lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): c1cc2c(ncn3nnc(C4CCCN(Cc5cncs5)C4)c23)[nH]1
InChIKey: FKXBAZKIIGGPFW-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 339.43, ALogP 2.44, HBA 7, HBD 1, PSA 75, QED 0.62
Compound (SMILES): CC(C)(O)c1ccc(N2CCN(c3nnc(Cc4ccc(F)cc4)c4c3CCCC4)CC2)nc1
InChIKey: UJHSHAOTDYEXHM-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Displacement of radio-labeled smoothened agonist from human Smo by radio-ligand competition binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 461.59, ALogP 4.03, HBA 6, HBD 1, PSA 65.38, QED 0.62
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(C(=O)NC4CCCC(O)(C(O)c5ccccc5)C4)cc23)ccn1
InChIKey: KFWTYLMHHSBSTI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: Active ERK2 (aERK) Assay: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 14 μl of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 293.8 nM (pChEMBL 6.53000020980835)
Descriptors: MW 456.55, ALogP 4.07, HBA 5, HBD 4, PSA 111.13, QED 0.36
Compound (SMILES): CCc1c(-c2cnc3ccc(N(CCO)c4cc(OC)cc(OC)c4)cc3n2)cnn1C
InChIKey: QMHOAFNGBZAYPM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 433.51, ALogP 3.74, HBA 8, HBD 1, PSA 85.53, QED 0.45
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cnccn3)CC2)C1
InChIKey: YRHXUFFDQFEJCC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 468.53, ALogP 1.84, HBA 9, HBD 1, PSA 132.51, QED 0.47
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCN(C(c2cocn2)c2cocn2)CC1
InChIKey: UJNMSEISYLPHCA-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MGLL derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 428.29, ALogP 3, HBA 7, HBD 0, PSA 84.84, QED 0.69
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccc4ncnc(N)c4c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: XKKHQLUQSIPLAZ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 539.6, ALogP 4.57, HBA 10, HBD 2, PSA 143.42, QED 0.33
Compound (SMILES): CC(c1cccs1)N(Cc1nc2c(c(=O)[nH]1)COCC2)C(=O)CN1CCC(C(=O)c2ccc(F)cc2)CC1
InChIKey: GNQUPDFWLAMRMB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Biochemical Assay: The autoparsylation activity of the TNKS 1/2 or PARP1/2 enzymes was measured by the liquid chromatography-mass spectrometry (LC/MS) detection of nicotinamide as readout. Compound activity in inhibiting the TNKS and PARP autoparsylation was evaluated by IC50 measurements. In the compound screening assays, the reaction is composed of 5 μL of compound in 8-point serial dilutions with concentrations ranging from 0.0086 to 18.75 μM, 20 nM of purified enzyme, and 250 μM of β-NAD+ in the 1× Assay Buffer. After 60 min incubation at room temperature, the reactions were quenched by the addition of 10 μL of 5× quenching solution (20% formic acid and 500 nM [d]-nicotinamide in water). For the background control wells, 10 μL of the 5× quenching solution per well was added prior to the addition of β-NAD+.
