lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C(=O)Nc1cncc(-c2cc3c(-c4cc5c(-c6cccc(F)c6)cncc5[nH]4)n[nH]c3cn2)c1
InChIKey: MSTRIVKUGGVLGU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 491.53, ALogP 5.96, HBA 5, HBD 3, PSA 112.24, QED 0.28
Compound (SMILES): Cc1c(CO)nnn1-c1ccc(Cl)cc1
InChIKey: JMYKCTGZPVOOLN-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 223.66, ALogP 1.72, HBA 4, HBD 1, PSA 50.94, QED 0.84
Compound (SMILES): COCC(CO)(OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)P(=O)(O)O
InChIKey: BQCRMLSBGAKPFW-RXUYWNQFSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Biochemical Assay: Assay Reaction ConditionsAssay Volume: 70 μlReaction Volume: 50 μlCD73: 0.3208 nMAMP: 15 μMAssay Buffer: 25 mM Tris-HCL, pH 7.4, 0.01% Brij-35, 0.01% BSA, 5 mM MgCl2Assay Procedure:Used 384 clear plate.Made dose titration of testing compounds in assay buffer, 10 points ½ log titrations in duplicates starting at 100 μM.Added 25 μl of CD73 to each well for a final concentration of 320 pM.Incubated at RT for 15 min.Added 25 μl of AMP to each well for a final concentration of 15 μM.Incubated at RT for 10 min.Added 10 μl of Malachite Green Reagent A, incubate at RT for 10 min.Added 10 of Malachite Green Reagent B, incubate at RT for 45 min.Read the Absorbance on Envision plate reader using excitation filter: Cy5 620 nM.The ability of the compounds disclosed herein to inhibit CD73 activity was quantified and the respective IC50 values were determined.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 537.89, ALogP -0.02, HBA 12, HBD 6, PSA 201.54, QED 0.17
Compound (SMILES): O=C(NCc1ccco1)Nc1ccccc1F
InChIKey: OHSAHFGWDMVFIZ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human soluble epoxide hydrolase by kinetic fluorescent assay
Measurement: IC50 = 635 nM (pChEMBL 6.199999809265137)
Descriptors: MW 234.23, ALogP 2.74, HBA 2, HBD 2, PSA 54.27, QED 0.86
Compound (SMILES): O=C(Nc1cccnc1)c1n[nH]c2ccc(-c3cncc(CN4CC5CC(C4)O5)c3)cc12
InChIKey: SZBCOWYOKDHMCB-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: Wnt activity assay: Reporter cell lines were generated by stably transducing cells of cancer cell lines (e.g., colon cancer) with a lentiviral construct that include a Wnt-responsive promoter driving expression of the firefly luciferase gene.Lentiviral constructs were made in which the SP5 promoter, a promoter having eight TCF/LEF binding sites derived from the SP5 promoter, was linked upstream of the firefly luciferase gene. The lentiviral constructs included a hygromycin resistance gene as a selectable marker. The SP5 promoter construct was used to transduce SW480 cells, a colon cancer cell line having a mutated APC gene that generates a truncated APC protein, leading to de-regulated accumulation of β-catenin. A control cell line was generated using another lentiviral construct containing the luciferase gene under the control of the SV40 promoter which does not require β-catenin for activation.Cultured SW480 cells bearing a reporter construct were distributed at approximately 10,000 cells per well into 384 well multiwell plates. Compounds were then added to the wells in half-log dilutions using a three micromolar top concentration. A series of control wells for each cell type received only buffer and compound solvent. Twenty-four hours after the addition of compound, reporter activity for luciferases was assayed, for example, by addition of the BrightGlo luminescence reagent (Promega) and the Victor3 plate reader (Perkin Elmer). Readings were normalized to DMSO only treated cells, and normalized activities were then used for the IC50 calculations.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 426.48, ALogP 3.25, HBA 6, HBD 2, PSA 96.03, QED 0.51
Compound (SMILES): Cc1cc(NC(=O)c2ccc(NS(=O)(=O)CCO)cc2N2CCC3(CC2)CC3)nc(OC2CCC2)n1
InChIKey: RTLWPYOCDKCRCM-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 515.64, ALogP 3.08, HBA 8, HBD 3, PSA 133.75, QED 0.46
Compound (SMILES): Cc1c([C@H](OC(C)(C)C)C(=O)O)c2n3cc(nc3c1CN(C)C)-c1cccc(c1)-c1cc(F)ccc1O[C@@H](C)CCCCOC1(C)CCN2CC1
