lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCC(C)C2CCCCC2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: DKQRSYXCMBPAAM-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 414.58, ALogP 4.35, HBA 4, HBD 4, PSA 118.42, QED 0.43
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2ccc(cc2)CSC(C)(C)[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: YQOPVQXIKMEFFV-SIXPOYHZSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 1135.43
Compound (SMILES): COc1cc(S(N)(=O)=O)cc(OC)c1OCCC(N)C1COc2ccccc2O1
InChIKey: RUMNOCQXRVXQHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 4346 nM (pChEMBL 5.360000133514404)
Descriptors: MW 424.48, ALogP 1.29, HBA 8, HBD 2, PSA 132.33, QED 0.65
Compound (SMILES): CCNC1=NC(c2ccc(F)cc2)NC(=O)N1
InChIKey: XWRLROSVVBGPPA-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: β-secretase (BACE-1, Sigma-Aldrich) inhibition studies were performed by employing a peptide mimicking APP sequence as substrate (Methoxycoumarin-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys-dinitrophenyl, M-2420, Bachem, Germany). The following procedure was employed: 5 μL of test compounds (or DMSO, if preparing a control well) were pre-incubated with 175 μL of enzyme (in 20 mM sodium acetate containing 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) 0.1% w/v) for 1 hour at rt. The substrate (3 μM, final concentration) was then added and left to react for 15 minutes at 37° C. The fluorescence signal was read at λem=405 nm (λexc=320 nm) using a Fluoroskan Ascent. The DMSO concentration in the final mixture maintained below 5% (v/v) guaranteed no significant loss of enzyme activity. The fluorescence intensities with and without inhibitor were compared and the percent inhibition due to the presence of test compounds was calculated. The background signal was measured in control wells containing all the reagents, except BACE-1 and subtracted. The % inhibition due to the presence of increasing test compound concentration was calculated by the following expression: 100−(IFi/IFo×100) where IFi and IFo are the fluorescence intensities obtained for BACE-1 in the presence and in the absence of inhibitor, respectively. Inhibition curves were obtained by plotting the % inhibition versus the logarithm of inhibitor concentration in the assay sample, when possible. The linear regression parameters were determined and the IC50 extrapolated (GraphPad Prism 4.0, GraphPad Software Inc.).
Measurement: IC50 = 12550 nM (pChEMBL 4.900000095367432)
Descriptors: MW 236.25, ALogP 1.1, HBA 3, HBD 3, PSA 65.52, QED 0.72
Compound (SMILES): Nc1nc(N)nc(NCCCCCCN2CCN(c3ccccc3)CC2)n1
InChIKey: URACJDWODSYSKR-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to human D2 receptor expressed in HEK293 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 1009 nM (pChEMBL 6)
Descriptors: MW 370.51, ALogP 1.83, HBA 8, HBD 3, PSA 109.22, QED 0.57
Compound (SMILES): c1cncc(-c2cnc(NCc3cccc4c3CCO4)n3cnnc23)c1
InChIKey: VFLXVDWCZHLLLM-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human Phosphodiesterase 4D
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 344.38, ALogP 2.73, HBA 7, HBD 1, PSA 77.23, QED 0.61
Compound (SMILES): CNCc1cc(Cl)ccc1Cn1c(=S)[nH]c(=O)c2[nH]ccc21
InChIKey: QNKLBACGOUFKKR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Competitive inhibition of human recombinant CYP3A4 using coumarin as substrate preincubated with enzyme for 10 mins followed by NADPH addition and measured after 20 to 50 mins by fluorescence based method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 334.83, ALogP 2.81, HBA 4, HBD 3, PSA 65.61, QED 0.64
Compound (SMILES): O=C(/C=C/c1ccc(CNc2ccc3nc4n(c(=O)c3c2)CCCCC4)cc1)NO
InChIKey: PXSXCOJDFYVRBV-FMIVXFBMSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin) by colorimetric method
Measurement: IC50 = 617 nM (pChEMBL 6.210000038146973)
Descriptors: MW 404.47, ALogP 3.25, HBA 6, HBD 3, PSA 96.25, QED 0.34
Compound (SMILES): Cl.Oc1c(Cl)cccc1C1NCCc2c1[nH]c1ccc(F)cc21
