2nc1Nc1ccc(O)cc1
InChIKey: OVFXYHHZLWWAJN-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of recombinant mouse CLK1 expressed in bacterial expression system using GRSRSRSRSRSR as substrate after 30 mins by ADP-Glo reagent based luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 281.27, ALogP 2.78, HBA 5, HBD 3, PSA 95.34, QED 0.64
Compound (SMILES): CCS(=O)(=O)c1ccc(C(NC(C)=O)C(=O)Nc2cc(-c3cc(C#N)cnc3OCC(F)(F)F)cs2)cc1
InChIKey: QQIBJFMXQBDPGQ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Displacement of [3H]ATRA from 6H-AVI-GST-TEV-human RORbeta (T221 to K470 residues) pre-incubated for 30 mins before [3H]ATRA addition and measurted ater 18 to 23 hrs by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 566.58, ALogP 4.23, HBA 8, HBD 2, PSA 138.25, QED 0.4
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2cc(-c3cccnc3OCc3ccc(OC(F)(F)F)cc3)cs2)cc1
InChIKey: XSLQEOSGBAUMSK-UHFFFAOYSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Displacement of [3H]ATRA from 6H-AVI-GST-TEV-human RORbeta (T221 to K470 residues) pre-incubated for 30 mins before [3H]ATRA addition and measurted ater 18 to 23 hrs by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.62, ALogP 6.26, HBA 7, HBD 1, PSA 94.59, QED 0.24
Compound (SMILES): COc1ccc(N2CCc3ncnc(-c4cccc(OC5CCN(C(C)=O)CC5)c4)c3C2)cn1
InChIKey: ZXFIIJCCESEKPZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of recombinant human myristoylated PI3Kbeta catalytic domain expressed in Rat1 cells assessed as reduction in Akt phosphorylation at Ser47 residue after 1 hr by alpha screen Surefire assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.55, ALogP 3.5, HBA 7, HBD 0, PSA 80.68, QED 0.58
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc2c(c1)B(O)OC2
InChIKey: HAEGPUNQGVPWAR-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase-2 incubated for 15 mins prior to testing by stopped flow CO2 hydrase assay
Measurement: Ki = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 268.08
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(N(C)c3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: FPBTZJZYQQHCSK-OYUWMTPXSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/duck/Guangdong/674/2014(H5N6)) neuraminidase activity using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 to 60 mins by chemiluminescence assay
Measurement: IC50 = 224.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 479.62, ALogP 4.41, HBA 5, HBD 3, PSA 90.9, QED 0.44
Compound (SMILES): CN1CCN(c2ccc3c(c2)CN(C(=O)OCc2ccccc2)C3)CC1
InChIKey: UETLZTFBKJSNHG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting method
Measurement: Ki = 1023 nM (pChEMBL 5.989999771118164)
Descriptors: MW 351.45, ALogP 3.09, HBA 4, HBD 0, PSA 36.02, QED 0.85
Compound (SMILES): O=C(Nc1cc(-c2cccc3[nH]ccc23)cc2[nH]ncc12)C1CC1
InChIKey: NREOZWPOBWZLGL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate pretreated for 15 mins followed by substrate addition measured after 1 hr
Measurement: IC50 > 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 316.36, ALogP 4.06, HBA 2, HBD 3, PSA 73.57, QED 0.53
Compound (SMILES): CSC1=NC(=O)/C(=C/c2cccc(OCc3ccc(Cl)cc3)c2)N1
InChIKey: WQJGSVBTMYODME-YBEGLDIGSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in CHO cell membranes after 2 hrs by liquid scintillation counting method
Measurement: Ki = 591 nM (pChEMBL 6.230000019073486)
Descriptors: MW 358.85, ALogP 4.11, HBA 4, HBD 1, PSA 50.69, QED 0.84
Compound (SMILES): CCCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1NCc1ccccc1
InChIKey: CFAJZNAOOOFZDC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 (38 to 414 residues) expressed in 293-F cells in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 395.91, ALogP 3.13, HBA 4, HBD 3, PSA 101.29, QED 0.6
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCC1CCCCCC1)C(=O)O
InChIKey: YLILOIOKZOPYFJ-UWVGGRQHSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 2454.71 nM (pChEMBL 5.610000133514404)