InChIKey: GJNGJGQODQELQP-HOYUZMNJSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of human PXR transfected in human HepG2 cells co-transfected with CYP3A4-Luc plasmid incubated for overnight by luciferase reporter gene assay
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 700.9, ALogP 8.44, HBA 8, HBD 1, PSA 88.77, QED 0.22
Compound (SMILES): CCC(c1nc2ccc(Cl)cc2[nH]1)[C@H]1CC[C@H](Oc2ccnc3ccccc23)CC1
InChIKey: JCOMZGDVMZZLPW-NTPOMRHGSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in recombinant IFN-gamma induced human HeLa cells incubated for 18 hrs by fluorescence microplate reader assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 419.96, ALogP 6.9, HBA 3, HBD 1, PSA 50.8, QED 0.38
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)Oc2cccc([N+](=O)[O-])c2)cc1)c1cccc(Cl)c1
InChIKey: JATWOSAOVIVTGV-UHFFFAOYSA-N
Target: P2Y purinoceptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41231
Assay: Antagonist activity at human P2Y2 receptor expressed in human 1321N1 cells assessed as inhibition of ATP-induced intracellular calcium influx preincubated for 20 mins followed by ATP addition measured at 0.4 secs interval for 60 times by Oregon Green BAPTA-1/AM dye-based fluorescence assay
Measurement: IC50 = 3010 nM (pChEMBL 5.519999980926514)
Descriptors: MW 432.84, ALogP 4.27, HBA 6, HBD 1, PSA 115.61, QED 0.35
Compound (SMILES): Cc1cc2nc(N[C@H]3CCOC3)c(N3CCC(Oc4ccc(F)cc4F)CC3)nc2cn1
InChIKey: MMWROZOZDDKSMH-INIZCTEOSA-N
Target: G-protein coupled receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P46095
Assay: Modulation of GPR6 (unknown origin) expressed in CHO-K1 cells assessed as inhibition of constitutive cAMP activity by HTRF assay
Measurement: EC50 = 49.6 nM (pChEMBL 7.300000190734863)
Descriptors: MW 441.48, ALogP 3.86, HBA 7, HBD 1, PSA 72.4, QED 0.64
Compound (SMILES): COc1cc(-c2noc([C@H](C)NC(=O)c3cc(C(F)(F)F)nn3C)n2)cc(C)n1
InChIKey: KNCOASIFPBUQHN-VIFPVBQESA-N
Target: Potassium channel subfamily T member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5JUK3
Assay: Inhibition of recombinant wild type human KNa1.1 expressed in human HEK-TREX cells at -80 mV holding potential by automated patch clamp assay
Measurement: IC50 = 505 nM (pChEMBL 6.300000190734863)
Descriptors: MW 410.36, ALogP 2.69, HBA 8, HBD 1, PSA 107.96, QED 0.69
Compound (SMILES): COc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)cc1OCc1ccc(CN2CCCC[C@H]2C(=O)O)cc1
InChIKey: DNMFPIOJKDEAOY-ZRUILDMBSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD1/PDL1 (unknown origin) protein-protein interaction measured after 15 mins by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 547.65, ALogP 5.91, HBA 7, HBD 1, PSA 86.69, QED 0.28
Compound (SMILES): COc1ccc(C(=O)N(CC(C)(C)C)c2cccc(C)n2)c(N2CCC(COc3cccc(C(CC(=O)O)OC)c3)CC2)c1
InChIKey: CBKGOXQXEKHBGC-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human GPR40 expressed in CHO cells incubated for 60 mins by FLIPR based Ca2+ mobilization assay
Measurement: EC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 603.76, ALogP 6.55, HBA 7, HBD 1, PSA 101.43, QED 0.25
Compound (SMILES): N#CCC(=C(c1ccc(O)cc1)c1ccc(O)cc1)c1ccc(O)c(F)c1
InChIKey: UGZUIRQJAWISOE-UHFFFAOYSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of recombinant human aromatase incubated for 30 mins using fluorometric substrate 7-methoxy-4-trifluoromethylcoumarin in presence of NADPH cofactor mix by fluorometric assay
Measurement: IC50 = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 361.37, ALogP 4.82, HBA 4, HBD 3, PSA 84.48, QED 0.58
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(C)(F)F
InChIKey: PPMFNADUOOVZPG-QUGAMOGWSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: ERalpha Binding Assay: The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.In total 120 nL of compound plus DMSO were added to each well and compounds were tested in a 12-point concentration response format over a final compound concentration range of 10, 2.917, 1.042, 0.2083, 0.1, 0.0292, 0.0104, 0.002083, 0.001, 0.0002917, 0.0001042, and 0.00001 μM respectively. TR-FRET dose response data obtained with each compound was exported into a suitable software package (such as Origin or Genedata) to perform curve fitting analysis. Competitive ER alpha binding was expressed as an IC50 value.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 501.6, ALogP 5.02, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): C=CC(=O)Nc1ccccc1C(=O)Nc1n[nH]c2nc(-c3cc(OC)ccc3F)ccc12
