lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCN3CCN(c4ccc(C(=O)CCC5CCN(Cc6cc[nH]c6)CC5)cc4)CC3)c2c1
InChIKey: JZXJYGZVLMGHLF-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) in HEK293 cells assessed as inhibition of 5-HT reuptake by spectrophotometric analysis
Measurement: IC50 = 14.87 nM (pChEMBL 7.829999923706055)
Descriptors: MW 562.76, ALogP 6, HBA 5, HBD 2, PSA 82.16, QED 0.22
Compound (SMILES): COC(=O)C(Cc1ccccc1)NC(=O)Nc1cccc(S(N)(=O)=O)c1
InChIKey: XWXOTPXPEGBLFK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 275.2 nM (pChEMBL 6.559999942779541)
Descriptors: MW 377.42, ALogP 1.24, HBA 5, HBD 3, PSA 127.59, QED 0.65
Compound (SMILES): Cc1nc(Nc2cccc(N3CCNC3=O)n2)sc1-c1cc2c(c(S(=O)(=O)NC3COC3)c1)C(=O)N([C@@H](C)C1CC1)C2
InChIKey: VFBCXKOMIUXVNH-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human PI3Kalpha assessed as reduction in ADP production using Dic8-PIP2 as substrate pre-treated for 15 mins followed by substrate addition measured after 60 mins by ADP-glo assay
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 609.73, ALogP 3.22, HBA 9, HBD 3, PSA 145.86, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc2c(c1)C(=O)C(=O)N2Cc1ccc([N+](=O)[O-])cc1
InChIKey: SXGPALQOTAXAEA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by phenol red based stopped flow CO2 hydration assay
Measurement: Ki = 95.7 nM (pChEMBL 7.019999980926514)
Descriptors: MW 361.34, ALogP 0.97, HBA 6, HBD 1, PSA 140.68, QED 0.49
Compound (SMILES): CCC(=O)N(CC1(N2CCN(Cc3ccccc3)CC2)CC1)c1cccc(F)c1
InChIKey: WEBBOVFNGZGZLV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by whole cell patch clamp assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 395.52, ALogP 3.92, HBA 3, HBD 0, PSA 26.79, QED 0.71
Compound (SMILES): Cc1n[nH]c2nc(-c3ccc(NS(=O)(=O)c4cc(Cl)ccc4F)cc3)nc(OC3CCN(C(C)C)CC3)c12
InChIKey: WLPOJBXKCGXWFV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Sgk1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9WVC6
Assay: Inhibition of mouse SGK1 in presence 500 uM presence of ATP
Measurement: IC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 559.07, ALogP 5.17, HBA 7, HBD 2, PSA 113.1, QED 0.32
Compound (SMILES): CCC(=O)N1CCC(c2ccccc2)(c2ccccc2)C1
InChIKey: FAZLAFLZRGLEFK-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor expressed in HEK293 cell membranes incubated for 60 mins by microbeta scintillation counting analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 279.38, ALogP 3.62, HBA 1, HBD 0, PSA 20.31, QED 0.84
Compound (SMILES): C[C@H](c1ccc(C(F)(F)F)cc1C(F)(F)F)n1cc(NC(=O)c2nnc(-c3cnccn3)s2)cn1
InChIKey: WOSRMIQXXBKGFN-SNVBAGLBSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate incubated for 20 mins in presence of NADPH and measured by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 513.43, ALogP 5.09, HBA 8, HBD 1, PSA 98.48, QED 0.37
Compound (SMILES): COc1cc(OC)c(NC(=O)Cn2nc(CC(=O)O)c3ccccc32)cc1Cl
InChIKey: UMPCYMRVLYIKGB-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of [35S]GTPgammaS binding
Measurement: IC50 = 8980 nM (pChEMBL 5.050000190734863)
Descriptors: MW 403.82, ALogP 2.97, HBA 6, HBD 2, PSA 102.68, QED 0.63
Compound (SMILES): COc1ccc(CC(=O)O)cc1Oc1ccc(NC(=O)C(C)(C)C)cc1CSC(C)(C)C
InChIKey: SDHFXINHZHARIB-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Extracellular Cytochrome P450 Inhibition Assay: Specific aspects of the incubation conditions for each assay (e.g., protein concentration, incubation time, etc.) are defined in Walsky & Obach, 2004 (Walsky, R. L., and Obach, R. S. Validated assays for human Cytochrome P450 activities. Drug Met. Disp. 32:647-660, 2004.). In general, microsomes at protein concentrations as defined in Table 12 were mixed with buffer (100 mM KH2PO4, pH 7.4), MgCl2 (6 mM)) and substrate, and were kept on ice. Aliquots of this mixture (89 μL) were delivered to each well of a 96-well polypropylene plate which contained an aliquot of inhibitor (1 μL) in acetonitrile:water (1:1). Final solvent concentrations were less than 1% (v/v). Incubations were initiated with the addition of 10 μL β-NADPH (10 mM stock) to a final volume of 100 μL. Incubations were terminated by the addition of 1.5-2× volume of acetonitrile containing internal standard (buspirone). Samples were centrifuged at 4° C., and supernatant was transferred for LC-MS/MS analysis.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 459.61, ALogP 6.13, HBA 5, HBD 2, PSA 84.86, QED 0.49
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(F)(F)F)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: UQZCQKXJAXKZQH-LBPRGKRZSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human recombinant N-terminal GST-tagged PARP5b (667 to 1166 end residues) expressed in baculovirus infected Sf9 cells expression system incubated for 1 hr by ELISA assay
Measurement: IC50 = 3446 nM (pChEMBL 5.460000038146973)
Descriptors: MW 523.44, ALogP 2.15, HBA 8, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): COc1ccc(Cl)c(C(=O)N2C3CCC2CN(Cc2c(-c4ccc(C(C)C)cc4)nc4ncccn24)C3)n1
InChIKey: VDKJCAWGDJJKNL-UHFFFAOYSA-N
Target: Potassium channel subfamily K member 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPC2
Assay: Inhibition of Recombinant TASK-1 and TASK-3 In Vitro: The investigations on the inhibition of the recombinant TASK-1 and TASK-3 channels were conducted using stably transfected CHO cells. The compounds according to the invention were tested in this case by application of 40 mM potassium chloride in the presence of a voltage-sensitive dye according to the method described in detail in the following references [Whiteaker et al., Validation of FLIPR membrane potential dye for high-throughput screening of potassium channel modulators, J. Biomol. Screen. 6 (5), 305-312 (2001); Molecular Devices FLIPR Application Note: Measuring membrane potential using the FLIPR® membrane potential assay kit on Fluorometric Imaging Plate Reader (FLIPR®) systems, http://www.moleculardevices.com/reagents-supplies/assay-kits/ion-channels/flipr-membrane-potential-assay-kits]. The activity of the test substances was determined as their ability to inhibit a depolarization induced in the recombinant cells by 40 mM potassium chloride. The concentration which can block half of this depolarization is referred to as IC50.
