lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2ncnc(N(C)[C@@H]3CCN(c4ncnc5[nH]ccc45)C3)c2cc1OC
InChIKey: NKZDARSZVOPRKB-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzymatic Assay: JAK1/2/3 kinase assay are performed in vitro using Kit-Tyr 6 Peptide (Invitrogen, Cat. No. PV4122). TYK2 kinase assay are performed in vitro using Z′-LYTE Kinase Assay Kit-Tyr 3 Peptide (Invitrogen, Cat. No. PV3192). Recombinant human JAK1/2/3 or TYK2 catalytic domains are from Invitrogen (Cat No. PV4774/PV4210/PV3855/PV4790); All reactions (20 μL) are started by adding 2.5 μL of the testing compound in 4% DMSO solution, 5 μL of Kinase/Peptide substrate Mixture (3.2, 0.04, 0.2 or 8 μg/mL for Recombinant human JAK1/2/3 catalytic domains, 4 μM for Z-LYTE Tyr 6 peptide or Z-LYTE Tyr 3 peptide) or Phospho-Peptide solution (Invitrogen, Cat. No. PV3192, diluted with 1.33× Kinase Buffer), 2.5 μL ATP Solution (300/100/40/100 μM, JAK1/JAK2/JAK3/TYK2) or 1.33× Kinase Buffer (Invitrogen, Cat. No. PV3189, 5× diluted with distilled water). The 384-well assay plate (Corning, Cat. No. 3575) is mixed and incubated at room temperature for 1 hour. 5 μL of the Development Solution (Dilute Development Reagent A (Cat. No. PV3297) is diluted to 1/64 with Development Buffer (Cat. No. PV3127) for JAK1, JAK2 and JAK3 assay; Development Reagent A (Cat. No. PV3297) is diluted to 1/2048 with Development Buffer (Cat. No. PV3127) for TYK2 assay. The diluted Development Solution is then added to each well, mixed and incubated at room temperature for another 1 hour. The kinase reaction is then stopped by adding 5 μL of the Stop Reagent (Invitrogen, Cat. No. PV3094), and the plate is read with Wallac 1420 VICTOR3 Multilabel Counter (PerkinElmer) at 445 nm and 520 nm fluorescence. All compounds are initially tested at 8 different concentrations (1 μM down to 0.0003 μM) using a 1:3 serial dilution scheme.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 405.46, ALogP 2.63, HBA 8, HBD 1, PSA 92.29, QED 0.54
Compound (SMILES): NC(=O)[C@H]1CC[C@H](C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: PPAUGFBGWSYFQG-UAVUOLJFSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human Gal4-fused RORbeta LBD (200 to 559 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 626.57, ALogP 5.31, HBA 4, HBD 1, PSA 97.54, QED 0.35
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(Cl)c(C(F)(F)F)c4)cs3)cccc2n(C)c1=O
InChIKey: GBLKNVFTITUYJG-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 508.91, ALogP 4.21, HBA 7, HBD 1, PSA 85.99, QED 0.45
Compound (SMILES): CCCN1CC[C@H]2c3cc4ccc(C(F)(F)F)cc4nc3[C@H](CC)[C@H]3CCC[C@@H]1[C@@H]32
InChIKey: LILDBTJYRFAMFE-VCSLONGPSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]Way100635 from human 5-HT1A receptor expressed in CHO cells measured after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 416.53, ALogP 6.75, HBA 2, HBD 0, PSA 16.13, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccncc2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SVPYHIXSUHWOCA-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 = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 476.54, ALogP 4.63, HBA 8, HBD 0, PSA 78.19, QED 0.33
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(/C(N)=N/C#N)CCO1
InChIKey: JICNDHPWMNFSTI-UHFFFAOYSA-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 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 502.36, ALogP 3.56, HBA 8, HBD 2, PSA 130.91, QED 0.3
Compound (SMILES): Cc1c(Cc2c(CN(C)CCS(C)(=O)=O)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: VMSCVSQPPSKFDR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to human MTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay
Measurement: Kd = 23442 nM (pChEMBL 4.630000114440918)
Descriptors: MW 540.61, ALogP 2.54, HBA 9, HBD 1, PSA 106.06, QED 0.46
Compound (SMILES): Cn1cc2c(nc(NNC(=S)Nc3ccc(-c4c5ccc(=O)cc-5oc5cc(O)ccc45)c(C(=O)O)c3)n3nc(-c4ccco4)nc23)n1
InChIKey: WNVCMUJTUUNZEO-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-CGS21680 from human adenosine A2A receptor expressed in HEK293 cells by radioligand competition analysis
