lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(CC)C(=O)c1nc(-c2nnc(C(C)(C)O)o2)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: TZBMJMWWRPOUKP-JTQLQIEISA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Binding affinity to RORbeta (unknown origin) assessed as dissociation constant by thermal shift binding assay
Measurement: Kd > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 630.5, ALogP 5.11, HBA 9, HBD 2, PSA 138.52, QED 0.33
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-FLVSMNSFSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): C[C@H]1C[C@H]2CC(F)(F)C(N)=N[C@@]2(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)CO1
InChIKey: QQHWYFAIJDVZQX-PVUDRZGPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.42, ALogP 3.19, HBA 7, HBD 2, PSA 111.72, QED 0.65
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cn(C)c3c(=O)[nH]ccc23)cc2c1ccn2C(C)(c1ccccn1)c1ccccn1
InChIKey: LMLIBNUOIWAJFC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human BRD2 isoform 1 bromodomain 1 and 2 (K71 to D455 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 552.66, ALogP 4.85, HBA 7, HBD 2, PSA 114.67, QED 0.29
Compound (SMILES): COc1ccc(C2CCCN2Cc2ccc(Oc3ccc(C(=O)NO)cc3)cc2)cc1
InChIKey: DLQCQSHURGAKKI-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Antagonist activity at human kappa opiod receptor expressed in CHO cells assessed as inhibition of U69593-induced [35S]GTPgammaS binding incubated for 4 hrs by microbeta liquid scintillation counting method
Measurement: IC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 418.49, ALogP 4.94, HBA 5, HBD 2, PSA 71.03, QED 0.42
Compound (SMILES): CN(C)Cc1ccccc1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: VBHIKBZBHGDIER-YLLCFIMHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 627.83, ALogP 6.87, HBA 6, HBD 1, PSA 58.06, QED 0.19
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@](c2ccccc2)(C2CCCCC2)O1
InChIKey: UFSZYKLBZJNXLV-UXHICEINSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 20.89 nM (pChEMBL 7.679999828338623)
Descriptors: MW 318.48, ALogP 3.58, HBA 2, HBD 0, PSA 18.46, QED 0.79
Compound (SMILES): Nc1nc(N2CCC(N3Cc4cc(F)ccc4OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: QOZFARNLHIXLOT-FQEVSTJZSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Human AMCase Activity Assay: An enzymatic assay with recombinant human AMCase was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-Methylumbelliferyl B-D-N,N′-diacetylchitobioside hydrate was used as a substrate for the enzyme. Upon hydrolysis by AMCase, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of hAMCase recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Buffer (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 456.95, ALogP 3.65, HBA 6, HBD 2, PSA 83.3, QED 0.62
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccncn5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: VEHJGWOVJCGIDX-LMUOQGPPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 572.71, ALogP 5.6, HBA 7, HBD 1, PSA 80.6, QED 0.28
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](C(=O)NC4CC4)CC3)c12
InChIKey: BBVXXRFQYGRLLY-XYPYZODXSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 in human STAT6-bla-RA1 cells assessed as reduction in IL4-induced STAT6-signalling pre-incubated for 1 hrs before human recombinant IL4 addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 314.39, ALogP 2.11, HBA 3, HBD 3, PSA 90.64, QED 0.81
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(O)cc2)cc1
InChIKey: CZUQDWSZRALHID-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 281.27, ALogP 1.82, HBA 3, HBD 3, PSA 86.63, QED 0.55
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(C(F)(F)F)cc2C(F)(F)F)cc1
InChIKey: FPBMEPDXSNHHAK-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 401.26, ALogP 4.15, HBA 2, HBD 2, PSA 66.4, QED 0.43
