lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1Nc2ccccc2C12CCN(CCN1CCN(c3ccccc3Cl)CC1)C2
InChIKey: MURZWGBCAWAQPT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK293 cell membranes after 1 hr at 37 degC by microbeta scintillation counting analysis
Measurement: Ki = 2843 nM (pChEMBL 5.550000190734863)
Descriptors: MW 410.95, ALogP 3.06, HBA 4, HBD 1, PSA 38.82, QED 0.84
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N)=O)C(C)C)[C@@H](C)O)[C@@H](C)CC
InChIKey: FPZHKUJVULNIRM-VETPPHEUSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 1080.34
Compound (SMILES): O=C(C[Se]c1ccccc1)Nc1c2c(nc3ccccc13)CCCC2
InChIKey: WKOIAZMVZIDTSH-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Mixed-type inhibition of electric eel AChE assessed as enzyme-inhibitor complex using p-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 8420 nM (pChEMBL 5.079999923706055)
Descriptors: MW 395.36
Compound (SMILES): Cc1cccc(-c2nc(Nc3ccncc3F)c3nc[nH]c3n2)n1
InChIKey: VTTVMOPKTBXKIB-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 321.32, ALogP 3, HBA 6, HBD 2, PSA 92.27, QED 0.6
Compound (SMILES): O=C(CCCCN1CCc2ccccc2C1c1ccccc1)NO
InChIKey: RREMAKLSNSMREF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 324.42, ALogP 3.31, HBA 3, HBD 2, PSA 52.57, QED 0.49
Compound (SMILES): CCS(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: CQRYWERSRKWMMT-AWEZNQCLSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.5, ALogP 4.29, HBA 6, HBD 0, PSA 81.5, QED 0.46
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(N)=O)c1
InChIKey: LWAKAHVTROSPCV-BSNUEQINSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 1234.6
Compound (SMILES): COc1ccccc1N1CCN(CCCOc2ccc(C)cc2C)CC1.Cl
InChIKey: KLUFPWHPNQQEIE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from recombinant human 5-HT6 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 354.49, ALogP 3.9, HBA 4, HBD 0, PSA 24.94, QED 0.7
Compound (SMILES): O=C(c1ccc(-c2cn3c(-c4ccc(O)cc4)cnc3cn2)cc1)N1CCOCC1
InChIKey: FXUCGEVPOQUSIH-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of GST-tagged MNK1 (37 to 341 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 400.44, ALogP 3.24, HBA 6, HBD 1, PSA 79.96, QED 0.57
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: IMHRKTSTOJYVSH-UBLLTGQXSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation measured after 3 mins
Measurement: EC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 866, ALogP -0.69, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): C[C@]12CC[C@H](O)C[C@@H]1C(=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChIKey: HMDPWEPMYLOZBE-ZLFVCLNVSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of C-terminal His-tagged recombinant human CYP17A1delta19H mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method
Measurement: IC50 = 12.4 nM (pChEMBL 7.909999847412109)
Descriptors: MW 365.52, ALogP 4.66, HBA 3, HBD 1, PSA 50.19, QED 0.79
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1CCC1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: JEJHTOLHMDLNMD-UFWKXQSMSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 8040 nM (pChEMBL 5.090000152587891)
Descriptors: MW 833.08, ALogP 0.82, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3cccc4cnccc34)c12
InChIKey: SSNBPEAGTWHUEY-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 435.49, ALogP 5.92, HBA 6, HBD 1, PSA 89.72, QED 0.37
Compound (SMILES): C[C@]12CC[C@H](O)CC1=C(C#N)C[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChIKey: XMYHDPOWFDNIDA-SQRYLOHGSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of C-terminal His-tagged recombinant human CYP17A1delta19H mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method