Measurement: Ki = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 659.64, ALogP 4.87, HBA 13, HBD 5, PSA 197.87, QED 0.09
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(C(F)(F)F)cc3)CC2)C1
InChIKey: TYKHFEPDQWPOMG-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 549.56, ALogP 4.46, HBA 7, HBD 2, PSA 118.76, QED 0.38
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3ccnc(Br)c3)CC2)C1
InChIKey: VIEXTUGLTBXVPQ-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 532.45, ALogP 3.57, HBA 8, HBD 1, PSA 102.55, QED 0.38
Compound (SMILES): CCCc1ccc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(NS(=O)(=O)CCC)c4F)c3c2)cn1
InChIKey: WOLYPRNZKMKQIC-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using CEC as substrate after 15 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.56, ALogP 5.24, HBA 5, HBD 2, PSA 104.81, QED 0.31
Compound (SMILES): Cc1cc(COc2ccc(C(=O)NC[C@@H](C(=O)NO)N3CCCCC3)cc2)c2ccccc2n1
InChIKey: UKKMFRSGWXZXCZ-DEOSSOPVSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13443
Assay: Inhibition Assay: The molecules are tested in dose-response studies on the following enzymes MMP1, MMP3, MMP9, ADAM9 and ADAM10 according to the same protocol as that described for the TACE enzyme in example 28 but with different substrates (MMP R&D system reference: P126-990 and ADAM R&D system reference: ES003).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 462.55, ALogP 3.21, HBA 6, HBD 3, PSA 103.79, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1=CC=NC(=O)C1
InChIKey: OMUDHMBLKINCCX-XXBNENTESA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Activity at human muscarinic acetylcholine receptor M3 transfected in CHO-K1 cells assessed as intracellular calcium levels in presence of acetylcholine by FLIPR assay
Measurement: Ki = 676.08 nM (pChEMBL 6.170000076293945)
Descriptors: MW 489.57, ALogP 4.58, HBA 6, HBD 0, PSA 63.38, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C5CCNCC5)c4)nc3c2)c1
InChIKey: UHPWIGXTFQRPCG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 474.57, ALogP 3.57, HBA 9, HBD 2, PSA 97.56, QED 0.4
Compound (SMILES): FC(F)(F)c1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cn1
InChIKey: DOPMYOXHSDZPKV-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 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 401.4, ALogP 3.4, HBA 6, HBD 1, PSA 75, QED 0.57
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(F)c(C(F)(F)F)c4)cs3)cccc2n(C)c1=O
InChIKey: SEZSWZYJAHZVBQ-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 492.45, ALogP 3.7, HBA 7, HBD 1, PSA 85.99, QED 0.44
Compound (SMILES): COc1ccc(OC)c2c1C[C@H]1c3cc4c(cc3CCN1C2)OCO4
InChIKey: OIKSHMCSVZMXCU-INIZCTEOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Reception Binding Assay: Different concentrations (10^−5 M-10^−11 M) of the compound of the invention and corresponding isotope receptor ligand as well as receptor protein were loaded into the reaction tube and incubated in 30° C. water bath for 60 minutes. The reaction was terminated in a refrigerator. The reaction mixture was put in a Millipore filter (millipore) cell sample collector, filtered through suction filtration using GF/C glass fiber filter paper, and dried. The resulting sample was placed into 0.5 mL tube. 500 μL liquid scintillation fluid was added and intensity of radioactivity was determined by counting. For dopamine D1 receptor: isotope receptor ligands [3H] SCH23390 (85.0 Ci/mmol) (D1-selective, purchased from Amersham Corporation), D1 receptor protein expressed in HEK-293 cells; For D2 dopamine receptor: isotope receptor ligands [3H] Spiperone (77.0 Ci/mmol) (D2-selective, purchased from Amersham Corporation); D2 receptor protein expressed in HEK-293 cells; For 5-HT1A receptor: isotope receptor ligands [3H] 8-OH-DPAT; 5-HT1A receptor protein expressed in HEK-293 cells; For 5-HT2A receptor: isotope receptor ligands [3H]-Ketanserin; 5-HT2A receptor protein expressed in HEK-293 cells.