Compound (SMILES): CCn1cnc2c(NCc3nc4ccc(F)c(F)c4[nH]3)nc(N3CCCC[C@H]3CCO)nc21
InChIKey: HVFVQLFPRQYJTR-ZDUSSCGKSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of GST-tagged recombinant human CDK12 (696 to 1082 residues) expressed in Insect cell in presence of ATP by Km ATP assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 456.5, ALogP 3.35, HBA 8, HBD 3, PSA 107.78, QED 0.39
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC1CC1)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: XOIHZLRGDVDAIX-PXJZQJOASA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 3129 nM (pChEMBL 5.5)
Descriptors: MW 571.77, ALogP 6.23, HBA 6, HBD 2, PSA 100.21, QED 0.22
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3cc(CC(C)(C)C(=O)O)ncn3)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: MNUCRODXGZMPCU-ZDUSSCGKSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 651.56, ALogP 6.8, HBA 7, HBD 2, PSA 122.14, QED 0.25
Compound (SMILES): CN(C)CC1COCC(c2ccccc2)(C2CCCCC2)O1
InChIKey: UOKGNINOAYOIDX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 2.399 nM (pChEMBL 8.619999885559082)
Descriptors: MW 303.45, ALogP 3.44, HBA 3, HBD 0, PSA 21.7, QED 0.85
Compound (SMILES): COc1cc(N(C)CCN(C)C)ccc1Nc1nccc(-c2cn(CCCO)c3ccccc23)n1
InChIKey: NXVBLFLXCQUOFT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S triple mutant (unknown origin)
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 474.61, ALogP 4.23, HBA 8, HBD 2, PSA 78.68, QED 0.34
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CCCCOc4cc(=O)oc5ccccc45)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: ACDPJDISLTXCFN-VLCRHTCISA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human CA5A pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 1725.8 nM (pChEMBL 5.760000228881836)
Descriptors: MW 509.52, ALogP 1.47, HBA 11, HBD 2, PSA 154.47, QED 0.25
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1
InChIKey: HLHFFFSVWKXFHJ-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 401.26, ALogP 4.15, HBA 2, HBD 2, PSA 66.4, QED 0.43
Compound (SMILES): CC1(C)O[C@H]2[C@H](O)[C@H]([C@H]3[C@H](O)[C@H]4OC[C@@H](O4)[C@H]3O)N(CCCCCCn3cc(CNc4ccc(S(N)(=O)=O)cc4)nn3)C[C@H]2O1
InChIKey: MWZLBQWPJOSIAH-DLJZWJNGSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5B preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 4353 nM (pChEMBL 5.360000133514404)
Descriptors: MW 652.77, ALogP -0.24, HBA 14, HBD 5, PSA 203.75, QED 0.19
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc4c(c3)COB4O)ncc2OC)c1
InChIKey: JKLAXQVAOGBHNQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human His-tagged full length BTK expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 418.22
Compound (SMILES): C[N+]1=C(/C=C/C=C/C=C2/N(CCCCCC(=O)NCCN3CCN(CCCCC4CCN(CC(=O)N5c6ccccc6NC(=O)c6ccccc65)CC4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: MHTWPMURDJJCHP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]-NMS from human muscarinic M5 receptor stably expressed in CHO-K9 cells by radioligand competitive binding assay
Measurement: Ki = 69.18 nM (pChEMBL 7.159999847412109)
Descriptors: MW 984.37, ALogP 10.59, HBA 7, HBD 2, PSA 94.48, QED 0.05
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(C(C)(C)O)o3)nc2C(=O)N2CCC(F)(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: DPLDVWYMOZMXLB-JTQLQIEISA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 678.49, ALogP 5.49, HBA 9, HBD 2, PSA 138.52, QED 0.31
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: SADYRRFJQXPSEH-ANULTFPQSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human Y4R expressed in HEK293T cells co-expressing ARRB2 assessed as induction of beta-arrestin2 recruitment measured for 40 mins by D-luciferin based luminescence assay
Measurement: EC50 = 4677.35 nM (pChEMBL 5.329999923706055)
Descriptors: MW 605.75, ALogP -2.23, HBA 8, HBD 12, PSA 300.44, QED 0.05
