lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)NCC(C(=O)O)c1ccccc1Cl
InChIKey: JQJVEYSPMJFZDV-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 523.81, ALogP 6.22, HBA 3, HBD 2, PSA 79.29, QED 0.31
Compound (SMILES): Cl.Clc1cccc(COc2cncc(N3CCNCC3)n2)c1
InChIKey: NMUNRTCTDLORDR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: PDSP Secondary Binding target: CHRM4 - 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 = 443.96 nM (pChEMBL 6.349999904632568)
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 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells assessed as inhibition constant incubated for 1 hr
Measurement: Ki = 81.28 nM (pChEMBL 7.090000152587891)
Descriptors: MW 499.35, ALogP 1.55, HBA 8, HBD 4, PSA 116.32, QED 0.35
Compound (SMILES): COc1cc(C(=O)N2CCC3(CC2)CC(=O)c2nn(C(C)(C)C)cc2O3)cc(-c2ccc(C(=O)O)cc2)n1
InChIKey: XOXUEBSSMXLBTF-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 518.57, ALogP 4.05, HBA 8, HBD 1, PSA 123.85, QED 0.55
Compound (SMILES): O=S1(=O)C=Cc2cc(-c3ccc(Cl)cc3)cnc2O1
InChIKey: NWQNYXANZPCQKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 293.73, ALogP 3.09, HBA 4, HBD 0, PSA 56.26, QED 0.76
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(-c4ccc(CC(=O)O)cc4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: PKLZNHMQTKAYEP-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 481.56, ALogP 4.34, HBA 6, HBD 2, PSA 113.82, QED 0.42
Compound (SMILES): COc1ccccc1N1CCN(CCCCOc2ccc3c(c2)C(=O)N(C)CC3)CC1
InChIKey: YCZWURFQDCDNKN-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Receptor Binding Assay: D2:Procedures(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 Butaclamol (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-Spiperone 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 of the reaction tubes was incubated at 37° C. for 20 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.(6) The scintillation vials were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 423.56, ALogP 3.3, HBA 5, HBD 0, PSA 45.25, QED 0.61
Compound (SMILES): CC(=O)Nc1nn2ccc(-c3cc(C)c4c(c3)CN([C@@H](C)C3CC3)C4=O)nc2c1-c1cnn(C)c1
InChIKey: MMBUORMVFSLTCE-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 469.55, ALogP 3.82, HBA 7, HBD 1, PSA 97.42, QED 0.48
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 tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 278.33, ALogP 2.82, HBA 5, HBD 3, PSA 82.45, QED 0.81
Compound (SMILES): COc1ccccc1C1c2c(C(C)(C)C)n[nH]c2C(=O)N1c1ccc(C(=O)N(C)C)cc1
InChIKey: AGZHJVCAVPPWCO-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 432.52, ALogP 4.17, HBA 4, HBD 1, PSA 78.53, QED 0.67
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 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human pooled liver microsomes using tolbutamide 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: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR cytoplasmic domain (669 to 1210 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 527.05, ALogP 4.85, HBA 8, HBD 4, PSA 127.93, QED 0.26
Compound (SMILES): CC(C)Oc1ccc(NC(=O)c2n[nH]c3ccc(-c4cncc(CN5CC6CC(C5)O6)c4)cc23)cn1
InChIKey: OLMDVYFVQFYWFE-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 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 484.56, ALogP 4.03, HBA 7, HBD 2, PSA 105.26, QED 0.41
Compound (SMILES): COCC(CO)(OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)P(=O)(O)O
InChIKey: BQCRMLSBGAKPFW-RXUYWNQFSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay
Measurement: IC50 = 0.53 nM (pChEMBL 9.279999732971191)
Descriptors: MW 537.89, ALogP -0.02, HBA 12, HBD 6, PSA 201.54, QED 0.17
Compound (SMILES): O=C(Nc1cccnc1)c1n[nH]c2ccc(-c3cncc(CN4CC5CC(C4)O5)c3)cc12
InChIKey: SZBCOWYOKDHMCB-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 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 426.48, ALogP 3.25, HBA 6, HBD 2, PSA 96.03, QED 0.51
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(C)(F)F
InChIKey: PPMFNADUOOVZPG-QUGAMOGWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 501.6, ALogP 5.02, HBA 5, HBD 2, PSA 56.42, QED 0.43
Compound (SMILES): Cl.Fc1ccc(CCCCN2CCN(c3cccc(-c4ccccc4)n3)CC2)cc1
InChIKey: AVSIXCCTQMDZPL-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting
Measurement: Ki = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 389.52, ALogP 5.03, HBA 3, HBD 0, PSA 19.37, QED 0.53
