lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4cn(C(C)C)c(=O)n(-c5ccc(F)cc5)c4=O)cc3F)c2cc1OC
InChIKey: FKCWHHYUMFGOPY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Kinase Assay: The ability of compounds to inhibit the kinase activity of recombinant human baculovirus-expressed AXL was measured by homogeneous TRF (HTRF) using Cisbio's KinEASE assay system in white 384-well Optiplates. Assay buffer contained 1 mM DTT, 2 mM MnCl2, 2% DMSO, 50 nM supplement enzymatic buffer, and 1× enzymatic buffer. A 2× concentration of tyrosine kinase (TK) substrate-biotin/ATP mixture made in assay buffer was added to plates at 10 μL/well using the Multidrop Combi (Thermo Fisher Scientific, Waltham, Mass.). The final concentrations were 0.3 μM TK substrate-biotin, and 1.3 μM ATP. Compounds (100 nL), diluted in 100% DMSO on the Biomek FX, (Beckman Coulter, Inc., Brea, Calif.), were transferred to the assay plates using the Biomek FX pintool (2.5% final DMSO in assay). A 2× concentration (final=12 ng/mL) of GST-AXL (diluted in assay buffer) was added to plates at 10 uL/well using the Multidrop Combi. Plates were sealed, briefly shaken and incubated at 25° C. for 30 minutes. A 4× stock of Streptavidin-XL665 (final=18.8 nM) and a 1:100 diluted stock of TK antibody-cryptate were made in HTRF detection buffer and mixed together just prior to adding 20 μL/well on the Multidrop Combi. Plates were sealed, briefly shaken and incubated at 25° C. for 1 hour. The fluorescence of the resulting solution was measured using the PerkinElmer EnVision 2102 multi-label plate reader (PerkinElmer, Waltham, Mass.) with an excitation wavelength of 337 nm (laser) and emission wavelengths of 590 and 665 nm. Raw data was expressed as the ratio of 665/590×10,000.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 588.57, ALogP 5.47, HBA 9, HBD 1, PSA 113.68, QED 0.26
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2cc(S(C)(=O)=O)ccc12
InChIKey: INTISBZMCLYGDB-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 399.52, ALogP 2.75, HBA 6, HBD 3, PSA 99.77, QED 0.61
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(n3)N(C3CCCC3)C3(CCNC3=O)C4)cc2F)CC1
InChIKey: HFPVKHFOWKBZPW-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human full-length N-terminal GST tagged CDK6 (1 to 326 residues)/cyclinD3 (1 to 292 residues) expressed in baculovirus expression system using PEP as substrate incubated for 3 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 465.58, ALogP 2.67, HBA 7, HBD 2, PSA 76.63, QED 0.72
Compound (SMILES): C=CC(=O)N1CCC(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)C1
InChIKey: MTKAWLWYYIKUDN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using ULight -mylein basic protein as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 1730 nM (pChEMBL 5.760000228881836)
Descriptors: MW 379.46, ALogP 2.93, HBA 4, HBD 2, PSA 90.98, QED 0.76
Compound (SMILES): CC(C)C(=O)Nc1cccc(CNC(=O)c2sc3ccccc3c2OCc2ccccc2)c1
InChIKey: HLUNIVBCMULTSG-UHFFFAOYSA-N
Target: Sentrin-specific protease 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96HI0
Assay: Inhibition of recombinant human SNEP5 (567 to 755 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 12800 nM (pChEMBL 4.889999866485596)
Descriptors: MW 458.58, ALogP 6, HBA 4, HBD 2, PSA 67.43, QED 0.34
Compound (SMILES): CCOc1cccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3c2)c1
InChIKey: YLMVVWJWKDSLGJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in sf9 insect cells using Boc-Lys(TFA)-AM as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 424.5, ALogP 4.41, HBA 5, HBD 4, PSA 116.34, QED 0.21
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)Cn2nnc3ccc(F)cc3c2=O)c(C)c1
InChIKey: FVQNXYAXDJPHPI-ZDUSSCGKSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Competition Binding Assay: This membrane based assay measures the ability of compounds to competitively bind GPR139 in stably transfected CHO-TRex membranes. CHO-TRex (Life Technologies) cells were stably expressed with human GPR139 receptor, whose expression is controlled by a tetracycline inducible element. The cells were cultured in medium containing F12K, 10% Tetracycline free FBS, 1% Penn/Strep, 200 μg/mL Hygromycin. GPR139 receptor expression was induced for 18 hrs with 1 μg/mL doxycycline (Sigma D9891) in growth media. After addition of doxycycline, cells were harvested in PBS and pelleted by centrifugation for 5 minutes at 200×G. Liquid was aspirated off and cells were resuspended in ice cold Lysis buffer (20 mM HEPES/5 mM EDTA pH 7.4/1× Roche protease inhibitor). Samples were vortexed until homogenous and then placed on ice and homogenized using Dounce homogenizer on 50% power 3 separate times for 10 strokes each time. Lysate was centrifuged at 4° C. for 10 minutes in a tabletop Sorvall at 2000×G and supernatant was recovered and centrifuged in a Sorvall Ultracentrifuge at 35,000 rpm for 30 minutes at 4° C. The supernatant was discarded and the remaining pellet resuspended in Lysis buffer (20 mM HEPES/0.1 mM EGTA/Roche protease inhibitor). Membrane protein concentration was determined using ThermoFisher BCA quantification kit and aliquoted into microtubes. Tubes were snap frozen in LN2 and stored at −80° C.
