lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cccc(C2(O)CCN(C(=O)Cc3cccc(Br)c3)CC2CN(C)C)c1
InChIKey: UPRVJLWWVFBOEL-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 461.4, ALogP 3.3, HBA 4, HBD 1, PSA 53.01, QED 0.72
Compound (SMILES): CCCCOc1ccc(F)c(-c2nc(C)c3nnc4ccc(OC)nc4n23)c1
InChIKey: JISGWKBRIFXTKG-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Proximity Ligation Assay: Isolated cardiomyocytes were washed twice in PBS at room temperature, transferred to 4% paraformaldehyde (PFA) and gently shaken for 30 min, then washed twice again in PBS. The cardiomyocyte suspension was next transferred to 0.8 cm2 wells, each coated with 8 μg laminin (Invitrogen), and incubated at 37° C. for 2 h. PBS was replaced by 0.1% Triton X100 in PBS, and incubated for 10 min at 37° C. Proximity ligation assay was then performed with the Duolink II proprietary system (Olink Bioscience, Uppsala, Sweden), according to the manufacturer's protocol (Soderberg, O., et al., Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods, 2006. 3(12): 995-1000).Cardiomyocytes were scanned on a Zeiss LSM 710 confocal microscope (excitation 543 nm HeNe laser, through a MBS 488/543 dichroic mirror, emission collected at 565-589 nm). ImageJ 1.44p software (http://imagej.nih.gov/ij) was used for analysis of single-cell intracellular fluorescence intensity by measuring whole cell mean gray value. Results were corrected for background fluorescence signal.
Measurement: IC50 = 4.12 nM (pChEMBL 8.380000114440918)
Descriptors: MW 381.41, ALogP 3.97, HBA 7, HBD 0, PSA 74.43, QED 0.47
Compound (SMILES): Cc1n[nH]c2cc(N(Cc3ccc(F)cc3)C(=O)NCCCn3cncc3C)ccc12
InChIKey: NCHAUVAOYPJJBW-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Inhibition of isoQC (unknown origin)
Measurement: IC50 = 79.6 nM (pChEMBL 7.099999904632568)
Descriptors: MW 420.49, ALogP 4.32, HBA 4, HBD 2, PSA 78.84, QED 0.44
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(C)=O
InChIKey: JOPCREHDUHDFAU-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 2710 nM (pChEMBL 5.570000171661377)
Descriptors: MW 408.91, ALogP 3.76, HBA 4, HBD 1, PSA 75.71, QED 0.84
Compound (SMILES): O=C1NCCN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)C1C(=O)NC1CCCCC1
InChIKey: JUBQDBNTYKHXPJ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 6918.31 nM (pChEMBL 5.159999847412109)
Descriptors: MW 524.49, ALogP 2.67, HBA 5, HBD 2, PSA 84.99, QED 0.54
Compound (SMILES): Nc1ccc(/N=N/c2ccc(/C=C/c3ccc(/N=N/c4ccc(N)c5ccc(S(=O)(=O)O)cc45)cc3S(=O)(=O)O)c(S(=O)(=O)O)c2)c2cc(S(=O)(=O)O)ccc12.[NaH]
InChIKey: DXMXZCHPIBYHHS-BKNXFVSTSA-N
Target: Sentrin-specific protease 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4L4
Assay: Inhibition of SENP3 (unknown origin)
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 838.88, ALogP 7.15, HBA 14, HBD 6, PSA 318.96, QED 0.03
Compound (SMILES): O=C(Cc1cnc(N2CCC(CN3CC(=O)N4[C@H](c5ccc6c(c5)OCO6)c5[nH]c6ccccc6c5C[C@@H]4C3=O)CC2)nc1)NO
InChIKey: DRGMFZDBUGVXOG-OOWIMERYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5A using fluorescence-labelled substrate
Measurement: IC50 = 653 nM (pChEMBL 6.179999828338623)
Descriptors: MW 623.67, ALogP 2.34, HBA 9, HBD 3, PSA 153.22, QED 0.22
Compound (SMILES): CC(C)(O)c1ccc(-c2cn3cc(F)cc3c(=O)[nH]2)cc1
InChIKey: BPRGXQTYABGOBA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 286.31, ALogP 2.66, HBA 3, HBD 2, PSA 57.5, QED 0.76