InChIKey: QMALRJOFZALGHA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 316.76, ALogP 3.9, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): CN1C=C(c2ccc3ccn(Cc4ccccn4)c3c2)C2C=CNC2C1=O
InChIKey: RUUNUTOBMVHUHT-UHFFFAOYSA-N
Target: Bromodomain and PHD finger-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULD4
Assay: Inhibition of His-tagged recombinant BRPF3 (unknown origin) (11 to 188 residues) using SGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH as substrate measured after 1 hr by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 356.43, ALogP 3, HBA 4, HBD 1, PSA 50.16, QED 0.78
Compound (SMILES): CCCOC(=O)C1CCN(C(=O)c2ccc(N(C)Cc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: AMDVLSYFJVONRJ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 478.56, ALogP 2.03, HBA 10, HBD 2, PSA 153.45, QED 0.48
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(Cl)n2)ccn1
InChIKey: ZVSNSFQQKSZZMY-IBGZPJMESA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Inhibition of BIKE (unknown origin)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 392.89, ALogP 4.12, HBA 6, HBD 2, PSA 99.36, QED 0.69
Compound (SMILES): NC(=S)c1ccc(C(=O)NC2CCN(Cc3ccccc3)CC2)cc1
InChIKey: MDRXXGMJEJFONZ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-U69593 from Dunkin-Hartley guinea pig brain membrane kappa opioid receptor incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 353.49, ALogP 2.72, HBA 3, HBD 2, PSA 58.36, QED 0.81
Compound (SMILES): O=C(Cc1ccccc1)N[C@@H](C[C@H]1COc2c(Cl)cccc21)B(O)O
InChIKey: NVIDCSSIOTZCLS-BBRMVZONSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Determination of Beta5 Activity: Measurement of Beta5 inhibition is performed in 384 well format based on fluorescence intensity assay.Purified human constitutive proteasome (1.25 nM) and serial diluted compounds in DMSO (range of concentrations from 30 μM to 15 μM) or controls are incubated for 20 minutes at 25° C. in assay buffer containing 50 mM Tris pH 7.4, 0.03% SDS, 1 mM EDTA and 1% DMSO. The reaction is initiated by the addition of the fluorogenic peptide substrate, Suc-LLVY-AMC (Bachem 1-1395), at a concentration of 40 μM. After 60 minutes of incubation at 37° C., fluorescence intensity is measured at λex=350 nm and λem=450 nm with a fluorescence reader (Perkin Elmer Envision reader or equivalent).
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 359.62
Compound (SMILES): CNCC(=O)N[C@@H]1[C@H](O)[C@H](O[C@H]2/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@]3(O)C[C@H](O)[C@@H](C(=O)NCCN)[C@H](C2)O3)O[C@H](C)[C@H]1O.NC(CCC(=O)O)C(=O)O
InChIKey: SXASWTOXGYYPEN-RYLHAJFVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsome using midazolam and testostrone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 36900 nM (pChEMBL 4.429999828338623)
Descriptors: MW 1037.26
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c(C(=O)N[C@H]3CC[C@](C)(O)CC3)c2)cc1F
InChIKey: PRKWSDOLROTYLX-KQUPGTECSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: ADPGlo Assay: The assays were performed in 384-well, low volume microtiter assay plates in a final reaction volume of 6 ul. Dose-response curves were generated by incubating 10 nM of each kinase in 50 mM Hepes pH 7.5, 0.02% Tween 20, 0.02% BSA, 1 mM DTT, 10 μm Na3VO4, 10 mM β-Glycerolphosphate, 1 mM MgCl2, 12 mM MnCl2 and 15 μm ATP for 60 min at 32° C. in the presence or absence of compound diluted in DMSO. The amount of generated ADP is a measure of kinase activity and is quantified using the ADP-Glo™ Kinase Assay (Promega) according to manufacturer's instructions. ADP is converted to ATP by adding 3 ul of ADP-Glo™ Reagent and incubation at 32° C. for 60 min. ATP is subsequently converted into a bioluminescent signal by adding 6 ul luciferase assay reagents (Kinase detection buffer+Kinase Detection Substrate (Promega)) and further incubation at 32° C. for 60 min. For the measurement of luminescence a PHERAstar™ Multilabel Reader was used at a measurement interval time of 0.1 second (optical module for luminescence measurements in the 230 nm to 750 nm wavelength range).
