lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCNNC(=O)c1ccc2ccccc2c1
InChIKey: KAROTAWAKPGPJD-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 1790 nM (pChEMBL 5.75)
Descriptors: MW 242.32, ALogP 2.87, HBA 2, HBD 2, PSA 41.13, QED 0.62
Compound (SMILES): CC(C)C(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: RWOHIVZSQHNUEH-NRFANRHFSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki < 0.28 nM (pChEMBL 9.553000450134277)
Descriptors: MW 442.52, ALogP 0.38, HBA 10, HBD 3, PSA 142.62, QED 0.57
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N2Cc3ccc(O)cc3C[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: HSTHLZHYPGORFI-IZFFCAOBSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 1.72 nM (pChEMBL 8.760000228881836)
Descriptors: MW 1406.7
Compound (SMILES): O=C(CCCCCNC(=O)COc1ccc(/C=C/C2=[N+]3C(=Cc4ccc(-c5cccs5)n4[B-]3(F)F)C=C2)cc1)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WRUQALAONUATIE-OIWVIQBMSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes measured after 3 hrs by radioligand competition binding assay
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 1117.15
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@@H]1CCN(Cc2cccc(OC)c2)C[C@H]1F
InChIKey: QYCQCEJRCQDCKL-RTBURBONSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 493.2 nM (pChEMBL 6.309999942779541)
Descriptors: MW 411.48, ALogP 2.96, HBA 5, HBD 3, PSA 82.28, QED 0.58
Compound (SMILES): CC(C)c1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(Cl)c1
InChIKey: QWMKBPOOVMOXIR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7b expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 3904 nM (pChEMBL 5.409999847412109)
Descriptors: MW 419.94, ALogP 2.85, HBA 7, HBD 1, PSA 80.12, QED 0.7
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: MFLAVNPTRFOLPB-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase F227L/V106A double mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 575.72, ALogP 4.7, HBA 9, HBD 2, PSA 137.47, QED 0.29
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC1(F)CC1
InChIKey: YZMMWVWLDOCLCK-CLYVBNDRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: ERalpha Binding Assay: The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.In total 120 nL of compound plus DMSO were added to each well and compounds were tested in a 12-point concentration response format over a final compound concentration range of 10, 2.917, 1.042, 0.2083, 0.1, 0.0292, 0.0104, 0.002083, 0.001, 0.0002917, 0.0001042, and 0.00001 μM respectively. TR-FRET dose response data obtained with each compound was exported into a suitable software package (such as Origin or Genedata) to perform curve fitting analysis. Competitive ER alpha binding was expressed as an IC50 value.
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 495.62, ALogP 4.87, HBA 5, HBD 2, PSA 56.42, QED 0.44
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(C5CNCCN5)cc4)ccn23)c2ccccc2n1
InChIKey: UQEFQNWFVJXGDE-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 419.53, ALogP 4.76, HBA 5, HBD 2, PSA 54.25, QED 0.44
Compound (SMILES): COc1cccc(Cn2cnc3ccc(-c4cn[nH]c4)cc3c2=O)c1
InChIKey: QQJKCGXOHWHBQV-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P43250
Assay: Inhibition of human GRK6
Measurement: IC50 = 3270 nM (pChEMBL 5.489999771118164)
Descriptors: MW 332.36, ALogP 2.84, HBA 5, HBD 1, PSA 72.8, QED 0.62
Compound (SMILES): Cc1cc(F)cnc1N1CCN(C(=O)CCCc2cccc3ncccc23)[C@@H](C)C1
InChIKey: OIZGGNJJLMUGKL-SFHVURJKSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human recombinant muscarinic receptor M1 expressed in CHO-K1 cells assessed as EC80 acetylcholine-induced calcium flux incubated for 30 mins
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 406.51, ALogP 4.14, HBA 4, HBD 0, PSA 49.33, QED 0.64
Compound (SMILES): Cl.Clc1cccc(COc2cncc(N3CCNCC3)n2)c1
InChIKey: NMUNRTCTDLORDR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: PDSP Secondary Binding target: CHRM5 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 293.13 nM (pChEMBL 6.53000020980835)
Descriptors: MW 304.78, ALogP 2.12, HBA 5, HBD 1, PSA 50.28, QED 0.94