Measurement: IC50 > 19000 nM (pChEMBL 4.7210001945495605)
Descriptors: MW 538.65, ALogP 3.73, HBA 7, HBD 1, PSA 95.6, QED 0.44
Compound (SMILES): Nc1cncc(-c2cn3ccnc3c(Nc3ccc(N4CCN(C5COC5)CC4)cc3)n2)n1
InChIKey: XCIGZBVOUQVIPI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) in macrophages assessed as reduction in immune complex-stimulated IL-1 beta secretion
Measurement: EC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 443.52, ALogP 2.03, HBA 10, HBD 2, PSA 109.73, QED 0.48
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccncc3F)CC2)C1
InChIKey: LHBDJRDLYJGHQC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 502.53, ALogP 3.33, HBA 7, HBD 1, PSA 106.73, QED 0.45
Compound (SMILES): O[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HPMRVSRZBKQEID-KYZUINATSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 0.084 nM (pChEMBL 10.079999923706055)
Descriptors: MW 257.3, ALogP 1.62, HBA 5, HBD 2, PSA 79.1, QED 0.69
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cnn(C)c3)c2c(=O)n1-c1ccccc1
InChIKey: XUMALORDVCFWKV-IBGZPJMESA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes after 5 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 528.58, ALogP 3.24, HBA 9, HBD 2, PSA 125.13, QED 0.34
Compound (SMILES): Cc1c(C(=O)Nc2ccc(Oc3ccnc4cc(OCC(C)(C)O)ccc34)c(F)c2)c(=O)n(-c2ccccc2)n1C
InChIKey: VQYYQSZNRVQLIS-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Kinase Assay: Met (h) is incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 250 μM KKKSPGEYVNIEFG, 10 mM MgAcetate and [γ-33P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 3% phosphoric acid solution. 10 μL of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 556.59, ALogP 5.37, HBA 8, HBD 2, PSA 107.61, QED 0.27
Compound (SMILES): COCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C(C)C)c3)nc2c1
InChIKey: WOMBJJKPVIDFFI-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.57, ALogP 4.24, HBA 9, HBD 1, PSA 94.76, QED 0.36
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cccc(Br)c3)CC2)C1
InChIKey: YYCCMMSVRTTYMR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 545.45, ALogP 3.81, HBA 7, HBD 1, PSA 106.73, QED 0.41
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCS(C)(=O)=O)c3)nc2c1
InChIKey: NXQWBKIKMLKVOS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.62, ALogP 2.91, HBA 10, HBD 1, PSA 111.47, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H]2C[C@H]2c2ccccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JARSMEDYFYAQRJ-UQBPGWFLSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 234.42 nM (pChEMBL 6.630000114440918)
Descriptors: MW 492.58, ALogP 5.38, HBA 8, HBD 0, PSA 78.19, QED 0.29
Compound (SMILES): Nc1c(C(=O)c2cc3cc(CN4CCOCC4)ccc3[nH]2)cnn1-c1cc(O)ccc1Cl
InChIKey: IWBVZILESKBVJL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 by time-resolved fluorescence or time-resolved fluorescence assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 451.91, ALogP 3.36, HBA 7, HBD 3, PSA 109.4, QED 0.4
Compound (SMILES): CC(C)[C@H](Nc1nc(Cl)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(CO)C[C@H]12)C1CC1
InChIKey: PSZUVLHNNPZVCD-ADZAWSABSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3 H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine from recombinant human adenosine receptor A2A expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 1520 nM (pChEMBL 5.820000171661377)
Descriptors: MW 407.9, ALogP 1.6, HBA 8, HBD 4, PSA 116.32, QED 0.54
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3nc(C(F)(F)F)cs3)CC2)C1
InChIKey: UCKYWCHSEKLWSK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 540.58, ALogP 4.13, HBA 8, HBD 1, PSA 106.73, QED 0.41
Compound (SMILES): COc1cccc(NC(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c1