Measurement: IC50 = 14600 nM (pChEMBL 4.840000152587891)
Descriptors: MW 440.56, ALogP 3.88, HBA 5, HBD 3, PSA 91.48, QED 0.66
Compound (SMILES): C[C@@H]1CN(Cc2ccc(C(=O)NO)cc2)C[C@H]1c1nc2c(cnn2C2CCCC2)c(=O)[nH]1
InChIKey: UWLURVWZRQXQEM-AUUYWEPGSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 436.52, ALogP 2.59, HBA 7, HBD 3, PSA 116.14, QED 0.42
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCC(F)(F)F)cc2)CC1
InChIKey: HCPZGSLTHYYAJZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 454.47, ALogP 3.97, HBA 4, HBD 1, PSA 57.7, QED 0.64
Compound (SMILES): Clc1cccc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: VCMBCXHABJNEBE-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST3 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 444.97, ALogP 5.14, HBA 4, HBD 2, PSA 75.18, QED 0.33
Compound (SMILES): COc1cc(/C=C2\N=C(Nc3ccc(N4CCNCC4)cc3)NC2=O)ccc1O
InChIKey: JMMKVTXEDIDGGS-ATVHPVEESA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-fused human recombinant DYRK1A expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 393.45, ALogP 1.75, HBA 7, HBD 4, PSA 98.22, QED 0.59
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(Cl)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: UFEKBPHSPFQBDC-CPIJZORTSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human adenosine A3 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 154.88 nM (pChEMBL 6.809999942779541)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43
Compound (SMILES): CCC(C)/C=C(\C)c1cc2c(cn1)C(=O)c1c(cc(OC)c(O)c1O)C2=O
InChIKey: KTTMOEJRXVCSJJ-IZZDOVSWSA-N
Target: Proteasome subunit beta type-10 (SINGLE PROTEIN), Homo sapiens
UniProt: P40306
Assay: Inhibition of human proteasome subunit beta type-2i using fluorogenic substrate by UV-spectrometry
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 367.4, ALogP 3.73, HBA 6, HBD 2, PSA 96.72, QED 0.68
Compound (SMILES): O=C(N[C@@H]1CCCN(c2ncnc3[nH]ccc23)C1)[C@H](Nc1cc(F)cc(Cl)c1)C1CC1
InChIKey: OETOLISJTPMUFM-VQIMIIECSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Binding affinity to human partial length TXK (L238 to W527 residues ) expressed in bacterial expression system assessed dissociation constant by Kinomescan method
Measurement: Kd = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 442.93, ALogP 3.73, HBA 5, HBD 3, PSA 85.94, QED 0.54
Compound (SMILES): COc1cc(OC)c2c(=O)[nH]c(-c3ccc(OCCOc4ccccc4C(N)=O)cc3)nc2c1
InChIKey: NQBBGPWFKFVWGM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Inhibition of BRD1 (unknown origin)
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 461.47, ALogP 3.16, HBA 7, HBD 2, PSA 125.76, QED 0.37
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@@H](CO)C5CC5)c4n3)cc(OC(F)(F)F)c2C1=O
InChIKey: NOENGAAEMPUVMU-SGTLLEGYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1790 nM (pChEMBL 5.75)
Descriptors: MW 544.53, ALogP 3.13, HBA 8, HBD 3, PSA 135.08, QED 0.4
Compound (SMILES): CCCCCCNNC(=O)c1cccc(NCc2ccccc2)c1
InChIKey: AMGYYKOEOSUCFG-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 325.46, ALogP 4.11, HBA 3, HBD 3, PSA 53.16, QED 0.45
Compound (SMILES): CCC(CC)CN1CCN(C(=O)Nc2cc(Oc3ccncc3)cc(Oc3ccc(F)cc3)c2)CC1
InChIKey: IMOBCXVGUHFSAP-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Binding affinity to S1PR5 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 492.6, ALogP 6.39, HBA 5, HBD 1, PSA 66.93, QED 0.37
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)C)c2cccnc21
InChIKey: QPPWYYZDLRQBMA-AWEZNQCLSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in mouse AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 1479.11 nM (pChEMBL 5.829999923706055)
Descriptors: MW 316.41, ALogP 2.08, HBA 4, HBD 2, PSA 90.01, QED 0.82
Compound (SMILES): CN(CCCNC(=O)c1ccco1)Cc1ccccc1
InChIKey: DJHZRLIPHWOFEC-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Binding affinity to KOR (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 272.35, ALogP 2.53, HBA 3, HBD 1, PSA 45.48, QED 0.79
Compound (SMILES): O=C(Nn1c(=O)c(=O)[nH]c2cc(C#Cc3ccccc3)ccc21)c1ccccc1
InChIKey: SLOVXFKSVLEKEA-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, kainate 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16478
Assay: Binding affinity to GluK5 receptor (unknown origin)