Measurement: IC50 = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 374.53, ALogP 5.29, HBA 3, HBD 1, PSA 56.91, QED 0.73
Compound (SMILES): Oc1ccccc1C1=NC(Cc2c[nH]cn2)C(c2ccccc2)S1
InChIKey: BDLSNMGOWYNTSL-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 HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 335.43, ALogP 3.96, HBA 4, HBD 2, PSA 61.27, QED 0.76
Compound (SMILES): COc1nc2ccc(C(O)c3cnnn3C)cc2c(Cl)c1Cc1ccc(-n2cccn2)cc1
InChIKey: QBBUJKOOLHBXRX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4 DBD-fused wild type human RORgammat LBD (850 to 1635 residues) expressed in HEK293T cells assessed as inhibition of transcriptional activity after 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 460.93, ALogP 3.88, HBA 8, HBD 1, PSA 90.88, QED 0.41
Compound (SMILES): C[C@H]1C[C@H]2CSC(N)=N[C@@]2(c2ccccc2C(F)(F)F)CO1
InChIKey: UASXOTVJCSRYMT-BHDSKKPTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells for 5 mins at -80 mV holding potential by patch clamp method
Measurement: IC50 = 55400 nM (pChEMBL 4.260000228881836)
Descriptors: MW 330.38, ALogP 3.39, HBA 4, HBD 1, PSA 47.61, QED 0.86
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=[Se])Nc2ccccc2F)cc1
InChIKey: LTFOMIRKXUJVML-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 catalytic domain preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 400.34
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4ccc5nc6n(c5c4)C(C)(C)CC6)n3)nc2)CC1
InChIKey: JLIDFAZKTWWWCN-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 500.63, ALogP 4.59, HBA 8, HBD 1, PSA 75, QED 0.42
Compound (SMILES): CNC(=O)c1cc(OCCCCN2CCC(c3noc4cc(F)ccc34)CC2)ccn1
InChIKey: UWPUFUJRTFJLEP-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonistic activity at alpha-1A adrenergic receptor (unknown origin) after 10 mins by FLIPR assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 426.49, ALogP 3.76, HBA 6, HBD 1, PSA 80.49, QED 0.55
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ncnc(-c3c(C)[nH]c4cnccc34)c12
InChIKey: PXCMCMUXYPGWLG-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 424.46, ALogP 5.24, HBA 6, HBD 2, PSA 105.51, QED 0.4
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)nc3)nn(Cc3cn(Cc4ccccc4)nn3)c2n1
InChIKey: USPKFTCYXHJXCN-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of wild-type human partial length VEGFR2 (R787 to P1253 residues) expressed in mammalian expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.57, ALogP 2.03, HBA 11, HBD 2, PSA 114.5, QED 0.36
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(C3CCCC3)nc2C1)C(F)(F)F
InChIKey: DSCZITNNZITYPG-ZDUSSCGKSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.42, ALogP 4.36, HBA 5, HBD 0, PSA 71.15, QED 0.74
Compound (SMILES): COc1cc2c(cc1OC)Nc1ncnc(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)c1NC2
InChIKey: BWXISLRRARTIGU-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET (unknown origin)
Measurement: IC50 = 162.8 nM (pChEMBL 6.789999961853027)
Descriptors: MW 588.57, ALogP 5.59, HBA 9, HBD 4, PSA 135.73, QED 0.19
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3Cc3ccc(/C=C/C(=O)NO)cc3)c2)cc1
InChIKey: GCPBYJXMWMXUHJ-AWNIVKPZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8 using RHKAcKAc peptide as substrate
Measurement: IC50 = 2810 nM (pChEMBL 5.550000190734863)
Descriptors: MW 426.47, ALogP 4.45, HBA 5, HBD 2, PSA 80.56, QED 0.2
Compound (SMILES): O=c1c2cn(C3COC3)nc2nc(SCc2cccc(F)c2)n1-c1ccccc1
InChIKey: IBYYWHNJSYBLSJ-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Inhibition of ALDH1A3 in human PEO1 cells assessed as reduction in aldefluor positive cells incubated for 30 mins by aldefluor assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 408.46, ALogP 3.58, HBA 7, HBD 0, PSA 61.94, QED 0.37