Compound (SMILES): COc1ccc(N2CCN(CC(=O)NCc3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: UYIUPEDAACQJKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 1096.9 nM (pChEMBL 5.960000038146973)
Descriptors: MW 418.52, ALogP 0.78, HBA 6, HBD 2, PSA 104.97, QED 0.69
Compound (SMILES): c1ccc(OCc2cc(OCCNC3CCC3)no2)cc1
InChIKey: BGNLRKAAEJHUCK-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Displacement of [3H]nisoxetine from norepinephrine 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: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08909
Assay: Displacement of [3H]mesulergine from rat cerebral cortex 5HT2C receptor measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 129.3 nM (pChEMBL 6.889999866485596)
Descriptors: MW 435.5, ALogP 4.47, HBA 6, HBD 0, PSA 60.5, QED 0.42
Compound (SMILES): Cc1ccc(-c2nnc(-c3ccc(Cl)cc3Cl)o2)cc1S(N)(=O)=O
InChIKey: RVLJIVHDJUPRRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 384.24, ALogP 3.67, HBA 5, HBD 1, PSA 99.08, QED 0.74
Compound (SMILES): Cc1ccccc1NC(=O)NCCS(=O)(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: ATRAHZJHRAFDIJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 659.8 nM (pChEMBL 6.179999828338623)
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: Antagonist activity at human FPR expressed in human Chem-1 cells assessed as inhibition of PGF2alpha-induced calcium flux preincubated for 10 mins followed by PGF2alpha stimulation and measured for 120 secs by fluo-8 AM dye based fluorescence assay
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
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 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49961
Assay: Inhibition of CD39 (unknown origin)
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-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta6 in human HT-29 cells assessed as reduction 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: IC50 > 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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
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 inhibition of forskolin induced cAMP production pretreated with forskolin for 30 mins followed by compound addition and measured after 18 to 24 hrs by DiscoverX HitHunter cAMP assay
Measurement: EC50 = 12.3 nM (pChEMBL 7.909999847412109)
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: 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 = 2191.04 nM (pChEMBL 5.659999847412109)
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 = 18 nM (pChEMBL 7.75)
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: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 992 nM (pChEMBL 6)
Descriptors: MW 413.56, ALogP 5.59, HBA 3, HBD 3, PSA 52.49, QED 0.44
Compound (SMILES): COc1ccc(Br)cc1S(=O)(=O)Nc1ccc2c(c1)C(=C(C)C)C(=O)N2
InChIKey: QUICABMRXTUSBQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of BRD2 BD2 (unknown origin) preincubated for 15 mins followed by peptide addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 437.32, ALogP 4, HBA 4, HBD 2, PSA 84.5, QED 0.71
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: Agonist activity at mouse MC4R by alphascreen cAMP assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
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 G1269A mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 488.01, ALogP 4.45, HBA 8, HBD 3, PSA 105.24, QED 0.45
Compound (SMILES): CC(C)n1nc2c(c1-c1ccc(C#N)cc1)CCNCC2
InChIKey: DYBWPBGEFFIVCW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 280.38, ALogP 2.69, HBA 4, HBD 1, PSA 53.64, QED 0.92
Compound (SMILES): N#Cc1ccc(-c2ccc(OCCCN3CCN(c4ccncc4)CC3)cc2)cc1
InChIKey: MROYQSNDBHFVIZ-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]histamine from Gialpha2/Gbeta1gamma2-coupled human H4R expressed in Sf9 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 398.51, ALogP 4.21, HBA 5, HBD 0, PSA 52.39, QED 0.56
Compound (SMILES): Cc1cc(=O)oc2cc(NC(=O)/C=C/c3ccccc3)ccc12
InChIKey: QXUCCPZPSBZBCN-JXMROGBWSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 648.6 nM (pChEMBL 6.190000057220459)
Descriptors: MW 305.33, ALogP 3.75, HBA 3, HBD 1, PSA 59.31, QED 0.59
Compound (SMILES): CC(=O)N1CCN(CCOCc2ccn(-c3ccc(F)c(F)c3)n2)CC1.Cl