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 531.06, ALogP 5.07, HBA 7, HBD 0, PSA 75.86, QED 0.35
Compound (SMILES): COCc1nn(Cc2ccc(Cn3cc(F)ccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: ZRUFVDPYHLTYPD-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of KLK1 (unknown origin)
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 509.51, ALogP 2.9, HBA 8, HBD 1, PSA 100.27, QED 0.35
Compound (SMILES): COc1cc(N2CCC3(CCN(C)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: ZPCCNHQDFZCULN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin)
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 569.09, ALogP 6.19, HBA 8, HBD 2, PSA 82.62, QED 0.33
Compound (SMILES): CCOC(=O)C1=C(CN2CCN3C(=O)N(CC(C)(C)C(=O)O)C[C@@H]3C2)N=C(c2nccs2)N[C@H]1c1cccc(F)c1C
InChIKey: YLJBFYZGSKMBEZ-MBSDFSHPSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 598.7, ALogP 3.03, HBA 9, HBD 2, PSA 127.67, QED 0.42
Compound (SMILES): Cc1n[nH]c(C)c1-c1cnn(C2(CC#N)CN(c3cc(F)c(C(=O)N[C@@H](C)C(F)(F)F)cc3F)C2)c1
InChIKey: MSGYSFWCPOBHEV-AWEZNQCLSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 507.47, ALogP 3.98, HBA 6, HBD 2, PSA 102.63, QED 0.49
Compound (SMILES): CC(C)c1c2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2nn1C
InChIKey: LLFOBMRPWNABCB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/Cyclin D1 (unknown origin)
Measurement: IC50 = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 446.53, ALogP 3.84, HBA 8, HBD 2, PSA 83.79, QED 0.48
Compound (SMILES): C[C@H](CC[C@](C)(O)C(F)(F)F)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: BVBRUQYHUXKZMQ-JNVAYQLDSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 456.63, ALogP 7.05, HBA 2, HBD 2, PSA 40.46, QED 0.45
Compound (SMILES): Cc1ccc(NC(=O)N2CC[C@@H](CC(F)(F)F)C2)cc1-c1cc(N[C@H](C)CO)nc(N2CCOCC2)c1
InChIKey: GZMYLSJUNSCMTD-MOPGFXCFSA-N
Target: Epithelial discoidin domain-containing receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08345
Assay: Inhibition of wild type DDR1 (unknown origin) at in presence of ATP by hotspot kinase assay
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 521.58, ALogP 4.49, HBA 6, HBD 3, PSA 89.96, QED 0.5
Compound (SMILES): CC(C)N1CCOc2c(F)cc(-c3nc(Nc4ccc(C5CCN(C)CC5)cn4)ncc3F)cc21
InChIKey: YZSCPLGKKMSBMV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Adapta Assay: CDK7 (cyclin H): IC50 values of compounds against CDK7 (cyclin H) were determined by Adapta™ Assay at Invitrogen Life Technologies (Grand Island, N.Y.) where total reaction volume was 10 μL/well in low volume, white 384-well plate (#4512, Corning). 0.100 μL of 100× test compound in 100% DMSO (at specific solutions) were mixed with 2.4 μL of HEPES (30 mM), 2.5 μL of 4×ATP solution (153 μM) and 5 μL of 2× Substrate/Kinase mixture (the 2×CDK7/cyclin H/MNAT1/CDK7/9tide mixture was prepared in 50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA). The final 10 μL Kinase Reaction consisted of 5-38.75 ng CDK7/cyclin H/MNAT1 and 200 μM CDK7/9tide in 32.5 mM HEPES pH 7.5, 0.005% BRIJ-35, 5 mM MgCl2, 0.5 mM EGTA. The plates were shaken for 30 seconds, centrifuged for 1 min at 1000×g, and incubated for 60 minutes at room temperature. 5 μL of Detection Mix (prepared in TR-FRET Dilution Buffer; the Detection mix consists of EDTA (30 mM), Eu-anti-ADP antibody (6 nM) and ADP tracer, and contains the EC60 concentration of tracer for 5-150 μM ATP) was added to the plates followed with another 30-second plate shake and centrifugation for 1 min at 1000×g, and the plates were further incubated at room temperature for one hour. The plates were read on fluorescence plate reader with Dual emission at 615 nm and 665 nm.
