lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)Nc2ccccc2)CC1
InChIKey: YNQDPOCMUJDKQJ-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 337.47, ALogP 4.34, HBA 2, HBD 1, PSA 35.58, QED 0.88
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)Cc2nnn[nH]2)CC1
InChIKey: NHHIJGZBBDURFV-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 328.42, ALogP 1.39, HBA 5, HBD 1, PSA 78.01, QED 0.92
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)c2nc[nH]n2)CC1
InChIKey: ZBRVJOIEFQDRHB-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 313.4, ALogP 2.06, HBA 4, HBD 1, PSA 65.12, QED 0.92
Compound (SMILES): CC(C)(C)c1cc(Br)ccc1N1CCN(C(=O)CC(=O)O)CC1
InChIKey: MEJPGICCEBLBIM-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 383.29, ALogP 2.87, HBA 3, HBD 1, PSA 60.85, QED 0.82
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)C2(C(=O)O)CC2)CC1
InChIKey: DDCFJEHFXGGYIG-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 330.43, ALogP 2.5, HBA 3, HBD 1, PSA 60.85, QED 0.87
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)C(=O)C2NC(=O)NC2=O)CC1
InChIKey: IFHBRKLSHWPNNP-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 372.43, ALogP 0.41, HBA 5, HBD 2, PSA 98.82, QED 0.45
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)C(O)CO)CC1
InChIKey: OHWQKVANIBBQSY-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 306.41, ALogP 0.99, HBA 4, HBD 2, PSA 64.01, QED 0.87
Compound (SMILES): CC(C)(C)c1ccccc1N1CCN(C(=O)C23CC4CC(CC(C(=O)O)(C4)C2)C3)CC1
InChIKey: UFIQNYCAFNWRET-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Binding Assay: Streptavidin (20 ul) (10 ug/ml Streptavidin type II (Wako Pure Chemical Industries, Ltd.), 10 mM Tris-HCl (pH 7.5), 10 mM NaCl) was added to a 384 well black plate (Nunc MaxiSorp, Thermo Fisher Scientific Inc.), and the plate was subjected to centrifugation (1000 rpm, 1 min) and coated overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well) and blocked with 25% Block Ace (Snow Brand Milk Products Co., Ltd., PBS, 100 ul/well). The plate was subjected to centrifugation (1000 rpm, 1 min) and incubated at room temperature for 4 hr or overnight at 4 C. The plate was washed twice with PBST (PBS, 0.05% Tween 20, 100 ul/well), and biotinylate human TTR (stock solution concentration 1.0 mg/ml) diluted 750-fold with PBST was added at 20 ul/well. The plate was subjected to centrifugation (1000 rpm, 1 min) and stood still at room temperature for 1.5 hr or overnight at 4 C. The plate was washed 3 times with PBST (100 ul/well).
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 424.59, ALogP 4.3, HBA 3, HBD 1, PSA 60.85, QED 0.79
Compound (SMILES): CSCC(CO)(CO)NCc1c[nH]c2c(=O)[nH]cnc12
InChIKey: MZTXOEPNHJMRKL-UHFFFAOYSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): O=c1[nH]cnc2c(CN(Cc3ccccc3)C[C@@H](O)CO)c[nH]c12
InChIKey: WBNKKFGASWUKMH-CQSZACIVSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8T9Z7
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 328.37, ALogP 0.61, HBA 5, HBD 4, PSA 105.24, QED 0.51
Compound (SMILES): O=c1[nH]cnc2c(CNCC(CO)[C@H](O)CO)c[nH]c12
InChIKey: MXMZHPBJYLDKFX-YGPZHTELSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 282.3, ALogP -1.7, HBA 6, HBD 6, PSA 134.26, QED 0.36
Compound (SMILES): CSC[C@H](NCc1c[nH]c2c(=O)[nH]cnc12)[C@H](O)CO
InChIKey: XZZAMLCSKGDMOZ-DTWKUNHWSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8T9Z7
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): CSC[C@@H](NCc1c[nH]c2c(O)ncnc12)[C@@H](O)CO
InChIKey: XZZAMLCSKGDMOZ-BDAKNGLRSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 298.37, ALogP -0.16, HBA 7, HBD 5, PSA 114.29, QED 0.48