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 381.39, ALogP 2.47, HBA 4, HBD 2, PSA 83.96, QED 0.41
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2cc(-c3cnc(C4CCCC4)[nH]3)oc12
InChIKey: QSRRNUBIKNVQHO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His6-fused BRD4 BD1 (unknown origin) assessed as dissociation constant in PBS incubated for 1 hrs by biolayer interferometry analysis
Measurement: Kd = 1887 nM (pChEMBL 5.71999979019165)
Descriptors: MW 555.65, ALogP 7.62, HBA 6, HBD 2, PSA 93.28, QED 0.22
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CCN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: DVLBRDUTBJVBQN-DRCDNIGYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes incubated in presence NADPH by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 443.5, ALogP 3.61, HBA 5, HBD 1, PSA 79.6, QED 0.78
Compound (SMILES): COc1cccc(F)c1-c1ncc2[nH]nc(-c3ccc(N4CCN(C)CC4)cc3)c2n1
InChIKey: QXMJRJYFRKDBBP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μl of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 418.48, ALogP 3.59, HBA 6, HBD 1, PSA 70.17, QED 0.55
Compound (SMILES): CCCSC1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1
InChIKey: JANQPHRPUAYQTA-POHAHGRESA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-fused human recombinant DYRK1A expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 290.34, ALogP 2.39, HBA 5, HBD 1, PSA 59.92, QED 0.87
Compound (SMILES): COc1ccc2[nH]cc(Cc3nnc(Cc4cccc(C(F)(F)F)c4)n3CCCc3c[nH]cn3)c2c1
InChIKey: FWYGJAUWVCVBHP-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST3 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 1129 nM (pChEMBL 5.949999809265137)
Descriptors: MW 494.52, ALogP 5.32, HBA 5, HBD 2, PSA 84.41, QED 0.29
Compound (SMILES): O=C(/C=C/C=C/c1csc(Br)n1)NO
InChIKey: IYHAVTYWOVUBNO-ZPUQHVIOSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length C-terminal his-tagged human recombinant HDAC8 expressed in Sf9 insect cells
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 275.13, ALogP 1.98, HBA 4, HBD 2, PSA 62.22, QED 0.38
Compound (SMILES): CC(C)S(=O)(=O)c1cc(-c2ccn3nc(N)c(C(=O)NC4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: SGRQFHRGTVOPPV-AWEZNQCLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes at 40 uM using midazolam as substrate measured after 5 to 20 mins in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 522.63, ALogP 2.81, HBA 8, HBD 2, PSA 139.76, QED 0.49
Compound (SMILES): COc1cccc(C(=O)[C@]2(C)C[C@@]34CC[C@]2(OC)[C@@H]2Oc5c(OC)ccc6c5[C@@]23CCN(CC2CC2)[C@@H]4C6)c1
InChIKey: IAGJTVXIRNIAKP-DTKTUBKVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Agonist activity at rat MOR expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 192.7 nM (pChEMBL 6.710000038146973)
Descriptors: MW 529.68, ALogP 5.2, HBA 6, HBD 0, PSA 57.23, QED 0.46
Compound (SMILES): COc1cc(C(=O)c2csc(-c3ccc(NC(=O)CCC(=O)NO)cc3)n2)cc(OC)c1OC
InChIKey: DOGMPVMOPMMAPD-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length C-terminal his-tagged human recombinant HDAC8 (142 to 143 residues) expressed in baculovirus in Sf9 insect cells using Ac-Leu-Gly-Lys (Tfa)-AMC as substrate pretreated for 5 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 5140 nM (pChEMBL 5.289999961853027)
Descriptors: MW 485.52, ALogP 3.29, HBA 9, HBD 3, PSA 136.08, QED 0.23
Compound (SMILES): COC(=O)c1cc(O)c2cc(NC(=O)NCCCCCNC(=N)NC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)ccc2c1
InChIKey: UBOFQOGNZXZZPE-HUBRGWSESA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of human full length recombinant GST-tagged PRMT6 (2 to 375 residues) using GST-GAR as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 636.67, ALogP 0.78, HBA 13, HBD 9, PSA 254.88, QED 0.05
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4ccccc4Cl)s3)cc2)CC1
InChIKey: ICKZVMJSCGSEBO-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant full length His-tagged CDK9/Cyclin T1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 427.96, ALogP 4.11, HBA 7, HBD 2, PSA 74.49, QED 0.6
Compound (SMILES): CCC(CC)CN1CCN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C(=O)N4CCN(C)CC4)cc3)c2)CC1
