lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cnc(C2=C(c3nnn[nH]3)C(=O)N[C@@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)nc1
InChIKey: OEUZUKOEKHJQBO-FQEVSTJZSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: MGAT LCMS Assay: The MGAT enzyme reactions were performed in Corning FALCON® 96-well polypropylene plates, in a total volume of 60 μL of 50 mM potassium phosphate buffer pH 7.4, containing a final concentration of 100 μM 2-oleoylglycerol, 15 μM oleoyl-coenzyme A and 0.0013 μg/μL human or mouse MGAT-2 or 0.0026 μg/μL rat recombinant MGAT-2 membranes expressed in Sf9 cells. Assay plates were run through a fully automated robotics system and shaken for 5 seconds every minute for a total 10 minutes. The reactions were then quenched with 120 μL of ice cold methanol containing 1 μg/mL 1,2-distearoyl-rac-glycerol as the internal standard. Plates were shaken for 2 minutes and spun down to remove protein precipitation. After the spin, samples were transferred to LC/MS compatible PCR plates. For LC/MS analysis, a ThermoFisher Surveyor pump, utilizing a Waters SYMMETRY C8, 50×2.1 mm column, was used for the chromatography of enzyme products. The buffer system consists of 0.1% formic acid in water with a mobile phase consisting 0.1% formic acid in methanol. The shallow gradient is 90-100% mobile phase in 0.2 min with a total run time of 2.3 min. The first 0.5 minutes of each injection was diverted to waste to eliminate the presence of phosphate buffer in the enzymatic reaction. The column was run at 0.6 mL/min and a temperature of 65° C. Mass spectrometry analysis of the samples was performed on a ThermoFisher Quantum Triple quad utilizing APCI (+) as the mode of ionization. Data was acquired in Single Ion Monitoring (SIM) mode analyzing Diolein=m/z 603.6 (PRODUCT) and 1,2-distearoyl-rac-glycerol (IS)=m/z 607.6. The ratio of Diolein to internal standard (Peak Area Ratio) is utilized to calculate IC50 values.
Measurement: IC50 = 34.3 nM (pChEMBL 7.460000038146973)
Descriptors: MW 527.43, ALogP 3.91, HBA 7, HBD 2, PSA 118.57, QED 0.35
Compound (SMILES): CN1CCC(N(C(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)C2CC2)CC1
InChIKey: ZSVCPMWFSPWQGY-CMCWBKRRSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) using fluorescein-poly GT and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 40 mins by LanthaScreen assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 496.57, ALogP 0.12, HBA 11, HBD 3, PSA 147.79, QED 0.45
Compound (SMILES): Cc1cnc(Nc2ccc(OCCN3CCCC3)cc2)nc1Nc1ccc(C(=O)Nc2ccccc2N)cc1
InChIKey: VYGGHIWUVSMRFX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant BRD4 BD1 (unknown origin) using H4KAc as substrate incubated for 30 mins by HTRF analysis
Measurement: IC50 = 1970 nM (pChEMBL 5.710000038146973)
Descriptors: MW 523.64, ALogP 5.58, HBA 8, HBD 4, PSA 117.43, QED 0.2
Compound (SMILES): O=C1NC(NCCCn2ccnc2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: QVYXLOYBJBMXNP-ZSOIEALJSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of N-terminal GST/His6-fused human full length CLK1 (1 to 484 residues) expressed in Sf9 cells assessed as inhibition of autophosphorylation using [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 352.42, ALogP 2, HBA 7, HBD 2, PSA 84.2, QED 0.54
Compound (SMILES): CCOP(=O)(OCC)C(Nc1ccc(S(N)(=O)=O)cc1)c1ccc(F)cc1
InChIKey: MXTYBSMRNGDIQI-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 1 hr prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 91.6 nM (pChEMBL 7.039999961853027)
Descriptors: MW 416.41, ALogP 3.85, HBA 6, HBD 2, PSA 107.72, QED 0.6
Compound (SMILES): c1ccc(-c2ccc(OCCCN3CCCC3)cc2)cc1
InChIKey: CHLIKLZJBHMZOW-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in Sprague-Dawley rat liver assessed as inhibition constant by liquid scintillation counter analysis
Measurement: Ki = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 281.4, ALogP 4.22, HBA 2, HBD 0, PSA 12.47, QED 0.74
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)CC[C@@H](NS(=O)(=O)c1ccc(NC(=O)c2ccc(C(N)=O)cc2)cc1)C(=O)O)C(=O)N(C)[C@@H](CCC(=O)O)C(=O)NCCCCC(N)=O
InChIKey: SBKWBGSLOANRHJ-ZLESDFJESA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human recombinant MMP13 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-N2 as substrate preincubated for 10 to 15 mins followed by substrate addition and measured after 60 to 120 mins by fluorescence based assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 901.01, ALogP 0.54, HBA 11, HBD 8, PSA 334.87, QED 0.06