InChIKey: XBJSSHAYDMFKEU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin)
Measurement: IC50 > 1500 nM (pChEMBL 5.823999881744385)
Descriptors: MW 431.43, ALogP 4.15, HBA 5, HBD 3, PSA 109, QED 0.4
Compound (SMILES): O=C(Nc1cccc([N+](=O)[O-])c1)Nc1ccc2nccnc2c1
InChIKey: PKYQADGQLRLNPX-UHFFFAOYSA-N
Target: Bromodomain adjacent to zinc finger domain protein 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRL2
Assay: Binding affinity to recombinant human N-terminal His6-tagged BAZ1A (1446 to 1516 residues) expressed in Escherichia coli BL21 (DE3) cells by MST assay
Measurement: Kd = 3090 nM (pChEMBL 5.510000228881836)
Descriptors: MW 309.29, ALogP 3.18, HBA 5, HBD 2, PSA 110.05, QED 0.57
Compound (SMILES): CNc1cc(C)nc(Nc2ccc(OC)c(C3=CCN(CCO)CCC3)c2)n1
InChIKey: DENKINSOAMJQNC-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition G9a (unknown origin)
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 383.5, ALogP 3.05, HBA 7, HBD 3, PSA 82.54, QED 0.68
Compound (SMILES): c1ccc(CNc2nccc3cc(Nc4n[nH]c5cccnc45)ccc23)cc1
InChIKey: UKIOKOMJEMUKSH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Positive allosteric modulator activity at human mGlu4 receptor/Gqi5 in presence of EC20 glutamate by calcium mobilization assay
Measurement: EC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 366.43, ALogP 4.86, HBA 5, HBD 3, PSA 78.52, QED 0.41
Compound (SMILES): CCc1cc(-c2sc(C)nc2C)n[nH]1
InChIKey: VQJUIGCHJWOHIB-UHFFFAOYSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21964
Assay: Inhibition of recombinant wild-type human COMT expressed in Escherichia coli BL21 using 4-nitrocatechol-Alexa488 as substrate in presence of cofactor SAM preincubated for 1 min followed by substrate addition and measured every 60 sec up to 180 times by fluorescence based microtiter plate reader analysis
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 207.3, ALogP 2.71, HBA 3, HBD 1, PSA 41.57, QED 0.82
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)C(=O)Nc1cccc2ccccc12
InChIKey: MKQGSJVZUQXJTG-FSEITFBQSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta 5 chymotrypsin-like activity in human H226 cell using Suc-LLVY-AMC as substrate for 10 mins by fluorescence based assay
Measurement: IC50 = 165.1 nM (pChEMBL 6.78000020980835)
Descriptors: MW 717.87, ALogP 6.43, HBA 6, HBD 5, PSA 158.49, QED 0.07
Compound (SMILES): O=[N+]([O-])c1cccc(-n2cc(COc3ccc4ncnc(NCc5ccccc5)c4c3)nn2)c1
InChIKey: ZLGMPHMTHYTJPP-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of AChE in rat brain using acetylthiocholine iodide as substrate by Ellman's UV-vis spectrophotometric method
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 453.46, ALogP 4.31, HBA 9, HBD 1, PSA 120.89, QED 0.27
Compound (SMILES): COC(=O)C1CN(S(=O)(=O)c2ccc(-c3ccccc3)cc2)CCN1S(=O)(=O)c1ccc(/C=C/c2ccccc2)cc1
InChIKey: WDTORDAALSEXOP-OUKQBFOZSA-N
Target: Falcilysin (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q76NL8
Assay: Inhibition of Plasmodium falciparum FLN
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 602.73, ALogP 4.76, HBA 6, HBD 0, PSA 101.06, QED 0.21
Compound (SMILES): O=C([O-])c1ccc(N(Cc2ccc(C3CCCCC3)cc2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O.[Na+]
InChIKey: SQGOENFTGBETTH-ZMBIFBSDSA-M
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Mus musculus
UniProt: P42227
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT3 SH2 domain in mouse NIH3T3/v-Src nuclear extract preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 638.61, ALogP 5.83, HBA 5, HBD 2, PSA 115.22, QED 0.18
Compound (SMILES): C/C(=C\CC/C(C)=C/CC[C@]1(C)CCc2cc(O)cc(C)c2O1)CC/C=C(\C)C(=O)NCc1ccccc1