InChIKey: XPMOPMQZEWJIKU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 511.59, ALogP 3.45, HBA 8, HBD 2, PSA 127.99, QED 0.41
Compound (SMILES): C[C@H](Oc1cc(C(=O)NC(c2noc(N)n2)C(C)(C)C)ncc1C1CC1)C(F)(F)F
InChIKey: SPCIZGDSHYOPNO-CUVJYRNJSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1×HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37° C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30° C. for 30 min. Compounds were added to a final assay volume of 100 μl and incubated for 30 min at 30° C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 μl lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN3) and 50 μl detection solutions (20 μM mAb Alexa700-cAMP 1:1, and 48 μM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated as follows: FRET=T730-Alexa730-P(T645-B645) with P=Ru730-B730/Ru645-B645, where T730 is the test well measured at 730 nM, T645 is the test well measured at 645 nm, B730 and B645 are the buffer controls at 730 nm and 645 nm, respectively. cAMP content is determined from the function of a standard curve spanning from 10 μM to 0.13 nM cAMP.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.43, ALogP 3.77, HBA 7, HBD 2, PSA 116.16, QED 0.72
Compound (SMILES): CCOc1ccc(-c2nc3ccccn3c2-c2ccnc(Nc3ccc(N4CCC(N5CCCCC5)CC4)c(C)c3OC)n2)cc1C(=O)Nc1c(F)cccc1F
InChIKey: NQBOWNPIRYVPJI-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 772.9, ALogP 8.9, HBA 10, HBD 2, PSA 109.15, QED 0.13
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C3(C(=O)O)CCCC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: AFGGMWNLRYRQDA-JCOAXYOVSA-N
Target: Vitamin K-dependent protein C (SINGLE PROTEIN), Homo sapiens
UniProt: P04070
Assay: Inhibition of activated protein C (unknown origin) at 37 degC by chromogenic substrate assay
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 639.73, ALogP 6.64, HBA 7, HBD 4, PSA 146.88, QED 0.19
Compound (SMILES): CC(C)COC(=O)[C@H](Cn1ccnc1)NC(=O)c1ccc(-c2ccccc2F)cc1
InChIKey: HNWAOXQUAXIEIQ-NRFANRHFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins followed by NADPH addition measured after 10 mins by LC/MS/MS method
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 409.46, ALogP 3.69, HBA 5, HBD 1, PSA 73.22, QED 0.58
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cc5ccccc5[nH]4)c3n2)c1
InChIKey: VLGNIXMNEJONBN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: In Vitro Inhibition Assay: ITK and JAK3 Kinase assay procedures:Enzyme was incubated with substrate peptide in reaction buffer in the presence and absence of test compounds or Staurosporine. All additions were done on ice, followed by the addition of ATP mix. Wells were uniformly mixed using an Eppendorff plate shaker and incubated at 30° C. for 20 min, and stopped by the addition of 5 μL of 3% phosphoric acid. Volume was increased to 100 μL by adding 0.8% phosphoric acid which was then transferred to PC filter mats (Millipore), pre-equilibrated with 70% ethanol and water. Plates were washed thrice with 100 μL 0.8% phosphoric acid and dried for an hour at 60° C. 100 μL scintillation fluid was added into each well and reading taken in Perkin Elmer TOPCOUNT beta counter. The data analysis was performed by averaging the duplicate top count readings for each standard, negative, positive control (enzyme control) and samples and subtracting the average negative control from each reading which results in corrected values.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 379.42, ALogP 4.9, HBA 3, HBD 3, PSA 86.46, QED 0.39
Compound (SMILES): Cn1cncc1C(O)(c1ccc(C(F)(F)F)nc1)c1ccc2nc(N3CCC3)c(Oc3ccc(Cl)cc3)c(Cl)c2c1