Compound (SMILES): O=C1NC(NCC(O)Cc2ccccc2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: MCNDTHVVURYHKT-MFOYZWKCSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of N-terminal GST/His6-fused human full length CLK1 (1 to 484 residues) expressed in Sf9 cells assessed as inhibition of autophosphorylation using [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 378.46, ALogP 2.32, HBA 6, HBD 3, PSA 86.61, QED 0.59
Compound (SMILES): CC(C)(C)c1cc(-c2cccc(COc3ccccc3CCC(=O)OCCCOP(=O)(O)OC[C@H](N)C(=O)O)c2)cc(C(C)(C)C)c1
InChIKey: JQPHXUKSKNLAOZ-HKBQPEDESA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse LPS2/P2Y10 transfected in HEK293-A cells co-transfected with AP-TGFalpha assessed as AP-TGFalpha release by TGFalpha shedding assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 669.75, ALogP 6.94, HBA 8, HBD 3, PSA 154.61, QED 0.08
Compound (SMILES): CCOP(=O)(OCC)C(Nc1ccc(S(N)(=O)=O)cc1)c1ccc(Cl)cc1
InChIKey: DCMRGNSARQJDLM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibition constant incubated for 1 hr prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 141.7 nM (pChEMBL 6.849999904632568)
Descriptors: MW 432.87, ALogP 4.36, HBA 6, HBD 2, PSA 107.72, QED 0.57
Compound (SMILES): CNc1cc(Nc2cccn(-c3ncccc3F)c2=O)nc2c(C(=O)N[C@H]3C[C@@H]3OC)cnn12
InChIKey: UACFRVQSXPAUJZ-HOTGVXAUSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Binding affinity to JAK3 JH1 domain (unknown origin)
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 464.46, ALogP 1.72, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@@H]2CO[P@@](=O)(S)O[C@@H]3[C@H](O)[C@@H](CO[P@@](=O)(S)O[C@H]2[C@H]1F)O[C@H]3c1cnn2c(=O)[nH]ncc12
InChIKey: MDMQNKNHZQRNKA-OSNITWMNSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at human STING HAQ variant overexpressed in STING knockout human THP1-Blue ISG cells expressing IRF inducible SEAP reporter construct assessed as increase in interferon production by measuring SEAP activity incubated for 24 hrs by Fingerprinting based QUANTI-Blue colorimetric assay
Measurement: EC50 = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 693.53, ALogP 0.77, HBA 18, HBD 5, PSA 242.42, QED 0.14
Compound (SMILES): O=c1[nH]cnc2ccc(N3CCc4ccccc4CC3)cc12
InChIKey: YVXLVHPVPSAISI-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PC2
Assay: Inhibition of IP6K3 (unknown origin) incubated for 2 hrs in presence of ATP by ADPGlo reagent based assay
Measurement: IC50 = 59400 nM (pChEMBL 4.230000019073486)
Descriptors: MW 291.35, ALogP 2.53, HBA 3, HBD 1, PSA 48.99, QED 0.75
Compound (SMILES): CN(C)C(=O)C(C)(C)c1ccc2c(-c3ccc(F)cc3)cc(C(N)=O)nc2c1
InChIKey: LHDAQCXAFSYLBX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]-MK-499 from hERG expressed in HEK293 cells by automated patch-clamp assay
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 379.44, ALogP 3.51, HBA 3, HBD 1, PSA 76.29, QED 0.75
Compound (SMILES): COc1cccc(CC2NC(=O)CN(Cc3ccccc3)C2=O)c1
InChIKey: DYFKEEZDCXNGNU-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DADLE from human DOR expressed in CHO cell membranes assessed as inhibition constant incubated for 60 mins by microbeta 2 scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 324.38, ALogP 1.76, HBA 3, HBD 1, PSA 58.64, QED 0.91
Compound (SMILES): O=C1NC(N[C@H]2CCCC[C@@H]2O)=N/C1=C\c1ccc2ncsc2c1
InChIKey: RUQXGVGYNKIGJD-HWRLVWNTSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of N-terminal GST/His6-fused human full length CLK1 (1 to 484 residues) expressed in Sf9 cells assessed as inhibition of autophosphorylation using [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 342.42, ALogP 2.02, HBA 6, HBD 3, PSA 86.61, QED 0.73
Compound (SMILES): CN(C)C(=O)CCN(C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)c1cc2cc(C(F)(F)P(=O)(O)O)ccc2s1)C(C)(C)C)c1ccc(Cl)cc1
InChIKey: RMNVEYYZLLGXKE-WNCULLNHSA-N
Target: Signal transducer and activator of transcription 5B (SINGLE PROTEIN), Homo sapiens
UniProt: P51692
Assay: Binding affinity to STAT5B (unknown origin) assessed as inhibition constant by FP assay
Measurement: Ki = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 727.17, ALogP 5.43, HBA 6, HBD 3, PSA 147.56, QED 0.24
Compound (SMILES): Cc1cc(-c2cnc(C)nc2C2CCN(CC(=O)N3CCOCC3)CC2)on1
InChIKey: WPQVNXMKHXSMKX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells at holding potential of -80 mV measured for 15 seconds by whole cell patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 385.47, ALogP 1.79, HBA 7, HBD 0, PSA 84.59, QED 0.79
Compound (SMILES): COCc1cc(Cn2cc(-c3c(-c4ccc(Cl)cc4)nc4ccccn34)nn2)ccc1Cl