InChIKey: YGQRZLRGGGLRPR-MONITXDDSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-LO expressed in Escherichia coli BL21(DE3) assessed as reduction in LTB4 and 5-H(P)ETE formation using arachidonic acid as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 10 mins by RP-HPLC method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 515.74, ALogP 8.28, HBA 3, HBD 2, PSA 58.56, QED 0.22
Compound (SMILES): Cl.Fc1ccc(CCCCN2CCN(c3cccc(-c4ccccc4)n3)CC2)cc1
InChIKey: AVSIXCCTQMDZPL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D2 receptor by liquid scintillation counting
Measurement: Ki = 641 nM (pChEMBL 6.190000057220459)
Descriptors: MW 389.52, ALogP 5.03, HBA 3, HBD 0, PSA 19.37, QED 0.53
Compound (SMILES): CS(=N)(=N)Cc1cc2cc(c1)OCCCCOc1cc(F)ccc1-c1nc(ncc1F)N2
InChIKey: HASNZZTVQOLZGN-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of His-tagged human CDK9/cyclin T1 expressed in insect cells using biotin Ttds-YISPLKSPYKISEG as substrate preincubated for 15 mins followed by ATP and substrate addition and measured after 25 mins by TR-FRET assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 459.52, ALogP 5.53, HBA 7, HBD 3, PSA 103.97, QED 0.47
Compound (SMILES): Cc1ccc(S(=O)(=O)N(C)C)cc1NC(=O)[C@@H](CC1CCCCC1)NC(=N)NC(=O)Cc1ccc(C(F)(F)F)cc1.O=C(O)C(F)(F)F
InChIKey: DAVZGJAQWZVCGH-GJFSDDNBSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human liver Cathepsin D preincubated for 10 mins followed by substrate addition and further incubated for 2 hrs in dark by fluorimetric analysis
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 595.69, ALogP 4.42, HBA 5, HBD 4, PSA 131.46, QED 0.25
Compound (SMILES): O=C1[C@H](F)C[C@@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)N1CCO
InChIKey: OZWSYBBGXBLWCW-WTEVXDJOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at Gal4-fused RORgammat LBD (unknown origin) by reporter gene assay
Measurement: EC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 672.57, ALogP 4.26, HBA 5, HBD 1, PSA 94.99, QED 0.37
Compound (SMILES): NC(Cc1c[nH]c2ccccc12)C(=O)N/N=C/c1cccc(/C=N/NC(=O)C(N)Cc2c[nH]c3ccccc23)c1
InChIKey: PYCKVEPDVWBIOR-KTGRAOHMSA-N
Target: Endothiapepsin (SINGLE PROTEIN), Cryphonectria parasitica
UniProt: P11838
Assay: Inhibition of Endothia parasitica endothiapepsin using Abz-Thr-Ile-Nle-p-nitro-Phe-Gln-Arg-NH2 as substrate by fluorescence method
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 534.62, ALogP 2.69, HBA 6, HBD 6, PSA 166.54, QED 0.12
Compound (SMILES): O=C(NCC1CC1)c1cc(N2CCOCC2)nc(NCc2ccccc2)n1
InChIKey: DHBMKTOGPJQIJM-UHFFFAOYSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ20
Assay: Inhibition of full length human NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 22908.68 nM (pChEMBL 4.639999866485596)
Descriptors: MW 367.45, ALogP 2.07, HBA 6, HBD 2, PSA 79.38, QED 0.78
Compound (SMILES): CN1Cc2cc(N3C(=S)N(c4ccc(C#N)c(C(F)(F)F)c4)C(=O)C3(C)C)ccc2C1=O
InChIKey: IAUNSDIJZQGAPL-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor (unknown origin) expressed in HEK293 cells using DHT as substrate preincubated for 30 mins followed by substrate addition measured after 24 hrs by Steady-Glo luciferase assay
Measurement: IC50 = 590.2 nM (pChEMBL 6.230000019073486)
Descriptors: MW 458.47, ALogP 4.08, HBA 4, HBD 0, PSA 67.65, QED 0.63
Compound (SMILES): CCOc1cccc(Nc2ccc([N+](=O)[O-])c3[nH]c(C(=O)NS(=O)(=O)c4ccc(OC)cc4)cc23)c1
InChIKey: YWAPYBHOXQDHJT-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase expressed in Escherichia coli BL21(DE3) using FBP as substrate in presence of PGI and G6PDH by spectrophotometric method
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 510.53, ALogP 4.35, HBA 8, HBD 3, PSA 152.66, QED 0.22
Compound (SMILES): COc1ccc(N2CCN(CC(=O)NCc3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: UYIUPEDAACQJKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 by stopped-flow CO2 hydration assay
Measurement: Ki = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 418.52, ALogP 0.78, HBA 6, HBD 2, PSA 104.97, QED 0.69
Compound (SMILES): O=C(O)C[C@H](C(=O)N1CC[C@@H](CCc2ccc3c(n2)NCCC3)C1)c1cccc(N2CCOCC2)c1