Compound (SMILES): Cn1ccc(CN(C(=O)Cn2nnc3ccccc32)c2ccc(NC(=O)C3CC3)cc2)c1
InChIKey: DUFQFRYUZLXBJG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 428.5, ALogP 3.35, HBA 6, HBD 1, PSA 85.05, QED 0.49
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CO)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: JYXQKMTVNRMKPN-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 421.52, ALogP 1.23, HBA 8, HBD 2, PSA 117.42, QED 0.75
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCNC(C)(C)C5)cc4)n[nH]c3n2)c1Cl
InChIKey: QNXOYMFBIACDSL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of N-terminal 6his tagged recombinant human FGFR3 (447 to 761 residues) expressed in baculovirus infected Sf21 cells by ELISA analysis
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 555.47, ALogP 5.39, HBA 7, HBD 3, PSA 104.4, QED 0.29
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3cc(C(C)(C)C)ccc3OCCN3CCOCC3)c2C)c1
InChIKey: UWLUETXVZQPQJV-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 523.63, ALogP 3.85, HBA 9, HBD 1, PSA 99.97, QED 0.45
Compound (SMILES): CN1CCC2(CC1)c1ccccc1N(Cc1ccc(C(=O)NO)cc1)C2c1ccccc1F
InChIKey: SMZDJOSANOVCSE-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using FLUOR DE LYS fluorometric substrate pre-incubated for 15 mins and followed by substrate addition and measured after 60 mins by microplate reader assay
Measurement: IC50 = 3490 nM (pChEMBL 5.460000038146973)
Descriptors: MW 445.54, ALogP 4.67, HBA 4, HBD 2, PSA 55.81, QED 0.45
Compound (SMILES): Cc1cn(-c2cccc(Cl)c2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: CXSICEXKLUHLDZ-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 362.84, ALogP 3.28, HBA 4, HBD 1, PSA 68.17, QED 0.78
Compound (SMILES): COC(=O)c1ccc(N[C@@H]2C[C@H](C)N(C(C)=O)c3ccc(-c4cccc(NC(C)=O)c4)cc32)cc1
InChIKey: WEQSOZXIXPNDJW-MRDQGFSESA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to BDR2-BD1 (unknown origin) by TR-FRET assay
Measurement: Kd = 931 nM (pChEMBL 6.03000020980835)
Descriptors: MW 471.56, ALogP 5.4, HBA 5, HBD 2, PSA 87.74, QED 0.49
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@H](CC)C(=O)N(C)C)c2C#N)cc1
InChIKey: WKKDZOOQOYFTAV-XMMPIXPASA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 479.58, ALogP 5.51, HBA 6, HBD 1, PSA 91.14, QED 0.36
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c4c3OCO4)c3c(=O)n(C)cnc32)c(Cl)c(F)n1
InChIKey: UMJJCRBHNLSKPZ-ZDUSSCGKSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 1.05 nM (pChEMBL 8.979999542236328)
Descriptors: MW 627.03, ALogP 1.9, HBA 12, HBD 3, PSA 170.07, QED 0.27
Compound (SMILES): O=c1c(/C=N/Nc2ccc(C(F)(F)F)cc2)coc2c1ccc1oc(-c3ccc(Cl)cc3)cc12
InChIKey: LCMWUFLTMJGHMS-PNQUVVCRSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 (unknown origin)
Measurement: IC50 = 10400 nM (pChEMBL 4.980000019073486)
Descriptors: MW 482.85, ALogP 7.32, HBA 5, HBD 1, PSA 67.74, QED 0.22
Compound (SMILES): COc1ccc(CC2NCCc3c2[nH]c2c(C)c(C)ccc32)c(Br)c1OC
InChIKey: VJNCSLQCBKBXPG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30994
Assay: Displacement of [3H]-ketanserin from rat 5-HT2B expressed in mouse NIH/3T3 cells assessed as inhibition constant by Cheng-Prusoff equation analysis
Measurement: Ki = 0.08 nM (pChEMBL 10.100000381469727)
Descriptors: MW 429.36, ALogP 4.99, HBA 3, HBD 2, PSA 46.28, QED 0.61