Measurement: Ki = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 354.39, ALogP 2.42, HBA 5, HBD 1, PSA 76.88, QED 0.78
Compound (SMILES): CC(C)c1ccc(NC(=O)OC2CCN(C3Cc4ccccc4C3)CC2)cc1
InChIKey: CDBAAXNYHDKTFF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 378.52, ALogP 4.99, HBA 3, HBD 1, PSA 41.57, QED 0.81
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(-c3cccc4ccccc34)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: AETQUGIIFBPWMW-YJLRWSCOSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Agonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as effect on cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: EC50 = 371.54 nM (pChEMBL 6.429999828338623)
Descriptors: MW 1150.36
Compound (SMILES): CN1C(=O)[C@@H](O)C[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: KAKUQEOIEAWDFB-VMIIQTFKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding Assay : The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA). The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM, for 10 min at rt in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% glycerol (Sigma Cat # G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined.
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 640.55, ALogP 3.92, HBA 5, HBD 1, PSA 94.99, QED 0.4
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccc(C(=O)O)cc4)cc23)c1F
InChIKey: ZCTBZCQFRUKGOT-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2 (unknown origin) using casein as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 500.48, ALogP 3.98, HBA 6, HBD 3, PSA 142.11, QED 0.31
Compound (SMILES): Cc1cc(-c2nn[nH]n2)nc(N2CCC(COc3ccccc3C(F)(F)F)C2)n1
InChIKey: HAUPESFXXGVGPB-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Displacement of FITC-diclofenac from human plasma derived TTR measured after overnight incubation by fluorescence polarization assay
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 405.38, ALogP 2.89, HBA 7, HBD 1, PSA 92.71, QED 0.7
Compound (SMILES): O=c1c2cc(-c3cncnc3)ccc2ncn1Cc1ccccc1
InChIKey: OYNPIMDIHUWMOE-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Binding affinity to GRK5 (unknown origin) by Thermofluor thermal shift assay
Measurement: Kd > 83300 nM (pChEMBL 4.078999996185303)
Descriptors: MW 314.35, ALogP 2.9, HBA 5, HBD 0, PSA 60.67, QED 0.58
Compound (SMILES): Cc1nn(C)cc1-c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: KSAUNOLTTIRZDD-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 455.49, ALogP 4.52, HBA 6, HBD 3, PSA 83.45, QED 0.42
Compound (SMILES): CCS(=O)(=O)Nc1cc(OC)cc(-c2cc(-c3ccc(N4CCNCC4)cc3)cnc2C)c1
InChIKey: QKIQUHJMKMTYPI-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Inhibition of human NOD2 expressed in HEK293 cells coexpressing NFkappaB-SEAP reporter measured after 7 to 9 hrs by HEKBIue reporter assay
Measurement: IC50 = 5239 nM (pChEMBL 5.28000020980835)
Descriptors: MW 466.61, ALogP 3.9, HBA 6, HBD 2, PSA 83.56, QED 0.55
Compound (SMILES): COc1ccc(S(=O)(=O)N2CC3(COC3)C2)cc1NC(=O)c1[nH]c(C)c2c1CCCCC2=O
InChIKey: FQZLYYSRDPJOHB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to human partial length BRD9 (R130 to V259 residues) by bromoKdELECT Discover assay
Measurement: Kd = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 473.55, ALogP 2.51, HBA 6, HBD 2, PSA 117.8, QED 0.64
Compound (SMILES): CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@@H](COCCC)OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: SORCBKREEKTZJV-MMHKTWFYSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 565.69, ALogP 5.91, HBA 8, HBD 3, PSA 154.61, QED 0.05
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@H]4CC[C@@H](N)C4)nc32)cc1
InChIKey: OSHLPUOBFBCDRP-MNOVXSKESA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Inhibition of recombinant full length His6-GST fusion tagged ERK3 (1 to 721 residues) (unknown origin) using MK5 K51A mutant as substrate by ADP-Glo assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 325.38, ALogP 1.51, HBA 8, HBD 2, PSA 103.77, QED 0.75
Compound (SMILES): CC(C)Nc1cncc(-c2cnc3[nH]nc(-c4nc5c(-c6ccoc6)nccc5[nH]4)c3c2)c1
InChIKey: VJMADAJQMWVYJY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 436.48, ALogP 5.04, HBA 7, HBD 3, PSA 121.2, QED 0.35
Compound (SMILES): FC(F)(F)c1cnc(Nc2cnc3[nH]ccc3c2)nc1NC1CC1