InChIKey: BWNJPAGNUZNVNX-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Binding affinity to S1PR5 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 617.77, ALogP 6.38, HBA 6, HBD 1, PSA 77.59, QED 0.28
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@@H]2NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@@H](N)CC(C)C)CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC2=O)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: IDDVSLRYKLDACE-OXOGCWQMSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 2969.59
Compound (SMILES): O=C(CCCCCCNC(=O)c1ccc(NC(=O)CCCCCCCNC(=O)COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)cc1)NO
InChIKey: FQLCLMHMOFLVSV-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 using ZMAL (Z-(Ac)Lys-AMC) as substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 274 nM (pChEMBL 6.559999942779541)
Descriptors: MW 734.81, ALogP 2.75, HBA 10, HBD 6, PSA 229.41, QED 0.05
Compound (SMILES): NC(=O)c1ccc(OCC2CCCC2)cc1
InChIKey: ONNDELCPTPJKGL-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Inhibition of human PARP14 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 219.28, ALogP 2.35, HBA 2, HBD 1, PSA 52.32, QED 0.84
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2ccccc2CSC[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: KYLMYZLCQJJVMF-RQTVHLMQSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 1107.38
Compound (SMILES): C=CC(=O)N[C@H]1CCC[C@H]1NC(=O)c1sc2nccc3c2c1NC(=O)N3[C@@H]1CN=C(CC(C)C)C=C1C
InChIKey: FHOKFOHRQUSPMF-NLWGTHIKSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of recombinant human BLK by radiometric kinase assay
Measurement: IC50 = 3130 nM (pChEMBL 5.5)
Descriptors: MW 520.66, ALogP 4.42, HBA 6, HBD 3, PSA 115.79, QED 0.47
Compound (SMILES): Cc1cnc(Nc2ccc(C(=O)NC3CCN(C(=O)CCOCCOCCOCCOCCOCCC(=O)N4CCC(NC(=O)c5ccc(Nc6ncc(C)c(Nc7ccc(Cl)c(NS(=O)(=O)C(C)(C)C)c7)n6)cc5F)CC4)CC3)c(F)c2)nc1Nc1ccc(Cl)c(NS(=O)(=O)C(C)(C)C)c1
InChIKey: VLYMRIROHVATMC-UHFFFAOYSA-N
Target: Bromodomain testis-specific protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q58F21
Assay: Inhibition of recombinant human BRDT-2 (250 to 382 residues) expressed in bacterial expression system by bromoscan assay
Measurement: Kd = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 1482.57
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(=O)N1CCC[C@H]1CC(N)=O)C(C)C
InChIKey: QTHGVXWBMQNWSU-CXZWWHDOSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP-12 (Leu17 to Cys470 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 769.24, ALogP 1.52, HBA 8, HBD 6, PSA 234.17, QED 0.13
Compound (SMILES): Cc1cc(-c2cc(Cl)c(OC[C@@](C)(N)CC(C)C)cn2)ccn1
InChIKey: XWZJJCICBZFART-SFHVURJKSA-N
Target: Citron Rho-interacting kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14578
Assay: Inhibition of CRIK (unknown origin)
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 333.86, ALogP 4.25, HBA 4, HBD 1, PSA 61.03, QED 0.86
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(C(C)(C)C#N)nc1
InChIKey: JDUUUKXVZOZLSS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate incubated for 60 mins in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 443.51, ALogP 5.62, HBA 6, HBD 1, PSA 96.07, QED 0.38
Compound (SMILES): CC(CNC(=O)/N=C(\N)NCCCc1nnc(N)s1)C1CCCCC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: JEOHHJMBZWYLOK-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 367.52, ALogP 1.88, HBA 5, HBD 4, PSA 131.31, QED 0.33
Compound (SMILES): COCC(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN[C@H](C)C5)nc4)c3n2)[C@@H](C)C1
InChIKey: KCDXXXPORYWJAK-ZACQAIPSSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 479.59, ALogP 1.29, HBA 9, HBD 2, PSA 115.4, QED 0.56
Compound (SMILES): CCCCCNC(=O)/N=C(\N)Nc1cccc(-c2sc(N)nc2C)c1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: SAHFQHAGSURLMS-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 360.49, ALogP 3.33, HBA 4, HBD 4, PSA 118.42, QED 0.36
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC(OCc2ccc(F)c(F)c2)CC1
InChIKey: NXHYXFTYHKKMBV-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 408.88, ALogP 4.55, HBA 3, HBD 1, PSA 41.57, QED 0.76
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2cc(-c3cnc(C4CCCCC4)[nH]3)oc12