InChIKey: CAPHSHOCGMQMCA-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR in human HepG2 cells incubated for 24 hrs by dual luciferase reporter assay
Measurement: EC50 = 4340 nM (pChEMBL 5.360000133514404)
Descriptors: MW 464.36, ALogP 5.76, HBA 6, HBD 0, PSA 57.24, QED 0.32
Compound (SMILES): O=C(O)/C=C/C(=O)O.[2H]C([2H])(Cc1c[nH]c2ccccc12)N(C)C
InChIKey: OHMVTPSXVQQKPA-IOHXQUACSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H] ketanserin from human recombinant 5-HT2A receptor expressed in CHO-K1 cells incubated for 60 mins by spectrophotometric analysis
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 188.27, ALogP 2.27, HBA 1, HBD 1, PSA 19.03, QED 0.78
Compound (SMILES): CCCc1[nH]c(-c2cc(N)ccc2Cl)c2c1C(=O)CCCC2
InChIKey: YOEMPBAQUPZDDO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to BRD9 (unknown origin) assessed as dissociation constant by site-directed competition binding assay
Measurement: Kd = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 316.83, ALogP 4.78, HBA 2, HBD 2, PSA 58.88, QED 0.63
Compound (SMILES): NC(=O)C1Cc2nc(-c3ccc(Cl)c(Cl)c3)n(-c3ccnc(N[C@@H]4CCCN(C(=O)C5CC5)C4)n3)c2C1
InChIKey: MKHLHLAXBRMALM-ZYMOGRSISA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin) incubated for 20 mins in presence of 33P-ATP
Measurement: IC50 = 160.2 nM (pChEMBL 6.789999961853027)
Descriptors: MW 540.46, ALogP 3.65, HBA 7, HBD 2, PSA 119.03, QED 0.49
Compound (SMILES): CC(C)(C)NC(=O)NC12CC3CC(CC(NCC(=O)N4Cc5ccc(F)cc5C4)(C3)C1)C2
InChIKey: DYNQKHKLYGOOQQ-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human seminal plasma DPP4 using Ala-Pro-paranitroanilide as substrate incubated for 15 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 442.58, ALogP 3.45, HBA 3, HBD 3, PSA 73.47, QED 0.67
Compound (SMILES): CC1=NN(c2nc(-c3ccc(Cl)cc3)cs2)C(=O)/C1=C/c1ccc(C(=O)O)cc1
InChIKey: BASVBEFRHZKYIH-LICLKQGHSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 in presence of 400 uM NAD+ by fluorescence based analysis
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 423.88, ALogP 4.97, HBA 5, HBD 1, PSA 82.86, QED 0.6
Compound (SMILES): O=C(O)C1(c2ccc(-c3cc(C(F)(F)F)cc(C(F)(F)F)c3)c(F)c2)CC1
InChIKey: GCJYSUDFMJUOKJ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04828
Assay: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells using S-tetralol as substrate assessed as inhibition of NADP+ dependent substrate oxidation incubated for 10 mins by fluorescence microplate reader assay
Measurement: IC50 = 8320 nM (pChEMBL 5.079999923706055)
Descriptors: MW 392.27, ALogP 5.65, HBA 1, HBD 1, PSA 37.3, QED 0.69
Compound (SMILES): C[C@H]1NC(=O)c2cc(C#N)ccc2SC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: XQQIIPUPHPWBDF-CPBYAEMQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Agonist activity at human MC4R stably expressed in human Flp-In-293 cells assessed as cAMP accumulation incubated for 45 mins in presence of IBMX by Lance Ultra cAMP assay
Measurement: EC50 = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 945.08, ALogP -0.11, HBA 11, HBD 12, PSA 347.85, QED 0.05
Compound (SMILES): CS(=O)(=O)c1ccc(-c2nc(C(=O)NCc3cn(-c4cc(Br)ccn4)nn3)cs2)cc1
InChIKey: ARUJVRWEJKETKN-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at P2X7 receptor in human THP-1 cells assessed as inhibition of ATP-induced IL-1beta secretion pretreated with LPS for 3 hrs followed by incubation with compound for 40 mins followed by treatment with ATP for 1 hr by ELISA
Measurement: IC50 = 326.9 nM (pChEMBL 6.489999771118164)
Descriptors: MW 519.41, ALogP 2.88, HBA 9, HBD 1, PSA 119.73, QED 0.42
Compound (SMILES): CC(C)C[C@H](COC(C)(C)C)NC1=N/C(=C\c2ccc3ncsc3c2)C(=O)N1
InChIKey: FRPUHWUHZZNNOB-GESOSKEOSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of N-terminal GST/His6-fused human full length CLK1 (1 to 484 residues) expressed in Sf9 cells assessed as inhibition of autophosphorylation using [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 400.55, ALogP 3.94, HBA 6, HBD 2, PSA 75.61, QED 0.72
Compound (SMILES): COC(=O)C(Cc1cccc(OC)c1)NC(=O)CNCc1ccccc1
InChIKey: GGJOFASZTXGRHL-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DADLE from human DOR expressed in CHO cell membranes assessed as inhibition constant incubated for 60 mins by microbeta 2 scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 356.42, ALogP 1.69, HBA 5, HBD 2, PSA 76.66, QED 0.67
Compound (SMILES): CC(C)(C)Cc1c(C#Cc2ccc(F)c(F)c2)sc(N)c1C(=O)c1ccc(Cl)cc1
InChIKey: GKIHDPUKDDKVKP-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Binding affinity to alpha2A adrenergic receptor (unknown origin)
