lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3cccc(c3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: AUCAZZWPUGEUHN-LTJSBYPUSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 8017 nM (pChEMBL 5.099999904632568)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3cccc(c3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: OSLGPDHWDMEVAV-LTJSBYPUSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 604 nM (pChEMBL 6.21999979019165)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: RPXSHXJWFUDNDF-FYGBZDAYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human recombinant CYP2D6 expressed in Trichoplusia ni BTI-TN-5B1-4 cells preincubated for 15 mins measured after 45 mins by spectrofluorimetry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3cccc(c3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: PKFMLTOTRJKTIB-FYGBZDAYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 3250 nM (pChEMBL 5.489999771118164)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4cccc(c4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: YPEBQDSZJKJSGR-FYGBZDAYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: OHHHKFISAUMLDW-CZZGGHMTSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 14143 nM (pChEMBL 4.849999904632568)
Descriptors: MW 807.98, ALogP 1.94, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: WZYRCJJNQVDXMC-MAVUKPMZSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using CH3SO2-D-Cha-Gly-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 11210 nM (pChEMBL 4.949999809265137)
Descriptors: MW 836.03, ALogP 2.72, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): Cn1nc(CC(=O)Nc2ccc3oc4c(c3c2)CCCC4)c2ccccc2c1=O
InChIKey: GMQDVIPGHXODOQ-UHFFFAOYSA-N
Target: Inosine-5'-monophosphate dehydrogenase (SINGLE PROTEIN), Cryptosporidium parvum
UniProt: Q8T6T2
Assay: Un-competitive inhibition of Cryptosporidium IMPDH preincubated for 10 mins before IMP substrate addition by spectrophotometry
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 387.44, ALogP 3.74, HBA 5, HBD 1, PSA 77.13, QED 0.58
Compound (SMILES): CN(CCC[C@]1(O)[C@H]2CCN(CC(F)(F)F)[C@@H]1Cc1ccc(O)c(O)c12)C(=O)/C=C/c1ccoc1.Cl
InChIKey: BDERJZADYUBBIL-MLKCUUANSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 494.51, ALogP 3.65, HBA 6, HBD 3, PSA 97.38, QED 0.4
Compound (SMILES): CN(CCC[C@]1(O)[C@H]2CCN(CC(F)F)[C@@H]1Cc1ccc(O)c(O)c12)C(=O)/C=C/c1ccoc1.Cl
InChIKey: WORUZMJUYDRGQU-AHIBZVSXSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 476.52, ALogP 3.35, HBA 6, HBD 3, PSA 97.38, QED 0.4
Compound (SMILES): CN(CCC[C@]1(O)[C@H]2CCN(CCF)[C@@H]1Cc1ccc(O)c(O)c12)C(=O)/C=C/c1ccoc1.Cl
InChIKey: ZAUJAXGERZUGPI-ANGYDEQASA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 8.394 nM (pChEMBL 8.079999923706055)
Descriptors: MW 458.53, ALogP 3.06, HBA 6, HBD 3, PSA 97.38, QED 0.42
Compound (SMILES): CC(C)CN1CC[C@H]2c3c(ccc(O)c3O)C[C@@H]1[C@]2(O)CCCN(C)C(=O)/C=C/c1ccoc1.Cl
InChIKey: DGLMDKGCPUGHSM-MZQOZTLGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 46.22 nM (pChEMBL 7.329999923706055)
Descriptors: MW 468.59, ALogP 3.74, HBA 6, HBD 3, PSA 97.38, QED 0.4
Compound (SMILES): CCCN1CC[C@H]2c3c(ccc(O)c3O)C[C@@H]1[C@]2(O)CCCN(C)C(=O)/C=C/c1ccoc1.Cl
InChIKey: VHPUVSPGEQGGQU-MTJRBIDCSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 19.17 nM (pChEMBL 7.71999979019165)
Descriptors: MW 454.57, ALogP 3.5, HBA 6, HBD 3, PSA 97.38, QED 0.42
Compound (SMILES): CCN1CC[C@H]2c3c(ccc(O)c3O)C[C@@H]1[C@]2(O)CCCN(C)C(=O)/C=C/c1ccoc1.Cl
InChIKey: LYNXFYAVPBNVGO-GKPOQEAPSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 10.99 nM (pChEMBL 7.960000038146973)
Descriptors: MW 440.54, ALogP 3.11, HBA 6, HBD 3, PSA 97.38, QED 0.45
Compound (SMILES): CN(CCC[C@]1(O)[C@H]2CCN(C)[C@@H]1Cc1ccc(O)c(O)c12)C(=O)/C=C/c1ccoc1.Cl
InChIKey: VEAGOAUEYICPOK-YTSCPZRUSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]DAMGO from mu opioid receptor in mouse whole brain membranes without cerebellum after 1 hr by liquid scintillation counting analysis