Compound (SMILES): CCOC(=O)C1=C(C)Cc2nc(N3CCC(C(=O)NS(=O)(=O)Cc4ccccc4)CC3)c(C#N)cc2C1
InChIKey: NLJJBXZIVNGFNU-UHFFFAOYSA-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 NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 399 nM (pChEMBL 6.400000095367432)
Descriptors: MW 522.63, ALogP 2.79, HBA 8, HBD 1, PSA 129.46, QED 0.55
Compound (SMILES): Clc1cc(Cl)cc(Nc2nc(-c3nc(-c4ccccc4)c(-c4ccccc4)s3)cs2)c1
InChIKey: SAGJHDVBNHBATA-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 381.2 nM (pChEMBL 6.420000076293945)
Descriptors: MW 480.45, ALogP 8.65, HBA 5, HBD 1, PSA 37.81, QED 0.27
Compound (SMILES): CCCCc1cc(=O)oc2[nH]c(=S)[nH]c(=O)c12
InChIKey: ZWMBILSXWJDTFK-UHFFFAOYSA-N
Target: Hydroxycarboxylic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDS4
Assay: Agonist activity at human HCA2 expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay
Measurement: EC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 252.29, ALogP 1.88, HBA 4, HBD 2, PSA 78.86, QED 0.82
Compound (SMILES): O=C(CCl)Nc1cccc(-c2ncnc3[nH]ccc23)c1
InChIKey: ZHCRJPWRXDWSOW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) preincubated for 1 hr followed by substrate addition and measured after 1 hr by Z-lyte assay
Measurement: IC50 = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 286.72, ALogP 2.8, HBA 3, HBD 2, PSA 70.67, QED 0.73
Compound (SMILES): CN1CCN(CCCOC(=O)c2ccc3ccccc3c2)CC1
InChIKey: XGWTYMRRVDFIEO-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Binding affinity to human H3 receptor assessed as inhibition constant incubated for 90 mins by scintillation counting method
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 312.41, ALogP 2.63, HBA 4, HBD 0, PSA 32.78, QED 0.63
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc[nH]c2c1=O
InChIKey: JGOZUFGBTSAWEI-NSCUHMNNSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.71
Compound (SMILES): CN1CCN(c2ncc3[nH]nc(-c4cnn(C)c4)c3n2)CC1=O
InChIKey: HEJWDMSZDBYDME-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (3 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 3 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 312.34, ALogP 0.03, HBA 7, HBD 1, PSA 95.83, QED 0.72
Compound (SMILES): CCCOc1c(CCC)cc(-c2ccccc2-c2nn[nH]n2)cc1NC(=O)Nc1ccc(C)cc1
InChIKey: UCPMUXOPKQHTIZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 470.58, ALogP 6.23, HBA 5, HBD 3, PSA 104.82, QED 0.27
Compound (SMILES): CN1CCCC[C@H](N(c2cc(C#CC(C)(C)C)sc2C(=O)O)C(=O)[C@H]2CC[C@H](C)CC2)C1=O
InChIKey: KPNFBUNNEPDDOK-BJLQDIEVSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated for 10 mins in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 472.65, ALogP 5.01, HBA 4, HBD 1, PSA 77.92, QED 0.62
Compound (SMILES): CC1CCCN1CCCOc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](N3CCCC3)CC[C@@H]12
InChIKey: BLISAYWDMSAMTN-OKSFETJPSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 450.71, ALogP 6.26, HBA 3, HBD 0, PSA 15.71, QED 0.48
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)OCc3ccccc3)nc2C2(CCCCC2)C1(C)C
InChIKey: VZHDZZCDHHJVAP-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 408.5, ALogP 4.57, HBA 5, HBD 1, PSA 84.42, QED 0.8
Compound (SMILES): COc1cc2ncnc(NCCOc3ccccc3F)c2cc1OC
InChIKey: SQUSZMTZUQQFKO-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of human recombinant ERBB2 expressed in Escherichia coli