Measurement: Ki = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 443.95, ALogP 6.48, HBA 3, HBD 1, PSA 43.09, QED 0.37
Compound (SMILES): O=C(Nc1ccccc1)N1CCN(c2nnc(Cc3ccccc3)c3ccccc23)CC1
InChIKey: OAFSEOBYSMNKHG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin) by FRET assay
Measurement: IC50 = 158.73 nM (pChEMBL 6.800000190734863)
Descriptors: MW 423.52, ALogP 4.57, HBA 4, HBD 1, PSA 61.36, QED 0.52
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)N4CCNC(=O)C4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: XMBSMCIWNHQQQD-QCUYGVNKSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) using 5- FAM-EAIYAAPFAKKK-CONH2 and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 60 mins by Caliper assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 442.44, ALogP -2.01, HBA 11, HBD 4, PSA 173.65, QED 0.36
Compound (SMILES): O=c1[nH]cnc2ccc(/C=C/c3ccccc3)cc12
InChIKey: VYVMXDBCNYURLK-VOTSOKGWSA-N
Target: Inositol hexakisphosphate kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PC2
Assay: Inhibition of IP6K3 (unknown origin) incubated for 2 hrs in presence of ATP by ADPGlo reagent based assay
Measurement: IC50 = 168000 nM (pChEMBL 3.7699999809265137)
Descriptors: MW 248.29, ALogP 3.09, HBA 2, HBD 1, PSA 45.75, QED 0.71
Compound (SMILES): O=c1[nH]c(N2CCCCC2)nc2nccc(/C=C/c3ccco3)c12
InChIKey: QKFRTLJTJHCXEK-VOTSOKGWSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at human A2AR expressed in Flp-In-CHO cells assessed as NECA-mediated cAMP accumulation incubated for 30 to 60 mins followed by NECA addition measured after 30 mins by LANCE cAMP assay (Rvb = 8.38 +/- 0.03 No_unit)
Measurement: EC50 = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 322.37, ALogP 3.07, HBA 5, HBD 1, PSA 75.02, QED 0.8
Compound (SMILES): Cc1noc(C)c1COc1ccc(Cl)cc1C(=O)Nc1ccccc1
InChIKey: CWZDZGZZXPRYQN-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of AKR1C4 (unknown origin) incubated for 10 mins by fluorometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 356.81, ALogP 4.78, HBA 4, HBD 1, PSA 64.36, QED 0.71
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc4ccc(-c5cnn(C)c5)cc4n3)cc2)CC1
InChIKey: VCCYOHCOICDUFL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVH8
Assay: Inhibition of GLK (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 398.51, ALogP 4.58, HBA 6, HBD 1, PSA 58.87, QED 0.55
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(N2CCC(N3CCOCC3)CC2)c2c(C3CCC3)nn(-c3ccccc3)c2n1
InChIKey: XYBQSRRFUUGKSB-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Corrector activity at CFTR F508del mutant in forskolin-stimulated human bronchial epithelial cells derived from primary CF assessed as GLPG1837-mediated potentiation of increase in membrane expression by measuring change in Ieq in presence of GLPG1837/GLPG2222 preincubated for 24 hrs followed by measured for 20 mins for every 2 mins by transepithelial clamp circuit (TECC) assay
Measurement: EC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 538.67, ALogP 2.68, HBA 9, HBD 1, PSA 109.66, QED 0.51
Compound (SMILES): N#CCc1cnc(-c2ccc3ccccc3c2)n1-c1ccnc(N[C@H]2CCCN(C(=O)C3CC3)C2)n1
InChIKey: MIFPZJRPCSILQA-QHCPKHFHSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of human GSK3alpha assessed as incorporation of 33P-ATP
Measurement: IC50 = 5780 nM (pChEMBL 5.239999771118164)
Descriptors: MW 477.57, ALogP 4.36, HBA 7, HBD 1, PSA 99.73, QED 0.44
Compound (SMILES): Cc1n[nH]c2ccc(-c3nnc(C)n3Cc3ccc(C(F)(F)F)cc3)cc12
InChIKey: IXRCZLGBPPMVSP-UHFFFAOYSA-N
Target: Casein kinase I isoform gamma-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6M4
Assay: Binding affinity to CSNK1G3 (unknown origin) assessed as dissociation constant by competitive binding assay
Measurement: Kd = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 371.37, ALogP 4.51, HBA 4, HBD 1, PSA 59.39, QED 0.58
Compound (SMILES): O=C1NC(N[C@H]2COCC[C@@H]2O)=N/C1=C\c1ccc2ncsc2c1
InChIKey: URXJBXVGNBGIJA-CGGDQNISSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 453 nM (pChEMBL 6.340000152587891)
Descriptors: MW 344.4, ALogP 0.86, HBA 7, HBD 3, PSA 95.84, QED 0.7
Compound (SMILES): CNc1cc(Nc2cccn(-c3ncccc3F)c2=O)nc2c(C(=O)N[C@@H]3CC[C@@]3(C)OC)cnn12
InChIKey: DYXHKXJLXNTKFI-MZNJEOGPSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Binding affinity to JAK3 JH1 domain (unknown origin)
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 492.52, ALogP 2.5, HBA 10, HBD 3, PSA 127.47, QED 0.36
Compound (SMILES): CCN1C(=O)CC(c2ccc(Cl)cc2)C(C(=O)OCc2ccccc2)=C1C