Measurement: Ki = 2.767 nM (pChEMBL 8.5600004196167)
Descriptors: MW 426.51, ALogP 2.72, HBA 6, HBD 3, PSA 97.38, QED 0.49
Compound (SMILES): Cc1cc(OCc2nnc(SC3CCCC3)n2-c2cccnc2)ccc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: UJGTUKMAJVCBIS-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Inhibition of p97 in human HeLa cells expressing UbG76V-GFP/ODD-Luc assessed as accumulation of Ub-GFP incubated for 6 hrs by confocal microscopic analysis
Measurement: EC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 520.68, ALogP 5.65, HBA 8, HBD 0, PSA 86.97, QED 0.3
Compound (SMILES): N#CCc1ccccc1C#Cc1ccc(CCC(=O)O)cc1
InChIKey: AMKACOPNIVQTHQ-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 assessed as calcium mobilization measured for 50 intervals of 0.4 secs by microplate reader analysis
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 289.33, ALogP 3.17, HBA 2, HBD 1, PSA 61.09, QED 0.88
Compound (SMILES): CO[C@@H]1COCC[C@@H]1N[C@@H]1C[C@H]2CCC[C@@]2(C(=O)N2CCc3ncc(C(F)(F)F)cc3C2)C1
InChIKey: SQIBVAVXYSKQBW-FZFRBNDOSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.53, ALogP 3.33, HBA 5, HBD 1, PSA 63.69, QED 0.74
Compound (SMILES): N#Cc1c(N)nc2sc(C(=O)c3cccc(Cl)c3)c(N)c2c1-c1ccccc1Cl
InChIKey: BXLXOBIMRFZEAE-UHFFFAOYSA-N
Target: Glycogen synthase kinase 3 (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: O77344
Assay: Inhibition of Plasmodium falciparum GSK3 measured after 2 hrs by luciferin-based luminescence assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 439.33, ALogP 5.54, HBA 6, HBD 2, PSA 105.79, QED 0.41
Compound (SMILES): O=C(NC1CCCCC1)Oc1ccc(O)c(-c2ccccc2)c1
InChIKey: KRJOFKFEYDSZAV-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of FAAH in Wistar rat brain membranes using [3H]-anandamide as substrate preincubated for 10 mins followed by substrate addition measured after 4 mins by liquid scintillation counting method
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 311.38, ALogP 4.48, HBA 3, HBD 2, PSA 58.56, QED 0.88
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)sc3ccccc23)cc(C)c1Cl
InChIKey: GFWMYYSJLSUPMD-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 374.89, ALogP 5.88, HBA 3, HBD 1, PSA 46.53, QED 0.55
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)sc3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: LDHKTVULLKPADL-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 409.33, ALogP 6.53, HBA 3, HBD 1, PSA 46.53, QED 0.47
Compound (SMILES): O=C(O)c1sc2cc(Cl)ccc2c1CCCOc1cccc2ccccc12
InChIKey: COLLXPQODXVGIQ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 396.89, ALogP 6.42, HBA 3, HBD 1, PSA 46.53, QED 0.38
Compound (SMILES): O=C(O)c1[nH]c2ccccc2c1CCCOc1cccc2ccccc12
InChIKey: IQTBMDSOBZUIII-UHFFFAOYSA-N
Target: Albumin (SINGLE PROTEIN), Homo sapiens
UniProt: P02768
Assay: Displacement of probe S1 from recombinant human serum albumin domain 3 after 5 mins by fluorescence polarization assay
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 345.4, ALogP 5.03, HBA 2, HBD 2, PSA 62.32, QED 0.48
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: MCMWRWKXPXXZAS-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of MCL-1 (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 392.28, ALogP 5.8, HBA 2, HBD 2, PSA 62.32, QED 0.52
Compound (SMILES): N#CC(C#N)=c1c(=O)c2cccc3cccc1c32
InChIKey: WYZUQHDRPNJOCG-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Binding affinity to his-tagged Mcl-1 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells by ITC analysis
Measurement: Kd = 52250 nM (pChEMBL 4.28000020980835)
Descriptors: MW 230.23, ALogP 1.71, HBA 3, HBD 0, PSA 64.65, QED 0.59
Compound (SMILES): O=C(O)c1sc2ccccc2c1CCCOc1cccc2ccccc12
InChIKey: WEKMYYBVUYSISQ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 362.45, ALogP 5.76, HBA 3, HBD 1, PSA 46.53, QED 0.44