Compound (SMILES): COc1ccccc1CC[C@@H]1CCc2cc([C@H]3CC[C@](N)(CO)C3)ccc2C1
InChIKey: QCMHGCDOZLWPOT-FMNCTDSISA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 379.54, ALogP 4.39, HBA 3, HBD 2, PSA 55.48, QED 0.78
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](CC(=O)N4CC(Cc5ccccc5)C4)CC3)c12
InChIKey: SXEUSRBRPAJJFS-KESTWPANSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 418.54, ALogP 3.92, HBA 3, HBD 2, PSA 81.85, QED 0.66
Compound (SMILES): CN(C)c1ccccc1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: ZSEGEZNFBCYZHP-BPSUTHQGSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 613.8, ALogP 6.88, HBA 6, HBD 1, PSA 58.06, QED 0.21
Compound (SMILES): CCN(C(=O)c1cccc(C(C)(C)C)c1)c1ccc(C(=O)NO)cc1
InChIKey: BQHABQWCVPOXCG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Binding affinity to His-tagged recombinant human HDAC8 by SPR assay
Measurement: Kd = 26.1 nM (pChEMBL 7.579999923706055)
Descriptors: MW 340.42, ALogP 3.77, HBA 3, HBD 2, PSA 69.64, QED 0.66
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCOCC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: KQCTYKLPOJQIET-NOZRDPDXSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 3089 nM (pChEMBL 5.510000228881836)
Descriptors: MW 518.66, ALogP 5.54, HBA 6, HBD 2, PSA 106.2, QED 0.31
Compound (SMILES): O=C(/C=C/c1nc2cc(F)c(F)cc2[nH]1)c1c(-c2ccc(F)c(F)c2)c2cc(F)ccc2[nH]c1=O
InChIKey: CRSXAJYRKIQUCU-AATRIKPKSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKKbeta (unknown origin)
Measurement: IC50 = 1640 nM (pChEMBL 5.789999961853027)
Descriptors: MW 481.38, ALogP 5.66, HBA 3, HBD 2, PSA 78.61, QED 0.2
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5cnccn5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: PICFOVXIBSJPBO-LMUOQGPPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 1.27 nM (pChEMBL 8.899999618530273)
Descriptors: MW 572.71, ALogP 5.6, HBA 7, HBD 1, PSA 80.6, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C(C)C)CC2)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: CTZUZSDLFUWGPJ-IAPPQJPRSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 32920 nM (pChEMBL 4.480000019073486)
Descriptors: MW 560.74, ALogP 6.5, HBA 7, HBD 1, PSA 97.56, QED 0.24
Compound (SMILES): CC(C)N(C(=O)c1cccc(C(F)(F)F)c1F)c1ccc(C(=O)NO)cc1
InChIKey: DGQMTANDEIDADK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Binding affinity to His-tagged recombinant human HDAC8 by SPR assay
Measurement: Kd = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 384.33, ALogP 4.02, HBA 3, HBD 2, PSA 69.64, QED 0.48
Compound (SMILES): CCCCCC(=O)N[C@H](C(=O)NCc1ccc(NC(=N)N)cc1)c1ccc(OCc2ccccc2)cc1.O=C(O)C(F)(F)F
InChIKey: RMLDGSREBIUICI-YCBFMBTMSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus serotype 2 NS2B-NS3 protease transfected in human HeLa cells measured after 24 hrs by Renilla-luciferase reporter gene assay
Measurement: EC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 501.63, ALogP 4.62, HBA 4, HBD 5, PSA 129.33, QED 0.13
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@H](c2ccc(S(=O)(=O)c3ccccc3)cc2)O1.[I-]
InChIKey: FPYOERQVOVHGLH-OGPPPPIKSA-M
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M5 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 6165.95 nM (pChEMBL 5.210000038146973)
Descriptors: MW 376.5, ALogP 2.68, HBA 4, HBD 0, PSA 52.6, QED 0.75
Compound (SMILES): Cc1cnc(-c2ccc(OC(F)(F)F)cc2)n1Cc1ccccc1OCCC[C@@H](C)CC(=O)O
InChIKey: GYNMVDMBFKGCCR-QGZVFWFLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Modulation of androgen receptor (unknown origin)
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.5, ALogP 6.08, HBA 5, HBD 1, PSA 73.58, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3cccc(F)c3)CC2)cc1
InChIKey: YBCUNRWDUZQOAB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 29.1 nM (pChEMBL 7.539999961853027)