InChIKey: TUASMCDFYZNBEE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: ULK1 inhibition assay: Gamma-32P assays to measure ULK1 kinase activity were performed as previously described. Briefly, Flag ULK1 was transfected into HEK293T cells and 20 hours later treated as indicated. The immmunoprecipitate was washed in IP buffer 3 times, and washed in kinase buffer (25 mM MOPS, pH 7.5, 1 mM EGTA, 0.1 mM Na3VO4, 15 mM MgCl2,). Hot and cold ATP were added at a 100 μM final concentration. As substrates, GST or the recombinant protein GST-Atg101 purified from E. coli were used at 1 μg for each reaction. Reactions were boiled, run out on SDS page gel. The gel was dried, and imaged using PhosphoImager software. For cold assays to asses ULK1, Flag ULK1 which was transiently overexpressed and immunoprecipited from HEK293T cells. Reactions were then run out on SDS page gel, transferred to PVDF membrane and blotted for total levelsFluorescence MicroscopyVps34flox/flox MEFs were reconstituted with Flag-VPS34 and either p40FX or GFP-DFCP1. 48 hours post infection with adenovirus expressing Cre recombinase (MOI of 100), cells were plated on glass coverslips at a density of 3×105 cells per well in 6-well tissue culture plates. 18 h later, cells were fixed in 4% PFA in PBS for 10 minutes and permeabilized in 0.2% Triton in PBS for 10 minutes. The following primary antibodies were used: mouse anti-Myc epitope and LC3B XP antibody (2276 and 3868 respectively, Cell Signaling Technologies). Secondary antibodies were anti-rabbit Alexa488 and anti-mouse Alexa594 (Molecular Probes, 1:1000. Cells were then fixed and counter stained with DAPI. Coverslips were mounted in FluoromountG (SouthernBiothech). Images were acquired on a Zeiss Axioplan2 epifluorescence microscope coupled to the Openlab software. Confocal images of mitotracker were taken on Zeiss LSM 710 laser scanning confocal microscope. 10 random fields per condition were acquired using the 100× objective and representative images shown. Glass coverslips were mounted directly on plate with FluoromountG and images taken on Zeiss Axioplan2 epifluorescence microscope.
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 334.31, ALogP 3.69, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): Cc1cncc(NC(=O)c2n[nH]c3ccc(-c4cncc(CN5CCCCC5)c4)cc23)c1
InChIKey: LIXXQBRPVXEVJX-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 352 nM (pChEMBL 6.449999809265137)
Descriptors: MW 426.52, ALogP 4.57, HBA 5, HBD 2, PSA 86.8, QED 0.49
Compound (SMILES): C[C@H](NC(=O)Cn1nnc2ccccc2c1=O)c1ccc(Br)cc1
InChIKey: YNTGGPUBNFJFLL-NSHDSACASA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Displacement of (S)-N-(1-(2-[3H]-4-methoxyphenyl)propan-2-yl)-2-(2,3-dimethyl-7-oxothieno[2,3-d]pyridazin-6(7H)-yl)acetamide from human GPR139 expressed in CHO-TRex membranes incubated for 20 mins by scintillation counting assay
Measurement: Ki = 486 nM (pChEMBL 6.309999942779541)
Descriptors: MW 387.24, ALogP 2.43, HBA 5, HBD 1, PSA 76.88, QED 0.75
Compound (SMILES): O=C(c1cc(O)c(-c2cc(Cl)ccc2Cl)c(O)c1)c1cccs1
InChIKey: WCVWIQCOIVCBIX-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human recombinant cannabinoid CB2 receptor expressed in HEK cells transfected with CNG assessed as increase in cAMP level measured up to 1 hr by ACTOne membrane potential dye based assay
Measurement: EC50 = 141.25 nM (pChEMBL 6.849999904632568)
Descriptors: MW 365.24, ALogP 5.36, HBA 4, HBD 2, PSA 57.53, QED 0.61
Compound (SMILES): CNC(=O)[C@H]1CNC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: QWTLJZSIFBCFBX-VXGBXAGGSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 418.42, ALogP 2.78, HBA 5, HBD 4, PSA 94.73, QED 0.52
Compound (SMILES): Cc1cc(C)cc([C@H](CC(=O)O)C(=O)N2CC[C@@H](CCc3ccc4c(n3)NCCC4)C2)c1
InChIKey: AXIJMLLLPVCDAY-XXBNENTESA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of human alphavbeta3 integrin stably expressed in human K562 cells assessed as inhibition of cell adhesion to GST-LAP1 incubated for 30 mins by BCECF-AM staining based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.57, ALogP 4.1, HBA 4, HBD 2, PSA 82.53, QED 0.68
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CCC2)c2cc(-c3cc(C(F)F)cs3)cnc21
InChIKey: UHUIEJUQWSPSJU-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 378.4, ALogP 2.63, HBA 6, HBD 0, PSA 60.13, QED 0.7
Compound (SMILES): CCS(=O)(=O)c1cnc(CNc2nc3cnc(-c4c(C)ncnc4C4CC4)nc3n([C@@H](C)C3CC3)c2=O)s1