InChIKey: UCJMBWXOKLINTN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His6-fused BRD4 BD2 (unknown origin) assessed as dissociation constant in PBS incubated for 1 hrs by biolayer interferometry analysis
Measurement: Kd = 44.2 nM (pChEMBL 7.360000133514404)
Descriptors: MW 569.68, ALogP 8.01, HBA 6, HBD 2, PSA 93.28, QED 0.22
Compound (SMILES): COc1cc2c(cc1OC)-c1c(OC)c(OCc3ccccc3)cc3c1[C@H](C2)N(C)CC3
InChIKey: WQTVQOIRXFVOPO-NRFANRHFSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Antagonist activity at 5-HT2C receptor (unknown origin) incubated for 60 mins followed by 10 mins incubation in dark at room temperature by FLIPR method
Measurement: IC50 = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 431.53, ALogP 5.04, HBA 5, HBD 0, PSA 40.16, QED 0.55
Compound (SMILES): CCC(=O)N1CC[C@H](Nc2ncnc3sc(-c4cnc(OC)c(OC)c4)cc23)C1
InChIKey: RQDDWMKILMSXBN-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in IgM stimulated human Raji cells incubated for 10 mins by AlphaLISA assay
Measurement: IC50 = 137.1 nM (pChEMBL 6.860000133514404)
Descriptors: MW 413.5, ALogP 3.19, HBA 8, HBD 1, PSA 89.47, QED 0.66
Compound (SMILES): Cc1ccc(C(=O)N2CCC3(CCNCC3)CC2)cc1
InChIKey: OJPBMIZUSSIFGI-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-1/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P14867
Assay: Antagonist activity at human alpha1beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): CNC(=O)[C@@H](CC(=O)[C@H](CC(C)C)[C@H](CSc1cccs1)C(=O)NO)Cc1ccccc1
InChIKey: FPSMXPGSVWPWCG-AQNXPRMDSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of MMP-9 (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 476.66, ALogP 4.19, HBA 6, HBD 3, PSA 95.5, QED 0.23
Compound (SMILES): COc1ccc(/C=C2\N=C(Nc3ccccc3)NC2=O)cc1
InChIKey: XSEOLUNNBOQVET-PTNGSMBKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 293.33, ALogP 2.63, HBA 4, HBD 2, PSA 62.72, QED 0.86
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCC(C)C2CCCCC2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: DKQRSYXCMBPAAM-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 414.58, ALogP 4.35, HBA 4, HBD 4, PSA 118.42, QED 0.43
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2ccc(cc2)CSC(C)(C)[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: YQOPVQXIKMEFFV-SIXPOYHZSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells assessed as maximal intracellular cAMP accumulation by fluorescence based analysis
Measurement: EC50 = 246 nM (pChEMBL 6.610000133514404)
Descriptors: MW 1135.43
Compound (SMILES): COc1cc(S(N)(=O)=O)cc(OC)c1OCCC(N)C1COc2ccccc2O1
InChIKey: RUMNOCQXRVXQHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human recombinant CA5B assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 231.7 nM (pChEMBL 6.630000114440918)
Descriptors: MW 424.48, ALogP 1.29, HBA 8, HBD 2, PSA 132.33, QED 0.65
Compound (SMILES): CCNC1=NC(c2ccc(F)cc2)NC(=O)N1
InChIKey: XWRLROSVVBGPPA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition Assay: Human recombinant GSK-3β was purchased from Millipore (Millipore Iberica S.A.U.) The prephosphorylated polypeptide substrate was purchased from Millipore (Millipore Iberica SAU). Kinase-Glo Luminescent Kinase Assay was obtained from Promega (Promega Biotech Iberica, SL). ATP and all other reagents were from Sigma-Aldrich. Assay buffer contained 50 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (pH 7.5), 1 mM ethylenediaminetetraacetic acid (EDTA), 1 mM ethylene glycol tetraacetic acid (EGTA), and 15 mM magnesium acetate. The method developed by Baki was followed [Baki et al. Assay and Drug Development Technologies 2007, 5(1),75-83] to analyze the inhibition of GSK-3β. Kinase-Glo assays were performed in assay buffer using white 96-well plates. In a typical assay, 10 μL (10 μM) of test compound (dissolved in DMSO at 1 mM concentration and diluted in advance in assay buffer to the desired concentration) and 10 μL (20 ng) of enzyme were added to each well followed by 20 μL of assay buffer containing 25 μM substrate and 1 μM adenosine triphosphate (ATP). The final DMSO concentration in the reaction mixture did not exceed 1%. After a 30 minutes incubation at 30° C., the enzymatic reaction was stopped with 40 μL of Kinase-Glo reagent. Glow-type luminescence was recorded after 10 minutes using a Fluoroskan Ascent multimode reader.