Compound (SMILES): CC(C)[C@@H](Nc1nc(I)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(CO)C[C@H]12)C1CC1
InChIKey: QRTOZRNSWLTZJK-XRPRFISDSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from human 5-HT2C expressed in Flp-In-T-REx-293 cells assessed as inhibition constant incubated for 1 hr
Measurement: Ki = 904 nM (pChEMBL 6.039999961853027)
Descriptors: MW 499.35, ALogP 1.55, HBA 8, HBD 4, PSA 116.32, QED 0.35
Compound (SMILES): COc1ccccc1N1CCN(CCCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: YCZWURFQDCDNKN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 11.3 nM (pChEMBL 7.949999809265137)
Descriptors: MW 423.56, ALogP 3.3, HBA 5, HBD 0, PSA 45.25, QED 0.61
Compound (SMILES): CC(C)C(=O)Nc1nc(-c2ccc(O)cc2O)cs1
InChIKey: WIDNAJNXDPHROL-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Homo sapiens
UniProt: P14679
Assay: Inhibition of human His-tagged tyrosinase expressed in HEK 293 cells using L-DOPA as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 278.33, ALogP 2.82, HBA 5, HBD 3, PSA 82.45, QED 0.81
Compound (SMILES): CNC(=O)NC1CCN(C(=O)[C@@H](CCCCN)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](Cc2ccccc2)NC(=O)CNC[C@H](C)c2ccccc2)CC1
InChIKey: POEKRJYEMCDIMO-SPYAMJAOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human pooled liver microsomes using dextromethorphan as substrate measured up to 20 mins by UHPLC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 720.96, ALogP 2.17, HBA 7, HBD 7, PSA 186.79, QED 0.1
Compound (SMILES): CS(=O)(=O)Nc1ccccc1Nc1nc(Nc2ccc3nc(CN4CCCCC4)[nH]c3c2)ncc1Cl
InChIKey: KHFZOBVPJLNOME-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged human FLT3 cytoplasmic domain (564 to 993 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 = 185.5 nM (pChEMBL 6.730000019073486)
Descriptors: MW 527.05, ALogP 4.85, HBA 8, HBD 4, PSA 127.93, QED 0.26
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(C)(F)F
InChIKey: PPMFNADUOOVZPG-QUGAMOGWSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 501.6, ALogP 5.02, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): Cl.Fc1ccc(CCCCN2CCN(c3cccc(-c4ccccc4)n3)CC2)cc1
InChIKey: AVSIXCCTQMDZPL-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 389.52, ALogP 5.03, HBA 3, HBD 0, PSA 19.37, QED 0.53
Compound (SMILES): c1ccc(OCc2cc(OCCNC3CCC3)no2)cc1
InChIKey: BGNLRKAAEJHUCK-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]citalopram from serotonin transporter (unknown origin) by liquid scintillation counting method
Measurement: Ki > 7000 nM (pChEMBL 5.15500020980835)
Descriptors: MW 288.35, ALogP 2.77, HBA 5, HBD 1, PSA 56.52, QED 0.76
Compound (SMILES): Cn1ccc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2c1=O
InChIKey: XJPFLUQFOAAHFE-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P31389
Assay: Displacement of [3H]pyrilamine from guinea pig cerebellum histamine H1 receptor measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 117.9 nM (pChEMBL 6.929999828338623)
Descriptors: MW 435.5, ALogP 4.47, HBA 6, HBD 0, PSA 60.5, QED 0.42
Compound (SMILES): Cc1ccccc1NC(=O)NCCS(=O)(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: ATRAHZJHRAFDIJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 412.49, ALogP 1.21, HBA 5, HBD 4, PSA 147.46, QED 0.54
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NCC(CCC(=O)O)c1ccccc1Cl
InChIKey: XDMSQVUSXYEOFO-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity: For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 30 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititre plate (from Greiner, TC plate, black with clear base) and incubated at 33° C., 5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 6.3 mM Probenecid, 5 μM Fluo-8 AM, 0.0112% Pluronic®] and incubated at 37° C., 5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode, 2 mM CaCl2, 0.002% SmartBlock (from CANDOR Bioscience GmbH). 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C., 5% CO2 for 10 minutes. The FP receptor is activated by adding 40 μl of 2 nM (final concentration) PGF2α in calcium-free Tyrode, 2 mM CaCl2, 0.002% SmartBlock, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra®, Molecular Devices) for 120 seconds.