InChIKey: TWKWAFCIHQUXAW-AWEZNQCLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Gene Assay: A nuclear receptor transactivation assay is performed to quantitate the ability of test compounds to inhibit RORγ transactivation of a luciferase reporter. A similar assay is described in: Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536. The system uses transiently transfected HEK 293 cells cotransfected with two plasmids (pGL4.3, luc2P/GAL4UAS/Hygro, and pBIND, Gal4DBD hRORC LBD1-3). The positive control is co-transiently transfected with both plasmids, and the negative control contains the pGL4.3 promoter sequence. Assays are assembled in 384 well plates where transiently transfected cells and test compound at varying concentrations are incubated for 20-24 h.The next day, assays plates are taken out and equilibrated at RT for 20-30 minutes. Bright-Glo Luciferase Assay System is used to detect Luciferase production. After addition of Bright GLO detection reagent, the plates are incubated at RT for 20 minutes. The plates are read on an Envision plate reader to measure luminescence signal. The RLU signal is converted to POC relative to control and blank wells.
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 552.69, ALogP 3.66, HBA 12, HBD 1, PSA 145.51, QED 0.33
Compound (SMILES): CCCc1cccc2c1CC[C@@H]1CNCCN21
InChIKey: GJVPUHJMJVJTOE-CYBMUJFWSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at 5-HT2CR (unknown origin) transfected in human HEK293 cells by IP3 accumulation assay
Measurement: EC50 = 0.1995 nM (pChEMBL 9.699999809265137)
Descriptors: MW 230.35, ALogP 2.36, HBA 2, HBD 1, PSA 15.27, QED 0.84
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccc(F)cc4)cc23)c1F
InChIKey: IJPGTKRRBCMKOP-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2 (unknown origin) using casein as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.39
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CCN2CCN(C(=O)OCc3ccccc3)CC2)cc1
InChIKey: WYRMCIGECHJLLQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 by stopped-flow CO2 hydration assay
Measurement: Ki = 387.3 nM (pChEMBL 6.409999847412109)
Descriptors: MW 460.56, ALogP 1.29, HBA 6, HBD 2, PSA 122.04, QED 0.61
Compound (SMILES): CN(c1cc(F)cc(F)c1)c1ccc2[nH]nc(/C=C/c3ccccn3)c2c1
InChIKey: UQLJOQKYBXUIFI-FNORWQNLSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TrkC (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 362.38, ALogP 5.17, HBA 3, HBD 1, PSA 44.81, QED 0.54
Compound (SMILES): COc1ccc(-c2ccc3c(NC(=O)CCCCCCC(=O)NO)n[nH]c3n2)cc1
InChIKey: DSKKGFQMLMVZBD-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in sf9 insect cells using Boc-Lys(TFA)-AM as substrate incubated for 60 mins by fluorescence assay
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 411.46, ALogP 3.42, HBA 6, HBD 4, PSA 129.23, QED 0.23
Compound (SMILES): CC[C@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: GTWHZKOJJZOTCX-ROUUACIJSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human AMCase expressed in CHO-K1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 404.95, ALogP 2.73, HBA 6, HBD 2, PSA 83.3, QED 0.8
Compound (SMILES): COc1cc(/C=C2\Cc3ccc(N4CCCC4)cc3C2=O)ccc1O
InChIKey: NVQINGBIQLEIMK-MHWRWJLKSA-N
Target: Liver carboxylesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23141
Assay: Inhibition of hCES1A in human liver microsome assessed as reduction in D-Iuciferin methyl ester hydrolysis preincubated for 10 mins followed by substrate addition measured after 10 mins by luminescence analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 335.4, ALogP 3.82, HBA 4, HBD 1, PSA 49.77, QED 0.87
Compound (SMILES): COc1cc(NS(=O)(=O)c2ccccc2)cc(-c2cc(-c3ccc(N4CCNCC4)cc3)cnc2N)c1
InChIKey: JBTJGPURAPMJSS-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Inhibition of human NOD2 expressed in HEK293 cells coexpressing NFkappaB-SEAP reporter measured after 7 to 9 hrs by HEKBIue reporter assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 515.64, ALogP 4.22, HBA 7, HBD 3, PSA 109.58, QED 0.34
Compound (SMILES): CC(C)(C)C(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccc(F)s6)ccnc5[nH]4)c3c2)c1
InChIKey: DFVKEYYIJWSLCG-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 754 nM (pChEMBL 6.119999885559082)
Descriptors: MW 511.59, ALogP 6.42, HBA 6, HBD 3, PSA 112.24, QED 0.25