Measurement: IC50 = 8730 nM (pChEMBL 5.059999942779541)
Descriptors: MW 343.36, ALogP 3.28, HBA 6, HBD 1, PSA 65.5, QED 0.66
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)COCCOCCNC(=O)c1ccc2c(c1)C(=O)OC21c2ccc(O)cc2Oc2cc(O)ccc21)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(=O)O)C(N)=O
InChIKey: KJUWGHYRRPQMKH-MOTFGSSMSA-N
Target: Albumin (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P49065
Assay: Binding affinity to rabbit albumin by fluorescence polarization assay
Measurement: Kd = 320 nM (pChEMBL 6.5)
Descriptors: MW 1729.9
Compound (SMILES): Cc1c(-c2cc(C#N)c(N)o2)c(=O)n(-c2ccccc2)n1C
InChIKey: QRZBWFJAYJYUJM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P21396
Assay: Inhibition of rat brain synaptosome MAO-A
Measurement: IC50 = 7.99 nM (pChEMBL 8.100000381469727)
Descriptors: MW 294.31, ALogP 2.2, HBA 6, HBD 1, PSA 89.88, QED 0.78
Compound (SMILES): Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(=O)(=O)[N-]C(=O)C(C)c3ccc(CC(C)C)cc3)cc2)cc1.[Na+]
InChIKey: MASBNQIOSNMFAQ-UHFFFAOYSA-M
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Inhibition of TRPV1 (unknown origin)
Measurement: IC50 = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 569.65, ALogP 6.67, HBA 5, HBD 1, PSA 81.06, QED 0.26
Compound (SMILES): COc1cccc(NC(=O)c2nnn(Cc3ccc(CN4CCOCC4)cc3)c2N)c1
InChIKey: DRHOOSHFHLLGDF-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.49, ALogP 2, HBA 8, HBD 2, PSA 107.53, QED 0.6
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c5c(c4)OCC5(C)C)nn32)CC1
InChIKey: IHJOVKPLSQINCA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 77.5 nM (pChEMBL 7.110000133514404)
Descriptors: MW 479.58, ALogP 3.11, HBA 7, HBD 2, PSA 111.71, QED 0.64
Compound (SMILES): C[C@@](N)(CO)CCc1ccc(OCc2ccc(Cl)c(Cl)c2)cc1
InChIKey: ZQQHXJCIFGMUPY-SFHVURJKSA-N
Target: Ceramide synthase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q924Z4
Assay: Inhibition of mouse CerS2
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 354.28, ALogP 4.21, HBA 3, HBD 2, PSA 55.48, QED 0.78
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(/C(=N/O)c3ccc(O)cc3)CC2)cc1
InChIKey: OGXFNEAZYVDSMA-HTXNQAPBSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 376.44, ALogP 1, HBA 6, HBD 3, PSA 119.46, QED 0.32
Compound (SMILES): CC[C@H]1CN(Cc2cc(C)cc(CC(=O)O)c2)CCN1c1nc2ccc(C(F)(F)F)cc2s1
InChIKey: ZBKXSRSXIGZPCY-IBGZPJMESA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 477.55, ALogP 5.35, HBA 5, HBD 1, PSA 56.67, QED 0.52
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(O)cn2)cc1Nc1ccccc1Cl
InChIKey: BDFXWFUXDCODKM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-fused JAK2 (808 to 1132 residues) (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): O=C(NO)c1ccc(NC(=O)[C@@H](NS(=O)(=O)c2cccc3ccccc23)c2ccccc2)cc1
InChIKey: UZYFIQWENUALSN-QHCPKHFHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 294.5 nM (pChEMBL 6.53000020980835)
Descriptors: MW 475.53, ALogP 3.62, HBA 5, HBD 4, PSA 124.6, QED 0.24
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: PXHIFOLPKHLYBX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 1039.63
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)[nH]1
InChIKey: WNBJBSFSPKVIPC-SANMLTNESA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 539.68, ALogP 4.52, HBA 6, HBD 3, PSA 118.84, QED 0.22