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 480.56, ALogP 4.98, HBA 7, HBD 1, PSA 66.41, QED 0.55
Compound (SMILES): CNC1CN(c2nc3ncc(Br)cc3n3cnnc23)C1
InChIKey: MMVBKZHQTLDYKG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Assay method 3: The binding assays of the human serotonin 3 receptor for present invention were performed at Cerep (Poitiers, France).
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 334.18, ALogP 0.84, HBA 7, HBD 1, PSA 71.24, QED 0.75
Compound (SMILES): CC(C)CCN[C@@H]1CCc2cc(O)c(N3CC(=O)NS3(=O)=O)c(F)c2C1
InChIKey: DVFCRTGTEXUFIN-GFCCVEGCSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin)
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 385.46, ALogP 1.21, HBA 5, HBD 3, PSA 98.74, QED 0.71
Compound (SMILES): CO[C@@H]1CCN(c2nccc(Nc3cc4c(C(C)C)ccc(N5C[C@H](CS(C)(=O)=O)[C@H]5C)c4cn3)n2)C[C@@H]1F
InChIKey: LIMFPAAAIVQRRD-BCGVJQADSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR in human A-431 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 544 nM (pChEMBL 6.260000228881836)
Descriptors: MW 556.71, ALogP 4.32, HBA 9, HBD 1, PSA 100.55, QED 0.43
Compound (SMILES): O=C1COc2ccc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc2N1
InChIKey: PMKMNTBZJOXTJW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Radioligand Binding Assay: Serotonin, 5HT1A: Materials and Methods:Receptor Source: Human recombinant 5-HT1A expressed mammalian cellsRadioligand: [3H]-8-OH-DPAT (221 Ci/mmol)Control Compound: 8-OH-DPATIncubation Conditions: The reactions were carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mM MgSO4, 0.5 mM EDTA and 0.1% Ascorbic acid at room temperature for 1 hour. The reaction was terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters was determined and compared to control values in order to ascertain any interactions of test compounds with the cloned serotonin5HT1A binding site
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 450.37, ALogP 4.31, HBA 5, HBD 1, PSA 54.04, QED 0.64
Compound (SMILES): COC[C@H](NC(=O)c1ccn(S(C)(=O)=O)c1)C(=O)Nc1nc(-c2cccc(N3C[C@@H](C)O[C@@H](C)C3)n2)cs1
InChIKey: JBLQNFBXKOAIHG-FCEWJHQRSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Inhibition of BRG1 in human MDA-MB-231 cells co-transfected with MMTV incubated for 6 hrs by bright-glo luciferase assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 562.67, ALogP 1.81, HBA 11, HBD 2, PSA 144.75, QED 0.4
Compound (SMILES): Oc1ccc2c3c(cnc2c1)-c1ccc(C(F)(F)F)cc1O[C@@H]3c1ccc(OCCN2CC(CF)C2)cc1
InChIKey: UVBQMXOKKDCBJN-MUUNZHRXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: ERalpha (Wild Type), ERalpha (Y537ERalpha (Wild Type), ERalph (Y537S Mutant) and ERbeta Competition Binding Assay: The purpose of the following ER competition binding assays is to determine the affinity of a test compound against ERα (wild type), ERα (Y537S mutant), and ERβ.Run the competition binding assay in a buffer containing 50 mM HEPES, pH 7.5, 1.5 mM EDTA, 150 mM NaCl, 10% glycerol, 1 mg/mL ovalbumin, and 5 mM DTT, using 0.025 μCi per well 3H-estradiol (118 μCi/mmol, 1 mCi/mL), 7.2 ng/well ERα (wild type), or 7.2 ng/well ERα (Y537S mutant) or 7.7 ng/well ERβ receptor. Add the test compound at 10 different concentrations ranging from 10,000 nM to 0.5 nM, and determine nonspecific binding in the presence of 1 μM of 17-β estradiol. Incubate the binding reaction (140 μL) for 4 hours at room temperature, and then add cold dextran-charcoal buffer (70 μL) (containing per 50 mL of assay buffer, 0.75 g of charcoal and 0.25 g of dextran) to each reaction. Mix the plates for 8 minutes on an orbital shaker at 4° C. and then centrifuge at 3000 rpm at 4° C. for 10 minutes. Transfer an aliquot (120 μL) of the mixture to another 96-well, white flat bottom plate (Costar) and add Perkin Elmer Optiphase Supermix scintillation fluid (175 μL) to each well. Seal the plates and shake vigorously on an orbital shaker. After an incubation of 2.5 hours, read the plates in a Wallac Microbeta counter. Calculate the IC50 using a 4-parameter logistic curve fit and calculate % inhibition at 10 μM. Convert the IC50 values for the compound to Ki using Cheng-Prusoff equation. The results of this assay demonstrate Examples 1, 1A, and 1B (and others) bind to recombinant ERα wild type and ERα mutant (Y537S) as shown in Table 7 below and Example 1B was also determined to bind to ERβ with a Ki (nM) ERβ competition of 0.11±0.07, n=3.