InChIKey: OENWZQMRYIUFTH-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor expressed in HEK293 cells cotransfected with pCMV AC6-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 383.88, ALogP 4.69, HBA 3, HBD 0, PSA 46.61, QED 0.7
Compound (SMILES): COc1ccc(N(CC(F)(F)F)S(=O)(=O)C2CC3OC2C(c2ccc(O)cc2)=C3c2ccc(O)cc2)cc1
InChIKey: SCNJQFZSGJGVDA-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to ERbeta (unknown origin) assessed as inhibition constant
Measurement: Ki = 1280 nM (pChEMBL 5.889999866485596)
Descriptors: MW 547.55, ALogP 4.96, HBA 6, HBD 2, PSA 96.3, QED 0.43
Compound (SMILES): Cc1ccnc(OCc2cn(-c3ccc(F)c(OC(F)F)c3)nn2)n1
InChIKey: CJARMIUZBYDZBZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in HEK293 cells
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.29, ALogP 2.69, HBA 7, HBD 0, PSA 74.95, QED 0.68
Compound (SMILES): Cc1[nH]nc(-c2ccncc2)c1-c1ccc(N2CC3(CCOC3)C2)cc1
InChIKey: ACLRNCDEYTZTFX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 G2019S mutant in HEK293 cells
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 346.43, ALogP 3.67, HBA 4, HBD 1, PSA 54.04, QED 0.79
Compound (SMILES): CC(C)[C@H](NC12CC3CC(CC(N)(C3)C1)C2)C(=O)N1Cc2ccccc2C1
InChIKey: OEKINQHMFQVBBQ-OSIZCDOHSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of human recombinant DPP2 using Lys-Ala-pNA as substrate incubated for 15 mins by fluorescence based analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 367.54, ALogP 3.19, HBA 3, HBD 2, PSA 58.36, QED 0.86
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc2cc1Nc1cc(cc(-c3ccn(C)n3)c1OC)CCOCc1cccc(n1)N2
InChIKey: ZEAJJEHCOSPUQW-FIBGUPNXSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.54, ALogP 3.2, HBA 10, HBD 3, PSA 128.11, QED 0.4
Compound (SMILES): C[n+]1cncc(I)c1
InChIKey: XTDXNOKSMWTDMK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 C102S/C153S/C244S triple mutant (unknown origin) using Boc-Lys(TFA)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hrs by fluorescence based method
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 221.02, ALogP 0.51, HBA 1, HBD 0, PSA 16.77, QED 0.46
Compound (SMILES): Nc1nnc(-c2ccco2)cc1-c1ccccc1
InChIKey: XDZOPVBNIQCJCD-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay
Measurement: Kd > 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 237.26, ALogP 2.99, HBA 4, HBD 1, PSA 64.94, QED 0.74
Compound (SMILES): O=C(Nc1cccnc1)c1cc(C(F)(F)F)nc(-n2ccnc2)n1
InChIKey: ALAIYMDMURYRDI-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes preincubated for 5 mins in presence of substrate followed by NADPH addition and measured after 20 mins by LC/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.26, ALogP 2.33, HBA 6, HBD 1, PSA 85.59, QED 0.79
Compound (SMILES): CN1CC[C@H](NC(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)C1
InChIKey: WKJFWQDWRXBVAI-DUBGADTFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3-ITD (unknown origin) using fluorescein-poly GT and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 40 mins by LanthaScreen assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 442.48, ALogP -1.15, HBA 11, HBD 4, PSA 156.58, QED 0.39
Compound (SMILES): C[C@@H](NC(=O)c1nn(-c2ccccc2Cl)c(-c2ccc(Cl)cc2)c1Cc1nn[nH]n1)c1ccc(C(F)(F)F)cc1
InChIKey: DANBLBWVACCFGQ-OAHLLOKOSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor expressed in CHO-K1 cell membrane in presence of CP55940 by GTP-gamma-S assay
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 586.41, ALogP 6.46, HBA 6, HBD 2, PSA 101.38, QED 0.23
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(C)C)NC1=O)C(=O)CCSC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N2
InChIKey: ALLSOGQLAFFHKM-VQKAUQHZSA-N
Target: Angiotensin-converting enzyme 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BYF1
Assay: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis
Measurement: Kd = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 2134.55
Compound (SMILES): O=C(NO)c1ccc(Cn2c(=O)n(CCc3ccccc3O)c(=O)c3ccccc32)cc1
InChIKey: NMIAETUCWFKGKM-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Enzymatic Assay: The IC50 values for aforementioned compounds against HDACs were determined. HDAC 1 to 11 can be assayed by using acetylated AMC-labeled peptide substrate. The Substrate 1, a fluorogenic peptide from p53 residues 379-382 (RHKKAc) is used for all MAC 1 to 11 but HDAC8, which has a substrate II (RHKAcKAc), a fluorogenic diacyl peptide based on residues 179-382 of p53. Compounds were tested in 10-dose 1050 mode in duplicate with 3-fold serial dilution starting at 10 uM.