Compound (SMILES): CSC[C@@H](NCc1c[nH]c2c(=O)[nH]cnc12)[C@H](O)CO
InChIKey: XZZAMLCSKGDMOZ-RKDXNWHRSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8T9Z7
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 10000 nM (pChEMBL 5)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): CSC[C@H](NCc1c[nH]c2c(=O)[nH]cnc12)[C@@H](O)CO
InChIKey: XZZAMLCSKGDMOZ-IUCAKERBSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8T9Z7
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): CSCC(CNCc1c[nH]c2c(=O)[nH]cnc12)[C@H](O)CO
InChIKey: WFVWGCCKITWGOG-QVDQXJPCSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 312.4, ALogP -0.33, HBA 6, HBD 5, PSA 114.03, QED 0.46
Compound (SMILES): CSCC(CNCc1c[nH]c2c(=O)[nH]cnc12)C(O)CO
InChIKey: WFVWGCCKITWGOG-UHFFFAOYSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 312.4, ALogP -0.33, HBA 6, HBD 5, PSA 114.03, QED 0.46
Compound (SMILES): CSCC(CN(Cc1ccccc1)Cc1c[nH]c2c(=O)[nH]cnc12)[C@H](O)CO
InChIKey: GMTNOMALWYVUCZ-ZYMOGRSISA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q8T9Z7
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 402.52, ALogP 1.59, HBA 6, HBD 4, PSA 105.24, QED 0.41
Compound (SMILES): CSC[C@H](O)[C@@H](O)CNCc1c[nH]c2c(=O)[nH]cnc12
InChIKey: ANFGJKWKGAPTFC-IUCAKERBSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): CSCC(O)C(O)CNCc1c[nH]c2c(=O)[nH]cnc12
InChIKey: ANFGJKWKGAPTFC-UHFFFAOYSA-N
Target: Purine nucleoside phosphorylase (SINGLE PROTEIN), Homo sapiens
UniProt: P00491
Assay: Inhibition Assay: The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation uÂ =(kcat x S)/(Km(1+l/Kd)+S), where uÂ  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
Measurement: Kd = 789 nM (pChEMBL 6.099999904632568)
Descriptors: MW 298.37, ALogP -0.57, HBA 6, HBD 5, PSA 114.03, QED 0.47
Compound (SMILES): CCn1c(=O)c2cnc3c(Cl)cccc3c2n(C2CCCC2)c1=O
InChIKey: RNTPXDNXVJTNNP-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 343.81, ALogP 3.5, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): CCCc1cccc2c1ncc1c(=O)n(CC)c(=O)n(C3CCCC3)c12
InChIKey: IAIFPELWEXGBKC-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 351.45, ALogP 3.8, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): CCn1c(=O)c2cnc3c(C(C)C)cccc3c2n(C2CCCC2)c1=O
InChIKey: IWWGJHDCEUWDTE-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 12400 nM (pChEMBL 4.909999847412109)
Descriptors: MW 351.45, ALogP 3.97, HBA 5, HBD 0, PSA 56.89, QED 0.67
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cc(C)cs3)c(=O)n(C3CCCC3)c12
InChIKey: XBMCCMKXNQMPDO-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 407.5, ALogP 4.19, HBA 7, HBD 0, PSA 66.12, QED 0.48
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(C)c3)c(=O)n(C3CCCC3)c12
InChIKey: NMCBQDCTQPGXHQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 401.47, ALogP 4.13, HBA 6, HBD 0, PSA 66.12, QED 0.48
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3ccc4c(c3)OCO4)c(=O)n(C3CCCC3)c12
InChIKey: JMKXHWHMULJLQG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 827 nM (pChEMBL 6.079999923706055)
Descriptors: MW 431.45, ALogP 3.55, HBA 8, HBD 0, PSA 84.58, QED 0.46
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n(C3CCN(S(C)(=O)=O)CC3)c12
InChIKey: MUQKVPSLHRVESB-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 514.99, ALogP 2.96, HBA 8, HBD 0, PSA 103.5, QED 0.39
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n([C@@H]3CCN(S(C)(=O)=O)C3)c12