InChIKey: MDPNKAIDFYRNEN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORγt Reporter Assay: The reporter assay was performed by transiently transfecting HEK293T cells with 5 μg of pBIND-RORγt LBD or pBIND-RORγt LBD-AF2 and 5 μg pGL4.31 (Promega Cat no. C935A) using Fugene 6 (Invitrogen Cat no. E2691) at a 1:6 ratio of DNA: Fugene 6 in a T-75 flask in which cells were at least 80% confluent. Twenty four hours after bulk transfection, cells were plated into 96-well plates at 50,000 cells/well in phenol-red free DMEM containing 5% Lipid Reduced FCS and Pen/Strep. Six hours after plating, cells were treated with compounds for 24 hours. Media was removed and cells were lysed with 50 μL 1x Glo Lysis Buffer (Promega). Dual Glo Luciferase Reagent (50 μL/well) was then added and firefly luciferase luminescence was read on an Envision after a ten minute incubation. Finally, Stop and Glo reagent (50 μL/well) was added and renilla luciferase luminescence was read on an Envision after a ten minute incubation.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 600.43, ALogP 6.98, HBA 7, HBD 1, PSA 76.3, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CC(NC(C)C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: OKTZBKLVRWLMBJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 488.64, ALogP 5.21, HBA 8, HBD 1, PSA 77.33, QED 0.33
Compound (SMILES): COc1cc(N2CCC(N3CCC[C@H](O)C3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: CNCUAAFKKXICSP-LJAQVGFWSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 760.85, ALogP 7.18, HBA 11, HBD 3, PSA 129.38, QED 0.13
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4cc(F)cc(C(F)(F)F)c4)cs3)nsc2n(C)c1=O
InChIKey: ODCGQSLLUGLMSU-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.47, ALogP 3.16, HBA 9, HBD 1, PSA 98.88, QED 0.44
Compound (SMILES): Fc1ccc(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: CDSUCRDXPZEYSK-KOMQPUFPSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 378.45, ALogP 3.81, HBA 5, HBD 2, PSA 70.9, QED 0.55
Compound (SMILES): CN(C)c1cccc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: ZNDKJNBPORYMQR-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 398.51, ALogP 4.64, HBA 6, HBD 0, PSA 50.08, QED 0.47
Compound (SMILES): Cc1nc(NCCCCCC(=O)NO)cc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)n1
InChIKey: MODCVOUAMASASZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of Lyn (unknown origin)
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 504.02, ALogP 4.68, HBA 9, HBD 5, PSA 141.16, QED 0.14
Compound (SMILES): CC1(C)CC2=NNC(=O)c3cccc4c3c2c(n4CCN2CCCCC2)C1
InChIKey: LNWPRZVIPZXIHL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O2
Measurement: EC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 364.49, ALogP 3.55, HBA 4, HBD 1, PSA 49.63, QED 0.91
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCN(C(=O)OC(C)(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.O=C(O)C(=O)O
InChIKey: NXLVPTVLMOJPJY-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 598.7, ALogP 4.95, HBA 10, HBD 1, PSA 115.07, QED 0.31
Compound (SMILES): CN(C)CCOc1cccc(Nc2nccc(-c3c(-c4cccc(C(=O)Nc5cc(C(F)(F)F)ccc5F)c4)nc4ccccn34)n2)c1
InChIKey: ZQOJOCBLMULSIQ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 655.66, ALogP 7.55, HBA 8, HBD 2, PSA 96.68, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(F)c(F)c(F)c3F)CC2)C1
InChIKey: DUOSIBBDSXMIMY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 538.51, ALogP 3.61, HBA 7, HBD 1, PSA 106.73, QED 0.24
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cnc(SC)nc4)cc23)c1F
InChIKey: YHJWUNOHRFFMNE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 503.56, ALogP 4.4, HBA 7, HBD 2, PSA 117.7, QED 0.21
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3N3CCN(C)CC3)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2F
InChIKey: UIBFVYOIDXCKPI-YPWPWMHZSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 564.45, ALogP 4.32, HBA 9, HBD 1, PSA 81.21, QED 0.47
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1noc(C2CCCNC2)n1