Descriptors: MW 391.42, ALogP 1.07, HBA 4, HBD 1, PSA 100.78, QED 0.85
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: UQTCOSRFOINFNG-FSJACQRISA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [3H]propionyl-pNPY from human Y2 receptor expressed in CHO cells measured after 2 hrs by microbeta liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 925.11, ALogP -3.04, HBA 12, HBD 18, PSA 440.77, QED 0.02
Compound (SMILES): Cc1cccc(C)c1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: HHPBPMMGXGLFBZ-GYVZUEEYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hr
Measurement: IC50 = 51.6 nM (pChEMBL 7.289999961853027)
Descriptors: MW 598.79, ALogP 7.43, HBA 5, HBD 1, PSA 54.82, QED 0.21
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(OC(F)(F)F)cc2)cc1
InChIKey: RMIKMESCOHMNMH-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 349.26, ALogP 3.01, HBA 3, HBD 2, PSA 75.63, QED 0.65
Compound (SMILES): N#Cc1ccc(C#Cc2ccc(NC(=O)C(=O)O)cc2)cc1
InChIKey: DREKYVXEUFPNQZ-UHFFFAOYSA-N
Target: Triple specificity protein phosphatase PtpB (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: I6WXK4
Assay: Inhibition Assay: Compounds were tested against mPTPB using the p-nitrophenyl phosphate (pNPP) assay system in a Cary 100 UV-Vis spectrophotometer by monitoring the increase in absorbance of product formed, p-nitrophenol (pNP) at 405 nm. The reaction was started by the addition of mPTPB into a final volume of 200 μL master mix containing pH 7.0 3,3-Dimethyl glutarate buffer (50.0 mM, 1 mM EDTA, 0.15M NaCl), 3.0 mM pNPP. IC50 values for each compound were determined by varying the concentration of the inhibitor at fixed concentrations of the enzyme and by fitting the dose-response data into the four-parameter logistic curve (eq 1) model of GraphPad prism 7.02, as follows. A I /A 0 =IC 50/(IC 50+[I]).The inhibition assay for these PTPs were performed under the same conditions as mPTPB except using a different pNPP concentration corresponding to the Km of the FTP studied.
Measurement: IC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 290.28, ALogP 1.98, HBA 3, HBD 2, PSA 90.19, QED 0.62
Compound (SMILES): CC(C)N(C(=O)c1cccc(OC(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: JTLGBSYAFABUCJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Binding affinity to His-tagged recombinant human HDAC8 by SPR assay
Measurement: Kd = 8.48 nM (pChEMBL 8.069999694824219)
Descriptors: MW 382.34, ALogP 3.76, HBA 4, HBD 2, PSA 78.87, QED 0.61
Compound (SMILES): CC(C)NCc1ccc(C[C@@H]2NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H]3CCC(=O)NCCCC(=O)NCC[C@@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@H](CCCCN)C(=O)N[C@H](Cc2ccccc2)C(=O)N3)cc1
InChIKey: DMUOHDWFEHIXQJ-SFYPIHDGSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Inhibition of 125I-[Leu8,D-Trp22,Tyr25]SRIF-28 binding to human somatostatin receptor type 5
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1697.02
Compound (SMILES): CC(C)NCc1ccc(C[C@@H]2NC(=O)[C@@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H]3CCC(=O)NCCCCCC[C@@H](NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)N[C@H](CCCCN)C(=O)N[C@H](Cc2ccccc2)C(=O)N3)cc1
InChIKey: PWNGKIWHLMJETN-BDRBHZDKSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Inhibition of 125I-[Leu8,D-Trp22,Tyr25]SRIF-28 binding to human somatostatin receptor type 5
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1668.02
Compound (SMILES): C[C@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3C(F)F)nc1-2)C(N)=O
InChIKey: SGEUNORSOZVTOL-CABZTGNLSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 407.38, ALogP 1.82, HBA 7, HBD 2, PSA 111.71, QED 0.78
Compound (SMILES): CO[C@]1(CN2CCN3CCCC[C@@H]3C2)/C=C/C[C@H](C)[C@@H](C)S(=O)(=O)NC(=O)c2ccc3c(c2)N(C[C@@H]2CC[C@H]21)C[C@@]1(CCCc2cc(Cl)ccc21)CO3
InChIKey: BJTFTQIBRVBSBH-VCQPVEJUSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Binding affinity to Mcl-1 (unknown origin) assessed as inhibition constant