Measurement: IC50 = 16700 nM (pChEMBL 4.78000020980835)
Descriptors: MW 431.45, ALogP 2.28, HBA 7, HBD 3, PSA 113.56, QED 0.32
Compound (SMILES): C[C@@]1(N2CCC(c3cc4cc(NC(=O)C5CC56CC6)ncc4cc3Cl)CC2)COC[C@@H]1O
InChIKey: ZUOYPKKUCQORTM-QYNLNAJJSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by QPatch voltage clamp assay
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 455.99, ALogP 3.96, HBA 5, HBD 2, PSA 74.69, QED 0.73
Compound (SMILES): Cc1c2cc(cc1C(=O)Nc1cc(Cl)cc(C(F)(F)F)c1)OCCCCCCCNC(=O)c1ccc3ncc(n3n1)C#C2
InChIKey: LYXIOTQYDYQDCB-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G595R mutant (unknown origin) expressed in baculovirus expression system Sf9 cells using Ser/Thr 06 as peptide substrate incubated for 1 hr in presence of ATP by FRET based Z-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 610.04, ALogP 6.43, HBA 6, HBD 2, PSA 97.62, QED 0.26
Compound (SMILES): COc1cc(-c2cn(Cc3cn4cc(CNCC5CCC5)ccc4n3)nn2)c2cn[nH]c2c1
InChIKey: SYFLFCXAJNSJDI-UHFFFAOYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 442.53, ALogP 3.42, HBA 8, HBD 2, PSA 97.95, QED 0.38
Compound (SMILES): O=C1NC(NC2CCCCC2(F)F)=N/C1=C\c1ccc2ncsc2c1
InChIKey: DCJOTKUJWJFCSP-GHXNOFRVSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 362.41, ALogP 3.29, HBA 5, HBD 2, PSA 66.38, QED 0.81
Compound (SMILES): COCCN1C(=O)CC(c2ccc(Cl)cc2)C(C(=O)OCc2ccccc2OC(F)(F)F)=C1C
InChIKey: VYXYRDQIAOQQAX-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: Agonist activity at mouse TGR5 receptor expressed in HEK293 cells cotransfected with pCMV AC6-TGR5 assessed as activation of intracellular cAMP production incubated overnight by luciferase reporter gene assay
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 497.9, ALogP 5.22, HBA 5, HBD 0, PSA 65.07, QED 0.47
Compound (SMILES): COC(=O)[C@@H](N)CCNC(=O)[C@H]1O[C@@H](n2cc(-c3ccn(C)n3)c3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: UGMFITXTVCKADG-GPNFVODBSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3-ITD (unknown origin) using fluorescein-poly GT and ATP as substrates preincubated for 10 mins followed by substrate addition and measured after 40 mins by LanthaScreen assay
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 474.48, ALogP -1.96, HBA 13, HBD 5, PSA 205.66, QED 0.24
Compound (SMILES): COc1ccc2c(c1)c(CCNC(C)=O)c(-c1cccc3ccccc13)n2C
InChIKey: HQKOXVDUAHSOBU-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[125I]iodoMLT from human MT2 receptor expressed in mouse NIH3T3 cells incubated for 90 mins by Cheng-Prusoff equation analysis
Measurement: Ki = 0.309 nM (pChEMBL 9.510000228881836)
Descriptors: MW 372.47, ALogP 4.69, HBA 3, HBD 1, PSA 43.26, QED 0.55
Compound (SMILES): CC(c1ccccc1)n1cc(-c2cccc3cn[nH]c23)c(=O)[nH]c1=O
InChIKey: NGIUEWQDJPVTOK-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET D1228V (unknown origin) using ATP and poly(L-glutamic acid-L-tyrosine) as substrate incubated for 60 mins measured by ADP-Glo kinase assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 332.36, ALogP 2.69, HBA 4, HBD 2, PSA 83.54, QED 0.6
Compound (SMILES): CCOc1cc2nn(CC(=O)N3CCOCC3)cc2cc1NC(=O)c1cccc(C(F)(F)F)n1
InChIKey: VDZFJGBNFBEPBN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human liver microsomes CYP1A2 using phenacetin as substrate by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.44, ALogP 2.96, HBA 7, HBD 1, PSA 98.58, QED 0.59
Compound (SMILES): CCC[C@@H](C(=O)Nc1ccc(C(N)=O)c(F)c1)n1cc(OC)c(-c2cc(Cl)ccc2-n2cc(C(F)F)nn2)cc1=O
InChIKey: WZUXJAUBKKDABN-QFIPXVFZSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: To determine the plasma kallikrein inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic plasma kallikrein substrate to determine the enzymatic activity of human plasma kallikrein. Here, plasma kallikrein cleaves from the peptic plasma kallikrein substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions is placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 588.97, ALogP 4.91, HBA 8, HBD 2, PSA 134.13, QED 0.27
Compound (SMILES): COC[C@@H](CC(C)C)NC1=N/C(=C\c2ccc3ncn(C)c3c2)C(=O)N1C
InChIKey: AKTCVLPOZVXXJU-GESOSKEOSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human DYRK1B assessed as incorporation of 33Pi using [gamma-33P]-ATP measured after 60 mins by microplate scintillation counting based radiometric analysis
Measurement: IC50 = 192.8 nM (pChEMBL 6.710000038146973)
Descriptors: MW 369.47, ALogP 2.39, HBA 6, HBD 1, PSA 71.75, QED 0.79
Compound (SMILES): CCc1ccccc1OC[C@@H](O)CNCCC(c1ccccc1)c1ccccc1
InChIKey: MBVZCWDDTQDBJD-DEOSSOPVSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Antagonist activity at human beta1-adrenergic receptor expressed in CHO-K1 cells co-expressing CRE-SPAP reporter gene assessed as inhibition of fenoterol-induced CRE-SPAP production by measuring rightward shift of the fenoterol concentration response curve measured after 5 hrs incubation