InChIKey: SHKAUSIXYOWPKS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 501.37, ALogP 5.12, HBA 9, HBD 2, PSA 107.22, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JRDGKLCLEFCXSH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 7079.46 nM (pChEMBL 5.150000095367432)
Descriptors: MW 476.54, ALogP 4.63, HBA 8, HBD 0, PSA 78.19, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NRHOUXIOIPPPMR-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 458.57, ALogP 4.28, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C2COC2)c1
InChIKey: ONSIKNVJAKVKOG-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 7413.1 nM (pChEMBL 5.130000114440918)
Descriptors: MW 417.47, ALogP 3.58, HBA 8, HBD 0, PSA 74.53, QED 0.47
Compound (SMILES): Cc1ccc(NC(=O)c2ccnc(C(C)(C)C#N)c2)cc1-c1cc(N2CCOCC2)ncn1
InChIKey: FYGPVPWZKUOBTA-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Activity Assay: C-Raf TR refers to a truncated C-Raf protein, a Δ1-324 deletion mutant.C-Raf FL refers to the full-length C-Raf protein.Full length MEK1 with an inactivating K97R ATP binding site mutation is utilized as a RAF substrate. The MEK1 cDNA was subcloned with an N-terminal (his)6 tag into a vector for E. Coli expression. The MEK1 substrate was purified from E. Coli lysate by nickel affinity chromatography followed by anion exchange. The final MEK1 preparation was biotinylated (Pierce EZ-Link Sulfo-NHS-LC-Biotin) and concentrated.Assay MaterialsAssay buffer: 50 mM Tris, pH 7.5, 15 mM MgCl2, 0.01% Bovine Serum Albumin (BSA), 1 mM dithiothreitol (DTT)Stop buffer: 60 mM ethylenediaminetetraacetic acid (EDTA), 0.01% Tween® 20b-Raf(V600E), activebiotinylated Mek, kinase deadAlpha Screen detection kit (available from PerkinElmer, #6760617R)Anti phospho-MEK1/2 (available from Cell Signaling Technology, Inc. #9121)384 well low volume assay plates (White Greiner® plates)Assay Conditionsb-Raf(V600E) approximately 4 μMc-Raf approximately 4 nMbiotinylated Mek, Kinase dead approximately 10 nMATP 10 μM for BRAF(V600E) and 1 uM for CRAFPre-incubation time with compounds 60 minutes at room temperatureReaction time 1 or 3 hours at room temperatureAssay ProtocolRaf and biotinylated Mek, kinase dead, were combined at 2× final concentrations in assay buffer (50 mM Tris, pH 7.5, 15 mM MgCl2, 0.01% BSA and 1 mM DTT) and dispensed 5 ml per well in assay plates (Greiner white 384 well assay plates #781207) containing 0.25 ml of 40× of a Raf kinase inhibitor test compound diluted in 100% DMSO. The plate was incubated for 60 minutes at room temperature.The Raf kinase activity reaction was started by the addition of 5 mL per well of 2×ATP diluted in assay buffer. After 3 hours (b-Raf(V600E)) or 1 hour (c-Raf). The reactions were stopped and the phosphorylated product was measured using a rabbit anti-p-MEK (Cell Signaling, #9121) antibody and the Alpha Screen IgG (ProteinA) detection Kit (PerkinElmer #6760617R), by the addition of 10 mL to the well of a mixture of the antibody (1:2000 dilution) and detection beads (1:2000 dilution of both beads) in Stop/bead buffer (25 mM EDTA, 50 mM Tris, pH 7.5, 0.01% Tween20). The additions were carried out under dark conditions to protect the detection beads from light. A lid was placed on top of the plate and incubated for 1 hour at room temperature, then the luminescence was read on a PerkinElmer Envision instrument. The concentration of each compound for 50% inhibition (IC50) was calculated b
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 442.52, ALogP 3.74, HBA 7, HBD 1, PSA 104.03, QED 0.64
Compound (SMILES): Cc1ccc(-c2csc(NC(=O)Cc3cccc4c3c(=O)n(C)c(=O)n4C)n2)cc1
InChIKey: NNNQVSUPWVEWSZ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 420.49, ALogP 2.85, HBA 7, HBD 1, PSA 85.99, QED 0.55
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1cncc(C(F)(F)F)c1