Measurement: Ki = 0.015 nM (pChEMBL 10.819999694824219)
Descriptors: MW 765.46, ALogP 6.44, HBA 8, HBD 1, PSA 91.42, QED 0.36
Compound (SMILES): C=CC(=O)N[C@H]1C=C(C)c2c(-c3cnc4ccccc4c3)c3c(N)ncnc3n2C1
InChIKey: MKCYPWYURWOKST-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant wildtype human N-terminal GST-tagged EGFR cytoplasmic domain (669 to 1210 residues) expressed in Sf21 insect cells using Poly(Glu,Tyr) peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 50 mins in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 396.45, ALogP 3.32, HBA 6, HBD 2, PSA 98.72, QED 0.52
Compound (SMILES): CCCNc1nc(Nc2ccc(C#N)cc2)ncc1C#CCCCNC(=O)[C@H](C)N(C)C(=O)/C=C/CN(C)C
InChIKey: HJFSVYUFOXAVAA-YUAYGMJFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 D835Y mutant (unknown origin)
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 530.68, ALogP 3.13, HBA 8, HBD 3, PSA 126.28, QED 0.2
Compound (SMILES): Nc1nn2cc(F)cnc2c1C(=O)Nc1cncc(F)c1N1CCC(C(=O)N2CCN(C3COC3)CC2)CC1
InChIKey: QAYHKBLKSXWOEO-UHFFFAOYSA-N
Target: ATR/ATRIP (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WXE1
Assay: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 541.56, ALogP 1, HBA 10, HBD 2, PSA 134.22, QED 0.49
Compound (SMILES): C[C@H](Oc1cc2cc(F)ccc2nc1N)c1[nH]c(=O)ccc1-n1cccn1
InChIKey: CLEFVPILGAPOTG-NSHDSACASA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 365.37, ALogP 2.97, HBA 6, HBD 2, PSA 98.82, QED 0.58
Compound (SMILES): O=C(O)CNC(=O)c1c(O)c2ccccc2n(OCC2CC2)c1=O
InChIKey: IKRKQQLJYBAPQT-UHFFFAOYSA-N
Target: Bifunctional peptidase and arginyl-hydroxylase JMJD5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N371
Assay: Inhibition of JMJD5 (unknown origin)
Measurement: IC50 = 48300 nM (pChEMBL 4.320000171661377)
Descriptors: MW 332.31, ALogP 0.36, HBA 6, HBD 3, PSA 117.86, QED 0.7
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(NC3CN(CCCF)C3)cc2F)N1CC(F)(F)CO
InChIKey: GQCXHIKRWBIQMD-AKJBCIBTSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Reversible inhibition of CYP2C9 in human liver microsomes using (s)-warfarin as substrate preincubated for 30 mins followed by NADPH addition by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 522.56, ALogP 4.87, HBA 4, HBD 3, PSA 54.53, QED 0.35
Compound (SMILES): COc1nc(C(=O)NC[C@](C)(O)C(F)(F)F)c(N)cc1C(F)(F)F
InChIKey: USHQRIKZLHNPQR-JTQLQIEISA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Potentiation of wild-type CFTR (unknown origin) expressed in FRT cells assessed as chloride transport by measuring membrane potential in presence of forskolin
Measurement: EC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 361.24, ALogP 1.73, HBA 5, HBD 3, PSA 97.47, QED 0.71
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: AZSRSNUQCUDCGG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of 6His-tagged TEV-GS fused EGFR D770_N771insNPG mutant (G696 to G1210 reisudes) (unknown origin) expressed in Sf21 cells using Poly(Glu,Tyr) peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP-Glo reagent based assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 585.71, ALogP 5.08, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): C=CC(=O)N1CCC(c2ccc(C(N)=O)c(-c3ccc(Oc4ccccc4)cc3)n2)CC1
InChIKey: MZPVEMOYADUARK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: ADP-Glo Kinase Assay: 1× and 2× assay buffer were made at first. BTK kinase was diluted with 1× assay buffer but substrate was diluted with 2× assay buffer. 1 ul of diluted compound was transferred into 384-well assay plate, and then 2.0 ul of enzyme solution was added, and spun at 2000 rpm for 1 min. This mixture was incubated at 24° C. for 30 mins. 2 ul of peptide substrate/ATP mixture was added into the assay plate to start the reaction. The mixture was mixed thoroughly and then the 384-well plate was spun and incubated at 24° C. for 60 mins. 5.0 ul of ADP-Glo Reagent was added to stop the kinase activity and deplete the ATP unconsumed, and the plate was mixed thoroughly and incubated at 24° C. for 40 min. Then, 10.0 ul of Kinase Detection reagent was added, and the plate was centrifuged and then kept at 24° C. for 30 min. The luminescence signal was read on Envision.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 427.5, ALogP 4.53, HBA 4, HBD 1, PSA 85.52, QED 0.59