Measurement: Kd = 134.9 nM (pChEMBL 6.869999885559082)
Descriptors: MW 389.54, ALogP 4.8, HBA 3, HBD 2, PSA 41.49, QED 0.46
Compound (SMILES): O=C1NC(N[C@@H](CO)CC2CC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: PEICIAVUWSXRGP-KXQKXUNCSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 342.42, ALogP 1.87, HBA 6, HBD 3, PSA 86.61, QED 0.72
Compound (SMILES): NC12CC3CC(C1)CC(NCC(=O)N1Cc4ccccc4C1)(C3)C2.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ZQUMUXSGKIACDN-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Inhibition of human recombinant DPP2 using Lys-Ala-pNA as substrate incubated for 15 mins by fluorescence based analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 325.46, ALogP 2.17, HBA 3, HBD 2, PSA 58.36, QED 0.9
Compound (SMILES): O=C(O)Cc1c(O)c(F)cc2c1-c1ccc(F)cc1C21NC(=O)NC1=O
InChIKey: MVPJMEDWDFMGBJ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14550
Assay: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 360.27, ALogP 1.36, HBA 4, HBD 4, PSA 115.73, QED 0.6
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CN)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: NFWLCSRZYLNMRU-PUHABZHSSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity against mouse MC5R expressed in HEK293 cells assessed as increase in cAMP level incubated for 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 771.66, ALogP -0.1, HBA 7, HBD 9, PSA 247.41, QED 0.04
Compound (SMILES): Cc1nc(-c2ccc(-c3ccccc3)c(C#N)c2)[se]c1C(=O)O
InChIKey: DJWSKQZSUPNTPC-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition Assay: The inhibition of the activity of xanthine oxidase (XO) is tested through a coupled enzymatic reaction of xanthine oxidase, horseradish peroxidase (HRP) and a substrate thereof. First, xanthine oxidase oxidizes hypoxanthine to produce xanthine and hydrogen peroxide, and further oxidizes xanthine to produce uric acid and hydrogen peroxide. Then, hydrogen peroxide reacts with 10-acetyl-3,7-dihydroxyphenoxazine (Ampliflu Red) under catalytic action of horseradish peroxidase so as to produce resorufin, a compound with strong fluorescence. The fluorescence intensity of resorufin is determined by using a fluorescence microplate, which is in direct proportion to the activity of xanthine oxidase.
Measurement: IC50 = 2.63 nM (pChEMBL 8.579999923706055)
Descriptors: MW 367.27
Compound (SMILES): CN(CC/C=C/c1ccccc1-c1ccccc1)C(CO)C(=O)NCc1ccc(F)cc1
InChIKey: QLFCWKOBGHTBLK-KPKJPENVSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 917 nM (pChEMBL 6.039999961853027)
Descriptors: MW 432.54, ALogP 4.51, HBA 3, HBD 2, PSA 52.57, QED 0.5
Compound (SMILES): O=C1NC(N[C@@H]2CCCOC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: JXQZHHAAJMQJKU-PZHUPROXSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 236 nM (pChEMBL 6.630000114440918)
Descriptors: MW 328.4, ALogP 1.89, HBA 6, HBD 2, PSA 75.61, QED 0.83
Compound (SMILES): CCNC(=O)c1c(OC)cc(-n2cnc3cc(-c4cnn(CC#N)c4)ccc32)cc1OC
InChIKey: CAWABSRZIMATJO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Abl1 (unknown origin) using poly (Glu,Tyr) as substrate incubated for 45 to 60 mins in presence of ATP by [33P]-gammaATP based Topcount scintillation counting analysis
Measurement: IC50 = 444 nM (pChEMBL 6.349999904632568)
Descriptors: MW 430.47, ALogP 3.18, HBA 8, HBD 1, PSA 106.99, QED 0.48
Compound (SMILES): OCC(CO)Nc1nc(Nc2cccc(C(F)(F)F)c2)nc(Nc2cccc(C(F)(F)F)n2)n1
InChIKey: YBHCSYSMWLYGNC-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin) expressed in human TF-1 cells assessed as inhibition of D2HG production incubated for 3 days by UHPL HRMS analysis
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 489.38, ALogP 3.56, HBA 9, HBD 5, PSA 128.11, QED 0.3
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@H]1CCN(Cc2ccc(C(F)(F)F)cc2)[C@@H](C)C1
InChIKey: LLXUFTFQOVBHRV-YOEHRIQHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant JAK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 16.8 nM (pChEMBL 7.78000020980835)
Descriptors: MW 445.49, ALogP 4.41, HBA 4, HBD 3, PSA 73.05, QED 0.54
Compound (SMILES): CN1CCN(c2ccc(NC3=N/C(=C\c4ccc5ncsc5c4)C(=O)N3)cc2)CC1
InChIKey: LYYKJBQTIFDJMU-UNOMPAQXSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 418.53, ALogP 2.99, HBA 7, HBD 2, PSA 72.86, QED 0.64
Compound (SMILES): Cc1cccc(CN(C)c2ncnc3[nH]c(-c4ccc(C(F)F)cc4)cc23)c1
InChIKey: BAENLCOORYABGD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) in presence of ATP by Z-LYTE based FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 378.43, ALogP 5.51, HBA 3, HBD 1, PSA 44.81, QED 0.5
Compound (SMILES): CSc1ccc(C(N)=O)cc1-c1ccc2c(cnn2C)c1