Measurement: IC50 = 15670 nM (pChEMBL 4.800000190734863)
Descriptors: MW 236.25, ALogP 1.1, HBA 3, HBD 3, PSA 65.52, QED 0.72
Compound (SMILES): c1cncc(-c2cnc(NCc3cccc4c3CCO4)n3cnnc23)c1
InChIKey: VFLXVDWCZHLLLM-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: EED-H3K27Me3 Peptide Competition Binding Assay by AlphaScreen: To assess the compounds potency in the EED-H3K27Me3 competition binding assay, compounds were serially diluted 3-fold in DMSO to obtain a total of twelve concentrations. Then compounds at each concentration (75 nL of each) were transferred by Mosquito into a 384-well Perkin Elmer ProxiPlate 384 plus plates. 8 uL of solutions containing 30 nM EED (1-441)-His protein and 15 nM biotin-H3K27Me3 (19-33) peptide in the buffer (25 mM HEPES, pH 8, 0.02% Tween-20, 0.5% BSA) were added to the wells and then incubated with compound for 20 min. AlphaScreen detection beads mix was prepared immediately before use by mixing nickel chelate acceptor beads and streptavidin donor beads in a 1:1 ratio (Perkin Elmer, Product No. 6760619C/M/R) into the buffer described above. Then 4 μL of detection beads mix was added to the plate and incubate in the dark at the rt for 1 h. The final concentration of donor and acceptor beads was 10 μg/mL for each. Plates were read on EnVision (PerkinElmer) using the AlphaScreen setting adapted for optimal signal detection with a 615 nm filter, after sample excitation at 680 nm. The emission signal at 615 nm was used to quantify compounds inhibition. AlphaScreen signals were normalized based on the reading coming from the positive (maximum signal control) and negative controls (minimum signal control) to give percentage of activities left. The data were then fit to a dose response equation using the program Helios (Novartis) to get the IC50 values. Helios is a Novartis in-house assay data analysis software using the methods described by Normolle, D. P., Statistics in Medicine, 12:2025-2042 (1993); Formenko, I. et al, Computer Methods and Programs in Biomedicine, 82, 31-37 (2006); Sebaugh, J. L., Pharmaceutical Statistics, 10:128-134 (2011); Kelly, C. et al., Biometrics, 46(4):1071-1085 (1990); and Kahm, M. et al., Journal of Statistical Software, 33(7): (2010) (grofit: Fitting Biological Growth Curves with R, pages 1-21, available at http://www.jstatsoft.org/).Each compound was counterscreened to determine if it interfered with the AlphaScreen beads. Compounds were diluted as described in the preceding section, and the assay was performed by adding 12 μL of 10 nM biotin-miniPEG-His6 peptide in the above buffer and incubating for 20 min at rt prior to addition of the beads to 10 μg/mL each. The plates were then incubated for 1 h at rt in dark before being read on EnVison.
Measurement: IC50 = 10.8 nM (pChEMBL 7.96999979019165)
Descriptors: MW 344.38, ALogP 2.73, HBA 7, HBD 1, PSA 77.23, QED 0.61
Compound (SMILES): CNCc1cc(Cl)ccc1Cn1c(=S)[nH]c(=O)c2[nH]ccc21
InChIKey: QNKLBACGOUFKKR-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibitory Activity: The pharmacological activity of compounds disclosed herein was tested in the following screen (Test A) in which the compounds were tested in the presence of ascorbate, which reacts with MPO-derived hypochlorous acid (HOCl) to form dehydro-ascorbate. The loss of ascorbate is followed by measuring absorbance at 260 nm.Assay buffer: 100 μM diethyl triamine pentaacetic acid (DTPA) in buffer consisting of 10 mM Na2HPO4/NaH2PO4, 3 mM KCl in 140 mM NaCl, pH 7.4.Enzyme solution: MPO purified from the human cell line HL60, 1.38 nM (final concentration 0.7 nM) and L-ascorbate, 100 μM (final concentration 50 μM) in Assay bufferSubstrate solution: H2O2, 98 μM (final concentration 49 μM) Forty μL of the enzyme solution was added to 0.6 μL compound serially diluted in DMSO. Absorbance was measured at 260 nm to obtain a compound blank value. After an additional 10 min, 40 μL of the substrate solution was added and the absorbance at 260 nm was recorded between 4 and 40 min to obtain kinetic readings of enzyme activity.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 334.83, ALogP 2.81, HBA 4, HBD 3, PSA 65.61, QED 0.64
Compound (SMILES): O=C(/C=C/c1ccc(CNc2ccc3nc4n(c(=O)c3c2)CCCCC4)cc1)NO
InChIKey: PXSXCOJDFYVRBV-FMIVXFBMSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) by colorimetric method
Measurement: IC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 404.47, ALogP 3.25, HBA 6, HBD 3, PSA 96.25, QED 0.34
Compound (SMILES): Cl.Oc1c(Cl)cccc1C1NCCc2c1[nH]c1ccc(F)cc21
InChIKey: QMALRJOFZALGHA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 87.1 nM (pChEMBL 7.059999942779541)
Descriptors: MW 316.76, ALogP 3.9, HBA 2, HBD 3, PSA 48.05, QED 0.64