Compound (SMILES): CCOc1cc(/C=C/C(=O)c2ccncc2)cc(OC)c1OCC
InChIKey: SQZFPRBIMUDDBG-VOTSOKGWSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in yeast microsomal membranes using 3-cyano-7-ethoxycoumarin as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 327.38, ALogP 3.78, HBA 5, HBD 0, PSA 57.65, QED 0.55
Compound (SMILES): C[C@]12CC[C@H](O)CC1=C(C(N)=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChIKey: CPGOQTKJUPLDPD-ACAUBTHISA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of C-terminal His-tagged recombinant human CYP21A2deltaH mutant expressed in Escherichia coli DH5alpha assessed as decrease in progesterone hydroxylation preincubated for 3 mins followed by NADPH addition measured after 10 mins in presence of cytochrome p450 reductase by LC-MS/MS method
Measurement: IC50 = 673 nM (pChEMBL 6.170000076293945)
Descriptors: MW 392.54, ALogP 4.25, HBA 3, HBD 2, PSA 76.21, QED 0.79
Compound (SMILES): O=C(Cc1ccc(Cl)cc1)Nc1cccc(-c2cccc(N3CCCC3)c2)c1
InChIKey: SKRNGXUJIZSKLC-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Negative allosteric modulation of human CB1 receptor expressed in HEK293 cells assessed as inhibition of 33 nM CP55,940-induced SRE transcriptional activity after 5 hrs by luciferase reporter gene assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 390.91, ALogP 5.79, HBA 2, HBD 1, PSA 32.34, QED 0.6
Compound (SMILES): CN1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)C[C@@H]1CO
InChIKey: FYPXUGNWIURDGX-ZWKOTPCHSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 419.96, ALogP 1.23, HBA 7, HBD 3, PSA 97.54, QED 0.67
Compound (SMILES): COc1ccc(-c2ccc(Sc3ccccc3CC(=O)NO)cc2)cc1
InChIKey: XZUJPJWGKJJUCO-UHFFFAOYSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human MMP-14 catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition measured every 10 secs for 15 mins by fluorometric assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 365.45, ALogP 4.56, HBA 4, HBD 2, PSA 58.56, QED 0.5
Compound (SMILES): COC(=O)Cc1ccc(OCc2oc(-c3ccccc3OC)nc2C)cc1
InChIKey: GWVLKHYLZIYXAO-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Antagonist activity at CMV-fused TRalpha-LBD-GAL4-DBD (unknown origin) expressed in HEK293T cells assessed as inhibition of T3-induced receptor transactivation after 16 hrs by bright-Glo luciferase reporter gene assay
Measurement: IC50 = 8400 nM (pChEMBL 5.079999923706055)
Descriptors: MW 367.4, ALogP 3.95, HBA 6, HBD 0, PSA 70.79, QED 0.59
Compound (SMILES): C[C@@H](CCCOc1ccccc1CN(C)C(=O)c1ccc(-c2ccco2)cc1)CC(=O)O
InChIKey: NOHPKKZHDRVOAF-IBGZPJMESA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human PPARgamma LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.52, ALogP 5.49, HBA 4, HBD 1, PSA 79.98, QED 0.4
Compound (SMILES): C=CC(=O)Nc1ccccc1Oc1nc(Nc2ccc(N3CCN(C)CC3)cc2OC)ncc1Cl
InChIKey: BUSXEFVPHHJABW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2920 nM (pChEMBL 5.539999961853027)
Descriptors: MW 494.98, ALogP 4.55, HBA 8, HBD 2, PSA 91.85, QED 0.44
Compound (SMILES): O=S(=O)(Oc1ccc(-c2ccccc2)cc1)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: VIDODFTVGQXIIG-VOTSOKGWSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at human ERbeta expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 630.72, ALogP 7.5, HBA 7, HBD 3, PSA 113.29, QED 0.12
Compound (SMILES): Cc1cccc(-c2nc(Nc3ccncc3F)c3cc[nH]c3n2)n1
InChIKey: GAWGUDTUQRRPQK-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 320.33, ALogP 3.61, HBA 5, HBD 2, PSA 79.38, QED 0.6
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc2cc(F)c([C@H]3CC[C@H](c4cc5[nH]c([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C6CCOCC6)nc5cc4F)N3c3cc(F)c(N4CCC(c5ccccc5)CC4)c(F)c3)cc2[nH]1)C1CCOCC1