Descriptors: MW 259.3, ALogP 0.84, HBA 4, HBD 3, PSA 109.85, QED 0.61
Compound (SMILES): COCC[Se]c1ccc(S(N)(=O)=O)cc1
InChIKey: WKTOCKPZCRWEKV-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human carbonic anhydrase 7 after 15 mins by stopped flow carbon dioxide hydration assay
Measurement: Ki = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 294.23
Compound (SMILES): CNCC(O)COc1ccc(S(=O)(=O)NC(C)C(C)C)cc1.Cl
InChIKey: XVHCDHLPPDVXOB-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]-CGP12177 from human beta2 ADR expressed in HEK293T cell membrane after 90 mins by scintillation counting
Measurement: Ki = 30199.52 nM (pChEMBL 4.519999980926514)
Descriptors: MW 330.45, ALogP 0.97, HBA 5, HBD 3, PSA 87.66, QED 0.63
Compound (SMILES): O=C(CCCCCCN(Cc1ccc(F)cc1)c1ncc(C(=O)NCCCn2ccnc2)s1)NO
InChIKey: WSTLKKSKCYMNAA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full length C-terminal flag-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells after 30 mins by fluorescence assay
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 502.62, ALogP 3.76, HBA 8, HBD 3, PSA 112.38, QED 0.17
Compound (SMILES): Cl.Cl.NCC#Cc1cnccc1-c1ccco1
InChIKey: DXLWXWLMWIUUCI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using omeprazole as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 198.22, ALogP 1.65, HBA 3, HBD 1, PSA 52.05, QED 0.71
Compound (SMILES): NCC1CC1CN(C[C@H]1Cc2ccccc2CN1)[C@H]1CCCc2cccnc21
InChIKey: ZKWKKAVOVBLNQA-HDJSHQJTSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 expressed in insect microsomes using AMMC as substrate preincubated for 30 mins followed by NADPH addition measured after 45 mins by fluorescence assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 376.55, ALogP 3.07, HBA 4, HBD 2, PSA 54.18, QED 0.81
Compound (SMILES): Cc1ccnc(OCc2ccc(F)cc2)c1C(=O)NC1CCCCCC1
InChIKey: FQBDLLQDJPGLMU-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL in human U937 cells using 2-OG containing [glycerol-1,2,3-3H]AEA as substrate preincubated for 30 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 356.44, ALogP 4.56, HBA 3, HBD 1, PSA 51.22, QED 0.8
Compound (SMILES): O=C(O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)n(C2CCCCC2)c1=O
InChIKey: NVTKJBXOBFRPLQ-UHFFFAOYSA-N
Target: Methylcytosine dioxygenase TET1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NFU7
Assay: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 393.44, ALogP 1.54, HBA 7, HBD 3, PSA 130.63, QED 0.7
Compound (SMILES): O=C(NC1CCCCCC1)c1c(-c2ccccc2)ccn(Cc2ccc(F)cc2)c1=O
InChIKey: XFCFHDRWNFQOJT-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in HEK293 cells using 2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.51, ALogP 5.16, HBA 3, HBD 1, PSA 51.1, QED 0.58
Compound (SMILES): Cc1nc2c(c(Nc3c[nH]nc3C(=O)Nc3ccc(N4CCNCC4)cc3)n1)CCC2
InChIKey: DXUDRTZDTCQOLU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 F594_R595insR mutant by Hotspot assay
Measurement: IC50 = 6.97 nM (pChEMBL 8.15999984741211)
Descriptors: MW 418.51, ALogP 2.4, HBA 7, HBD 4, PSA 110.86, QED 0.5
Compound (SMILES): COc1ccc2c(c1)c(C(=O)Nc1cc(C(=O)O)cc(-c3cnn(C)c3)c1)cn2C(C)=O
InChIKey: GMINUTRRQLVDKN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Inhibition of biotinylated-H4KAc4 binding to human His6-tagged BRD9 (L14 to Q134 residues) expressed in Escherichia coli BL21(DE3) after 2.5 hrs by luminescence-based AlphaScreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 432.44, ALogP 3.66, HBA 7, HBD 2, PSA 115.45, QED 0.5
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-MOVYNIQHSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of human recombinant CDK12/CyclinK assessed as reduction in substrate phosphorylation using His-c-Myc as substrate preincubated with enzyme for 5 mins followed by substrate addition for 15 mins in presence of [gamma 32P-ATP] by radioactive kinase assay