Compound (SMILES): O=C(O)c1oc2ccccc2c1CCCOc1cccc2ccccc12
InChIKey: XCFJIAWXXGRBEJ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 346.38, ALogP 5.3, HBA 3, HBD 1, PSA 59.67, QED 0.48
Compound (SMILES): CS(=O)(=O)CC[C@@H]1OCC[C@@]2(S(=O)(=O)c3ccc(C(F)(F)F)cc3)c3c(F)ccc(F)c3OC[C@@H]12
InChIKey: DGRSGSKYRNNKNH-XERREHJYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of gamma-secretase (unknown origin) expressed in HEK293 cells co-expressing Awe-Lon mutant assessed as reduction of amyloid beta-40 production
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 540.53, ALogP 3.89, HBA 6, HBD 0, PSA 86.74, QED 0.54
Compound (SMILES): COc1ccccc1NC(=O)c1ccc(NC(=O)CCc2nc3ccccc3c(=O)[nH]2)cc1
InChIKey: WWKKOAKRYQQEBT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of TEV cleavable N-terminal His6-tagged TNKS2 SAM/catalytic domain (873 to 1162 residues) (unknown origin) extracted from Escherichia coli BL21(DE3) cells incubated for 20 hrs in presence of NAD+ by fluorescence based assay
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 442.48, ALogP 3.76, HBA 5, HBD 3, PSA 113.18, QED 0.4
Compound (SMILES): COc1cc2cc(NC(=O)[C@H]3CCC[C@@H](NCc4ccccc4)C3)c(=O)oc2cc1OC
InChIKey: UGTGSTDFYWUXNH-PKOBYXMFSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Mixed type inhibition of human AChE using acetylthiocholineiodide as substrate measured for every 30 sec for 5 mins by Ellman's method
Measurement: Ki = 93.4 nM (pChEMBL 7.03000020980835)
Descriptors: MW 436.51, ALogP 4.1, HBA 6, HBD 2, PSA 89.8, QED 0.54
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: BSPJDKCMFIPBAW-JPBGFCRCSA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant His-tagged SAR-CoV-2 Main protease expressed in Escherichia coli BL21/DE3 using Edans-labeled substrate by FRET-based assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 485.56, ALogP 0.54, HBA 7, HBD 5, PSA 171.13, QED 0.28
Compound (SMILES): O=C(NCC1CC1)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: NSYOWNMYXMUFHH-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 459.35, ALogP 5.84, HBA 3, HBD 1, PSA 51.22, QED 0.46
Compound (SMILES): O=C(c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1)N1CCCC1
InChIKey: ZDUFQAJHKGKMQW-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 459.35, ALogP 5.93, HBA 3, HBD 0, PSA 42.43, QED 0.46
Compound (SMILES): O=C(NC1CCC1)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: YRORDIALXSEBNJ-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 459.35, ALogP 5.98, HBA 3, HBD 1, PSA 51.22, QED 0.47
Compound (SMILES): CC(C)CNC(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: SIDBKCIQXCEIJS-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 461.36, ALogP 6.08, HBA 3, HBD 1, PSA 51.22, QED 0.44
Compound (SMILES): CCC(C)NC(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: JSHKOWWOAAWJJF-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 461.36, ALogP 6.23, HBA 3, HBD 1, PSA 51.22, QED 0.43
Compound (SMILES): CC(C)(C)NC(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: SXONLDCVNFEQCH-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 461.36, ALogP 6.23, HBA 3, HBD 1, PSA 51.22, QED 0.47
Compound (SMILES): CCN(CC)C(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: AWFBHJQNBWSWAR-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 461.36, ALogP 6.18, HBA 3, HBD 0, PSA 42.43, QED 0.4
Compound (SMILES): O=C(NC1CC2CCC1C2)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: AYUGSPUFYVWZLP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 499.41, ALogP 6.62, HBA 3, HBD 1, PSA 51.22, QED 0.4
Compound (SMILES): NC(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: WCTJTYALDQBUBV-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 405.26, ALogP 4.8, HBA 3, HBD 1, PSA 65.21, QED 0.64