Measurement: Ki = 2.79 nM (pChEMBL 8.550000190734863)
Descriptors: MW 524.51, ALogP 6.39, HBA 5, HBD 1, PSA 54.82, QED 0.3
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: TVGAHWWPABTBCX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-tagged PDGFRbeta (unknown origin) (557 to 1106 residues) measured by spectrophotometric analysis
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 431.5, ALogP 3.56, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): C[C@@H](N)c1cc(Cl)ccc1Cn1c(=S)[nH]c(=O)c2[nH]ccc21
InChIKey: BHKKSKOHRFHHIN-MRVPVSSYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of MPO in human HL-60 cells measured after 15 mins in presence of H2O2 by chemiluminescence assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 334.83, ALogP 3.11, HBA 4, HBD 3, PSA 79.6, QED 0.64
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4ccc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: WQAVGRAETZEADU-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Binding affinity to PARP10 (unknown origin) assessed as apparent dissociation constant
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): CNC(=O)c1ccc(N2CCN(Cc3ccc4nc(C)c(=O)[nH]c4c3F)CC2)c(F)n1
InChIKey: WXRCLFFPZXJCLS-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin) expressed in Escherichia coli BL21 incubated for 60 mins
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 428.44, ALogP 1.59, HBA 6, HBD 2, PSA 94.22, QED 0.61
Compound (SMILES): Cc1cnc(-c2cc(O[C@@H]3CCOC3)cc(C(=O)N[C@H](C)c3cnc(C(F)(F)F)nc3)c2)s1
InChIKey: GTQPEQGDLVSFJO-CXAGYDPISA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: CYP Inhibition and Pre-Incubation CYP Inhibition Assays: Use of in vitro assays to evaluate the inhibition potential of new drug candidates towards CYP-mediated metabolism has been shown to be effective as part of a strategy to minimise the chances of drug interactions with co-administered drugs. The inhibitory potency of the test compound towards 5 human cytochrome P450 isoforms (CYP1A2, 2C8, 2C9, 2D6, and 3A4) was determined. More preferred examples of the present invention have CYP inhibition IC50≥10 μM.For CYP3A4 time dependent inhibitory potential was also tested by applying a 30 min pre-incubation time of the test compound in metabolically active incubation system. If a time-dependent inhibition of CYP3A4 is observed, this is a hint of an irreversible mechanism-based inhibition of the CYP3A4 activity by the test compound. More preferred examples of the present invention have pre-incubation CYP inhibition IC50≥20 μM.Method Description CYP Inhibition AssayHuman liver microsomes (pooled, >30 male and female donors) were incubated with individual CYP isoform-selective standard probes (phenacetin for CYP1A2, amodiquine for CYP2C8, diclofenac for CYP2C9, dextromethorphan for CYP2D6 and midazolam for CYP3A4) in the absence and presence of increasing concentrations of the test compound in order to compare the extent of formation of the respective metabolite. In addition, a set of incubation in the absence of test compound was used as a negative control. Furthermore, the inhibitory potency of standard inhibitors was included as positive controls (fluvoxamine for CYP1A2, montelukast for CYP2C8, sulfaphenazole for CYP2C9, fluoxetine for CYP2D6, ketoconazole for CYP3A4 and mibefradil for CYP3A4-preincubation). Incubation conditions (protein and probe substrate concentration, incubation time) were optimised with regard to linearity and metabolite turnover. Incubation medium consisted of 50 mM potassium phosphate buffer (pH 7.4) containing 1 mM EDTA, NADPH regenerating system (1 mM NADP, 5 mM glucose 6-phosphate, glucose 6-phosphate dehydrogenase (1.5 U/mL). Sequential dilutions and incubations were performed on a Genesis Workstation (Tecan, Crailsheim, FRG) in 96-well plates at 37° C. A final incubation volume of 200 μL was used. Reactions were stopped by addition of 100 μL acetonitrile containing the respective internal standard. Precipitated proteins were removed by centrifugation of the well plate, supernatants were combined and analyses were performed by LC-MS/MS. The LC-MS/MS quantification of the metabolites paracetamol (CYP1A2), desethylamodiaquine (CYP2C8), 4-hydroxydiclofenac (CYP2C9), dextrorphan (CYP2D6), and 1-hydroxyidazolam (CYP3A4) was performed with a PE SCIEX API 3000 LC/MS/MS system (Applied Biosystems, MDS Sciex, Concord, Ontario, Canada).