Measurement: IC50 = 482.6 nM (pChEMBL 6.320000171661377)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3c(C)[nH]c4ccccc34)c12
InChIKey: ONTCKBVHGQBHTF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 437.5, ALogP 6.16, HBA 5, HBD 2, PSA 92.62, QED 0.35
Compound (SMILES): CCOCc1cn(-c2ccc(Cl)cc2)nn1
InChIKey: FJULFFCNBYKZJR-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z1M0
Assay: Antagonist activity at P2X7 receptor in LPS/IFNc-differentiated Swiss mouse peritoneal macrophages assessed as inhibition of ATP-induced IL-1beta release preincubated for 30 mins followed by LPS stimulation for 4 hrs using cells treated with ATP for 15 mins by ELISA
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 237.69, ALogP 2.46, HBA 4, HBD 0, PSA 39.94, QED 0.82
Compound (SMILES): CC(=O)OCCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1Cl
InChIKey: ZYZYGWWRCWBUMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant N-terminal His6-tagged human carbonic anhydrase 6 (21 to 290 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 1180 nM (pChEMBL 5.929999828338623)
Descriptors: MW 369.23, ALogP 1.32, HBA 5, HBD 2, PSA 115.56, QED 0.58
Compound (SMILES): COc1cc2ccn(CCOc3cccc(NC(=O)CCCCCCC(=O)NO)c3)c2c(OC)c1OC
InChIKey: SFICPVORFVXNPV-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of N-terminal GST-tagged human HDAC7 expressed in baculovirus infected Sf9 insect cells preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.59, ALogP 4.53, HBA 8, HBD 3, PSA 120.28, QED 0.16
Compound (SMILES): COc1cc2c(NC3CCN(C(C)C)CC3)cc(C3CCCCC3)nc2cc1OCCCN1CCCC1
InChIKey: FQOJFAZVDGPADJ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of recombinant human GLP using histone H3 peptide as substrate after 120 mins in presence of [3H]SAM by radiometric assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 508.75, ALogP 6.44, HBA 6, HBD 1, PSA 49.86, QED 0.37
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCc1cccc(NC(=O)c2ccccc2C(F)(F)F)c1)C(=O)O
InChIKey: RSBUOFNPLDYKRF-GJZGRUSLSA-N
Target: Excitatory amino acid transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P43005
Assay: Inhibition of human EAAT3 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 524.81 nM (pChEMBL 6.28000020980835)
Descriptors: MW 426.35, ALogP 2.34, HBA 5, HBD 4, PSA 138.95, QED 0.51
Compound (SMILES): COc1ccncc1-c1ccc(CN)o1.Cl.Cl
InChIKey: MQUODVTXNIMMFG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 204.23, ALogP 1.81, HBA 4, HBD 1, PSA 61.28, QED 0.83
Compound (SMILES): COCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1NC1CCCCC1
InChIKey: NKYZAALBVOKIMZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant N-terminal His-tagged human carbonic anhydrase 7 (3 to 264 residues) expressed in Escherichia coli BL21 (DE3) strain in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 2860 nM (pChEMBL 5.539999961853027)
Descriptors: MW 389.91, ALogP 2.11, HBA 5, HBD 3, PSA 110.52, QED 0.62
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(N(CC)c3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: PZPWWBWBYANFAR-UPRLRBBYSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/goose/Jiangsu/1306/2014(H5N8)) neuraminidase activity using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 to 60 mins by chemiluminescence assay
Measurement: IC50 = 817.37 nM (pChEMBL 6.090000152587891)
Descriptors: MW 493.65, ALogP 4.8, HBA 5, HBD 3, PSA 90.9, QED 0.39
Compound (SMILES): O=C(O)CNC(=O)c1ncc(C#CCOc2ccc(Cl)cc2)cc1O
InChIKey: AIKDJELJHUPYNG-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of FITC-HIF1alpha (556 to 574 residues) binding to PHD2 (181 to 426 residues) (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 64.2 nM (pChEMBL 7.190000057220459)
Descriptors: MW 360.75, ALogP 1.69, HBA 5, HBD 3, PSA 108.75, QED 0.7
Compound (SMILES): COc1ccc(F)c(-c2ccc(C3CCc4ccc([C@H](C5CC5)[C@H](C)C(=O)[O-])cc4O3)nc2)c1.[Na+]