InChIKey: YJZGDOPAALDWAT-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 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: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells assessed as reduction in S35-MK-0499 binding
Measurement: IC50 = 2840 nM (pChEMBL 5.550000190734863)
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 CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Affinity Biochemical interaction (NanoBRET assay (in HEK293T cells)) EUB0000009b CLK1
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): CC(C)c1cc(Oc2c(Cl)cc(NCc3noc(=O)[nH]3)cc2Cl)n[nH]c1=O
InChIKey: PKZQKRHFNDZRHB-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay for Thyroid Hormone Receptor Agonist Screening: LanthaScreen TR-FRET Thyroid Receptor alpha Coactivator Assay kit (ThermoFisher) and LanthaScreen TR-FRET Thyroid Receptor beta Coactivator Assay kit (ThermoFisher) were used for agonist compound screening. Compounds in DMSO were diluted using ECHO Liquid Handler (Labcyte Inc.) into 384 plates in 10-point 3-fold series in duplicate (5 micro M final top concentration). Buffer C (ThermoFisher) was added to each well before the 4× mixture of fluorescein-SCR2-2 coactivator (200 nM final concentration), Terbium-labeled anti-GST antibody (2 nM final concentration), and TR alpha-LBD (0.4 nM final concentration) or TR beta-LBD (1.0 nM final concentration) was added. After 2 hour incubation at room temperature in dark, the TR-FRET signal was measured on an EnVision plate reader (PerkinElmer) with excitation at 340 nm and dual emission readout at 495 and 520 nm with the delay time of 100 micro second and the integration time of 200 micro second. The ratio of emission signal at 520 and at 495 was used to calculate EC50 using GraphPad Prism (GraphPad Software). In every batch of compound screening, T3 (L-3,3′,5-Triiodothyronine sodium salt, >95%) (Calbiochem) was used as reference compound. The EC50 of T3 measured were within 3-fold of the reference value provided by the assay kit manufacturer (ThermoFisher Scientific). The Z′ factors measured in every batch of screening using T3 as high percent effect (HPE) control and 0.5% DMSO as zero percent effect (ZPE) control were in the range of 0.5 to 0.8. Compounds' THR-beta selectivity values are derived from T3-selectivity normalized data.
Measurement: EC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 412.23, ALogP 3.28, HBA 7, HBD 3, PSA 125.9, QED 0.57
Compound (SMILES): CCCCCCCCOc1ccc(C(=O)N[C@H](C(=O)O)C(C)C)cc1
InChIKey: JIIPBCFIUGBDHZ-SFHVURJKSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Binding affinity to PPARa (unknown origin) by SPR assay
Measurement: Kd = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 349.47, ALogP 4.26, HBA 3, HBD 2, PSA 75.63, QED 0.55
Compound (SMILES): CN1CCN(CCCOc2ccc(-c3nn(C)c4nc(N)ncc34)cc2F)CC1
InChIKey: JOFZICSYCUPGPF-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 399.47, ALogP 1.77, HBA 8, HBD 1, PSA 85.33, QED 0.63
Compound (SMILES): COc1cc(-c2nnc(-c3cccc(S(N)(=O)=O)c3)o2)cc(OC)c1OC
InChIKey: OFIBSBAGSQHBSX-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki = 38.5 nM (pChEMBL 7.420000076293945)
Descriptors: MW 391.41, ALogP 2.08, HBA 8, HBD 1, PSA 126.77, QED 0.68
Compound (SMILES): O=S1(=O)C=Cc2cc(-c3ccc(OC(F)(F)F)cc3)cnc2O1
InChIKey: WTWOOTOUPJQVDE-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 343.28, ALogP 3.34, HBA 5, HBD 0, PSA 65.49, QED 0.78
Compound (SMILES): CCCCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: ODKMGQLTBYKABQ-LFIBNONCSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.19, ALogP 2.44, HBA 4, HBD 3, PSA 81.92, QED 0.32
Compound (SMILES): C=C(C)c1ccc(-c2coc3ccc(-c4cn[nH]c4)nc23)cc1
InChIKey: UQRGNUXIYRRBER-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human recombinant CLK4 using YRRAAVPPSPSLS substrate by radiometric scintillation assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
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: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using isoform-specific probe substrates by LC/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
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: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA-II using 4-nitrophenylacetate as substrate by spectrophotometry
Measurement: IC50 = 514 nM (pChEMBL 6.289999961853027)