Measurement: IC50 = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 551.87, ALogP 7, HBA 3, HBD 2, PSA 79.29, QED 0.25
Compound (SMILES): C[C@H](Nc1nc(Cl)nc2c1cnn2[C@@H]1O[C@H](COP(=O)(O)CP(=O)(O)O)[C@@H](O)[C@H]1O)c1ccccc1
InChIKey: DHXTWICBRMULOC-KXELVBGISA-N
Target: Ectonucleoside triphosphate diphosphohydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5L3
Assay: Inhibition of NTPDase 2 (unknown origin) expressed in CHO cells using ATP as substrate preincubated for 1 hr followed by substrate addition and measured after 50 mins by PiColorLock gold reagent based colorimetric assay
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 563.83, ALogP 1.61, HBA 11, HBD 6, PSA 209.38, QED 0.16
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)C[C@H]1C(=O)NCCC(=O)O
InChIKey: IVVOOUBTAXUXMJ-NSHDSACASA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha5beta1 in human K562 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 319.32, ALogP 0.72, HBA 4, HBD 3, PSA 115.81, QED 0.69
Compound (SMILES): Cc1c(-c2ccc3[nH]ncc3c2)ccc2c3oc(CN)nc3c(=O)n(C3CC3)c12
InChIKey: JEPHRUBKXWKGFQ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 385.43, ALogP 3.79, HBA 6, HBD 2, PSA 102.73, QED 0.49
Compound (SMILES): [O-][n+]1cccc(CCOc2ccc(Cl)c3ccccc23)c1
InChIKey: FXOVKEUUTXBOJZ-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as beta-arrestin recruitment treated for 90 mins by luminescence based microplate reader analysis
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 299.76, ALogP 3.75, HBA 2, HBD 0, PSA 36.17, QED 0.54
Compound (SMILES): Cl.O=C(O)c1cc(-c2ccc(C3CCNCC3)cc2)c2ccc(-c3ccc(C(F)(F)F)cc3)cc2c1
InChIKey: FKMVYPCBLWYNAV-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: PDSP Secondary Binding target: DRD5 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 1048.94 nM (pChEMBL 5.980000019073486)
Descriptors: MW 475.51, ALogP 7.36, HBA 2, HBD 2, PSA 49.33, QED 0.32
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(F)cccn2c1=O
InChIKey: AXNKUCHUGAZVMO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos B cells assessed as reduction in goat anti human IgM-stimulated calcium flux preincubated for 1 hr followed by goat anti human IgM addition and measured for 180 secs by FLIPR assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 536.56, ALogP 4.53, HBA 6, HBD 3, PSA 122.59, QED 0.31
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(C2CCNCC2)cc1)c1ccccc1
InChIKey: ASRUDRRSDDQRHE-RXQWRGDBSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 413.56, ALogP 5.59, HBA 3, HBD 3, PSA 52.49, QED 0.44
Compound (SMILES): CN1CC(=O)N[C@@H](Cc2ccccc2)C(=O)N2CCC[C@@H]2C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CN)C1=O
InChIKey: OYZSBZSOEVDVQW-BUXPKPHFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 949.13, ALogP -1.19, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CNCC2
InChIKey: ZTQDHDMZXGLFHJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of crizotinib-resistant ALK F1174L mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 488.01, ALogP 4.45, HBA 8, HBD 3, PSA 105.24, QED 0.45
Compound (SMILES): N#Cc1ccc(-c2ccc(OCCCN3CCN(c4ccncc4)CC3)cc2)cc1
InChIKey: MROYQSNDBHFVIZ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain membrane assessed as inhibition constant by liquid scintillation counter analysis
Measurement: Ki = 2958 nM (pChEMBL 5.53000020980835)