InChIKey: URVJPHDSDQPGJZ-UCXMRBTASA-M
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at GPR120 (unknown origin)
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 461.53, ALogP 6.18, HBA 4, HBD 1, PSA 68.65, QED 0.46
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Cl)s4)ccc3o2)cc1)c1ccc(Cl)s1
InChIKey: GIIMHZLVJHKFRO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 586.53, ALogP 6.53, HBA 8, HBD 2, PSA 118.37, QED 0.22
Compound (SMILES): Cc1nnn2c1-c1ccccc1N(c1ccc(Cl)cc1)CC2CCO
InChIKey: PBZMPCXVZAPRES-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding Assay: BRD binding and inhibition was assessed by measuring the interaction of biotinylated acetyl-histone H4 peptide (Anaspec #64989) with the BRD target protein utilising AlphaScreen® technology (Perkin Elmer). In a white 384-well low volume plate (Greiner #784076), 100 nL of compound series in DMSO (0.5% final concentration) was added to the BRD target protein (80 nM final). After 30 min incubation at RT, H4 peptide was added to a final concentration of 2.5 nM. AlphaScreen streptavidin donor beads and AlphaScreen nickel chelate acceptor beads were added to a final concentration of 10 ug/mL each and allowed to incubate in a darkened environment for 1 h at RT. Plates were read on an EnVision plate reader (Perkin Elmer) and IC50's calculated using a four parameter non-linear curve fit.These conditions are identical for all BRDs screened except BRD2D2 which uses 160 nM protein and 1.25 nM peptide.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 354.84, ALogP 3.98, HBA 5, HBD 1, PSA 54.18, QED 0.77
Compound (SMILES): CN(C)c1ccc([C@H]2C[C@@]3(C)[C@@H](CC[C@@]3(O)C#CC(C)(C)C)[C@@H]3CCC4=CC(=O)CCC4=C32)cc1
InChIKey: MKYOYWSMPLRHDW-SSKMXYOESA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: In Vitro GR Luciferase Reporter Assay: Cell Line: CHO-K1-GR-MMTV-Luc reporter cellsCulture Media: DMEM (with phenol red)+10% FBSAssay Media: DMEM (without phenol red)+10% CSSCulture CHO-K1-GR-MMTV-Luc reporter cells in 15 cm plates in Culture Media at conditions less than 90% confluence.Prepare 200×DMSO 1:5 serial dilutions of control and test compounds in 96-well non-sterile V bottom plate in DMSO, 8 serial dilutions for each compound.Prepare 5× Assay Media diluted compound serial dilutions in 96-well non-sterile V bottom plate: Add 97.5 uL/well of Assay Media into 96-well then add 2.5 ul of 200× concentration of compounds and mix well.Seed cells for Antagonist Assay: 1.5×106 CHO-K1-GR-MMTV-Luc reporter cells were seeded in a Corning 3707 flat clear bottom 384-well white TC plate in 20 ul of Assay Media containing 12.5 nM Dexamethasone (final concentration=10 nM).Add compounds: 5 ul of assay media diluted compounds were added to appropriate wells and followed a quick spin (1000 rpm, 10 sec) to bring media and cells to the bottom of plate. The plates were covered with SealMate film to avoid evaporation and placed in 37° C. incubator for approximately 18-24 hours.Read plates: Equilibrate appropriate amount of Promega OneGlo luciferase reagent to room temperature. Remove the plates from incubator and add 25 uL of OneGlo reagent/well by multiple channel pipette and read the plates with Tecan F500 luminometer within 3 minutes.The ability of the compounds disclosed herein to inhibit GR activity was quantified and the respective IC50 value was determined.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 471.69, ALogP 6.43, HBA 3, HBD 1, PSA 40.54, QED 0.51
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)N(C)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)OC(=O)[C@H](Cc1ccccc1)N(C)C)C(=O)N[C@@H](C)C(=O)N(C)[C@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OC
InChIKey: FVCUETVFTFPUEO-CHLGYZHBSA-N
Target: Cathepsin E (SINGLE PROTEIN), Homo sapiens
UniProt: P14091