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)nccc32)C1
InChIKey: KOEUOFPEZFUWRF-LJQANCHMSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of FLAG-tagged TEC autophosphorylation in HEK293 cells incubated for 2 hrs by MSD electrochemiluminescence immunoassay
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 455.52, ALogP 3.91, HBA 7, HBD 1, PSA 95.38, QED 0.46
Compound (SMILES): C[C@H]1CN(C(=O)CC[C@@]2(C3CC3)NC(=O)NC2=O)CCN1c1cc(F)cc(F)c1
InChIKey: CMLVKUWQFZQPPS-YUNKPMOVSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of human recombinant MMP14 (AA112 to 298) assessed as cleavage of fluorescent substrate using 390 MMP FRET as substrate incubated for 30 mins by biochemical assay
Measurement: IC50 > 3198 nM (pChEMBL 5.494999885559082)
Descriptors: MW 406.43, ALogP 1.77, HBA 4, HBD 2, PSA 81.75, QED 0.73
Compound (SMILES): CNC[C@@H]1OCCc2ccsc21
InChIKey: ABDDQTDRAHXHOC-QMMMGPOBSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Agonist activity at recombinant human 5-HT7 expressed in HEK293 cells by FLIPR calcium assay
Measurement: EC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 183.28, ALogP 1.58, HBA 3, HBD 1, PSA 21.26, QED 0.75
Compound (SMILES): COC(=O)N1CCC[C@H](NS(C)(=O)=O)[C@@H]1CO[C@H]1CC[C@@H](c2ccccc2)CC1
InChIKey: UXZAJSZFFARTEI-YRPNKDGESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Measurement of Orexin Type 2 Receptor Agonist Activity: Chinese hamster ovary (CHO) dhfr-cells forcibly expressing human orexin type 2 receptor (hOX2R) were seeded in each well of Black clear bottom plate (384 wells) (Becton, Dickinson and Company) by 10,000 cells, and cultured for 16 hr in an MEM-alpha (Nikken-Bio Co., Ltd.) medium containing 100 U/ml penicillin, 100 μg/ml streptomycin, 0.5 g/ml G418 (all above Invitrogen), and 10% fetal calf serum (Thermo), under the conditions of 37° C., 5% CO2. After removal of the medium, 30 μL of assay buffer 1 (0.1% bovine serum albumin (Wako Pure Chemical Industries, Ltd.), 1.25 mM probenecid, 10% B2-Quencher, 2.5 μg/mL Fluo-4AM, 10 mM HEPES (DOJINDO)) was added, and the cells were incubated for 60 min under the conditions of 37° C., 5% CO2. A test compound was dissolved in dimethyl sulfoxide to 10 mM, and then diluted with assay buffer 2 (20 mM HEPES, Hanks' balanced salt solution (Invitrogen), 0.1% bovine serum albumin). For the reaction, a test compound solution (10 μL) was added using Fluorescent Imaging Plate Reader TETRA (FLIPR TETRA; manufactured by Molecular Devices), a fluorescence value (excitation wavelength 488 nm, measurement wavelength 570 nm) of each well was measured every one second for 1 min, and the agonist activity was determined using the area of the fluorescence value as an indicator of intracellular Ca2+ concentration. The agonist activity of the test compound was calculated assuming that the fluorescence value of the well added with only the dilution buffer was 0% and the fluorescence value of the well added with 10 nM human orexin B (PEPTIDE INSTITUTE, INC.) buffer was 100%. The agonist activity values EC50 and Emax of each compound are shown below. As used herein, Emax indicates the value at 30 uM concentration when orexin B is converted to a full agonist (maximum value of agonist activity: 100%). As is clear from the results, the compound of the present invention was shown to have an agonist activity on hOX2R.