Descriptors: MW 398.51, ALogP 4.21, HBA 5, HBD 0, PSA 52.39, QED 0.56
Compound (SMILES): CC(=O)N1CCN(CCOCc2ccn(-c3ccc(F)c(F)c3)n2)CC1.Cl
InChIKey: YJZGDOPAALDWAT-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 364.4, ALogP 1.83, HBA 5, HBD 0, PSA 50.6, QED 0.73
Compound (SMILES): Cc1cc(-c2ccc3c(c2)-c2nnc(Oc4ccccc4OC(F)(F)F)n2CCO3)ccn1
InChIKey: NJQURMFJVYUYIB-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 expressed in CHO cells measured for 3 mins by Fluo-4M dye based FLIPR assay
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 454.41, ALogP 5.4, HBA 7, HBD 0, PSA 71.29, QED 0.41
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4ccccc4-c4ccccc4)c3n2)cn1
InChIKey: QSBNKGGRYOLZND-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Affinity Biochemical interaction (NanoBRET assay (in HEK293T cells)) EUB0000009b CLK2
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 351.41, ALogP 5.56, HBA 4, HBD 0, PSA 43.85, QED 0.43
Compound (SMILES): CCCCCCCCOc1ccc(C(=O)N[C@H](C(=O)O)C(C)C)cc1
InChIKey: JIIPBCFIUGBDHZ-SFHVURJKSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARg-LBD (unknown origin) expressed in HEK293 cells assessed as displacement of NCoR incubated for 16 hrs by luciferase reporter gene based mammalian two hybrid assay
Measurement: IC50 = 956.2 nM (pChEMBL 6.019999980926514)
Descriptors: MW 349.47, ALogP 4.26, HBA 3, HBD 2, PSA 75.63, QED 0.55
Compound (SMILES): Cc1ccc(S(=O)(=O)n2cc(-c3ccccc3)c3ccc(CO[C@H](C(=O)O)[C@H](N)C(=O)O)cc32)cc1.O=C(O)C(F)(F)F
InChIKey: KVPZVYMQZPGMBN-UKOKCHKQSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of human EAAT2 transfected in HEK293 cells assessed as inhibition of [3H]-D-aspartate uptake incubated for 4 mins by TopCount scintillation counting analysis
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 508.55, ALogP 3.24, HBA 7, HBD 3, PSA 148.92, QED 0.31
Compound (SMILES): C=C(C)c1ccc(-c2coc3ccc(-c4cn[nH]c4)nc23)cc1
InChIKey: UQRGNUXIYRRBER-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 1368 nM (pChEMBL 5.860000133514404)
Descriptors: MW 301.35, ALogP 4.92, HBA 3, HBD 1, PSA 54.71, QED 0.58
Compound (SMILES): CC(=O)Nc1ncc(CN2CCC3(CCN(c4cc(C)nc5ccccc45)C3)C2)s1
InChIKey: FUYGWQMTUVYXTP-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of OGA in HEK293 cells induced with human Tau P30IL mutant assessed as increase in O-GlcNAcylated protein levels measured after 6 hrs by Hoechst 33342 dye based fluorescence analysis
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 421.57, ALogP 4.06, HBA 6, HBD 1, PSA 61.36, QED 0.69
Compound (SMILES): C[C@H](CO)Nc1nc(Nc2ccc(S(N)(=O)=O)cc2)ncc1Br
InChIKey: MJIALGDLOLWBRQ-MRVPVSSYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 402.27, ALogP 1.42, HBA 7, HBD 4, PSA 130.23, QED 0.57
Compound (SMILES): CN(C)C1CCN(c2cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)ccn2)CC1
InChIKey: DTBDRQJSYYMFRU-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 455.57, ALogP 3.81, HBA 7, HBD 1, PSA 79.18, QED 0.49
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)cc2C(F)F)nc(N2CCOCC2(C)C)n1
InChIKey: BIKQHHNLLORGLD-GFCCVEGCSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Binding affinity to wild-type human partial length PIK3CD (R108 to Q1044 residues) expressed in HEK293 cells measured after 1 hr by Kinomescan method
Measurement: Kd = 2450 nM (pChEMBL 5.610000133514404)
Descriptors: MW 435.48, ALogP 2.29, HBA 9, HBD 1, PSA 102.52, QED 0.77