Measurement: Ki = 485.43 nM (pChEMBL 6.309999942779541)
Descriptors: MW 339.39, ALogP 3.09, HBA 5, HBD 0, PSA 40.16, QED 0.84
Compound (SMILES): CC1Cc2ccccc2N1C(=O)CN1CCO[C@H](COc2cccc(Cl)c2)C1
InChIKey: XRYWJXIFEBMFIK-FZCLLLDFSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Mus musculus
UniProt: P51436
Assay: Radioligand Binding Assay: The detailed experimental protocols for the radioligand and functional receptor assays are available on the NIMH PDSP website at http://pdsp.med.unc.edu/UNC-CH %20Protocol %20Book.pdf. A. Serotonin receptors: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT6 and 5-HT7. Assay Buffer: Standard Binding Buffer (50 mM Tris-HCl, 10 mM MgCl2, 1 mM EDTA, pH 7.4) Membrane Fraction Source: Transiently or stably transfected cell lines (e.g., HEK293, COS, CHO, NIH3T3). Protocol adapted from Roth et al. (1986), J. Pharmacol. Exp. Ther., 238(2): 480-485; and Roth et al. (1994), J. Pharmacol. Exp. Ther., 268(3): 1403-1410. Adrenergic Receptors: alpha1A, alpha1B, alpha2A, alpha2B, alpha2C, beta1, beta2, beta3 Assay Buffers: For alpha1 receptors, alpha1 Binding Buffer (20 mM Tris-HCl, 145 mM NaCl, pH 7.4); for alpha2 receptors, alpha2 Binding Buffer (50 mM Tris-HCl, 5 mM MgCl2, pH 7.7); for beta receptors.
Measurement: Ki = 2394 nM (pChEMBL 5.619999885559082)
Descriptors: MW 400.91, ALogP 3.4, HBA 4, HBD 0, PSA 42.01, QED 0.77
Compound (SMILES): CN(C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)c1ccc(C#N)cc1
InChIKey: AZAMJOCDWNIKMW-QAQDUYKDSA-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 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 385.48, ALogP 3.89, HBA 6, HBD 1, PSA 85.9, QED 0.58
Compound (SMILES): Cc1cc(OC(F)(F)F)ccc1NC1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: MZWOQMOZWLVFBD-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 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 430.43, ALogP 4.95, HBA 6, HBD 2, PSA 80.13, QED 0.48
Compound (SMILES): COc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: BTNQULFFKVGNOL-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 423.45, ALogP 2.76, HBA 8, HBD 2, PSA 96.53, QED 0.45
Compound (SMILES): Cn1c(Nc2c(F)cccc2Cl)nc2cc(C(=O)Nc3cc(F)cc(C(F)(F)F)c3)c3c(c21)OCCO3
InChIKey: HOTSVKDMIYWWIY-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES-1 in human A549 cells assessed as reduction in IL-1beta-induced PGF2alpha production incubated for 24 hrs by enzyme immunoassay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 538.86, ALogP 6.29, HBA 6, HBD 2, PSA 77.41, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCN(C)CC2)n1
InChIKey: IQEZRSQHZBKCOU-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of recombinant human N-terminal His6-tagged EphA2 (N598 to R890 residues) expressed in baculovirus using poly-EY as substrate after 180 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 530.48, ALogP 6.53, HBA 8, HBD 1, PSA 72.4, QED 0.29
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CC3CCC(C2)N3C(=O)c2ccnc(C(F)(F)F)c2)C1
InChIKey: PICIYDGRNWDBPV-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 561.57, ALogP 4, HBA 8, HBD 1, PSA 119.62, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCN)c4)nc3c2)c1
InChIKey: VCNJSFBAEBDCKK-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 4.41, HBA 8, HBD 1, PSA 91.32, QED 0.38
Compound (SMILES): Cn1cc(-c2nc3c(N4CCN(Cc5cccnc5)CC4)c(Br)cnc3[nH]2)cn1
InChIKey: KLCAJPNNJWCSJD-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Assays: Inhibition of CYP isozymes was determined using a mixture of probe substrates. The samples were incubated for 10 minutes followed by protein precipitation with methanol. The substrate metabolites in each sample were measured by LC/MS/MS using reverse-phase liquid chromatography and positive ion mode ESI with multiple reaction monitoring (MRM).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 453.35, ALogP 2.84, HBA 7, HBD 1, PSA 78.76, QED 0.51
Compound (SMILES): O=C1NN=C2CCCc3c2c2c1cccc2n3CCN1CCCC1