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 478.5, ALogP 4.59, HBA 7, HBD 1, PSA 86.23, QED 0.56
Compound (SMILES): NCCCC[C@H](NC(=O)C1CCCC1)C(=O)COc1c(F)ccc(F)c1F
InChIKey: OLIMBXKACVCIMM-HNNXBMFYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of Lysine Gingipain: The capacities of compounds of the present invention to inhibit the activity of lysine gingipain were measured in a fluorogenic assay similar to those described by Barret (Biochemical Journal. 1980, 187(3), 909). The specific assay conditions were as follows. Buffer: pH=7.5, 100 mM Tris-HCl, 75 mM NaCl, 2.5 mM CaCl2), 10 mM cysteine, 1% DMSO after all additions. Protein: 0.1 nM Kgp, isolated from culture of Porphyromonas gingivalis, as described by Pike et al. (J. Biol. Chem. 1994, 269(1), 406), and Potempa and Nguyen (Current Protocols in Protein Science. 2007, 21.20.1-21.20.27). Fluorogenic substrate: 10 μM Z-His-Glu-Lys-MCA. Time=90 minutes. Temperature=37° C. Each compound: 10 concentrations, starting at either 100 μM or 100 nM, with lower concentrations generated by serial 3-fold dilutions. By testing a range of concentrations for each compound, the concentration required to inhibit the activity of lysine gingipain by 50% (the IC50) was determined. Under the described assay conditions, the signal-to-noise ratio was excellent, and the Z factor was greater than 0.6. Compounds in Table 1 were tested, as well as the compounds set forth in Table 2 below.The capacities of compounds of the present invention to inhibit the activity of cathepsins B, H, K, L, and S were measured in similar assays. Boc-Leu-Arg-Arg-AMC (20 μM) in sodium acetate buffer (50 mM, pH 5.5) containing DTT (1 mM) and EDTA (2 mM) was used for the Cathepsin B assay. L-Arg-AMC (20 μM) in sodium acetate buffer (50 mM, pH 5.5) containing DTT (1 mM) and EDTA (2 mM) was used for the Cathepsin H assay. Z-Phe-Arg-AMC (10 μM) in HEPES buffer (50 mM, pH 7.4) containing DTT (2.5 mM) and EDTA (1 mM) was used for the Cathepsin K assay. Z-Phe-Arg-AMC (20 μM) in sodium acetate buffer (50 mM, pH 5.5) containing DTT (1 mM) and EDTA (2 mM) was used for the Cathepsin L assay. Z-Leu-Arg-AMC (10 μM) in sodium acetate buffer (25 mM, pH 4.5) containing DTT (2.5 mM) and NaCl (50 mM) was used for the Cathepsin S assay.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 386.41, ALogP 2.86, HBA 4, HBD 2, PSA 81.42, QED 0.48
Compound (SMILES): CC(=O)N1CCN([C@H]2CCC[C@@H](NC(=O)c3cc4c(F)ccc(C)c4[nH]3)C2)CC1
InChIKey: PGNLXEBQMQHFNK-SJORKVTESA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 5 mins followed by NADPH addition measured after 20 mins by LC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 400.5, ALogP 2.82, HBA 3, HBD 2, PSA 68.44, QED 0.83
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1nccc(OC)c1F
InChIKey: KGMPDQIYDKKXRD-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes assessed as reduction in hydroxybupropion metabolite formation incubated for 30 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 491.52, ALogP 2.76, HBA 8, HBD 1, PSA 100.27, QED 0.37
Compound (SMILES): Cc1c(Nc2c(F)ccc(NS(=O)(=O)CCCF)c2Cl)ccc2ncn(C)c(=O)c12
InChIKey: VVLVISDSGRHLMB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: BRAF V600E and V600K Enzyme Assay: A competitive displacement assay was configured for B-Raf that monitors the amount of a fluorescently-tagged tracer bound to B-Raf via TR-FRET from an anti-tag Eu-labeled antibody also bound to B-Raf. For full-length FLAG-tagged B-Raf(V600E), the assay mixtures consisted of 25 mM K+HEPES, pH 7.4, 10 mM MgCl2, 0.01% Triton X-100, 1 mM DTT, 2% DMSO (from compound), 50 nM Tracer 1710 (ThermoFisher, PR9176A), 0.5 nM Eu anti-FLAG (M2)-cryptate Ab (Cisbio, 61FG2KLB) and 5 nM full-length, N-terminally FLAG-tagged B-Raf(V600E) (Origene Technologies, TP700031. When B-Raf(V600K) was assayed, the following substitutions were made: 15 nM Tracer 178 (ThermoFisher, PV5593), 2 nM Eu-anti-GST Ab (ThermoFisher, PV5595) and 5 nM N-terminally GST-tagged B-Raf(V600K) (331-end, SignalChem, B08-12DG). Compounds were typically diluted in DMSO across an 11-point dosing range created using a 3-fold serial dilution protocol at a top dose of 10 μM. The assay was run in 384-well, polystyrene, low-volume, non-treated, white microtiter plates (Costar 4512) in a final volume of 12 μL. Low control wells included 1 μM of a potent B-Raf inhibitor as a control.