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: MAWNVWBEHNFLCH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant CYP2D6 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 407.5, ALogP 3.67, HBA 9, HBD 1, PSA 82.68, QED 0.54
Compound (SMILES): NC1CN(c2cc(C(=O)Nc3cc4cc(-c5cnco5)ccc4cn3)ccn2)C1
InChIKey: YUPJLBUUQOSGNF-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 1019 nM (pChEMBL 5.989999771118164)
Descriptors: MW 386.42, ALogP 2.68, HBA 7, HBD 2, PSA 110.17, QED 0.55
Compound (SMILES): C[C@H](NC(=O)c1cc(C(F)(F)F)nn1C)c1nc(-c2ccnc(C(F)(F)F)c2)no1
InChIKey: SFSLHKNGLMRBTO-ZETCQYMHSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin) by patch clamp analysis
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 434.3, ALogP 3.39, HBA 7, HBD 1, PSA 98.73, QED 0.63
Compound (SMILES): CC(C)N1CC=C(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: HTBFUVXJBZTWPQ-FJISBNMDSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Inverse agonist activity at ERRgamma (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 453.63, ALogP 6.62, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2)CC1
InChIKey: DXWRIDGYFFSIIY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in calcium mobilization measured at 2 sec intervals for 180 secs by Fluo-4AM dye based fluorescence assay
Measurement: EC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 408.88, ALogP 4.09, HBA 3, HBD 1, PSA 41.57, QED 0.7
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CCCCN)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: NKIQDONKAOALDB-FDDRLWOQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 445.56, ALogP 1.37, HBA 7, HBD 4, PSA 117.28, QED 0.44
Compound (SMILES): N#Cc1c(-c2ccccc2)nc2c(/N=N/c3ccc(S(N)(=O)=O)cc3)c(N)nn2c1N
InChIKey: CCJFFHRRJCAICV-OCEACIFDSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 433.46, ALogP 2.5, HBA 10, HBD 3, PSA 190.9, QED 0.41
Compound (SMILES): CN1CCC(c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)CC1
InChIKey: BWUOLNXJAQPJKF-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 372.47, ALogP 4.7, HBA 5, HBD 0, PSA 47.09, QED 0.52
Compound (SMILES): CNC(=O)c1cn(C[C@H](F)CCc2ccc(NC(=O)Cc3cc(OC4CC(F)(F)C4)cc(C)n3)nn2)nn1
InChIKey: GEHZIZWHNLQFAS-OAHLLOKOSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.53, ALogP 2.46, HBA 9, HBD 2, PSA 136.81, QED 0.38
Compound (SMILES): C#CCN(C)Cc1ccc(OCCCCCN2CCN(c3cccc4c3ccn4S(=O)(=O)c3ccccc3)CC2)cc1
InChIKey: CUFJQHNVDRIQJL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2 receptor expressed in HEK293 cells measured after 1 hr by microbeta plate reader analysis
Measurement: Ki = 813 nM (pChEMBL 6.090000152587891)
Descriptors: MW 584.79, ALogP 5.31, HBA 7, HBD 0, PSA 58.02, QED 0.16
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(N)=O)C(C)C
InChIKey: ILQNQNXHECHYOX-RBAYCRCTSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 expressed in HEK293 cells assessed as decrease in peak current at pulses to 0 mV by whole cell patch clamp assay
Measurement: EC50 = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 7596.8
Compound (SMILES): CC(Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)nc12)c1ccccc1F
InChIKey: JGVFDTLFVROGOH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 437.91, ALogP 5.28, HBA 6, HBD 2, PSA 83.82, QED 0.44
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccnc2)CC1