InChIKey: CJDXCNMXBFZNDX-VIFPVBQESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 501.86, ALogP 3.45, HBA 10, HBD 3, PSA 161.42, QED 0.38
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CCC(=O)NCC[C@@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(N)=O)NC1=O
InChIKey: JXWMBIOMMZLSIR-IOQDMCFNSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: cAMP Assay: Accumulation of intracellular cAMP was examined as a measure of the ability of the peptides of the present invention to elicit a functional response in a human melanoma cell line, HBL, that express hMCR-1 (see Kang, L., et al., A selective small molecule agonist of melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice, J. Leuk. Biol. 80:897-904 (2006)) or HEK-293 cells that express hMCR-4. Confluent HBL cells that express hMCR-1 or HEK-293 cells that express recombinant hMCR-4 were detached from culture plates by incubation in enzyme-free cell dissociation buffer. Dispersed cells were suspended in Earle's Balanced Salt Solution containing 10 mM HEPES (pH 7.5), 1 mM MgCl2, 1 mM glutamine, 0.5% albumin and 0.3 mM 3-isobutyl-1-methyl-xanthine (IBMX), a phosphodiesterase inhibitor. The cells were plated in 96-well plates at a density of 0.4Ã¿105 cells per well for HBL cells and 0.5x105 cells per well for HEK-293 cells and pre-incubated for 10 minutes. Cells were exposed for 15 minutes at 37° C. to peptides of the present invention dissolved in DMSO (final DMSO concentration of 1%) at a concentration range of 0.05-5000 nM in a total assay volume of 200 uL. NDP-α-MSH was used as the reference agonist. cAMP levels were determined by an HTRF cAMP cell-based assay system from Cisbio Bioassays utilizing cryptate-labeled anti-cAMP and d2-labeled cAMP, with plates read on a Perkin-Elmer Victor plate reader at 665 and 620 nM. Data analysis was performed by nonlinear regression analysis with Graph-Pad Prism software. Maximum efficacy (Emax) values were determined for each test peptide of the present invention, compared to that achieved by the reference melanocortin agonist NDP-α-MSH.
Measurement: EC50 = 0.065 nM (pChEMBL 10.1899995803833)
Descriptors: MW 1030.2
Compound (SMILES): COc1cc(OCCO)cc(N(CCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: UWEWBDWQUZMSKJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.5, ALogP 2.51, HBA 9, HBD 2, PSA 111.55, QED 0.41
Compound (SMILES): COC(=O)[C@H](CO)NC(=O)[C@H](CCCCN1CCCCCC1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)c1ccccc1
InChIKey: IAUNQJODSCIDIR-WMUVQLMLSA-N
Target: Chromobox protein homolog 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P45973
Assay: Antagonist activity at recombinant human N-terminal His-tagged CBX5 chromodomain (18 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using ARTKQTARK(Me3)STGGKAPRKQL-K(Biotin)-NH2 measured after 30 mins by AlphaScreen assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 822.02, ALogP 1.36, HBA 10, HBD 7, PSA 224.37, QED 0.06
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: HFEQYAZFGMQKFJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 552.54, ALogP 4.21, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): Cc1nc(N2Cc3cn(-c4cccc(S(C)(=O)=O)c4)nc3[C@H]2C(C)C)cc(C(F)(F)F)n1
InChIKey: IGGSXCWSHVYVMA-HXUWFJFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 21100 nM (pChEMBL 4.679999828338623)
Descriptors: MW 465.5, ALogP 4.11, HBA 7, HBD 0, PSA 80.98, QED 0.58
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: PTJOSDRUWHLFGF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 342.4, ALogP 2.72, HBA 6, HBD 1, PSA 88.41, QED 0.73