Measurement: IC50 = 4.25 nM (pChEMBL 8.369999885559082)
Descriptors: MW 456.9, ALogP 3.88, HBA 6, HBD 2, PSA 93.09, QED 0.56
Compound (SMILES): C[C@@H]1COCCN1c1cc([C@]2(O)C[C@H]3CC[C@@H](C2)O3)c2cnn(-c3cc[nH]n3)c2n1
InChIKey: YIHHYCIYAIVQKX-MBIULKOWSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in gemcitabine-stimulated human LoVo cells assessed as decrease in CHK1 phosphorylation at Ser345 residue
Measurement: IC50 = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 410.48, ALogP 1.9, HBA 8, HBD 2, PSA 101.32, QED 0.68
Compound (SMILES): COc1nsc(NC(=O)N2C[C@H]3C[C@H](N(C)c4ncnc5[nH]ccc45)C[C@H]3C2)n1
InChIKey: DNBCBAXDWNDRNO-GDNZZTSVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: In vitro kinase assays described below can be used to determine the activity of a test compound for inhibiting the activity of JAK2 kinase. The test compounds were dissolved in dimethyl sulfoxide and diluted with water to a serial concentration gradient as required in the experiment. JAK2 substrates (Cell Signaling Technology, Catalog Number: 1305s) and ATP (2 mM) solution were diluted with water to obtain a final concentration of 20 uM ATP and 1.2 uM substrate solution. The appropriate amount of JAK2 kinase (Invitrogen, Catalog Number: pv4210) was mixed with 4x buffer (prepared by user, and comprising 50 mM HEPES, pH 7.3, 125 mM NaCl, 24 mM MgCl2, 1.25 mM DTT) to a final concentration of 8 ng/uL. To each well of a microplate [DELFIA Streptavidin-coated clear plate (Perkin Elmer, Catalog Number: AAAND-0005)]17.5 uL of ATP/substrate mixture, 5 uL of aqueous solution of a test compound (5 uL of pure water only were added to control and blank), and 7.5 uL of the kinase solution prepared above (4x buffer only was added to control) were added. Each well was mixed sufficiently, then incubated at room temperature (27° C.) for 50 minutes, washed with wash buffer, and dried three times, then HRP conjugated antibody [Phospho-Tyrosine Mouse mAb (P-Tyr-100) (HRP Conjugate, Cell signaling Technology, Catalog Number: 5465)] was added, and incubated for 1 hour. The microplate was washed with wash buffer and dried three times, and then TMB (Sigma, Catalog Number: T4444) was added and incubated for 5 to 15 minutes to allow for color change. Stop solution (1 N sulfuric acid solution) was added to stop the reaction. Absorbance was measured on a Novostar microplate reader at a wavelength of 450 nm. IC50 values of test compounds were calculated from the data of the test compounds for inhibiting the activity of JAK2 kinase at different concentrations.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 414.5, ALogP 2.2, HBA 8, HBD 2, PSA 112.16, QED 0.67
Compound (SMILES): CC1(C)Cn2nc(-c3ccc(F)cn3)c(-c3ccnc4[nH]ncc34)c2CO1
InChIKey: WZMIWVZGYMKUDV-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 364.38, ALogP 3.33, HBA 6, HBD 1, PSA 81.51, QED 0.59
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human CK1epsilon expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)c2cc(-c3cccc(Cl)c3)nc3ccccc23)cc1
InChIKey: CGEUZPONROHUFH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 72.8 nM (pChEMBL 7.139999866485596)
Descriptors: MW 437.91, ALogP 4.45, HBA 4, HBD 2, PSA 102.15, QED 0.49
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOCCOc1cc(Cl)ccc1N3
InChIKey: ZWNHCTNZGMTQTA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) L858R/T790M mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 = 326 nM (pChEMBL 6.489999771118164)
Descriptors: MW 431.88, ALogP 3.84, HBA 8, HBD 1, PSA 83.96, QED 0.62
Compound (SMILES): CCCCCCCCOc1c2cccc1Cc1cc(C(=O)P(=O)(O)O)cc(c1O)Cc1cccc(c1OCCCCCCCC)Cc1cc(C(=O)P(=O)(O)O)cc(c1O)C2
InChIKey: GJHAXLHKYOVJBX-UHFFFAOYSA-N
Target: Glutathione S-transferase P (SINGLE PROTEIN), Homo sapiens
UniProt: P09211
Assay: Inhibition of recombinant human GSTP1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 864.91, ALogP 9.89, HBA 8, HBD 6, PSA 208.12, QED 0.03
Compound (SMILES): CC(C)C(=O)Nc1ncc(C(=O)NCCN(Cc2ccccc2)C(=O)c2ccc(S(=O)(=O)Nc3ccccc3)cc2)s1
InChIKey: YVPYJSSYGACUSE-UHFFFAOYSA-N
Target: LIM domain kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P53671
Assay: Inhibition of recombinant LIMK2 (330 to 632 residues) (unknown origin) expressed in baculovirus infected insect cells using CFL1 as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by RapidFire mass spectrometry
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 605.74, ALogP 4.61, HBA 7, HBD 3, PSA 137.57, QED 0.22
Compound (SMILES): N#Cc1ccc(Nc2ccc3[nH]nc(-c4ccncc4)c3c2)c(C#N)c1
InChIKey: PKFBFGKCNDVUJU-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of pcDNA5FRT-TO-GFP fused - LRRK2 G2019S mutant (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 336.36, ALogP 4.11, HBA 5, HBD 2, PSA 101.18, QED 0.59
Compound (SMILES): CN(CCCNC(=O)c1cc2ccccc2o1)Cc1ccccc1
InChIKey: JOJSGPZOAORNJM-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Binding affinity to DOR (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 322.41, ALogP 3.68, HBA 3, HBD 1, PSA 45.48, QED 0.67
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)CC(=O)N3)[C@H]2C[C@H]21)c1ccc(Cl)cc1