InChIKey: XGRYGIWQWQUCIB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in calcium mobilization measured at 2 sec intervals for 180 secs by Fluo-4AM dye based fluorescence assay
Measurement: EC50 = 45.71 nM (pChEMBL 7.340000152587891)
Descriptors: MW 409.86, ALogP 3.49, HBA 4, HBD 1, PSA 54.46, QED 0.71
Compound (SMILES): O=C(Nc1nc2ccccc2s1)C(c1ccccc1)S(=O)(=O)O
InChIKey: VEVZMUHLTRGYHA-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05209
Assay: Inhibition of His-tagged PTP-PEST (unknown origin) expressed in Escherichia coli BL21 cells using para-nitrophenyl phosphate as substrate incubated for 5 to 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 = 43500 nM (pChEMBL 4.360000133514404)
Descriptors: MW 348.41, ALogP 2.86, HBA 5, HBD 2, PSA 96.36, QED 0.71
Compound (SMILES): C[C@@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-DYVFJYSZSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 390.92, ALogP 2.34, HBA 6, HBD 2, PSA 83.3, QED 0.83
Compound (SMILES): CN(C)CCN1C(=O)c2ccccc2N(C)C(=O)c2ccccc21
InChIKey: JRBXXARYECIAQB-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to D2 receptor (unknown origin)
Measurement: Ki = 65300 nM (pChEMBL 4.179999828338623)
Descriptors: MW 323.4, ALogP 2.49, HBA 3, HBD 0, PSA 43.86, QED 0.87
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N2Cc3ccc(O)cc3C[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: HSTHLZHYPGORFI-IZFFCAOBSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR stably expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 1 hr by liquid scintillation counting assay
Measurement: EC50 = 4.56 nM (pChEMBL 8.34000015258789)
Descriptors: MW 1406.7
Compound (SMILES): O=C(CCCCCNC(=O)COc1ccc(/C=C/C2=[N+]3C(=Cc4ccc(-c5cccs5)n4[B-]3(F)F)C=C2)cc1)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WRUQALAONUATIE-OIWVIQBMSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Binding affinity to human muscarinic M2 receptor expressed in CHO-K9 cells assessed as unspecific binding at Kd incubated in dark at 22 degree C for 2 hrs in presence of atropine by FACSCantoII flow cytometric saturation binding study relative to control
Measurement: Kd = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 1117.15
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@@H]1CCN(Cc2cccc(OC)c2)C[C@H]1F
InChIKey: QYCQCEJRCQDCKL-RTBURBONSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant JAK1 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 411.48, ALogP 2.96, HBA 5, HBD 3, PSA 82.28, QED 0.58
Compound (SMILES): CC(C)c1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(Cl)c1
InChIKey: QWMKBPOOVMOXIR-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L expressed in CHO-K1 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 1332 nM (pChEMBL 5.880000114440918)
Descriptors: MW 419.94, ALogP 2.85, HBA 7, HBD 1, PSA 80.12, QED 0.7
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(N)(=O)=O)CC3)cc2)nc2ccsc12
InChIKey: MFLAVNPTRFOLPB-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase assessed as inhibition of biotin-dUTP incorporation into wild type RT measured after 1 hr by ELISA
Measurement: IC50 = 961 nM (pChEMBL 6.019999980926514)
Descriptors: MW 575.72, ALogP 4.7, HBA 9, HBD 2, PSA 137.47, QED 0.29
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC1(F)CC1