Compound (SMILES): CN1C=C(c2ccc3ccn(Cc4ccccn4)c3c2)C2C=CNC2C1=O
InChIKey: RUUNUTOBMVHUHT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Inhibition of His-tagged recombinant BRD1 (unknown origin) (11 to 190 residues) using SGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH as substrate measured after 1 hr by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 356.43, ALogP 3, HBA 4, HBD 1, PSA 50.16, QED 0.78
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(Cl)n2)ccn1
InChIKey: ZVSNSFQQKSZZMY-IBGZPJMESA-N
Target: Death-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53355
Assay: Inhibition of DAPK1 (unknown origin)
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 392.89, ALogP 4.12, HBA 6, HBD 2, PSA 99.36, QED 0.69
Compound (SMILES): NC(=S)c1ccc(C(=O)NC2CCN(Cc3ccccc3)CC2)cc1
InChIKey: MDRXXGMJEJFONZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG potassium channel expressed in CHO-K1 cells by Qube-automated patch clamp assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 353.49, ALogP 2.72, HBA 3, HBD 2, PSA 58.36, QED 0.81
Compound (SMILES): CNCC(=O)N[C@@H]1[C@H](O)[C@H](O[C@H]2/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@]3(O)C[C@H](O)[C@@H](C(=O)NCCN)[C@H](C2)O3)O[C@H](C)[C@H]1O.NC(CCC(=O)O)C(=O)O
InChIKey: SXASWTOXGYYPEN-RYLHAJFVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells at -80 mV holding potential by automated patch clamp method
Measurement: IC50 > 13300 nM (pChEMBL 4.875999927520752)
Descriptors: MW 1037.26
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c(C(=O)N[C@H]3CC[C@](C)(O)CC3)c2)cc1F
InChIKey: PRKWSDOLROTYLX-KQUPGTECSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: Caliper Assay: In the applied method, this separation takes place inside a chip that contains a complex capillary system for simultaneous analysis of 12 samples (12-sipper chip, Caliper Technologies Corp., Mountain View, USA). In order to allow the detection and quantification of the peptides in the capillary system, the peptides carry a fluorescent label (fluorescein). With this label the peptides can be quantified by fluorescence intensity through the instruments laser and detection system (LC3000, Caliper Life Sciences).The assays were performed in 384-well, low volume microtiter assay plates in a final reaction volume of 9 ul. Dose-response curves were generated by incubating 10 nM of each kinase together with 2 μm of the fluorescently labeled substrate peptide 5-Fluo-Ahx-KKYQAEEN-T-YDEYENKK-amid (10 mM stock solution in DMSO) in 50 mM Hepes pH 7.5, 0.02% Tween 20, 0.02% BSA, 1 mM DTT, 10 μm Na3VO4, 10 mM β-Glycerolphosphate, 1 mM MgCl2, 12 mM MnCl2 (ALK1 and ALK6 7 mM) and 15 μm ATP for 60 min at 30° C. in the presence or absence of compound diluted in DMSO.Kinase reaction were terminated by adding 15 ul STOP buffer (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35.Plates with terminated kinase reactions were transferred to the Caliper LC3000 workstation (Caliper Technologies Corp., Mountain View, USA) for reading. The relative amount of phosphorylated peptide r, was calculated using the heights of the substrate peak, s, and the product peak, p: r=p/(p+s).
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 440.56, ALogP 3.88, HBA 5, HBD 3, PSA 91.48, QED 0.66
Compound (SMILES): C[C@@H]1CN(Cc2ccc(C(=O)NO)cc2)C[C@H]1c1nc2c(cnn2C2CCCC2)c(=O)[nH]1
InChIKey: UWLURVWZRQXQEM-AUUYWEPGSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human SH-SY5Y cells measured after 2 hrs by Western blot analysis
Measurement: IC50 = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 436.52, ALogP 2.59, HBA 7, HBD 3, PSA 116.14, QED 0.42
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCC(F)(F)F)cc2)CC1
InChIKey: HCPZGSLTHYYAJZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor at 25 uM incubated for 1 hr by microbeta2 beta-counter analysis
Measurement: Ki = 138.7 nM (pChEMBL 6.860000133514404)
Descriptors: MW 454.47, ALogP 3.97, HBA 4, HBD 1, PSA 57.7, QED 0.64
Compound (SMILES): Clc1cccc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: VCMBCXHABJNEBE-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 444.97, ALogP 5.14, HBA 4, HBD 2, PSA 75.18, QED 0.33
Compound (SMILES): COc1cc(/C=C2\N=C(Nc3ccc(N4CCNCC4)cc3)NC2=O)ccc1O
InChIKey: JMMKVTXEDIDGGS-ATVHPVEESA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of GST-fused human recombinant DYRK1B expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 393.45, ALogP 1.75, HBA 7, HBD 4, PSA 98.22, QED 0.59
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(Cl)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: UFEKBPHSPFQBDC-CPIJZORTSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43