InChIKey: RXNPEQZHMGFNAY-GEALJGNFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes at 0.01 to 30 uM using phenacetin as substrate in presence of NADPH by UPLC-MS/MS analysis
Measurement: IC50 = 15200 nM (pChEMBL 4.820000171661377)
Descriptors: MW 483.02, ALogP 3.15, HBA 6, HBD 2, PSA 90.46, QED 0.66
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H](NC(=O)CN)CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](CC(N)=O)C(=O)N4C[C@@H](O)C[C@H]4C(=O)N4C[C@@H](O)C[C@H]4C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)O)NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC(=O)CNC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC1=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC2=O
InChIKey: ZVNYDGYMISSIMY-MCQYGHRBSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Modulator activity at human Nav1.5 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay
Measurement: EC50 = 132.7 nM (pChEMBL 6.880000114440918)
Descriptors: MW 3318.76
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc3c(c2)C(F)(F)C[C@@H]3N2CCN(C)CC2)cc1C#Cc1cnc2cccnn12
InChIKey: BPLVEFPXYUJTQJ-MHZLTWQESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 11100 nM (pChEMBL 4.960000038146973)
Descriptors: MW 526.59, ALogP 4.47, HBA 6, HBD 1, PSA 65.77, QED 0.4
Compound (SMILES): Nc1nc(-c2ccc(OCCCN3CCCCC3)cc2)c2c(n1)-c1ccc(OCCCN3CCCCC3)cc1C2
InChIKey: WBLFYMQYQYGVGK-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H] N-alpha methylhistamine from human recombinant histamine H3 receptor expressed in HEK293 cells measured after 90 mins
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 541.74, ALogP 5.81, HBA 7, HBD 1, PSA 76.74, QED 0.24
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@H](Cc1ccccc1)C(=O)N(C)[C@@H](CCCNC(=N)N)C(=O)N(C)[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: YMCLJESYNLOGEG-SOJQCDDKSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 1695.06
Compound (SMILES): O=C1NC2(CC2)COc2ncc(F)cc2[C@H]2CCCCN2c2ccn3ncc1c3n2
InChIKey: WUOOWFKJQHKXHK-MRXNPFEDSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin) incubated for 120 mins in presence of 33P-ATP
Measurement: IC50 = 18.5 nM (pChEMBL 7.730000019073486)
Descriptors: MW 408.44, ALogP 2.65, HBA 7, HBD 1, PSA 84.65, QED 0.62
Compound (SMILES): C=CC(=O)Nc1cc(N2CCN(C)CC2)ccc1Nc1ncc2c(n1)-n1ccc(C(=O)Nc3c(CC)cccc3CC)c1CC2
InChIKey: QMTKZAHTDPRIFJ-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Covalent inhibition of human full length N-terminal GST-fused MPS1 (1 to 857 residues) assessed as inhibition constant by TR-FRET assay
Measurement: Ki = 14.2 nM (pChEMBL 7.849999904632568)
Descriptors: MW 604.76, ALogP 5.36, HBA 8, HBD 3, PSA 107.42, QED 0.22
Compound (SMILES): CNS(=O)(=O)c1cc(-c2sc(Nc3cccc(N4C[C@H](O)CC4=O)n3)nc2C)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: IUKKLFSDRNELCN-HNAYVOBHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Enzymatic Activity Assay : The activity of recombinant human PI3Kγ ((aa144-1102)-6His) and PI3Kα, β, δ (6-His(p110-p85α)) was determined by measuring the ADP level after phosphorylation of DiC8-PIP2 using a commercially available ADP-Glo kit from Promega. The assay was carried out in white low volume 384 well plates in a final volume of 14 μl at R.T. The assay conditions contained the following: 50 mM Tris buffer pH 7.4, 2.1 mM DTT, 3 mM MgCl2, 0.05% CHAPS, 20 μM ATP, 80 μM DiC8-PIP2 and 1.2 nM PI3Kα, β, γ or 0.6 nM PI3Kδ. Potential inhibitors were made up in DMSO and then diluted in the assay to give a final concentration of not exceeding 1% (v/v) DMSO. A 10-point half-log dilution series of the inhibitors (highest concentration typically 0.1 μM for δ or γ and 33 μM for a or 1) was tested and the pIC50 determined using a 4-parameter logistic equation in a non-linear curve fitting routine. Routinely, inhibitors were pre-incubated with 3 μl of enzyme for 15 min prior to the addition of 2 μl substrate mixture for a further 60 min enzyme reaction. The phosphorylation was stopped with the addition of 3 μl ADP-Glo reagent (stop solution) followed by a 40 min incubation. Prior to detection 6 μl of ADP-Glo Kinase Detection Reagent was added and the plates were read in a micro plate reader using a Luminescence filter. All additions were followed by a short centrifugation step.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 582.71, ALogP 3.02, HBA 9, HBD 3, PSA 144.83, QED 0.37
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(N[C@@H](C)CO)c2nc(NCCOCCN(C)C)ncc2c1
InChIKey: XXYVYULKAZLNBS-INIZCTEOSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human TYK2 (888 to 1178 residues) expressed in insect cells using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 30 mins in presence of ATP by FRET assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 471.58, ALogP 3.49, HBA 8, HBD 4, PSA 102.77, QED 0.3
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@H](Cc1ccccc1)C(=O)N(C)[C@@H](CCCNC(=N)N)C(=O)N(C)[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: VDHCRROJIVFVLM-BCHBBXIYSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 1995.38
Compound (SMILES): O=C(NCCCn1ccnc1)c1cc2nc(-c3ccccc3)cc(-c3ccccc3)n2n1
InChIKey: RIGHCDSORZCRDE-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: HyPerBlu KDM1A enzymatic assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 422.49, ALogP 4.08, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](C)C(=O)N2