InChIKey: ASIFNLNMOYRKGY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Enzymatic Assay: PARP-1 enzymatic assay was conducted using a method modified from HT F Homogeneous PARP Inhibition Assay Kit (Trevigen). 8.8 nM PARP-1 was pre-incubated with different concentrations of compounds in a buffer containing 100 mM Tris-HCl pH 8.0, 100 mM NaCl, 20 mM MgCl2, and 1% DMSO for 30 min at RT. The auto-PARylation reaction was initiated by addition of 500 nM NAD and 20 ng/ul activated DNA (Sigma) and incubated at RT for 40 min. The remaining NAD was detected by incubation with cycling assay solution containing 1% ethanol, 0.30 U/ml alcohol dehydrogenase, 25 uM resazurin, and 0.25 U/ml diaphorase for 50 min at RT. The concentration of NAD is proportional to the fluorescence signal at Ex540 nm/Em 590 nm. The IC50s were calculated based on residual enzyme activity (the rate of NAD decrease) in presence of increasing concentrations of compounds.
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 322.41, ALogP 2.52, HBA 4, HBD 1, PSA 49.63, QED 0.94
Compound (SMILES): COc1nc2ccc(C(C)(O)c3cnnn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
InChIKey: KCEVZBCVYHCXBO-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: 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 1× 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 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 476.89, ALogP 4.89, HBA 6, HBD 1, PSA 73.06, QED 0.44
Compound (SMILES): Cc1oc2c(c1CC(=O)Nc1nc(-c3ccc(C(F)(F)F)c(F)c3F)cs1)c(=O)n(C)c(=O)n2C
InChIKey: MQPVCEGYFVTWDL-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 514.43, ALogP 3.74, HBA 8, HBD 1, PSA 99.13, QED 0.42
Compound (SMILES): Cl.O=C1c2ccc(Cl)cc2CC1CCN1CCc2ccccc2C1
InChIKey: CDKCTEJHUVKKNR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by liquid scintillation counting method
Measurement: Ki = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 325.84, ALogP 4.14, HBA 2, HBD 0, PSA 20.31, QED 0.84
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4c(C)nn(C)c4C)nc3c2)c1
InChIKey: WCHAWRNEALMUFZ-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 4.18, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)Cl)cc1)c1cnc(N2C[C@H](O)[C@@H](O)C2)c(-c2cncnc2)c1
InChIKey: INMCQZXOLSELDJ-ROUUACIJSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL1 (64 to 515 residues)(unknown origin) expressed in Escherichia coli using FITC-Ahx-EAIYAAPFAKKK-NH2 peptide as substrate after 60 mins by caliper assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 477.86, ALogP 2.5, HBA 8, HBD 3, PSA 120.7, QED 0.46
Compound (SMILES): CN(C)c1ccc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)cc1C#N
InChIKey: GCCGLVIEPMZLEX-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 534.63, ALogP 2.99, HBA 9, HBD 1, PSA 133.76, QED 0.4
Compound (SMILES): COc1cc(N2CCN(S(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: NLPVVRIYZYTTIS-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 724.79, ALogP 6.13, HBA 10, HBD 2, PSA 134.06, QED 0.18
Compound (SMILES): CCCCc1cc(N2CCN(CCc3ccc(OCCCN4CCCCCC4)cc3)CC2)c2nc(CCC(=O)O)ccc2c1
InChIKey: JQNSYTMOXNMQTB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human ERG expressed in CHOK1 cell membranes incubated for 4 hrs in dark by luminescent assay
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 600.85, ALogP 6.6, HBA 6, HBD 1, PSA 69.14, QED 0.2
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](C)N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AHWOGVXLWKIELS-OAHLLOKOSA-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 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: JDDJMJIAWGNUGT-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 = 6025.6 nM (pChEMBL 5.21999979019165)
Descriptors: MW 405.46, ALogP 3.56, HBA 7, HBD 2, PSA 96.39, QED 0.46
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(C3(C(=O)O)CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)ncc(F)c2c1
InChIKey: RFKOYFYQZZFWKX-ADXZGYQBSA-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 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 611.67, ALogP 5.86, HBA 7, HBD 4, PSA 146.88, QED 0.22