Assay: Inhibition of cathepsin E in human MDA-MB-231 cells using Mca-Gly-Lys-Pro-Ile-Leu-PhePhe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate pretreated for 4 hrs followed by compound washout and subsequent 10 mins trypsinization prior to substrate addition measured at 30 secs interval for 30 mins by fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 1134.43
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCc1cccs1)C(=O)O
InChIKey: JMKFNKYDQCSAJT-BQBZGAKWSA-N
Target: Excitatory amino acid transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P43005
Assay: Inhibition of human EAAT3 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 1174.9 nM (pChEMBL 5.929999828338623)
Descriptors: MW 245.26, ALogP 0.13, HBA 5, HBD 3, PSA 109.85, QED 0.66
Compound (SMILES): COc1ccc(N2CCc3ncnc(-c4cccc(OC5CCN(C(C)=O)CC5)c4)c3C2)cn1
InChIKey: ZXFIIJCCESEKPZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human myristoylated PI3Kdelta catalytic domain expressed in Rat1 cells assessed as reduction in Akt phosphorylation at Ser47 residue after 1 hr by alpha screen Surefire assay
Measurement: IC50 = 374 nM (pChEMBL 6.429999828338623)
Descriptors: MW 459.55, ALogP 3.5, HBA 7, HBD 0, PSA 80.68, QED 0.58
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc2c(c1)B(O)OC2
InChIKey: HAEGPUNQGVPWAR-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of full length DENV2 NS2B-NS3 protease in human HeLa cells expressing luciferase reporter gene incubated for 24 hrs by luminescence analysis
Measurement: EC50 = 22500 nM (pChEMBL 4.650000095367432)
Descriptors: MW 268.08
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(N(C)c3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: FPBTZJZYQQHCSK-OYUWMTPXSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/goose/Jiangsu/1306/2014(H5N8)) neuraminidase activity using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 to 60 mins by chemiluminescence assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 479.62, ALogP 4.41, HBA 5, HBD 3, PSA 90.9, QED 0.44
Compound (SMILES): CN1CCN(c2ccc3c(c2)CN(C(=O)OCc2ccccc2)C3)CC1
InChIKey: UETLZTFBKJSNHG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in stable HEK cells after 90 mins by microbeta scintillation counting method
Measurement: Ki = 1117 nM (pChEMBL 5.949999809265137)
Descriptors: MW 351.45, ALogP 3.09, HBA 4, HBD 0, PSA 36.02, QED 0.85
Compound (SMILES): CCCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1NCc1ccccc1
InChIKey: CFAJZNAOOOFZDC-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 (30 to 291 residues) expressed in Escherichia coli Rosetta 2 (DE3) strain in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 333 nM (pChEMBL 6.480000019073486)
Descriptors: MW 395.91, ALogP 3.13, HBA 4, HBD 3, PSA 101.29, QED 0.6
Compound (SMILES): N[C@H](C(=O)O)[C@H](OCC1CCCCCC1)C(=O)O
InChIKey: YLILOIOKZOPYFJ-UWVGGRQHSA-N
Target: Excitatory amino acid transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P43005
Assay: Inhibition of human EAAT3 expressed in HEK293 cells assessed as reduction in [3H]-D-Asp uptake incubated for 4 mins by scintillation counting method
Measurement: IC50 = 10471.29 nM (pChEMBL 4.980000019073486)
Descriptors: MW 259.3, ALogP 0.84, HBA 4, HBD 3, PSA 109.85, QED 0.61
Compound (SMILES): O=C(CCCCCCN(Cc1ccc(F)cc1)c1ncc(C(=O)NCCCn2ccnc2)s1)NO
InChIKey: WSTLKKSKCYMNAA-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in baculovirus infected Sf9 insect cells after 30 mins by fluorescence assay
Measurement: IC50 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 502.62, ALogP 3.76, HBA 8, HBD 3, PSA 112.38, QED 0.17
Compound (SMILES): Cl.Cl.NCC#Cc1cnccc1-c1ccco1
InChIKey: DXLWXWLMWIUUCI-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 198.22, ALogP 1.65, HBA 3, HBD 1, PSA 52.05, QED 0.71
Compound (SMILES): NCC1CC1CN(C[C@H]1Cc2ccccc2CN1)[C@H]1CCCc2cccnc21
InChIKey: ZKWKKAVOVBLNQA-HDJSHQJTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 376.55, ALogP 3.07, HBA 4, HBD 2, PSA 54.18, QED 0.81