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin)
Measurement: IC50 = 2012 nM (pChEMBL 5.699999809265137)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): CCCOc1nc(-c2cncc(C3COB(O)C3)c2)c(F)cc1OC
InChIKey: CECUZGKZZDAYHR-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4 catalytic domain expressed in Escherichia coli
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 346.17
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 5620 nM (pChEMBL 5.25)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): C[C@@H]1OC(=O)NN=C1c1ccc(-c2ccc(F)cc2)c(C(F)(F)F)c1
InChIKey: JNTJTCXFIXNXDV-VIFPVBQESA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: PDE3B Enzyme Inhibition: The commercially available 3H-cAMP Scintillation Proximity Assay (SPA, Perkin Elmer) system was used for enzyme inhibition studies. For the determination of the in vitro effect of example compounds on the PDE3B reactions 2 μl of the respective example compound solution in DMSO (serial dilutions) were placed in wells of microtiter plates (Isoplate-96/200W; Perkin Elmer). 50 μl of a dilution of PDE3B cell extract from Sf9 cells overexpressing human full length PDE3B (SB Drug Discovery, UK) in buffer A (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA) was added. The dilution of the PDE3B cell extract was chosen such that the reaction kinetics was linear and less than 70% of the substrate was consumed (typical dilution 1:6000). The reaction was started by addition of 50 μl (0.025 μCi) of 1:2000 in buffer A w/o BSA diluted substrate [8-3H]adenosine 3′, 5′-cyclic phosphate (1 μCi/μl; Perkin Elmer). After incubation at room temperature for 60 min, the reaction was stopped by addition of 25 μl of a suspension containing 18 mg/ml yttrium scintillation proximity beads (Perkin Elmer) in water. The microtiter plates were sealed and measured in a Microbeta scintillation counter (PerkinElmer Wallac). IC50 values were determined from sigmoidal curves by plotting percentage PDE3B activity vs log compound concentration.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 352.29, ALogP 4.34, HBA 3, HBD 1, PSA 50.69, QED 0.82
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)C[C@H]2C)c1
InChIKey: HUAKZZAZJGNQFD-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: QKXAMYHLNVXQGM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 408.54, ALogP 5.25, HBA 5, HBD 1, PSA 54.7, QED 0.33
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2cc(Br)ccc2O3)c([N+](=O)[O-])c1
InChIKey: FWVJADLNFOKENV-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 199.3 nM (pChEMBL 6.699999809265137)
Descriptors: MW 496.34, ALogP 3.01, HBA 7, HBD 1, PSA 132.84, QED 0.51
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(F)cc3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SZPOIQZUDFAZMU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 416.44, ALogP 5.21, HBA 4, HBD 3, PSA 82.28, QED 0.37
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C#N)c2)c2cc(C)[nH]c2c1=O
InChIKey: BQAKOVGAYWUDIT-ONEGZZNKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 416.48, ALogP 3.23, HBA 5, HBD 1, PSA 91.12, QED 0.66
Compound (SMILES): O=C(CCCCCCNCc1ccc(F)cc1)NO
InChIKey: SJHLXQGXRUFBKJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 268.33, ALogP 2.37, HBA 3, HBD 3, PSA 61.36, QED 0.37
Compound (SMILES): Nc1ncc(-c2cc(N3CCC(F)(F)C3)nc(N3C[C@@H]4C[C@H]3CO4)c2)nc1OC(F)F