Compound (SMILES): CC(C)n1cnnc1-c1cccc(NC(=O)Nc2ccccn2)n1
InChIKey: RLTVBHOYTGZPMF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of TAK1 (unknown origin)
Measurement: IC50 = 734.4 nM (pChEMBL 6.130000114440918)
Descriptors: MW 323.36, ALogP 2.96, HBA 6, HBD 2, PSA 97.62, QED 0.77
Compound (SMILES): CCC(=O)N[C@@H]1CNC[C@H](Nc2ccc(C(F)(F)F)c(-c3c[nH]c4c(S(C)(=O)=O)cccc34)c2)C1
InChIKey: NEFGSTFCOAETMW-CVEARBPZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 508.57, ALogP 3.93, HBA 5, HBD 4, PSA 103.09, QED 0.4
Compound (SMILES): O=C([C@H]1CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1)N1CCCC1
InChIKey: WTZPCQTWWNDNCQ-IFXJQAMLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 458.49, ALogP 3.8, HBA 5, HBD 3, PSA 85.94, QED 0.55
Compound (SMILES): C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@H](CC(C)(C)O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: YEJWIEPCSOSHIJ-CUYCEIPOSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Agonist activity at human VDR expressed in African green monkey COS7 cells expressing mouse osteopontin VDRE assessed as induction of receptor transactivation incubated for 16 hrs by luciferase reporter gene assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 432.69, ALogP 6.92, HBA 2, HBD 2, PSA 57.53, QED 0.48
Compound (SMILES): CNC(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)cn(COC)c12
InChIKey: CEBJBOHJQVCCGF-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 462.48, ALogP 3.24, HBA 7, HBD 3, PSA 93.1, QED 0.52
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@@H]2COP(=O)(O)O[C@H]3[C@@H](O)[C@H](n4cnc5c(O)ncnc54)O[C@@H]3COP(=O)(O)O[C@H]2[C@H]1O
InChIKey: SBNULQXUGGEMOY-XPWFQUROSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human THP-1-Dual cells assessed as induction of type I IFNs by measuring stimulation of NF-kappaB pathway incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 15900 nM (pChEMBL 4.800000190734863)
Descriptors: MW 659.4, ALogP -1.51, HBA 20, HBD 6, PSA 303.89, QED 0.13
Compound (SMILES): O=C(Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccccc6F)ccnc5[nH]4)c3n2)c1)C(F)(F)F
InChIKey: RSVPXGXBCNRHSS-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 518.43, ALogP 5.27, HBA 6, HBD 3, PSA 125.13, QED 0.27
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1[nH]c(-c2ccccc2)nc1C(N)=O
InChIKey: XGWNKDSIJSHVCT-IBGZPJMESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 18.1 nM (pChEMBL 7.739999771118164)
Descriptors: MW 439.56, ALogP 2.82, HBA 5, HBD 3, PSA 121.18, QED 0.44
Compound (SMILES): CC#CCN1CCc2cc(Nc3ncc(C)c(-c4cnn(C(C)C)c4)n3)ccc2C1
InChIKey: QNWWMLQKGGMJEW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 400.53, ALogP 4.35, HBA 6, HBD 1, PSA 58.87, QED 0.65
Compound (SMILES): CCCCNc1nc2ccc([N+](=O)[O-])cc2[nH]1
InChIKey: KCMYEMHXIIFYLP-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of recombinant human RIPK1 kinase domain (8 to 322 residues) using myelin basic protein as substrate measured after 120 mins by [gamma-32P]ATP based scintillation counting method
Measurement: IC50 = 12120 nM (pChEMBL 4.920000076293945)
Descriptors: MW 234.26, ALogP 2.68, HBA 4, HBD 2, PSA 83.85, QED 0.47
Compound (SMILES): O=C(/C(=N/O)Nc1ccc(F)c(Br)c1)C1CCN(C(=O)Nc2ccccc2)CC1
InChIKey: GQHRWAQCVMFJPK-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 = 57970 nM (pChEMBL 4.239999771118164)
Descriptors: MW 463.31, ALogP 4.3, HBA 4, HBD 3, PSA 94.03, QED 0.27
Compound (SMILES): O=C(CCCCCc1ccc(-c2ccccc2)cc1)OCc1ccc2c(c1)OCO2
InChIKey: WAFJKVGCIWVHQC-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Mus musculus
UniProt: O35678
Assay: Inhibition of mouse MAGL
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 402.49, ALogP 5.93, HBA 4, HBD 0, PSA 44.76, QED 0.33
Compound (SMILES): CCN1CC2(CCN(CCc3cccc(F)c3F)CC2)O[C@H](C)C1=O
InChIKey: LBFPJQQSFFGKLC-CQSZACIVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 352.43, ALogP 2.61, HBA 3, HBD 0, PSA 32.78, QED 0.84
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(-c2nccc(OC)n2)c1OC
InChIKey: XRWVUYRJQUAYSL-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human whole blood assessed as decrease in IFNalpha-induced STAT5 phosphorylation
Measurement: IC50 = 461 nM (pChEMBL 6.340000152587891)
Descriptors: MW 449.47, ALogP 2.4, HBA 9, HBD 3, PSA 140.25, QED 0.47