InChIKey: QBTZSDNOQVLDBB-MRXNPFEDSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: ELISA Assay: Add 100 μL of sample or standards in Reagent Diluent, or an appropriate diluent, per well. Cover with an adhesive strip and incubate 2 hours at room temperature. Repeat the aspiration/wash as in step 2 of Plate Preparation. Add 100 μL of the Detection Antibody, diluted in Reagent Diluent, to each well. Cover with a new adhesive strip and incubate 2 hours at room temperature. Repeat the aspiration/wash as in step 2 of Plate Preparation. Add 100 μL of the working dilution of Streptavidin-HRP to each well. Cover the plate and incubate for 20 minutes at room temperature. Avoid placing the plate in direct light. Repeat the aspiration/wash as in step 2. Add 100 μL of Substrate Solution to each well. Incubate for 20 minutes at room temperature. Avoid placing the plate in direct light. Add 50 μL of Stop Solution to each well. Gently tap the plate to ensure thorough mixing. Determine the optical density of each well immediately, using a microplate reader set to 450 nm. If wavelength correction is available, set to 540 nm or 570 nm. If wavelength correction is not available, subtract readings at 540 nm or 570 nm from the readings at 450 nm. This subtraction will correct for optical imperfections in the plate. Readings made directly at 450 nm without correction may be higher and less accurate.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 500.96, ALogP 2.57, HBA 8, HBD 0, PSA 103.5, QED 0.4
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n([C@H]3CCN(S(C)(=O)=O)C3)c12
InChIKey: QBTZSDNOQVLDBB-INIZCTEOSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 500.96, ALogP 2.57, HBA 8, HBD 0, PSA 103.5, QED 0.4
Compound (SMILES): CCS(=O)(=O)N1CCC(n2c(=O)n(-c3cccc(Cl)c3)c(=O)c3cnc4c(OC)cccc4c32)CC1
InChIKey: IISWCMIDUMTUPJ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 529.02, ALogP 3.35, HBA 8, HBD 0, PSA 103.5, QED 0.37
Compound (SMILES): COc1cccc2c1ncc1c(=O)n(-c3cccc(Cl)c3)c(=O)n(C3CCN(S(=O)(=O)CS(C)(=O)=O)CC3)c12
InChIKey: SMPOHPYMVGJQOO-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: TR-FRET-Based Phosphodiesterase Assay: A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 593.08, ALogP 2.33, HBA 10, HBD 0, PSA 137.64, QED 0.31
Compound (SMILES): O=c1nc2n(cc1NCc1ccccc1)[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O2
InChIKey: OOTIGCOHBDTXKO-GUIRCDHDSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 331.33, ALogP -0.13, HBA 8, HBD 3, PSA 105.84, QED 0.72
Compound (SMILES): CCOCc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
InChIKey: IVOLNKFVMNSOJV-SDNRWEOFSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 284.27, ALogP -1.21, HBA 8, HBD 2, PSA 103.04, QED 0.71
Compound (SMILES): O=c1nc2n(cc1COCc1ccccc1)[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O2
InChIKey: CLKFFUKGOSPBQS-HGTKMLMNSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 346.34, ALogP -0.03, HBA 8, HBD 2, PSA 103.04, QED 0.78
Compound (SMILES): COCc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
InChIKey: WSIVUJPDBLOOCP-BDNRQGISSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 270.24, ALogP -1.6, HBA 8, HBD 2, PSA 103.04, QED 0.68
Compound (SMILES): CC(=N)OCc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
InChIKey: DQEWYQZILQRCJZ-SDNRWEOFSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 297.27, ALogP -1.23, HBA 9, HBD 3, PSA 126.89, QED 0.47
Compound (SMILES): Cc1cn2c(nc1=O)O[C@H]1[C@H](O)[C@@H](CN=[N+]=[N-])O[C@H]12
InChIKey: SCHUDNUFKXZTFR-JAGXHNFQSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 265.23, ALogP -0.12, HBA 7, HBD 1, PSA 122.34, QED 0.45
Compound (SMILES): Cc1cn2c(nc1=O)O[C@H]1C(O)[C@@H](CF)O[C@H]12
InChIKey: QTKLHMLQXNPHTE-AOXOCZDOSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 242.21, ALogP -0.46, HBA 6, HBD 1, PSA 73.58, QED 0.72