InChIKey: CMXUWUGBGXEFFR-RYUDHWBXSA-N
Target: Protein delta homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P80370
Assay: Inhibition of DLK (unknown origin)
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 440.4, ALogP 2.55, HBA 8, HBD 1, PSA 89.63, QED 0.71
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCCCN(C)Cc1ccc(OC)c(OC)c1
InChIKey: VNMUKEWBYJPDPC-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 522.73, ALogP 7.51, HBA 6, HBD 0, PSA 52.93, QED 0.12
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-NOCHOARKSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 639.8, ALogP 3.83, HBA 8, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): O=C(CCCCCCNc1nc2ccccc2nc1-c1nc2ccccc2o1)NO
InChIKey: UPTYYNWPPBPUMA-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin)
Measurement: IC50 = 15.47 nM (pChEMBL 7.809999942779541)
Descriptors: MW 405.46, ALogP 4.31, HBA 7, HBD 3, PSA 113.17, QED 0.22
Compound (SMILES): COc1ccc(S(=O)(=O)N(Cc2ccccn2)c2c(C)cc(-c3cccc(C(F)(F)F)c3)cc2C(=O)NO)cc1
InChIKey: HJPPIRCRVNMSQH-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE (unknown origin)
Measurement: IC50 = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 571.58, ALogP 5.6, HBA 6, HBD 2, PSA 108.83, QED 0.21
Compound (SMILES): COc1ccc(/C=N/NC(=O)CCCCCCCC(=O)NO)cc1
InChIKey: GAZWXVIVAKKMPK-QGOAFFKASA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant GST-tagged HDAC6 incubated for 20 mins by HDAC Glo assay
Measurement: IC50 = 35.8 nM (pChEMBL 7.449999809265137)
Descriptors: MW 335.4, ALogP 2.38, HBA 5, HBD 3, PSA 100.02, QED 0.25
Compound (SMILES): Cc1ccc(S(=O)(=O)NC(=O)c2cc(C(=O)O)ccn2)cc1
InChIKey: XTGQLLNXJPAVEA-UHFFFAOYSA-N
Target: RNA demethylase ALKBH5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P6C2
Assay: Inhibition of N-terminal truncated human ALKBH5 (66 to 292 residues) expressed in Escherichia coli BL21 (DE3) Rosetta cells
Measurement: IC50 = 75500 nM (pChEMBL 4.119999885559082)
Descriptors: MW 320.33, ALogP 1.21, HBA 5, HBD 2, PSA 113.43, QED 0.87
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C(C)(C)N(C)C)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: AOFDLXVBRYIAGS-QHCPKHFHSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 expressed in baculovirus infected insect cells using FLUOR DE LYS-SIRT1 as fluorogenic substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by spectrophotometer based analysis
Measurement: IC50 < 3.5 nM (pChEMBL 8.456000328063965)
Descriptors: MW 494.64, ALogP 5.33, HBA 7, HBD 1, PSA 97.56, QED 0.32
Compound (SMILES): COc1ccc(-c2cnc(NC(=O)CCCCCCNC(=O)C(O)(O)C(F)(F)F)s2)cc1
InChIKey: LBYUKUIOYGHLJO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) incubated for 3 hrs by chemiluminescent assay
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 475.49, ALogP 3.07, HBA 7, HBD 4, PSA 120.78, QED 0.29
Compound (SMILES): O=C1CCc2cc(OCCN3CCC[C@@H]3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-HXUWFJFHSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n(C4CCCCCC4)c3n2)CC1
InChIKey: NIVRVOZNYYXNJT-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 419.55, ALogP 2.52, HBA 7, HBD 1, PSA 97.19, QED 0.77
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P28593
Assay: Inhibition of HIS-tagged recombinant Trypanosoma cruzi TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13