InChIKey: LAJCSSWPGDDWCX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by Q-patch clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 297.38, ALogP 3.06, HBA 4, HBD 1, PSA 60.91, QED 0.76
Compound (SMILES): C=CC(=O)N1CCC(OC(=O)NCc2ccc(C(=O)Nc3ccccc3N)cc2)CC1
InChIKey: WKCLLRPFCAPVDU-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using 6-carboxyfluorescein peptide as substrate preincubated with compound for 6 hrs followed by substrate addition by electrophoretic mobility shift assay
Measurement: IC50 = 379 nM (pChEMBL 6.420000076293945)
Descriptors: MW 422.49, ALogP 2.92, HBA 5, HBD 3, PSA 113.76, QED 0.49
Compound (SMILES): Cc1cnc(OCc2nnn(-c3cccc(C(F)F)c3)c2C)nc1
InChIKey: VCMPLIZYKYHCOI-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: NR2B standard assay: 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 149 mM NaCl, 4 mM KCl, 2 mM CaCl2, and 1.5 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 (149 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 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 ¿EC80 (standard assay) or EC40 (HTS assay) is used to maximize the assay's signal window or the ability to detect NMDA receptor antagonists and negative allosteric modulators, respectively. 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 = 952 nM (pChEMBL 6.019999980926514)
Descriptors: MW 331.33, ALogP 3.19, HBA 6, HBD 0, PSA 65.72, QED 0.72
Compound (SMILES): Cc1cccc(CN(C)c2ncnc3[nH]c(-c4ccc(O)cc4)cc23)c1
InChIKey: VMBRRMNXXVZGCB-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R (unknown origin) using ultra ULight GT peptide as substrate incubated for 1 hr in presence of 25 uM of ATP by LANCE Ultra TR-FRET assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 344.42, ALogP 4.28, HBA 4, HBD 2, PSA 65.04, QED 0.58
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=S)N[C@H]2CCN(c3ccc(C(F)(F)F)cn3)C2)cc1
InChIKey: TWNBFLYFNRTBNB-ZDUSSCGKSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human CA7 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 15.7 nM (pChEMBL 7.800000190734863)
Descriptors: MW 445.49, ALogP 2.31, HBA 5, HBD 3, PSA 100.35, QED 0.62
Compound (SMILES): CN1CCN(c2nc(N)nc(C[Se]Cc3ccccc3)n2)CC1
InChIKey: WAEJJMMPQBTBEI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from 5-HT7 receptor (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki = 4450 nM (pChEMBL 5.349999904632568)
Descriptors: MW 377.35
Compound (SMILES): CC(C)[C@H](NC(=O)c1cccs1)C(=O)Nc1nncs1
InChIKey: BOOCGYQJICPSDC-VIFPVBQESA-N
Target: Heat shock 70 kDa protein 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P17066
Assay: Inhibition of HspA6 (unknown origin) by FP assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 310.4, ALogP 1.99, HBA 6, HBD 2, PSA 83.98, QED 0.88
Compound (SMILES): CCNC(=O)c1ccc2c(C3CCN(CC4(O)C5CC6CC(C5)CC4C6)CC3)c(C)nn2c1
InChIKey: QSSAFMJRJQJFKL-YNMSWQDYSA-N
Target: YEATS domain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95619
Assay: Binding affinity to C-terminal biotin-tagged YEATS4 (unknown origin) by SPR analysis
Measurement: Kd = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 450.63, ALogP 3.76, HBA 5, HBD 2, PSA 69.87, QED 0.73
Compound (SMILES): CCCN(CCC(C(=O)N(C)C)(c1ccccc1)c1ccccc1)[C@@H]1C[C@H]1c1ccc(Cl)cc1
InChIKey: XIDCICLXZSWQGO-WUFINQPMSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Partial agonist activity at Rluc8 fused mouse MOR transfected in HEK293T cells assessed as Nb33 recruitment using coelenterazine as substrate incubated for 40 mins by BRET assay
Measurement: EC50 = 2089.3 nM (pChEMBL 5.679999828338623)
Descriptors: MW 475.08, ALogP 6.37, HBA 2, HBD 0, PSA 23.55, QED 0.34
Compound (SMILES): CN(CCOCCN1c2ccccc2Sc2ccccc21)C(CCO)C(=O)NCc1ccccc1Cl
InChIKey: LZMGFBSYUJBWOZ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 3550 nM (pChEMBL 5.449999809265137)
Descriptors: MW 526.1, ALogP 4.96, HBA 6, HBD 2, PSA 65.04, QED 0.33
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC[C@@H](NC(=O)Nc3cc(C(F)(F)F)cc(C(F)(F)F)c3)C2)nc1
InChIKey: YSCAFGPFKLJWHV-GFCCVEGCSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human CA7 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 40.8 nM (pChEMBL 7.389999866485596)
Descriptors: MW 497.42, ALogP 3.17, HBA 5, HBD 3, PSA 117.42, QED 0.56
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: UTYIBRLTBCAPEN-JVVMDBNWSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q01727
Assay: Antagonist activity at mouse MC1R expressed in HEK293 cells assessed as reduction in NDP-MSH induced cAMP formation incubated for 2 hrs by AlphaScreen based schild plot analysis
Measurement: Kd = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 822.71, ALogP 0.9, HBA 7, HBD 9, PSA 250.07, QED 0.03