Measurement: EC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 424.56, ALogP 2.88, HBA 5, HBD 1, PSA 84.94, QED 0.76
Compound (SMILES): Cc1cc(Nc2cc3ncccc3c(N[C@@H]3C[C@H]4CC[C@@H](C3)N4CCC#N)n2)n[nH]1
InChIKey: DADAEARVGOQWHV-OSYLJGHBSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Biochemical JAK Assays: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies.Serially diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.Test compounds having a higher pKi value in each of the four JAK assays show greater inhibition of JAK activity. Compounds of the invention tested in this assay typically exhibited pKi values between about 7 and about 10.3
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 402.51, ALogP 3.73, HBA 7, HBD 3, PSA 105.55, QED 0.58
Compound (SMILES): COc1ccc(-c2c(-c3ccc(C#N)c(F)c3)nc(N3CCC(N)CC3)n(C)c2=O)cc1F.O=S(=O)(O)c1ccccc1
InChIKey: AWZCBGWZNHQCIZ-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 in human NCI-H1417 cells assessed as suppression of GRP mRNA expression incubated for 4 days by qPCR analysis
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 451.48, ALogP 3.2, HBA 7, HBD 1, PSA 97.17, QED 0.65
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: WDHOIABIERMLGY-CMJOXMDJSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ERalpha expression in presence of cycloheximide by Western blot analysis
Measurement: IC50 = 0.1259 nM (pChEMBL 9.899999618530273)
Descriptors: MW 476.52, ALogP 4.31, HBA 5, HBD 2, PSA 60.08, QED 0.5
Compound (SMILES): COc1ccc(F)cc1C(=O)NCc1ccc(-c2nn([C@@H](C)C(F)(F)F)c(N)c2C(N)=O)cc1
InChIKey: FWZAWAUZXYCBKZ-NSHDSACASA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK C481R mutant (unknown origin)
Measurement: IC50 = 11.73 nM (pChEMBL 7.929999828338623)
Descriptors: MW 479.43, ALogP 3.43, HBA 6, HBD 3, PSA 125.26, QED 0.45
Compound (SMILES): C[C@@H]1OCC2(CCN(c3cnc(Sc4ccnc(N)c4Cl)c(N)n3)CC2)[C@@H]1N
InChIKey: UCJZOKGUEJUNIO-IINYFYTJSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) using DiFMUP as substrate incubated for 60 mins followed by substrate addition for 30 mins by microplate reader method
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 421.96, ALogP 2.17, HBA 9, HBD 3, PSA 129.2, QED 0.68
Compound (SMILES): C[Si]1(C)C[C@@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](Cc3ccccc3)C(=O)N2C1.O=C(O)C(F)(F)F
InChIKey: PGOCUMIEUZYJSO-GSWLFNFOSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Inhibition of fibrinogen binding to human platelet integrin alpha2b beta3 by ELISA based solid phase binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 616.75
Compound (SMILES): O=c1cc(C2CCCCC2)c2c(C3CC3)[nH]nc2[nH]1
InChIKey: FGXYVPZOBRZUPC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 257.34, ALogP 3.18, HBA 2, HBD 2, PSA 61.54, QED 0.87
Compound (SMILES): CNCCc1c[nH]c2cccc(O)c12
InChIKey: MTJOWJUQGYWRHT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human smBiT-fused 5HT2A receptor expressed in CHO-K1 cells co-expressing IgBiT-fused beta-arrestin2 assessed as beta-arrestin2 recruitment by measuring increase in chemiluminescence intensity incubated for 2 hrs by NanoBiT luciferase assay
Measurement: EC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 190.25, ALogP 1.64, HBA 2, HBD 3, PSA 48.05, QED 0.69
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(COc4ccc5c(c4)C=CS(=O)(=O)O5)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: CMDJJRDLUGCOEH-QXAKKESOSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 5852.3 nM (pChEMBL 5.230000019073486)
Descriptors: MW 503.49, ALogP 0.23, HBA 12, HBD 2, PSA 167.63, QED 0.44
Compound (SMILES): Cc1cc2c(-c3ccco3)cnc(N[C@@H]3CCN(C)C[C@H]3C(=O)NC3CCCCC3)c2[nH]c1=O
InChIKey: NDEORODKVUYMFQ-NHCUHLMSSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: BET mutant TR-FRET assay (BRD4 BD2)
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 463.58, ALogP 3.67, HBA 6, HBD 3, PSA 103.26, QED 0.53
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3ccc4c(c3)CNC4=N)c2O)cc1