Compound (SMILES): Fc1ccc(OC[C@@H]2CN(Cc3ccc4[nH]cnc4c3)CCO2)cc1F
InChIKey: MSYCGACUZCZLFO-HNNXBMFYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 426.58 nM (pChEMBL 6.369999885559082)
Descriptors: MW 359.38, ALogP 3.12, HBA 4, HBD 1, PSA 50.38, QED 0.76
Compound (SMILES): O=C(Nc1cccnc1)c1ccnn2cc(-c3ccccc3)nc12
InChIKey: UVTJZQHSPPYGDG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of full length GST-tagged human recombinant GSK3-alpha using FL-KRREILSRRP[ps]ERYR-NH2 as substrate incubated for 20 hrs
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 315.34, ALogP 3.04, HBA 5, HBD 1, PSA 72.18, QED 0.63
Compound (SMILES): CCN(CCN(C)C)C(=O)CNCc1cc(C(=O)N(C)C)ccn1
InChIKey: VHKSSHRSJGZQOV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin ) by Alphascreen assay
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 335.45, ALogP 0.28, HBA 5, HBD 1, PSA 68.78, QED 0.7
Compound (SMILES): CCCOC(c1ccccc1)c1cccc(NC(=O)c2cc(C(F)(F)F)nn2-c2cccc(CN)c2)c1
InChIKey: ODVQLXVRAUDBCL-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader.
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 508.54, ALogP 6.12, HBA 5, HBD 2, PSA 82.17, QED 0.29
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n([C@@H]5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: JJEGWIJBJXWVDU-HSZRJFAPSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 472 nM (pChEMBL 6.329999923706055)
Descriptors: MW 540.67, ALogP 3.98, HBA 10, HBD 2, PSA 104.34, QED 0.35
Compound (SMILES): Fc1ccc(CN2CCCC23CCN(Cc2cn4ccccc4n2)C3)cc1F
InChIKey: MZEWTMVKHJXAGJ-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 382.46, ALogP 3.85, HBA 4, HBD 0, PSA 23.78, QED 0.68
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2C[C@H]3C[C@@H]2CN3)n1
InChIKey: JKHBVOCOHYSWTQ-HUUCEWRRSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of MAP4K2 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 437.45, ALogP 3.23, HBA 6, HBD 2, PSA 79.38, QED 0.64
Compound (SMILES): COc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: QWJHDFPZYMYNPX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-fused JAK2 (808 to 1132 residues) (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 369.81, ALogP 3.72, HBA 6, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): CCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: OEBTWRYFDAUETA-ZMBIFBSDSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 467.01, ALogP 4.02, HBA 5, HBD 1, PSA 67.23, QED 0.52
Compound (SMILES): CCC(=O)c1sc(-c2cccc(F)c2)nc1O
InChIKey: ANUOYWLYYBOAMH-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in icilin induced Ca2+ efflux preincubated for 5 mins followed by icilin addition and measured for 3 mins by FLIPR assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 251.28, ALogP 3.25, HBA 4, HBD 1, PSA 50.19, QED 0.85
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(N)c(C(=O)NCc3cncnc3)cc21
InChIKey: KFIKODBQLOMHNX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 363.38, ALogP 0.97, HBA 8, HBD 2, PSA 120.2, QED 0.52
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(CC)c(OC)c4)nn32)CC1
InChIKey: LBCWQLSBINGIBS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 29.1 nM (pChEMBL 7.539999961853027)
Descriptors: MW 467.57, ALogP 3.01, HBA 7, HBD 2, PSA 111.71, QED 0.61
Compound (SMILES): COc1ccc(/C=C/C(=N/Oc2ccc(/C=C/C(=O)c3ccc(F)cc3)cc2)c2ccc(OC)cc2)cc1