InChIKey: HGWMSQIIHVZYGE-NLFFAJNJSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphavbeta3 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 492.62, ALogP 3.32, HBA 6, HBD 2, PSA 95, QED 0.58
Compound (SMILES): c1ccc(OCc2cc(OCCNC3CCC3)no2)cc1
InChIKey: BGNLRKAAEJHUCK-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain homogenate incubated for 150 mins by liquid scintillation counting method
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 288.35, ALogP 2.77, HBA 5, HBD 1, PSA 56.52, QED 0.76
Compound (SMILES): Cn1cc(-c2ccc(-c3cnc(NC4CC(C)(C)NC(C)(C)C4)nn3)c(O)c2)cn1
InChIKey: TWAQQEOIIQZKOT-UHFFFAOYSA-N
Target: Huntingtin (SINGLE PROTEIN), Homo sapiens
UniProt: P42858
Assay: Inhibition of Huntingtin protein (unknown origin) incubated for overnight in presence of MW1/MAB2166 monoclonal antibody by ELISA-based MSD electrochemiluminescence assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 407.52, ALogP 3.37, HBA 8, HBD 3, PSA 100.78, QED 0.61
Compound (SMILES): CNc1nc2nc3c1[nH]c(=O)n3Cc1cccc(c1)OCCN(C)C(=O)CO2
InChIKey: FAWCFZQRMUDEAE-UHFFFAOYSA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 384.4, ALogP 0.44, HBA 8, HBD 2, PSA 114.37, QED 0.63
Compound (SMILES): O=C(O)CCc1ccc(COc2cc(F)ccc2Br)cc1
InChIKey: FROMBFNPGOZGFH-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at human FFA4 receptor expressed in CHO-K1 cells assessed as increase in amplitude of dynamic mass redistribution response by DMR assay
Measurement: EC50 = 5754.4 nM (pChEMBL 5.239999771118164)
Descriptors: MW 353.19, ALogP 4.18, HBA 2, HBD 1, PSA 46.53, QED 0.85
Compound (SMILES): Cn1ccc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2c1=O
InChIKey: XJPFLUQFOAAHFE-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]spiperone from D2 receptor in rat striatum measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 435.5, ALogP 4.47, HBA 6, HBD 0, PSA 60.5, QED 0.42
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)c(CO)c2)n2nc(C3CC3)nc12
InChIKey: OIYBQXFVTYXDNE-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human PDE4D catalytic domain using cAMP and FAM-conjugated cAMP by IMAP FRET progressive binding assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 339.35, ALogP 2.47, HBA 6, HBD 2, PSA 96.95, QED 0.74
Compound (SMILES): c1cc(-c2ccnc3[nH]c(-c4n[nH]c5ccc(-c6cncc(CNCC7CCCC7)c6)nc45)cc23)ccn1
InChIKey: JQUMSRDVDNOWDG-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 500.61, ALogP 5.91, HBA 6, HBD 3, PSA 108.06, QED 0.25
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@@H](NC(=O)c2cccc(OCc3ccccc3)c2)COCCCCOC[C@@H](C(=O)N(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC1=O
InChIKey: QOKRWRFYLSBGNQ-YNUAGZMFSA-N
Target: Telomeric repeat-binding factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15554
Assay: Binding affinity to TRFH domain of TRF2 (residues 42 to 245) (unknown origin) by FP based assay
Measurement: Ki = 32000 nM (pChEMBL 4.5)
Descriptors: MW 764.92, ALogP 1.79, HBA 9, HBD 4, PSA 184.71, QED 0.31
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O
InChIKey: DRIDSVGIMZVWPU-IISPIPJLSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in HEK293 cells assessed as stimulation of cAMP accumulation incubated for 20 mins
Measurement: EC50 = 0.052 nM (pChEMBL 10.279999732971191)
Descriptors: MW 4254.73
Compound (SMILES): COc1cccc2nc(Nc3cccc(NC(=O)c4ccc(N5CCOCC5)c(C(F)(F)F)c4)c3)ccc12
InChIKey: UJDNEVXCAKHSDH-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of human CRAF using MEK1 (K97R) as substrate in presence of [gamma-33P]ATP by scintillation counting method
Measurement: IC50 = 1440 nM (pChEMBL 5.840000152587891)
Descriptors: MW 522.53, ALogP 6.09, HBA 6, HBD 2, PSA 75.72, QED 0.32
Compound (SMILES): CN1CCC[C@H]1[C@@H]1COc2c(O)cccc2O1
InChIKey: HEOLZYAUVLBZIB-CABZTGNLSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]-epibatidine from human alpha3beta4 transfected in HEK293 cell membranes preincubated for 5 mins followed by [3H]-epibatidine addition and measured after overnight incubation by liquid scintillation beta counter analysis
Measurement: Ki = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 235.28, ALogP 1.63, HBA 4, HBD 1, PSA 41.93, QED 0.8