Compound (SMILES): O=c1ccoc2ccc(OCCCCN3CCCCC3)cc12
InChIKey: YCJCZVUHPAFTTR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE
Measurement: IC50 = 5580 nM (pChEMBL 5.25)
Descriptors: MW 301.39, ALogP 3.44, HBA 4, HBD 0, PSA 42.68, QED 0.77
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n2cc(C(C)(C)C)nc12
InChIKey: QCXLRAYMDUWMRT-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human full-length N-terminal GST tagged CDK6 (1 to 326 residues)/GST-tagged cyclinD3 (1 to 292 residues) expressed in baculovirus expression system using ULight-elF4E-binding protein 1 peptide as substrate measured after 30 mins by LANCE assay
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 457.58, ALogP 4.24, HBA 8, HBD 2, PSA 87.45, QED 0.44
Compound (SMILES): O=C(Nc1cncc(-c2ccc3[nH]nc(-c4cc5cccnc5[nH]4)c3c2)c1)C1CCCC1
InChIKey: UQVNERCUZRJKOQ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 365 nM (pChEMBL 6.440000057220459)
Descriptors: MW 422.49, ALogP 5.3, HBA 4, HBD 3, PSA 99.35, QED 0.37
Compound (SMILES): NC(=O)CC[C@H](NC(=O)[C@@H]1CC[C@@H]2CCN(C(=O)CCCCCC#Cc3cccc4c3CN(C3CCC(=O)NC3=O)C4=O)C[C@H](NC(=O)c3cc4cc(C(=O)P(=O)(O)O)ccc4[nH]3)C(=O)N21)C(=O)NC(c1ccccc1)c1ccccc1
InChIKey: OHDMEJTVYXXZNQ-OPKPGBGESA-N
Target: Signal transducer and activator of transcription 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52630
Assay: Binding affinity to human recombinant STAT2 assessed as dissociation constant incubated for 15 mins by biolayer interferometry
Measurement: Kd > 10 nM (pChEMBL 8)
Descriptors: MW 1136.17
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCC1CCN(Cc2cccc(F)c2)CC1
InChIKey: IWBHCAPYMPYPRE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 537.66, ALogP 4.86, HBA 7, HBD 2, PSA 110.44, QED 0.34
Compound (SMILES): Cn1cc(-c2cc(C(C)(C)O)ccc2Oc2ccc(F)cc2F)c2cc(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)[nH]c2c1=O
InChIKey: UIINOGWJPAPJTM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 677.71, ALogP 6.6, HBA 7, HBD 5, PSA 151.47, QED 0.11
Compound (SMILES): N#Cc1ccc(N2CCN([C@H]3C=C(c4cc5ncccc5c(=O)[nH]4)CC3)CC2)cc1
InChIKey: IBBZXRLLZKUNIM-HXUWFJFHSA-N
Target: Protein mono-ADP-ribosyltransferase PARP3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F1
Assay: Inhibition of PARP3 (unknown origin)
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 397.48, ALogP 3.16, HBA 5, HBD 1, PSA 76.02, QED 0.73
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3cccc(OC)c3)nc3c2CSCC3)c1
InChIKey: PGEUNGPQYYKVCP-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R mutant (unknown origin) using FAM-labelled peptide as substrate incubated for 10 mins in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 638.4 nM (pChEMBL 6.199999809265137)
Descriptors: MW 434.52, ALogP 4.93, HBA 7, HBD 2, PSA 85.37, QED 0.51
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC)ncnc4C4CC4)nc3n(CC(C)C)c2=O)nc1
InChIKey: UFFIHRJOQVISSJ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Gene Assay: A nuclear receptor transactivation assay is performed to quantitate the ability of test compounds to inhibit RORγ transactivation of a luciferase reporter. A similar assay is described in: Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536. The system uses transiently transfected HEK 293 cells cotransfected with two plasmids (pGL4.3, luc2P/GAL4UAS/Hygro, and pBIND, Gal4DBD hRORC LBD1-3). The positive control is co-transiently transfected with both plasmids, and the negative control contains the pGL4.3 promoter sequence. Assays are assembled in 384 well plates where transiently transfected cells and test compound at varying concentrations are incubated for 20-24 h.The next day, assays plates are taken out and equilibrated at RT for 20-30 minutes. Bright-Glo Luciferase Assay System is used to detect Luciferase production. After addition of Bright GLO detection reagent, the plates are incubated at RT for 20 minutes. The plates are read on an Envision plate reader to measure luminescence signal. The RLU signal is converted to POC relative to control and blank wells.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 550.65, ALogP 2.99, HBA 12, HBD 1, PSA 154.74, QED 0.31
Compound (SMILES): Cc1cc(=O)oc2cc(NC(=O)Cn3cc(F)c(=O)[nH]c3=O)ccc12
InChIKey: HNENAVXBRJIOOI-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 6 hrs measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 345.29, ALogP 0.73, HBA 6, HBD 2, PSA 114.17, QED 0.68