InChIKey: LICCWOCOLMEXQP-HKMYQXKPSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16-23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 707.95 nM (pChEMBL 6.150000095367432)
Descriptors: MW 1826.19
Compound (SMILES): CCNCCc1ccc(Cl)c(-c2ccccc2OC)c1.Cl
InChIKey: SXOXLJQRLIFVCQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5-HT1AR (unknown origin)
Measurement: Ki = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 289.81, ALogP 4.17, HBA 2, HBD 1, PSA 21.26, QED 0.81
Compound (SMILES): CN1CCN(c2cc(F)c(-c3ccc(C(=O)N(C)C)cc3)cc2Nc2ncnc(Cl)c2N)CC1
InChIKey: LXONEMNSYOAQJT-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of DOT1L (unknown origin) assessed as effect on H3K79 methylation incubated for 30 mins by Alphascreen assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 483.98, ALogP 3.72, HBA 7, HBD 2, PSA 90.62, QED 0.53
Compound (SMILES): Nc1nc(-c2ccccc2)c2c(n1)-c1ccc(OCCCN3CCCC3)cc1C2
InChIKey: CQKVWEYZUVUWJT-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H] N-alpha methylhistamine from human recombinant histamine H3 receptor expressed in HEK293 cells measured after 90 mins
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 386.5, ALogP 4.16, HBA 5, HBD 1, PSA 64.27, QED 0.5
Compound (SMILES): COc1cc(CN(c2cc(-c3cc(OC4CCOCC4)c4ncnc(C)c4c3)cnc2OC)S(=O)(=O)c2ccc(F)cc2F)c([N+](=O)[O-])cc1OC
InChIKey: MZNFIPXMASIVMQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K alpha (unknown origin) using PIP2 as substrate irradiated with 365 nm of UV exposure for 2 mins and incubation in dark at room temperature for 1 hr in presence of ATP measured by ADP-Glo luminescent assay
Measurement: IC50 = 0.58 nM (pChEMBL 9.239999771118164)
Descriptors: MW 737.74, ALogP 6.17, HBA 12, HBD 0, PSA 165.34, QED 0.11
Compound (SMILES): Cc1nc(Nc2cccc(N3CCCC3=O)n2)sc1-c1cc2c(c(S(=O)(=O)NC3COC3)c1)C(=O)N([C@@H](C)C1CC1)C2
InChIKey: BHFJVMZATJXYCO-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Enzymatic Activity Assay : The activity of recombinant human PI3Kγ ((aa144-1102)-6His) and PI3Kα, β, δ (6-His(p110-p85α)) was determined by measuring the ADP level after phosphorylation of DiC8-PIP2 using a commercially available ADP-Glo kit from Promega. The assay was carried out in white low volume 384 well plates in a final volume of 14 μl at R.T. The assay conditions contained the following: 50 mM Tris buffer pH 7.4, 2.1 mM DTT, 3 mM MgCl2, 0.05% CHAPS, 20 μM ATP, 80 μM DiC8-PIP2 and 1.2 nM PI3Kα, β, γ or 0.6 nM PI3Kδ. Potential inhibitors were made up in DMSO and then diluted in the assay to give a final concentration of not exceeding 1% (v/v) DMSO. A 10-point half-log dilution series of the inhibitors (highest concentration typically 0.1 μM for δ or γ and 33 μM for a or 1) was tested and the pIC50 determined using a 4-parameter logistic equation in a non-linear curve fitting routine. Routinely, inhibitors were pre-incubated with 3 μl of enzyme for 15 min prior to the addition of 2 μl substrate mixture for a further 60 min enzyme reaction. The phosphorylation was stopped with the addition of 3 μl ADP-Glo reagent (stop solution) followed by a 40 min incubation. Prior to detection 6 μl of ADP-Glo Kinase Detection Reagent was added and the plates were read in a micro plate reader using a Luminescence filter. All additions were followed by a short centrifugation step.
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 608.75, ALogP 3.82, HBA 9, HBD 2, PSA 133.83, QED 0.37
Compound (SMILES): CC(C)Oc1ccc(-c2c[nH]cc2CN(C)CCO)cc1
InChIKey: GNAKYUUZAXUXKB-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Selectivity interaction (Scintillation proximity assay) EUB0000261b PRMT1
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 288.39, ALogP 2.89, HBA 3, HBD 2, PSA 48.49, QED 0.82
Compound (SMILES): Nc1nc(-c2ccccc2)c2c(n1)-c1ccc(OCCCN3CCCCC3)cc1C2
InChIKey: ZMHMTMQAABMRBO-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H] N-alpha methylhistamine from human recombinant histamine H3 receptor expressed in HEK293 cells measured after 90 mins
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 400.53, ALogP 4.55, HBA 5, HBD 1, PSA 64.27, QED 0.48
Compound (SMILES): CCCN(CCC)CCc1ccc(Cl)c(-c2ccccc2OC)c1
InChIKey: IOJLDPRGTSPRBT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5-HT1AR (unknown origin)
Measurement: Ki = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 345.91, ALogP 5.68, HBA 2, HBD 0, PSA 12.47, QED 0.58
Compound (SMILES): Cl.O=C(CCc1ccco1)N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: KUOBSOJCPUJLSG-CHKFEDFBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 3.55 nM (pChEMBL 8.449999809265137)
Descriptors: MW 464.56, ALogP 2.67, HBA 6, HBD 3, PSA 95.17, QED 0.61
Compound (SMILES): CCC(=O)N(c1ccc(Cl)c(Cl)c1)C1CCN(C(=O)[C@H](Cc2ccc(Cl)cc2)NC(=O)CNC(=O)[C@H]2Cc3ccccc3CN2C(=O)[C@@H](N)Cc2cc(C)c(O)c(C)c2)CC1
InChIKey: JVAGZHNHHXCZDH-XUTHUYCTSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in mouse HN9.10 cells by radioligand binding assay
Measurement: IC50 = 1.905 nM (pChEMBL 8.720000267028809)
Descriptors: MW 890.31, ALogP 6.07, HBA 7, HBD 4, PSA 165.38, QED 0.13