InChIKey: XRWOGUBTQNJHSD-NAYFDBJDSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using benzylamine as substrate
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 507.56, ALogP 7.24, HBA 5, HBD 0, PSA 57.12, QED 0.1
Compound (SMILES): Cn1cnc2c(c(-c3cc(Cl)c(O)c(C(N)=O)c3)cn2CC(=O)Nc2cc(N3CCOCC3)ncc2Cl)c1=O
InChIKey: LYPIBXVPZCTMSW-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 26.5 nM (pChEMBL 7.579999923706055)
Descriptors: MW 572.41, ALogP 2.38, HBA 10, HBD 3, PSA 157.6, QED 0.32
Compound (SMILES): CCCCOc1ccc(F)c(-c2nc(C)c3nnc4ccc(OC)nc4n23)c1
InChIKey: JISGWKBRIFXTKG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Proximity Ligation Assay: Isolated cardiomyocytes were washed twice in PBS at room temperature, transferred to 4% paraformaldehyde (PFA) and gently shaken for 30 min, then washed twice again in PBS. The cardiomyocyte suspension was next transferred to 0.8 cm2 wells, each coated with 8 μg laminin (Invitrogen), and incubated at 37° C. for 2 h. PBS was replaced by 0.1% Triton X100 in PBS, and incubated for 10 min at 37° C. Proximity ligation assay was then performed with the Duolink II proprietary system (Olink Bioscience, Uppsala, Sweden), according to the manufacturer's protocol (Soderberg, O., et al., Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods, 2006. 3(12): 995-1000).Cardiomyocytes were scanned on a Zeiss LSM 710 confocal microscope (excitation 543 nm HeNe laser, through a MBS 488/543 dichroic mirror, emission collected at 565-589 nm). ImageJ 1.44p software (http://imagej.nih.gov/ij) was used for analysis of single-cell intracellular fluorescence intensity by measuring whole cell mean gray value. Results were corrected for background fluorescence signal.
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 381.41, ALogP 3.97, HBA 7, HBD 0, PSA 74.43, QED 0.47
Compound (SMILES): Cc1n[nH]c2cc(N(Cc3ccc(F)cc3)C(=O)NCCCn3cncc3C)ccc12
InChIKey: NCHAUVAOYPJJBW-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q9CYK2
Assay: Inhibition of mouse glutaminyl cyclase
Measurement: IC50 = 29.9 nM (pChEMBL 7.519999980926514)
Descriptors: MW 420.49, ALogP 4.32, HBA 4, HBD 2, PSA 78.84, QED 0.44
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(C)=O
InChIKey: JOPCREHDUHDFAU-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as inhibition of dexamethasone-induced transactivation of receptor incubated for 18 hrs by firefly luciferase assay
Measurement: IC50 = 12110 nM (pChEMBL 4.920000076293945)
Descriptors: MW 408.91, ALogP 3.76, HBA 4, HBD 1, PSA 75.71, QED 0.84
Compound (SMILES): Cn1ccc(CN(C(=O)Cn2nnc3ccccc32)c2ccc(NC(=O)C3CC3)cc2)c1
InChIKey: DUFQFRYUZLXBJG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 7700 nM (pChEMBL 5.110000133514404)
Descriptors: MW 428.5, ALogP 3.35, HBA 6, HBD 1, PSA 85.05, QED 0.49
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCNC(C)(C)C5)cc4)n[nH]c3n2)c1Cl
InChIKey: QNXOYMFBIACDSL-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1-R (unknown origin) by Z'-LYTE Kinase assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 555.47, ALogP 5.39, HBA 7, HBD 3, PSA 104.4, QED 0.29
Compound (SMILES): Cc1cn(-c2cccc(Cl)c2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: CXSICEXKLUHLDZ-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 362.84, ALogP 3.28, HBA 4, HBD 1, PSA 68.17, QED 0.78