InChIKey: KTPXCZXUIDLHIU-HBIASZOZSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Con1) (HCV)
UniProt: Q9WMX2
Assay: Inhibition of HCV genotype 1b Con1 NS5A expressed in HuH7 cell infected HCV genotype 6a assessed as decrease in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.012 nM (pChEMBL 10.920000076293945)
Descriptors: MW 1147.28
Compound (SMILES): COc1ccc(CN(CCN(C)C)c2ccc(C(=O)Nc3ccccc3N)cn2)cc1
InChIKey: XRDCTVBYPFNFSI-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human HDAC10 expressed in baculovirus infected Sf9 insect cells using HDAC substrate 3 measured after 30 mins by fluorescence assay
Measurement: IC50 = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 419.53, ALogP 3.49, HBA 6, HBD 2, PSA 83.72, QED 0.52
Compound (SMILES): COc1ccc(NC(=O)N2CCN(c3nc(N)nc4sc(-c5ccccc5)nc34)CC2)cc1
InChIKey: GOCXVAMNAGUMGS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes assessed as decrease in midazolam 1-hydroxylation by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 461.55, ALogP 3.7, HBA 8, HBD 2, PSA 109.5, QED 0.48
Compound (SMILES): C[C@H]1CN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)CN1S(C)(=O)=O
InChIKey: CEFNJZNGSTZXAC-KSSFIOAISA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 55000 nM (pChEMBL 4.260000228881836)
Descriptors: MW 468.03, ALogP 1.59, HBA 7, HBD 2, PSA 111.45, QED 0.69
Compound (SMILES): c1ccc(Cn2nnc3c(Sc4nc5ccccc5o4)ncnc32)cc1
InChIKey: HZSOKHVVANONPV-UHFFFAOYSA-N
Target: NADPH oxidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPH5
Assay: Inhibition of human NOX4 transfected in HEK293-T-REx cells assessed as PMA-induced hydrogen peroxide production pre-incubated for 10 mins and measured after 15 mins by Amplex-res based fluorescence assay
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 360.4, ALogP 3.56, HBA 8, HBD 0, PSA 82.52, QED 0.45
Compound (SMILES): Cl.Cl.FCCOc1ccccc1CCN1CCN(CCc2ccc(F)cc2)CC1
InChIKey: FXNWJEHBMFZDFW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]Dofetilide from human ERG expressed in HEK293 cells after 60 mins by scintillation spectrometry
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 374.48, ALogP 3.58, HBA 3, HBD 0, PSA 15.71, QED 0.67
Compound (SMILES): CS(=O)(=O)c1ccc(N2CCC(F)(F)CC2)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: GIRFLANIOVOTNP-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.52, ALogP 3.2, HBA 7, HBD 0, PSA 88.4, QED 0.54
Compound (SMILES): CCN(CC)[C@@H](C)CNC(=O)c1cc(-c2cnn3ccc(-c4cccs4)nc23)nc(N2CC(O)C2)c1
InChIKey: OFBABNCAYHDFSH-KRWDZBQOSA-N
Target: CaM kinase II alpha/beta (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P08413
Assay: Inhibition of CaMK2alpha/beta in neonatal rat cortical neurons assessed as phospholamban phosphorylation after 4 hrs by Hoechst 33342 fluorescence-based assay
Measurement: EC50 = 274 nM (pChEMBL 6.559999942779541)
Descriptors: MW 505.65, ALogP 3.16, HBA 9, HBD 2, PSA 98.89, QED 0.36
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)NCC(=O)NCC(N)=O)C(C)C)c1
InChIKey: MSKAIELHPGTGHE-MCHZRRGRSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 1269.64
Compound (SMILES): Cc1ccccc1C[n+]1ccc(COc2ccc3c(C)cc(=O)oc3c2)cc1.[Br-]
InChIKey: SXYXVHCWGYVMER-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated for 6 mins followed by substrate addition measured up to 180 secs by Ellman's method
Measurement: IC50 = 35.4 nM (pChEMBL 7.449999809265137)
Descriptors: MW 372.44, ALogP 4.32, HBA 3, HBD 0, PSA 43.32, QED 0.39
Compound (SMILES): CC(=O)N1c2ccc(-c3ccsc3)cc2[C@H](NC(=O)OC(C)C)C[C@@H]1C
InChIKey: VDHPCDUFNMXSRQ-SCLBCKFNSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to His-tagged BRD2 bromodomain 2 (unknown origin) by SPR assay