Compound (SMILES): Nc1cc(Cc2cccc(Cl)c2)c2nn[nH]c2n1
InChIKey: AUCPUCQOIPILNJ-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen catalog # A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2(Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at room temperature.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).IC50 values were calculated by determining the slope of the linear portion of the kinetic trace (180-540 secs), and using that calculated slope to determine % inhibition occurring at each concentration of inhibitor using the following equation:Y = A + B - A 1 + ( C / x ) D where A=minimal Y value (activity level of inhibited sample), B=maximal Y value (activity level of uninhibited sample), C=Log IC50, D=Hill Slope, x=concentration of inhibitor.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 259.7, ALogP 2.18, HBA 4, HBD 2, PSA 80.48, QED 0.74
Compound (SMILES): O=C1CCOCC1C1CC(=O)N(c2ccccc2)C1=O
InChIKey: HTUNDUQXODSRNH-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5LOX expressed in baculovirus infected Sf insect cells using linoleic acid as substrate preincubated for 5 mins followed by substrate addition
Measurement: IC50 = 26830 nM (pChEMBL 4.570000171661377)
Descriptors: MW 273.29, ALogP 1.17, HBA 4, HBD 0, PSA 63.68, QED 0.76
Compound (SMILES): CO[C@@]12CC[C@H](NCCC(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: YVIWVBIKSGCPNJ-ZFGDZNOMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.7
Compound (SMILES): O=C(N[C@H]1C[C@@H]1c1ccccc1)c1n[nH]c2ccc(-c3cccnc3)cc12
InChIKey: MUJCJYXCJZCTGK-XLIONFOSSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 6145 nM (pChEMBL 5.210000038146973)
Descriptors: MW 354.41, ALogP 3.91, HBA 3, HBD 2, PSA 70.67, QED 0.58
Compound (SMILES): CCP(=O)(CC)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: UPZJNTPMBHVKAX-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 465.46, ALogP 4.84, HBA 5, HBD 3, PSA 82.7, QED 0.45
Compound (SMILES): Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Oc3ccc(O)c(C(C)(C)C)c3)cc21
InChIKey: BSKLWHSTAUOABL-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at full-length PPARgamma (unknown origin) expressed in MG63 cells assessed as transcriptional activation incubated for 18 hrs by dual-Glo luciferase assay
Measurement: EC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 531.63, ALogP 5.84, HBA 8, HBD 2, PSA 102.68, QED 0.31
Compound (SMILES): CC(=O)N[C@H](CCCN)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: YLVUKTHOPXMSDE-YAGLTGEFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as reduction in alpha-MSH-induced cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1075.25
Compound (SMILES): CCN1CC2(CCN(CCc3ccccc3F)CC2)O[C@H](C)C1=O
InChIKey: LYZONYJDSRWDIH-OAHLLOKOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 334.44, ALogP 2.47, HBA 3, HBD 0, PSA 32.78, QED 0.85
Compound (SMILES): CC1(C)Oc2cnccc2-c2[nH]c(C(N)=O)c(-c3ccccc3C(F)(F)F)c21
InChIKey: ZYDJMSALOSSIES-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Haspin Kinase Assay: The kinase assay relies on ADP-GloKM biochemical kinase assay (Promega). This is a luminescent kinase assay that measures ADP formed from a kinase reaction. Then ADP is converted into ATP, which is transformed into a light signal by Ultra-Glo Luciferase. The luminescent signal positively correlates with kinase activity. The assay measures the intrinsic ATPase activity (in the absence of peptidic substrate as phosphate acceptor).The enzyme was purchase from Invitrogen (PV5708) as the kinase domain of GST tagged recombinant human proteins.Assay conditions were as indicated by the kit manufacturers with the following adaptations:Assay buffer: 15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.1 mg/ml BGGAssay volume: 20 μlIncubation time and temperature: 60 min at 30° C.Haspin concentration: 20 nMATP concentration: 150 μMTested compound: Serial 1:3 dilutionsFinal DMSO concentration in the assay: 1%Assays were performed in 384-well plates. The final read out was generated using an EnVision plate reader (Perkin-Elmer). Luminescent relative units are normalized against the control activity included for each compound (i.e., 100% Haspin activity, without compound) and the percentage of inhibition is calculated.