InChIKey: YZMMWVWLDOCLCK-CLYVBNDRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: MCF-7 ER Down-Regulation Assay: The ability of compounds to down-regulate Estrogen Receptor (ER) numbers was assessed in a cell based immuno-fluorescence assay using the MCF-7 human ductal carcinoma breast cell line. MCF-7 cells were revived directly from a cryovial (approx 5×106 cells) in Assay Medium (phenol red free Dulbecco's Modified Eagle's medium (DMEM); Sigma D5921) containing 2 mM L-Glutamine and 5% (v/v) Charcoal/Dextran treated foetal calf serum. Cells were syringed once using a sterile 18G×1.5 inch (1.2×40 mm) broad gauge needle and cell density was measured using a Coulter Counter (Beckman). Cells were further diluted in Assay Medium to a density of 3.75×104 cells per mL and 40 μL per well added to transparent bottomed, black, tissue culture-treated 384 well plates (Costar, No. 3712) using a Thermo Scientific Matrix WellMate or Thermo Multidrop. Following cell seeding, plates were incubated overnight at 37° C., 5% CO2 (Liconic carousel incubator). Test data was generated using the LabCyte Echo model 555 compound reformatter which is part of an automated workcell (Integrated Echo 2 workcell). Compound stock solutions (10 mM) of the test compounds were used to generate a 384 well compound dosing plate (Labcyte P-05525-CV1). 40 μL of each of the 10 mM compound stock solutions was dispensed into the first quadrant well and then 1:100 step-wise serial dilutions in DMSO were performed using a Hydra II (MATRIX UK) liquid handling unit to give 40 μL of diluted compound into quadrant wells 2 (0.1 mM), 3 (1 μM) and 4 (0.01 μM), respectively. 40 μL of DMSO added to wells in row P on the source plate allowed for DMSO normalisation across the dose range. To dose the control wells 40 μL of DMSO was added to row O1 and 40 μL of 100 μM fulvestrant in DMSO was added to row O3 on the compound source plate.
Measurement: IC50 = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 495.62, ALogP 4.87, HBA 5, HBD 2, PSA 56.42, QED 0.44
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(C5CNCCN5)cc4)ccn23)c2ccccc2n1
InChIKey: UQEFQNWFVJXGDE-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: O00238
Assay: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 54.5 nM (pChEMBL 7.260000228881836)
Descriptors: MW 419.53, ALogP 4.76, HBA 5, HBD 2, PSA 54.25, QED 0.44
Compound (SMILES): COc1cccc(Cn2cnc3ccc(-c4cn[nH]c4)cc3c2=O)c1
InChIKey: QQJKCGXOHWHBQV-UHFFFAOYSA-N
Target: Rhodopsin kinase GRK7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WTQ7
Assay: Inhibition of human GRK7
Measurement: IC50 = 9137 nM (pChEMBL 5.039999961853027)
Descriptors: MW 332.36, ALogP 2.84, HBA 5, HBD 1, PSA 72.8, QED 0.62
Compound (SMILES): Cl.Clc1cccc(COc2cncc(N3CCNCC3)n2)c1
InChIKey: NMUNRTCTDLORDR-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: PDSP Secondary Binding target: DRD3 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 284.08 nM (pChEMBL 6.550000190734863)
Descriptors: MW 304.78, ALogP 2.12, HBA 5, HBD 1, PSA 50.28, QED 0.94
Compound (SMILES): CC(C)[C@@H](Nc1nc(I)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(CO)C[C@H]12)C1CC1
InChIKey: QRTOZRNSWLTZJK-XRPRFISDSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from human 5-HT2C expressed in Flp-In-T-REx-293 cells assessed as inhibition constant incubated for 1 hr
Measurement: Ki = 912.01 nM (pChEMBL 6.039999961853027)
Descriptors: MW 499.35, ALogP 1.55, HBA 8, HBD 4, PSA 116.32, QED 0.35