Measurement: Kd = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 372.49, ALogP 4.74, HBA 4, HBD 1, PSA 58.64, QED 0.85
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: JRIVTLCAZKSBNE-XSTSSERXSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 807.05, ALogP 0.29, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3cccc4ccncc34)c12
InChIKey: BJKLUCNVBMHLON-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 52.3 nM (pChEMBL 7.28000020980835)
Descriptors: MW 435.49, ALogP 5.92, HBA 6, HBD 1, PSA 89.72, QED 0.37
Compound (SMILES): O=C(NCCCN1CCN(Cc2ccc3c(c2)OCO3)CC1)c1ccccn1
InChIKey: WRRIRYQLTJZUKS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Antagonist activity at 5-HT2A receptor in Sprague-Dawley rat ielum assessed as reduction in 5-HT-evoked contraction
Measurement: EC50 = 6480 nM (pChEMBL 5.190000057220459)
Descriptors: MW 382.46, ALogP 1.75, HBA 6, HBD 1, PSA 66.93, QED 0.74
Compound (SMILES): COc1ccc(C2=NN(C3CCCCCC3)C(=O)[C@@H]3CC=CC[C@H]23)cc1-c1ccc(C(=O)NCC(N)=O)cc1
InChIKey: VZKJWTFPORBEEH-LOSJGSFVSA-N
Target: Class 1 phosphodiesterase PDEB1 (SINGLE PROTEIN), Trypanosoma brucei
UniProt: Q8WQX9
Assay: Inhibition of full length Trypanosoma brucei PDEB1 expressed in Sf21 insect cells using cAMP as substrate by scintillation proximity assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 528.65, ALogP 4.43, HBA 5, HBD 2, PSA 114.09, QED 0.41
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3)nc2C1)C(F)(F)F
InChIKey: FLOKUNMZCPFDCT-AWEZNQCLSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.48, ALogP 3.76, HBA 6, HBD 0, PSA 81.5, QED 0.56
Compound (SMILES): Cl.NCc1ccc(Oc2ccc(S(=O)(=O)CC3CS3)cc2)cc1
InChIKey: DRGIZFGSEKSFIC-UHFFFAOYSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Slow binding inhibition of human recombinant MMP14 catalytic domain using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 substrate
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 335.45, ALogP 2.83, HBA 5, HBD 1, PSA 69.39, QED 0.82
Compound (SMILES): O=S(=O)(Oc1ccc(/C=C/c2cc(O)cc(O)c2)cc1)C1CC2OC1C(c1ccc(O)cc1)=C2c1ccc(O)cc1
InChIKey: RHNPKEKHLZQMJA-OWOJBTEDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at human ERalpha expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 570.62, ALogP 5.54, HBA 8, HBD 4, PSA 133.52, QED 0.17
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1)C(F)(F)F
InChIKey: VKGADGOKBFTLBI-ZDUSSCGKSA-N
Target: Sodium- and chloride-dependent glycine transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y345
Assay: Inhibition of recombinant human GlyT2 expressed in HEK293 cells assessed as reduction in [14C]glycine uptake after 2 hrs by microbeta scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.39, ALogP 4.37, HBA 5, HBD 0, PSA 71.15, QED 0.56
Compound (SMILES): CCOc1ccc(-c2c(C#N)c(N)nc(SCc3ncc[nH]3)c2C#N)cc1
InChIKey: MIKJZSSGWVFBKS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as induction of cAMP accumulation by AlphaScreen assay
Measurement: EC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 376.45, ALogP 3.49, HBA 7, HBD 2, PSA 124.4, QED 0.63
Compound (SMILES): O=C(O)CCC(=O)N(C1CC1)[C@H]1c2ccccc2N(C(=O)c2ccc(F)cc2)[C@H]2CC[C@H]21
InChIKey: YKQQDFBLNIXCDS-IZIIKQMZSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity at CRTh2 in human whole blood assessed as inhibition of DK-PGD2-induced eosinophils shape change preincubated for 10 mins followed by DK-PGD2 addition measured after 4 mins by flow cytometry
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 436.48, ALogP 4.16, HBA 3, HBD 1, PSA 77.92, QED 0.74
Compound (SMILES): Nc1nc(/C=C/CNC(=O)c2cc3cc(Cl)ccc3[nH]2)c[nH]1
InChIKey: KZGCMSHMRDZXCJ-OWOJBTEDSA-N
Target: Potassium voltage-gated channel subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22459