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: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The DYRK1A kinase assa: Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
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 beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Binding affinity to wild-type human partial length PIK3CB (P118 to S1070 residues) expressed in HEK293 cells measured after 1 hr by Kinomescan method
Measurement: Kd = 1350 nM (pChEMBL 5.869999885559082)
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 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
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: 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 = 40 nM (pChEMBL 7.400000095367432)
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: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 by patch clamp analysis
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
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: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 453.63, ALogP 6.62, HBA 3, HBD 2, PSA 43.7, QED 0.38
Compound (SMILES): Cn1cc(-c2cc3c(C(=O)Nc4ccc(CN5CCCC5)cc4)n[nH]c3cc2F)cn1
InChIKey: WPENABQDALBNCS-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: GSK3β: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 M to 0.0003 M) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 418.48, ALogP 3.95, HBA 5, HBD 2, PSA 78.84, QED 0.51
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccc(NC(=O)CCCCC(=O)NO)cc3C2)c(O)cc1O
InChIKey: XQJICAHHMDZSIJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using RHK-K(Ac)-AMC as substrate by fluorescence based assay
Measurement: IC50 = 7415 nM (pChEMBL 5.130000114440918)
Descriptors: MW 455.51, ALogP 3.38, HBA 6, HBD 5, PSA 139.2, QED 0.23
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 Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 10.47 nM (pChEMBL 7.980000019073486)
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: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 45.1 nM (pChEMBL 7.349999904632568)
Descriptors: MW 445.56, ALogP 1.37, HBA 7, HBD 4, PSA 117.28, QED 0.44
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2ccccn2c1=O
InChIKey: ZBUAACUFPJCODX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as reduction in goat anti human IgM/human IL4-stimulated CD69 cell surface expression on peripheral B cells incubated for 18 hrs by FACS analysis
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 518.57, ALogP 4.39, HBA 6, HBD 3, PSA 122.59, QED 0.32
Compound (SMILES): N#Cc1c(-c2ccccc2)nc2c(/N=N/c3ccc(S(N)(=O)=O)cc3)c(N)nn2c1N
InChIKey: CCJFFHRRJCAICV-OCEACIFDSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 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): FC(F)(F)c1cnc(Nc2ccc3nc[nH]c3c2)nc1NC1CC1
InChIKey: HTSMUTPVZNMYSW-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): CN1CCC(c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)CC1
InChIKey: BWUOLNXJAQPJKF-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 = 568 nM (pChEMBL 6.25)
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 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-Mephenytoin as substrate measured after 45 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): COc1cc(SCc2ccc(CN3CCCC3)o2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: QOEFDQQUMQBVOB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR (669 to 1210 residues) expressed in baculovirus expression system using Srctide as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 615.18, ALogP 6.48, HBA 10, HBD 3, PSA 121.62, QED 0.15
Compound (SMILES): C#CCN(C)Cc1ccc(OCCCCCN2CCN(c3cccc4c3ccn4S(=O)(=O)c3ccccc3)CC2)cc1
InChIKey: CUFJQHNVDRIQJL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells measured after 1 hr by microbeta plate reader analysis
Measurement: Ki = 7996 nM (pChEMBL 5.099999904632568)
Descriptors: MW 584.79, ALogP 5.31, HBA 7, HBD 0, PSA 58.02, QED 0.16
Compound (SMILES): CC[C@@H](C)n1c(=O)c(NCc2ccc(S(=O)(=O)CC)cn2)nc2cnc(-c3c(OC)ncnc3C3CC3)nc21
InChIKey: DCSACVSUKUQBSN-OAHLLOKOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human PBMC assessed as reduction in anti-CD3/IL-23 stimulated IL-17 level measured after 3 days by MSD assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 550.65, ALogP 3.3, HBA 12, HBD 1, PSA 154.74, QED 0.31