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(Cl)cc1)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: LQPMZZIIOKLZQG-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 579.86, ALogP 6.47, HBA 5, HBD 1, PSA 85.36, QED 0.26
Compound (SMILES): O=C(NS(=O)(=O)c1cc(Cl)ccc1Cl)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: BPZOEMKYRIFPIG-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 614.31, ALogP 7.12, HBA 5, HBD 1, PSA 85.36, QED 0.23
Compound (SMILES): Cc1ccc(S(=O)(=O)NC(=O)c2cccc(Cc3cc(Cl)ccc3OCc3ccc(Cl)cc3F)n2)cc1
InChIKey: NVPDIBBYSPFSSM-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 559.45, ALogP 6.12, HBA 5, HBD 1, PSA 85.36, QED 0.28
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(Cl)c(Cl)c1)c1cccc(Cc2cc(Cl)ccc2OCc2ccc(Cl)cc2F)n1
InChIKey: LDFRXJWXVDCNFQ-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Mus musculus
UniProt: Q62053
Assay: Antagonist activity at mouse EP2 receptor
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 614.31, ALogP 7.12, HBA 5, HBD 1, PSA 85.36, QED 0.23
Compound (SMILES): NCc1cnn(O)c1
InChIKey: SGFQVPARKZCZOT-UHFFFAOYSA-N
Target: GABA A receptor alpha-2/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47869
Assay: Agonist activity at human GABAA alpha2beta2gamma2S receptor expressed in TSA201 cells after 1 min by FLIPR assay
Measurement: EC50 = 4466.84 nM (pChEMBL 5.349999904632568)
Descriptors: MW 113.12, ALogP -0.42, HBA 4, HBD 2, PSA 64.07, QED 0.49
Compound (SMILES): C[C@@H]1CN2CC(=O)Nc3ccc(cc3)C[C@@H](C(=O)NCc3ccc(C(=N)N)cc3)NC(=O)[C@H](NS(=O)(=O)Cc3ccccc3)Cc3ccc(cc3)NC(=O)CN1C[C@@H]2C.O=C(O)C(F)(F)F
InChIKey: ILXNFZFJPGWGAV-NSDLUCIFSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): C[C@H]1CN2CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N[C@H](C(=O)NCc3ccc(C(=N)N)cc3)Cc3ccc(cc3)NC(=O)CN1C[C@@H]2C.O=C(O)C(F)(F)F
InChIKey: ILXNFZFJPGWGAV-YBMCEFHMSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)NCc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: AGWPISFQDMJINO-CZZGGHMTSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 807.98, ALogP 1.23, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCCN(CC3)CC(=O)NCc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: PAIBNCBSDJSBKP-FYGBZDAYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 822, ALogP 1.62, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): C[C@H]1CN2CC(=O)Nc3ccc(cc3)C[C@@H](C(=O)NCc3ccc(C(=N)N)cc3)NC(=O)[C@H](NS(=O)(=O)Cc3ccccc3)Cc3ccc(cc3)CNC(=O)CN1C[C@@H]2C.O=C(O)C(F)(F)F
InChIKey: ULKLAIIVICWYFS-YXKZONPNSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 836.03, ALogP 2.01, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: WMLLWXCYJMFXSU-LTJSBYPUSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in Trichoplusia ni BTI-TN-5B1-4 cells preincubated for 15 mins measured after 30 mins by spectrofluorimetry
Measurement: IC50 > 22000 nM (pChEMBL 4.6579999923706055)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3cccc(c3)NC(=O)CN3CCN(CC3)CC(=O)Nc3cccc(c3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: XBLBJCJDIRIFMO-LTJSBYPUSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3cccc(c3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: AUCAZZWPUGEUHN-LTJSBYPUSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3cccc(c3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: OSLGPDHWDMEVAV-LTJSBYPUSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 793.95, ALogP 1.55, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: RPXSHXJWFUDNDF-FYGBZDAYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in Trichoplusia ni BTI-TN-5B1-4 cells preincubated for 15 mins measured after 30 mins by spectrofluorimetry
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3cccc(c3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: PKFMLTOTRJKTIB-FYGBZDAYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4cccc(c4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: YPEBQDSZJKJSGR-FYGBZDAYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 822, ALogP 2.33, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NS(=O)(=O)Cc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F