Compound (SMILES): Clc1ccc(-n2cccn2)cc1
InChIKey: CLGKHQCZJWOXGO-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human Notum (S81-T451 residues) C330S mutant expressed in HEK293S cells using OPTS substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 69000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 178.62, ALogP 2.53, HBA 2, HBD 0, PSA 17.82, QED 0.66
Compound (SMILES): Cc1ccc(-c2nnc(-c3ccc(Cl)cc3Cl)o2)cc1S(N)(=O)=O
InChIKey: RVLJIVHDJUPRRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 384.24, ALogP 3.67, HBA 5, HBD 1, PSA 99.08, QED 0.74
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1c(=O)n(CCCN1CCC(c3nc(-c4ccccc4)cs3)CC1)c(=O)n2C
InChIKey: VAAJNAMUPMCDNN-RUZDIDTESA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 (unknown origin) using Gly-Pro-p-nitroanilide as substrate incubated for 1 hr
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 600.79, ALogP 3.24, HBA 11, HBD 1, PSA 107.21, QED 0.31
Compound (SMILES): COc1ccccc1N1C(=O)CSC1c1ccc2cccc(O)c2n1
InChIKey: PNQHKTCQJQECIK-UHFFFAOYSA-N
Target: Methionine aminopeptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53582
Assay: Inhibition of human MetAP1 expressed in Escherichia coli BL21 (DE3) using L-methionine-4-methyl-coumary1-7-amide as substrate preincubated for 30 mins followed by substrate addition and measured at 1 min interval for 30 mins by spectrofluorometric method
Measurement: IC50 = 98700 nM (pChEMBL 4.010000228881836)
Descriptors: MW 352.42, ALogP 3.73, HBA 5, HBD 1, PSA 62.66, QED 0.78
Compound (SMILES): Cc1occc1C(=O)N1CCC(NC(=O)Nc2ccc(OC(F)(F)F)cc2)CC1
InChIKey: UMAOSXFOMFFLAU-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 411.38, ALogP 3.91, HBA 4, HBD 2, PSA 83.81, QED 0.8
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)CSCC(=O)NCCCCNC(=O)CSC[C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: OZMODCLXKCJMKZ-WDMLACRYSA-N
Target: Prolactin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P49683
Assay: Activation of human GPR10 overexpressed in CHO-K1 cells assessed as increase in beta arrestin recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 3708.25
Compound (SMILES): C/C=C/C(=O)Nc1cccc(-c2ccnc(Nc3ccc(N4CCOCC4)cc3)n2)c1
InChIKey: IUAXUAZRNPUMBD-DUXPYHPUSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 cytoplasmic domain (781 to 1124 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 415.5, ALogP 4.24, HBA 6, HBD 2, PSA 79.38, QED 0.59
Compound (SMILES): Cc1ccc(-c2nnc(N3CCN(c4ccccn4)CC3)o2)cc1
InChIKey: GEYOUWOYXCLTLH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 using MOCA-SEV-NL-DAEFR-DNP-RR as substrate preincubated with substrate followed by enzyme addition by FRET assay
Measurement: IC50 = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 321.38, ALogP 2.77, HBA 6, HBD 0, PSA 58.29, QED 0.74
Compound (SMILES): O=C(CC1SCCNC1=O)Nc1ccc(OC(F)F)cc1
InChIKey: MCIRMIHLIXFLAF-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Binding affinity to full length biotinylated 6His/Avi-tagged/Tev-fused human MEK1 expressed in Escherichia coli in presence of AMP-PNP by SPR assay
Measurement: Kd = 10000 nM (pChEMBL 5)
Descriptors: MW 316.33, ALogP 1.85, HBA 4, HBD 2, PSA 67.43, QED 0.87
Compound (SMILES): O=C(CCC(=O)OCCCCCCSc1ccc([N+](=O)[O-])c2nonc12)Nc1ccc(F)cc1
InChIKey: YRVMFCKFEZZGMJ-UHFFFAOYSA-N
Target: Glutathione S-transferase P (SINGLE PROTEIN), Homo sapiens
UniProt: P09211
Assay: Inhibition of GSTP1-1 (unknown origin) using reduced GSH and CDNB as substrate incubated for 10 mins followed by substrate addition by microplate reader analysis
Measurement: IC50 = 8570 nM (pChEMBL 5.070000171661377)
Descriptors: MW 490.51, ALogP 4.88, HBA 9, HBD 1, PSA 137.46, QED 0.12
Compound (SMILES): Cc1nc2c(C(=O)O)cc(-c3c(F)c(F)c(-c4ccc(CN5CCCC(F)(F)C5)cc4)c(F)c3F)cc2[nH]1
InChIKey: QJCCYGXHWOBKES-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of DHODH (unknown origin) using L-dihydroorotic acid as substrate preincubated for 30 mins followed by substrate addition measured every 10 mins in presence of decylubiquinone by DCIP dye based coupled enzyme assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 533.47, ALogP 6.69, HBA 3, HBD 2, PSA 69.22, QED 0.22