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 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 7596.8
Compound (SMILES): CCC(=O)CCCCCC(NC(=O)c1cncs1)c1[nH]c(-c2ccccc2)nc1C(N)=O
InChIKey: IWHILOQIJOWDKF-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 453.57, ALogP 4.03, HBA 6, HBD 3, PSA 130.83, QED 0.36
Compound (SMILES): CC(C)c1cc(-c2cnn3ccc(-c4cc5c(c(C(F)(F)F)c4)C(=O)N([C@@H](C)C4CC4)C5)nc23)ccc1C(=O)O
InChIKey: VHCSLWRCKYDLOT-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human THP-1 cells assessed as reduction in Akt phosphorylation at S473 residue incubated for 60 mins by alphalisa assay
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 548.57, ALogP 6.66, HBA 5, HBD 1, PSA 87.8, QED 0.29
Compound (SMILES): CC(Nc1c(Cl)cnc2ccc(-c3cnc(C(C)(C)O)nc3)nc12)c1ccccc1F
InChIKey: JGVFDTLFVROGOH-UHFFFAOYSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Inhibition of exogenous human TNFalpha in HEK-Blue-CD40L cells assessed as reduction in TNF-alpha-induced NFkappaB activation incubated for 18 hrs by quanti-blue based SEAP assay
Measurement: IC50 = 473 nM (pChEMBL 6.329999923706055)
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 Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as stimulation of beta-arrestin recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 134.9 nM (pChEMBL 6.869999885559082)
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 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of His-tagged FAP1 (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 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 348.41, ALogP 2.86, HBA 5, HBD 2, PSA 96.36, QED 0.71
Compound (SMILES): CNc1ccccc1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: DMLMKQIHOFYZPV-VWLOTQADSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 538.68, ALogP 5.8, HBA 6, HBD 4, PSA 111.8, QED 0.16
Compound (SMILES): O=C(c1cccc(F)c1-c1ncccn1)N1C2CCC1C(Oc1ccc(C(F)(F)F)cn1)C2
InChIKey: FPUDTUWRAHVTMS-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Human Orexin 2 Receptor Radioligand Binding Assay: HEK293 stably expressing human orexin 2 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat #SH30022), 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 10 mM HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat #SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 40° C.), the supernatant was aspirated and the pellets frozen and stored at −800° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec just prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H]-EMPA (Moraveck Corporation, specific activity=29.6 Ci/mmol), diluted to a 5 nM concentration in PBS (2 nM final concentration). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentration (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]-EMPA diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate). The plates were washed 3 times by aspirating 30 ml PBS through the plates. Plates were dried in 55° C. oven for 60 min, scintillation fluid was added, and the radioactivity was counted on a Topcount (Packard).
Measurement: Ki = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 458.42, ALogP 4.52, HBA 5, HBD 0, PSA 68.21, QED 0.54
Compound (SMILES): CONC(=O)c1ccccc1Nc1cc(Nc2cc(C)nn2C(C)C)ncc1Cl
InChIKey: BVAHPPKGOOJSPU-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Binding affinity to FAK (unknown origin) assessed as inhibition constant
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 414.9, ALogP 4.6, HBA 7, HBD 3, PSA 93.1, QED 0.49
Compound (SMILES): C[C@@H]1CN(C2CCN(c3nc(N)n[nH]3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: STWVLEKJQQRGMO-DYVFJYSZSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Human AMCase Activity Assay: An enzymatic assay with recombinant human AMCase 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 B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, 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 hAMCase 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 Buffer (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 = 550 nM (pChEMBL 6.260000228881836)
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: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Binding affinity to H1 receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 323.4, ALogP 2.49, HBA 3, HBD 0, PSA 43.86, QED 0.87