InChIKey: OHHHKFISAUMLDW-CZZGGHMTSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 807.98, ALogP 1.94, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F
InChIKey: WZYRCJJNQVDXMC-MAVUKPMZSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-pNA as substrate after 5 to 10 mins by micro plate reader analysis
Measurement: Ki = 422 nM (pChEMBL 6.380000114440918)
Descriptors: MW 836.03, ALogP 2.72, HBA 9, HBD 7, PSA 218.92, QED 0.1
Compound (SMILES): Cn1nc(CC(=O)Nc2ccc3oc4c(c3c2)CCCC4)c2ccccc2c1=O
InChIKey: GMQDVIPGHXODOQ-UHFFFAOYSA-N
Target: Inosine-5'-monophosphate dehydrogenase (SINGLE PROTEIN), Bacillus anthracis
UniProt: A0A6L8P2U9
Assay: Non-competitive inhibition of Bacillus anthracis IMPDH preincubated for 10 mins before NAD+ substrate addition by spectrophotometry
Measurement: Ki = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 387.44, ALogP 3.74, HBA 5, HBD 1, PSA 77.13, QED 0.58
Compound (SMILES): Cc1cc(OCc2nnc(SC3CCCC3)n2-c2cccnc2)ccc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: UJGTUKMAJVCBIS-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Inhibition of human p97 in human HeLa cells harboring UbG76V-GFP assessed as accumulation of UbG76V after 6 hrs by microscopic analysis
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 520.68, ALogP 5.65, HBA 8, HBD 0, PSA 86.97, QED 0.3
Compound (SMILES): N#CCc1ccccc1C#Cc1ccc(CCC(=O)O)cc1
InChIKey: AMKACOPNIVQTHQ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARgamma (unknown origin)
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 289.33, ALogP 3.17, HBA 2, HBD 1, PSA 61.09, QED 0.88
Compound (SMILES): CO[C@@H]1COCC[C@@H]1N[C@@H]1C[C@H]2CCC[C@@]2(C(=O)N2CCc3ncc(C(F)(F)F)cc3C2)C1
InChIKey: SQIBVAVXYSKQBW-FZFRBNDOSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 (unknown origin) assessed as inhibition of MCP1-induced chemotaxis
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 467.53, ALogP 3.33, HBA 5, HBD 1, PSA 63.69, QED 0.74
Compound (SMILES): N#Cc1c(N)nc2sc(C(=O)c3cccc(Cl)c3)c(N)c2c1-c1ccccc1Cl
InChIKey: BXLXOBIMRFZEAE-UHFFFAOYSA-N
Target: Glycogen synthase kinase 3 (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: O77344
Assay: Inhibition of recombinant Plasmodium falciparum GSK3 using GS-1 as substrate measured after 30 mins in presence of [gamma 32P-ATP] by SDS-PAGE based autoradiography
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 439.33, ALogP 5.54, HBA 6, HBD 2, PSA 105.79, QED 0.41
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)sc3ccccc23)cc(C)c1Cl
InChIKey: GFWMYYSJLSUPMD-UHFFFAOYSA-N
Target: Bcl2-associated agonist of cell death (SINGLE PROTEIN), Homo sapiens
UniProt: Q92934
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 374.89, ALogP 5.88, HBA 3, HBD 1, PSA 46.53, QED 0.55
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)sc3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: LDHKTVULLKPADL-UHFFFAOYSA-N
Target: Bcl2-associated agonist of cell death (SINGLE PROTEIN), Homo sapiens
UniProt: Q92934
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 409.33, ALogP 6.53, HBA 3, HBD 1, PSA 46.53, QED 0.47
Compound (SMILES): O=C(O)c1sc2cc(Cl)ccc2c1CCCOc1cccc2ccccc12
InChIKey: COLLXPQODXVGIQ-UHFFFAOYSA-N
Target: Bcl2-associated agonist of cell death (SINGLE PROTEIN), Homo sapiens
UniProt: Q92934
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 396.89, ALogP 6.42, HBA 3, HBD 1, PSA 46.53, QED 0.38
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)O)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: MCMWRWKXPXXZAS-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of BCL-2 (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 392.28, ALogP 5.8, HBA 2, HBD 2, PSA 62.32, QED 0.52