InChIKey: YJXLTNFWFWJAIE-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 331.38, ALogP 3.33, HBA 5, HBD 4, PSA 93.92, QED 0.59
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn(Cc2cccc3[nH]ccc23)c1=O
InChIKey: PDCBJZVPIGAEBL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to 6His-Thr-BRD3 (1 to 435 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 364.41, ALogP 1.63, HBA 4, HBD 3, PSA 95.99, QED 0.64
Compound (SMILES): Clc1ccc2c3c1OCCN3CCNC2
InChIKey: MYTVVUAXKLOULI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2A receptor (unknown origin)
Measurement: Ki = 2430 nM (pChEMBL 5.610000133514404)
Descriptors: MW 224.69, ALogP 1.64, HBA 3, HBD 1, PSA 24.5, QED 0.73
Compound (SMILES): N=C(N)c1ccc(Nc2ccc(-c3cc4ccc(C(=N)N)cc4[nH]3)cc2)cc1
InChIKey: TZRXNWCLKYWDNH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Inhibition of recombinant GST-tagged PRMT7 (unknown origin) expressed in Escherichia coli using biotin-labeled SMD1 as substrate incubated for 120 mins in presence of [3H]-SAM cofactor by scintillation proximity assay
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 368.44, ALogP 4.15, HBA 3, HBD 6, PSA 127.56, QED 0.23
Compound (SMILES): Cc1c(NCc2ccccc2N2CCN(C)CC2)cnn(C)c1=O
InChIKey: HONYBLSJNSYWKQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human partial length BRD4 (1) (N44 to E168 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 327.43, ALogP 1.45, HBA 6, HBD 1, PSA 53.4, QED 0.92
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc(C3CC4CCC3CC4)c12
InChIKey: OSPGWPLTUVOFKX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 257.34, ALogP 2.85, HBA 2, HBD 2, PSA 61.54, QED 0.82
Compound (SMILES): C[C@@H]1[C@@H]2CN(c3nc(Nc4cnn(C)c4)ncc3F)C[C@]12NC(=O)[C@H]1C[C@@H]1C#N
InChIKey: AJIADPABISZKBM-OXCAWISSSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as EPO signalling in CD34+ cells by flow cytometry
Measurement: IC50 = 9368 nM (pChEMBL 5.03000020980835)
Descriptors: MW 396.43, ALogP 1.19, HBA 8, HBD 2, PSA 111.76, QED 0.78
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cn5)c(=O)c4c3)cc12
InChIKey: RDUBBDFCMXNFDY-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 643.67, ALogP 5.26, HBA 8, HBD 1, PSA 127.4, QED 0.25
Compound (SMILES): Cc1ccc(NC(=O)c2cc3cccc(O)c3oc2=N)cc1
InChIKey: SKZQOFVKMNLPBF-UHFFFAOYSA-N
Target: Carbonyl reductase [NADPH] 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P16152
Assay: Inhibition of CBR1 (unknown origin)
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 294.31, ALogP 3.18, HBA 4, HBD 3, PSA 86.32, QED 0.68
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3C[C@H]4C[C@@H]3C[C@H]4CC#N)c12
InChIKey: KGKZRAAHCZTDQA-WYUUTHIRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human STAT5-irf1-bla TF1 cells assessed as reduction in EPO-induced STAT5-signalling pre-incubated for 1 hrs before EPO addition and further incubated for 4 hrs fluorescence based assay
Measurement: IC50 > 43000 nM (pChEMBL 4.367000102996826)
Descriptors: MW 282.35, ALogP 2.6, HBA 3, HBD 2, PSA 85.33, QED 0.89
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-FLVSMNSFSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin)
Measurement: IC50 = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cn(C)c3c(=O)[nH]ccc23)cc2c1ccn2C(C)(c1ccccn1)c1ccccn1
InChIKey: LMLIBNUOIWAJFC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to human partial length BRD3 bromodomain 1 (P24 to E144 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 552.66, ALogP 4.85, HBA 7, HBD 2, PSA 114.67, QED 0.29
Compound (SMILES): COc1ccc(C2CCCN2Cc2ccc(Oc3ccc(C(=O)NO)cc3)cc2)cc1
InChIKey: DLQCQSHURGAKKI-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Antagonist activity at human delta opiod receptor expressed in human HEK293 cells assessed as inhibition of DPDPE-induced [35S]GTPgammaS binding incubated for 2 hrs by microbeta liquid scintillation counting method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 418.49, ALogP 4.94, HBA 5, HBD 2, PSA 71.03, QED 0.42