Compound (SMILES): CC(C)N(Cc1nc(-c2cccnc2)no1)C(=O)COc1ccc(Oc2ccccc2)cc1
InChIKey: VWEUXLRWSIATAB-UHFFFAOYSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human 20S proteasome beta 5
Measurement: IC50 = 1610 nM (pChEMBL 5.789999961853027)
Descriptors: MW 444.49, ALogP 4.74, HBA 7, HBD 0, PSA 90.58, QED 0.37
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1cc2ccccc2[nH]1)c1ccc(Cl)cc1
InChIKey: YBJXAHOAKUETTQ-UNRNKIOXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to estrogen receptor (unknown origin)
Measurement: IC50 = 1.74 nM (pChEMBL 8.760000228881836)
Descriptors: MW 427.93, ALogP 7.29, HBA 1, HBD 2, PSA 53.09, QED 0.25
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]1CSCC(=O)N[C@@H](C(=O)NCCOCCOCCOCCNC(=O)CCCCCCCCCCCCCCCCC(=O)O)CCCNC(=O)CSC[C@@H](C(=O)N[C@H](C(N)=O)[C@@H](C)O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N1)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O)C(C)C
InChIKey: IPIGFSKZGPMZAL-VPIDZPJMSA-N
Target: Prolactin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P49683
Assay: Activation of human GPR10 overexpressed in CHO-K1 cells assessed as increase in beta arrestin recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 2901.5
Compound (SMILES): c1ccc(C(SCCNCc2ccccn2)(c2ccccc2)c2ccccc2)cc1
InChIKey: OIVXPYXDLHRGHL-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant SIRT2 (unknown origin) using FAM-labeled RHKK(Ac) LM peptide as substrate incubated for 60 mins by electrophoretic mobility shift assay
Measurement: IC50 = 39300 nM (pChEMBL 4.409999847412109)
Descriptors: MW 410.59, ALogP 5.9, HBA 3, HBD 1, PSA 24.92, QED 0.27
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H](NC(=O)N[C@@H](CCCCN)C(=O)O)Cc2ccc(cc2)NC(=O)c2coc1n2
InChIKey: YGCAFIQDVRSRNM-SCTDSRPQSA-N
Target: Carboxypeptidase B2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96IY4
Assay: Inhibition of TAFIalpha in human plasma incubated for 15 mins by chromogenic assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 500.56, ALogP 1.55, HBA 7, HBD 6, PSA 188.68, QED 0.29
Compound (SMILES): Cc1c(-c2ccc(-c3ccccc3F)cc2)nc2ccc(F)cc2c1C(=O)NC#N
InChIKey: GNLUODHDGXUZKH-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 399.4, ALogP 5.37, HBA 3, HBD 1, PSA 65.78, QED 0.37
Compound (SMILES): Cn1c2cc(N3CCC(N4CCOCC4)CC3)ccc2c(=O)c2c3ccc(C#N)cc3[nH]c21
InChIKey: RNZOWTZPISMIQT-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058-1620 amino acids) expressed Sf9 cells pre-incubated for 30 mins before addition of Ulight-CKKSRGDYMTMQIG substrate and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 2503 nM (pChEMBL 5.599999904632568)
Descriptors: MW 441.54, ALogP 3.35, HBA 6, HBD 1, PSA 77.29, QED 0.52
Compound (SMILES): Nc1ncc(-c2cnn(C3CCNCC3)c2)cc1CCc1ccccc1
InChIKey: FQMGFUMIMWDXLI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVH8
Assay: Inhibition of GLK (unknown origin) by alphascreen assay
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 347.47, ALogP 3.24, HBA 5, HBD 2, PSA 68.76, QED 0.74
Compound (SMILES): CCOC(=O)C1=C(N)OC(c2ccccc2)=C(C(=O)OCC)C12C(=O)Nc1ccc(S(=O)(=O)N3CCCCC3)cc12
InChIKey: ZDZDQKMAYJUTAV-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase using relaxed pBR322 DNA as substrate incubated for 45 mins by agarose gel electrophoresis method
Measurement: IC50 = 23150 nM (pChEMBL 4.630000114440918)
Descriptors: MW 581.65, ALogP 2.79, HBA 9, HBD 2, PSA 154.33, QED 0.47
Compound (SMILES): NCc1cc(-c2cccc(C(=O)Nc3ccccc3CC(=O)O)c2)ccc1Cl
InChIKey: ZFAJPOLKQKSTMN-UHFFFAOYSA-N
Target: Succinate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXA5
Assay: Antagonist activity at human SUCNR1 expressed in human CHEM1 cells incubated for 60 mins in presence of [35S]GTPgammaS by scintillation proximity assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 394.86, ALogP 4.35, HBA 3, HBD 3, PSA 92.42, QED 0.58
Compound (SMILES): Cc1ccccc1NC(=O)NCCS(=O)(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: ATRAHZJHRAFDIJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 611.8 nM (pChEMBL 6.210000038146973)