Compound (SMILES): COc1cc(OC)cc(N(CC(O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SBMUXRCSESCJIO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.54, ALogP 4.2, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): COCCn1cc(-c2cnc3ccc(N(Cc4cc(C)no4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: SYVJHJOWIMUQMA-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 500.56, ALogP 4.79, HBA 10, HBD 0, PSA 100.56, QED 0.27
Compound (SMILES): CC(C)Oc1ccc(Nc2nc(=O)n(CC(C)(C)C(=O)O)c(=O)n2Cc2ccc(Cl)cc2)cc1F
InChIKey: CAYYASMSWISXDA-UHFFFAOYSA-N
Target: P2X purinoceptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99571
Assay: Antagonist activity at human P2X4 receptor expressed in rat C6-BU-1 cells
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 504.95, ALogP 3.89, HBA 8, HBD 2, PSA 115.45, QED 0.45
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(CCCOC)cc4)cc23)c1F
InChIKey: ZMIRSJROOOVBFH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 527.59, ALogP 5.47, HBA 5, HBD 2, PSA 101.15, QED 0.2
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CC(=O)NCCO)c4)nc3c2)c1
InChIKey: WAKJUGXHBUNUIT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.58, ALogP 3.17, HBA 9, HBD 2, PSA 114.63, QED 0.32
Compound (SMILES): COc1cc(N2CCC(OC)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: KIIVREBRPAALRW-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 661.71, ALogP 7.36, HBA 9, HBD 2, PSA 105.91, QED 0.17
Compound (SMILES): Cc1ccc(S(=O)(=O)[C@@]2(c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)CCN(C(=O)[C@H]3CC[C@H](C(=O)O)CC3)C2)cc1
InChIKey: PSNZDXCQJULFRM-MHPIHPPYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXRbeta (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 623.59, ALogP 6.08, HBA 4, HBD 1, PSA 91.75, QED 0.39
Compound (SMILES): O=C(COc1ccc2cc(C(O)(C(F)(F)F)C(F)(F)F)c(O)cc2c1)N1c2ccccc2Sc2ccccc21
InChIKey: VHRWHERHGHJJJL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of recombinant FAP1 (unknown origin) using pNPP as substrate by spectrophotometric method
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 565.49, ALogP 7.07, HBA 5, HBD 2, PSA 70, QED 0.26
Compound (SMILES): CNc1nc2ccccc2n1-c1nc2c(c(C(C)(C)S(C)(=O)=O)n1)OC[C@@H]1COCCN21
InChIKey: JEWXHIMACGOZFL-ZDUSSCGKSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Luciferase-Based P450-Glo Assay: Five CYP isoforms (0.5 pmol) were tested, namely 1A2, 2C9, 2C19, 2D6 and 3A4 (each isoform was assayed in a separate assay plate). Each assay plate contained several compounds at 2 concentrations (10 uM and 1 uM), with 2 replicates at each concentration or a small number of compounds per plate in dose response by duplicate (50, 16.5, 5.4, 1.8, 0.6, 0.2, 0.066, 0.022, 0.007 uM). In addition, each assay plate contained 8 different concentrations of an isoform-specific inhibitor (Furafylline, Sulfaphenazole, N-3-benzylnirvanol, Quinidine and Ketoconazole as inhibitors of CYP 1A2, 2C9, 2C19, 2D6 and 3A4, respectively), with two replicates at each concentration. The test compounds and the reference inhibitors were tested at a final DMSO concentration of 0.5%. The assay plate included also 8 replicates a vehicle control containing 0.5% DMSO/H2O. The membranes containing the CYPs, test compound and the probe substrate were pre-incubated 10 min at 37°C. in the absence of NADPH, NADPH was then added following incubation for 60 minutes at 37°C., the reaction was terminated by the addition of Luciferin detection reagent. After 20 min incubation at 37°C., the assay plate was read in the Envision 2104 Multilable reader. Values were normalized against the control activity included for each CYP. These values were plotted against the inhibitor concentration and were fitted to a sigmoid dose-response curve by using the model sigmoidal Four-Parameter Logistc inplement for Activity baseÂ  software.
Measurement: IC50 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 458.54, ALogP 1.73, HBA 10, HBD 1, PSA 111.47, QED 0.62