Measurement: IC50 = 743 nM (pChEMBL 6.130000114440918)
Descriptors: MW 387.36, ALogP 4.49, HBA 3, HBD 2, PSA 81, QED 0.68
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCC(Cc3ccccc3)CC2)cc1
InChIKey: MNNPXTZWADKUJP-SDNWHVSQSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 406.53, ALogP 4.63, HBA 3, HBD 0, PSA 49.85, QED 0.66
Compound (SMILES): CC1(N)CCN(c2cnc3c(-c4cccc(Cl)c4F)n[nH]c3n2)CC1
InChIKey: QROQTLNVCIGXBV-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: PTPN11 Enzymatic Assay: Recombinant full-length wild-type and E76K mutant human PTPN11 proteins were cloned, expressed (E. coli system), and isolated via a two-step purification of Ni affinity followed by S75 size exclusion chromatography.Phosphatase activity of full length wild-type PTPN11(PTPN11-WT) or PTPN11-E76K mutant enzyme was measured using the fluorogenic 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP; Molecular Probes) as the substrate. Enzyme (250 pM) was incubated with or without increasing concentrations of compounds in assay buffer (62.5 mM HEPES, 125 mM NaCl, 1 mM EDTA, 1.25 mM TECP, 0.1% BSA) for 30 min at room temperature. Reaction was initiated by addition of DiFMUP (50 μM) at room temperature in 384-well black plate with a final reaction volume of 20 uL in assay buffer. After 1 hour, DiFMUP fluorescence signal was measured (Ex: 340/Em: 460) using Envision plate reader. Dose-response curves were analyzed using IC50 regression curve fitting (GeneData Screener). Curves were normalized to a high controls without inhibitor, and low controls without enzyme. Results are given below in Table 1. Other compounds disclosed herein are expected to have activity similar to the results below, showing activity as PTPN11 inhibitors.
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 360.82, ALogP 3.13, HBA 5, HBD 2, PSA 83.72, QED 0.73
Compound (SMILES): Clc1cnc(NC2CN3CCC2CC3)nc1-c1c[nH]c2ccccc12
InChIKey: PMUBYPSZTKVHAW-UHFFFAOYSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 353.86, ALogP 3.78, HBA 4, HBD 2, PSA 56.84, QED 0.75
Compound (SMILES): O=C(Nc1cccc(CNC(=O)c2sc3ccccc3c2OCc2ccccc2)c1)c1ccco1
InChIKey: KUIKFKVGTYSNAG-UHFFFAOYSA-N
Target: Sentrin-specific protease 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96HI0
Assay: Inhibition of recombinant human SNEP5 (567 to 755 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 24800 nM (pChEMBL 4.610000133514404)
Descriptors: MW 482.56, ALogP 6.26, HBA 5, HBD 2, PSA 80.57, QED 0.27
Compound (SMILES): N#C[C@@H]1CC(F)(F)CN1C(=O)CNC(=O)c1csc(CSc2ccc(C(F)(F)F)cc2)n1
InChIKey: MZKOGMKOZUXLIX-LBPRGKRZSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 508 nM (pChEMBL 6.289999961853027)
Descriptors: MW 490.48, ALogP 3.94, HBA 6, HBD 1, PSA 86.09, QED 0.49
Compound (SMILES): O=C(CCCCCNC(=S)N/N=C(\c1ccccc1)c1cccc([N+](=O)[O-])c1)NO
InChIKey: SURINXAQALSLAY-ZBJSNUHESA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorimetric assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 429.5, ALogP 2.88, HBA 6, HBD 4, PSA 128.89, QED 0.11