Descriptors: MW 412.49, ALogP 1.21, HBA 5, HBD 4, PSA 147.46, QED 0.54
Compound (SMILES): CCOC(=O)c1cc(-c2ccc(Cl)cc2)n(-c2ccc(S(N)(=O)=O)cc2)c1
InChIKey: KPOBGGUXMKIZIQ-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Agonist activity at recombinant human nAChRalpha7 expressed in HEK293 Flip-In cells co-expressing RIC3 assessed as increase in intra cellular calcium level after 10 mins by fluorescence relative to control
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 404.88, ALogP 3.62, HBA 5, HBD 1, PSA 91.39, QED 0.66
Compound (SMILES): C[C@@H](NC(=O)c1ccc(-c2ccccc2)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: YLKLADCUHQUIFY-LGVFNWMJSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma/LPS-stimulated human whole blood preincubated for 4 hrs followed by IFNgamma/LPS stimulation and incubated for 18 hrs by Rapid-fire mass spectrometry analysis
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 452.57, ALogP 7.13, HBA 2, HBD 1, PSA 41.99, QED 0.35
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NCC(CCC(=O)O)c1ccccc1Cl
InChIKey: XDMSQVUSXYEOFO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.87, ALogP 7, HBA 3, HBD 2, PSA 79.29, QED 0.25
Compound (SMILES): O=C1NCCC12CCN(c1c(Cl)cncc1-c1csc3ccccc13)CC2
InChIKey: BOXRYRKZIFAJDP-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of CDK8/cyclin C (unknown origin) using RBER-IRStide as substrate incubated for 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 397.93, ALogP 4.72, HBA 4, HBD 1, PSA 45.23, QED 0.68
Compound (SMILES): Oc1ccc(CN2CC(CNc3ccccc3)C3(C2)CN(c2ccccc2)C3)cc1
InChIKey: QGLKGYOCOVVFKT-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG incubated for 4 hrs by fluorescene microplate reader assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 399.54, ALogP 4.44, HBA 4, HBD 2, PSA 38.74, QED 0.64
Compound (SMILES): O=C(Nc1nn[nH]n1)N1C[C@H]2CN(Cc3cccc(Oc4ccc(Cl)cc4)c3)C[C@H]2C1
InChIKey: WQXDPMSQQFNMQB-IYBDPMFKSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human FAAH1 incubated for 60 mins
Measurement: IC50 = 4333 nM (pChEMBL 5.360000133514404)
Descriptors: MW 439.91, ALogP 3.24, HBA 6, HBD 2, PSA 99.27, QED 0.63
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)NC(=O)N12
InChIKey: WZPMQYIJDLMIFG-GSBZAIBZSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Inhibition of recombinant CETP (unknown origin) assessed as inhibition of transfer of [3H] cholesteryl oleate or [3H] triolein between exogenous LDL and HDL in 2% human serum
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 722.6, ALogP 10.06, HBA 3, HBD 2, PSA 78.87, QED 0.19
Compound (SMILES): Cc1cc(-c2ccccc2)nc2nc(C(=O)Nc3ccccc3C(N)=O)nn12
InChIKey: XJCLHNWHERQQAB-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (PROTEIN COMPLEX), Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
UniProt: P03433
Assay: Inhibition of RdRP activity in Influenza A virus A/PR/8/34 (H1N1) infected in HEK293T cells co-transfected with NP/PA/PB1/PB2/pPolI-Flu-ffLuc/pRL-SV40 incubated for 24 hrs by minireplicon based dual luciferase assay
Measurement: EC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 372.39, ALogP 2.45, HBA 6, HBD 2, PSA 115.27, QED 0.57
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)c(F)c1
InChIKey: BHWRKMUPUMBQKW-OAQYLSRUSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Mus musculus
UniProt: P42227
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT3 SH2 domain in mouse NIH3T3/v-Src nuclear extract preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 641.59, ALogP 5.66, HBA 5, HBD 1, PSA 107.88, QED 0.19
Compound (SMILES): O=c1[nH]cc(-c2ccccc2)c2ncc(Br)n12
InChIKey: RDZWIRNVBCHOTA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) using peptide substrate in presence of [gamma33P]ATP by image analyser
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 290.12, ALogP 2.45, HBA 3, HBD 1, PSA 50.16, QED 0.75
Compound (SMILES): CC(C)C(=O)N1CCC(NC(=O)Nc2ccc(OC(F)(F)F)c(F)c2)CC1
InChIKey: KCYFENQWYLTXQO-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 391.37, ALogP 3.49, HBA 3, HBD 2, PSA 70.67, QED 0.77