Assay: Inhibition of human Kv1.4 expressed in CHO cells at -80 mV holding potential by whole cell automated patch clamp method
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 315.76, ALogP 2.57, HBA 3, HBD 4, PSA 99.59, QED 0.6
Compound (SMILES): CCOC(=O)c1c(C)oc2cc(OCCc3ccccc3)c(OCc3oc4cc(OC)c(OS(=O)(=O)[O-])cc4c3C(=O)OCC)cc12.[Na+]
InChIKey: UKKMFJZHHXIETC-UHFFFAOYSA-M
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using spectrozyme TH as substrate pretreated for 10 mins followed by substrate addition measured in absence of exosite 1 competitor hirudine peptide by spectrophotometric method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 668.67, ALogP 6.23, HBA 12, HBD 1, PSA 170.17, QED 0.1
Compound (SMILES): CN(C)S(=O)(=O)c1cc(NC(=O)CCl)ccc1Cl
InChIKey: YEHYODCKTNLFQU-UHFFFAOYSA-N
Target: Glutathione S-transferase omega-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P78417
Assay: Inhibition of recombinant GSTO1-1 (unknown origin) expressed in Escherichia coli assessed as inhibitor constant using S-(4-nitrophenacyl)glutathione as substrate preincubated for 1 to 6 mins followed by substrate addition by spectrophotmetric analysis
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 311.19, ALogP 1.77, HBA 3, HBD 1, PSA 66.48, QED 0.86
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(C4=CCC(CC(=O)NO)CC4)ccc3OCC)nc12
InChIKey: SXCSLLBVFPUGIZ-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 465.55, ALogP 3.75, HBA 7, HBD 3, PSA 122.13, QED 0.34
Compound (SMILES): CC1(C)CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(CCF)CC6)cn5)ncc4F)cc3n21
InChIKey: PYAFOBDKPDBAIO-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 536.61, ALogP 4.68, HBA 8, HBD 1, PSA 75, QED 0.37
Compound (SMILES): COc1ccc(Cn2cc(C(=O)NCCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)c(=O)c3ccccc32)cc1
InChIKey: MXLDMFKZOSQDCE-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of human erythrocyte AChE assessed as enzyme-inhibitor complex using varying levels of acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Lineweaver-Burk plot analysis
Measurement: Ki = 3.28 nM (pChEMBL 8.479999542236328)
Descriptors: MW 581.12, ALogP 6.37, HBA 6, HBD 2, PSA 85.25, QED 0.2
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NC)c12
InChIKey: GVIUZMOSJDBOBT-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 273.34, ALogP 1.78, HBA 5, HBD 3, PSA 92.93, QED 0.72
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(N)c2)n1
InChIKey: AFYVDDVXNBWDRP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 440.94, ALogP 4.01, HBA 8, HBD 2, PSA 88.77, QED 0.56
Compound (SMILES): Cc1cc2ncn(CC(=O)c3cc(S(N)(=O)=O)c(Cl)cc3Cl)c2cc1C
InChIKey: KQWDYZRSOUJMMK-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 (1 to 260 residues) expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 412.3, ALogP 3.49, HBA 5, HBD 1, PSA 95.05, QED 0.66
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3cncc4ccccc34)c12
InChIKey: MZYYXUKEWJJZAY-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 435.49, ALogP 5.92, HBA 6, HBD 1, PSA 89.72, QED 0.37
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCNCCCC[C@@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: DVNLPYWUFMLUBP-DVNNJGNOSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Agonist activity at Galphaq-Rluc2/Gbeta1/GFP10-Ggamma1 fused human NTS1 expressed in CHO-K1 cell membranes assessed as Galphaq activation after 5 mins by BRET assay
Measurement: EC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 813.05, ALogP 1.37, HBA 10, HBD 9, PSA 258.31, QED 0.1
Compound (SMILES): CC(C)c1n[nH]c2c(NCc3ccccc3)nc(NC3CCCCC3N)nc12
InChIKey: NVTINYQXFHNHIJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of recombinant human full length N-terminal GST/His6-tagged CDK5 (M1 to P292 residues)/N-terminal His6-tagged p25NCK (A104 to R307 residues) expressed in Sf9 insect cells
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 379.51, ALogP 3.77, HBA 6, HBD 4, PSA 104.54, QED 0.52
Compound (SMILES): O=C(/C=C/c1ccc2c(c1)OCO2)c1ccncc1
InChIKey: GPOGQKDGSULXOE-HNQUOIGGSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in yeast microsomal membranes using 3-cyano-7-ethoxycoumarin as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 253.26, ALogP 2.71, HBA 4, HBD 0, PSA 48.42, QED 0.62
Compound (SMILES): Cc1ccc(-c2n[nH]c3c2CCNCC3)cc1
InChIKey: LWNZEHWQIHUHGP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Displacement of [3H]LSD from human 5-HT1B receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 227.31, ALogP 2.07, HBA 2, HBD 2, PSA 40.71, QED 0.78
Compound (SMILES): CC[C@](C)(NC(=O)[C@H]1C[C@H](O)CN1C(=O)[C@H](CO)NC(=O)c1c[nH]cn1)C(=O)N[C@@H](Cc1ccncc1)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@@H](CC(C)(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NC(C)(C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1CCCCC1)C(N)=O)[C@@H](C)O
InChIKey: XSWVCJPBSYFGDH-SGUWVVKZSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Agonist activity at human neuropeptide Y1 receptor by [35S]GTPgammaS binding assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1861.23
Compound (SMILES): C[C@@H]1SC(c2cc3ccccc3cc2O)=N[C@H]1CO
InChIKey: OHKDLICNPQPHJS-ZANVPECISA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A (unknown origin) receptor after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 273.36, ALogP 2.79, HBA 4, HBD 2, PSA 52.82, QED 0.88
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N1CCSc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
InChIKey: NMKUHNALTSCROZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Agonist activity at Gal4-tagged human RORalpha ligand binding domain expressed in human Jurkat cells by native IL17 promoter driven luciferase reporter gene assay
Measurement: EC50 > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 475.41, ALogP 4.44, HBA 4, HBD 1, PSA 57.61, QED 0.67
Compound (SMILES): O=C1C(c2ccccc2)N(S(=O)(=O)c2ccc(Cl)cc2)C(=O)C(c2ccccc2)N1S(=O)(=O)c1ccc(Cl)cc1
InChIKey: AWDIEUWPIRIVDC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Non-competitive inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Dixon plot analysis
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 615.52, ALogP 5.22, HBA 6, HBD 0, PSA 108.9, QED 0.29
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)nc(CCc1ccc(OCCCN(C)C)cc1)n2CCN1CCOCC1
InChIKey: HCDQWCDANVEBQR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to recombinant BRD4 bromodomain1 (unknown origin) by isothermal titration calorimetry
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 531.7, ALogP 4.76, HBA 8, HBD 0, PSA 68.79, QED 0.24
Compound (SMILES): C=CC(=O)N1CC[C@]2(C1)C[C@H](n1c(NC(=O)c3ccc(C#N)cc3)nc3cc(CN[C@@H](C)C(C)(C)C)ccc31)C2
InChIKey: WFTDUNFLISNELR-QABJAWOTSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay
Measurement: IC50 = 4.32 nM (pChEMBL 8.369999885559082)
Descriptors: MW 538.7, ALogP 5.42, HBA 6, HBD 2, PSA 103.05, QED 0.39
Compound (SMILES): Cl.FCCOc1ccccc1CCC1CCN(CCc2ccccc2Cl)CC1
InChIKey: BLPONRMLPXTWII-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]Dofetilide from human ERG expressed in HEK293 cells after 60 mins by scintillation spectrometry
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 389.94, ALogP 5.58, HBA 2, HBD 0, PSA 12.47, QED 0.56
Compound (SMILES): Cl.N[C@@H]1CCC=C(c2ccc(F)cc2)[C@H]1CNc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl
InChIKey: BBOCDUNYRYILGP-LJLRIERRSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 26200 nM (pChEMBL 4.579999923706055)
Descriptors: MW 511.02, ALogP 5.11, HBA 6, HBD 3, PSA 97.11, QED 0.41
Compound (SMILES): Cn1cnc(-c2cnc(O[C@H]3CCN(C(=O)Cc4ccc(OC(F)(F)F)cc4)C[C@H]3F)c(C(N)=O)c2)c1
InChIKey: XJIIVPVOGYFVME-QUCCMNQESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 521.47, ALogP 3.04, HBA 7, HBD 1, PSA 112.57, QED 0.48
Compound (SMILES): N[C@H]1CCN(c2cc3c(cc2F)n2ccnc2c(=O)n3C2CC2)C1
InChIKey: FBYRCTKKXBIHCM-JTQLQIEISA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG transfected in CHO cells by patch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 327.36, ALogP 1.66, HBA 6, HBD 1, PSA 68.56, QED 0.78
Compound (SMILES): COc1cccc(C(=O)c2ccc3c(ccn3Cc3ccc(C(=O)NO)cc3)c2)c1
InChIKey: JUCXGZCQWAXAJZ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8 using RHKAcKAc peptide as substrate
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 400.43, ALogP 4.05, HBA 5, HBD 2, PSA 80.56, QED 0.29
Compound (SMILES): CCc1nn2c(C)cc(C)nc2c1Cc1ccc(/C=C/CN2CCNC(=O)C2)cc1
InChIKey: RCLGGYHTKGHRBY-AATRIKPKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 403.53, ALogP 2.94, HBA 5, HBD 1, PSA 62.53, QED 0.69
Compound (SMILES): CC(C)(C)Cn1ncn(-c2ccc(C(F)(F)C(O)(Cn3cnnn3)c3ccc(F)cc3F)nc2)c1=O
InChIKey: RLVSHXDYKHPCOY-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 10 mins with substrate followed by NADPH addition measured after 15 mins by LC/MS/MS analysis
Measurement: IC50 = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 506.46, ALogP 2.42, HBA 10, HBD 1, PSA 116.54, QED 0.38
Compound (SMILES): O=C(CCN1CCc2ccccc2C1c1ccccc1)NO
InChIKey: IJOBHJNSELHMJE-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 296.37, ALogP 2.53, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): CCCCC/C=C\[C@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NC1CCCC1
InChIKey: AFIUMLLAIMWORC-RBSVARDCSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from human CB2 receptor expressed in HEK293 cell membranes in absence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 385.64, ALogP 7.44, HBA 1, HBD 1, PSA 29.1, QED 0.23
Compound (SMILES): C[C@]12CC[C@H](O)C[C@@H]1NC(=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
InChIKey: SYPKJLJKIQLEPA-FQFVHWNASA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Enzyme Activity Assay: Complementary assays were utilized for the quantitative comparison of compound activity data for CYP17A1 and CYP21A2. Progesterone is a substrate for both CYP17A1 and CYP21A2, and was the substrate studied for enzyme activity, IC50 determinations, and selectivity comparison. Two methods for detecting enzymatic activity were utilized. Analytical High Pressure Liquid Chromatography (HPLC) for biochemical assays was performed on a Prominence HPLC system (Shimadzu Scientific Instruments, Inc., Columbia, Md.) equipped with a C18 reverse phase 100 mm Luna Column (Phenomenex, Torrance, Calif.). The mobile phase consisted of 40% acetonitrile, 59% water, and 1% acetic acid with a 1 mL/min flow rate at 40° C. An injection volume of 32 μL (CYP17A1) or 45 μL (CYP21A2) was used. The presence of the CYP17A1 product 17α-hydroxyprogesterone was detected with an absorption wavelength of 248 nm as reported by Devore, N. M.; Scott, E. E. Structure and function of human cytochromes P450 enzymes: Xenobiotic metabolism by CYP2A and steroid biosynthesis by CYP17A1. University of Kansas, Lawrence, K S, 2011. The presence of the CYP21A2 product 21-hydroxyprogesterone was detected with an absorption wavelength of 248 nm.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 380.53, ALogP 3.96, HBA 3, HBD 2, PSA 62.22, QED 0.78