Compound (SMILES): Cc1c(C)c2c(c(C)c1O)CC(CN1CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC1)C(C)O2
InChIKey: SCUZVSHLJVHGDP-UHFFFAOYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Inhibition of human recombinant DTT-activated caspase-5 expressed in Escherichia coli using Ac-WEHD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 520.72, ALogP 4.07, HBA 8, HBD 1, PSA 68.2, QED 0.63
Compound (SMILES): OC1CCCCCCCNc2ncc3c(-c4ccccn4)cn(c3n2)CCCC1
InChIKey: NGJAXUZGEAUCFH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MerTK (unknown origin) by microfluidic capillary electrophoresis assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 393.54, ALogP 4.79, HBA 6, HBD 2, PSA 75.86, QED 0.62
Compound (SMILES): COc1cc(CCN2CCCCC2)c(F)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: LZLZAMJAYXYMOK-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 677.73, ALogP 7.91, HBA 8, HBD 2, PSA 96.68, QED 0.15
Compound (SMILES): FC(F)(F)c1cc(CN2CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC2)cc(C(F)(F)F)c1
InChIKey: TWGFWBPIHYEITI-UHFFFAOYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Inhibition of human recombinant DTT-activated caspase-5 expressed in Escherichia coli using Ac-WEHD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: Ki = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 528.54, ALogP 5.04, HBA 6, HBD 0, PSA 38.74, QED 0.51
Compound (SMILES): Oc1ccc(-c2ccc3c(/C=C/c4ccccc4)n[nH]c3c2)cc1OCc1ccccc1
InChIKey: XNXRPRVBGWBMQP-RVDMUPIBSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human GST-tagged CDK4/cyclin D1 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 418.5, ALogP 6.68, HBA 3, HBD 2, PSA 58.14, QED 0.32
Compound (SMILES): COCC[C@@H]1C[C@H]1c1cncc(N2CCCNCC2)c1
InChIKey: FTYHMMVUGBYQCJ-CZUORRHYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]epibatidine from rat alpha4beta2 nAChR by liquid scintillation counting
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 275.4, ALogP 2.02, HBA 4, HBD 1, PSA 37.39, QED 0.89
Compound (SMILES): CC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(C(C)(C)C)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN(CC)CC)C(=O)N[C@@H](CO)C(=O)OC
InChIKey: YUNDLGQJZQUDNB-LTLCPEALSA-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 809.06, ALogP 3.4, HBA 9, HBD 6, PSA 195.27, QED 0.07
Compound (SMILES): CC1c2ncn(-c3cnccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: MGIXWTWNCJHXKS-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321 N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250Ã¿ the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate. Cells were incubateÂ  with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 uL/well of BzATP (final concentration is 250 uM BzATP (human and rat) or 600 (mouse)). The fluorescence change was measured 180 seconds after adding the agonist.
Measurement: IC50 = 125.9 nM (pChEMBL 6.900000095367432)
Descriptors: MW 421.81, ALogP 4.09, HBA 5, HBD 0, PSA 63.91, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: NAFMCDLLMRKVNJ-GOSISDBHSA-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 469.55, ALogP 4.02, HBA 8, HBD 1, PSA 103.19, QED 0.41
Compound (SMILES): CO[C@H]1C[C@@H](n2c(=O)n(C)c3cnc4cc(F)c(-c5ccc(OCCCN(C)C)nc5F)cc4c32)C1
InChIKey: GCCDCEIIJOUYDQ-IYBDPMFKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 497.55, ALogP 3.91, HBA 8, HBD 0, PSA 74.41, QED 0.27
Compound (SMILES): CC(c1ccccc1)c1ccc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
InChIKey: BSXBVSWEULDBKN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Homogeneous Time Resolved Fluorescence Assay (HTRF): The assay for the determination of Pim activity is based on the formation of phosphorylated biotinylated-BAD peptide at the Serine 112 residue (S112) and employs HTRF® (homogeneous time resolved fluorescence) technology to detect the product in a 96-well plate format. The phosphorylation of biotinylated-BAD (S112) peptide by full length recombinant Pim-1, Pim-2, or Pim-3 protein was detected with streptavidin:Allophycocyanin (APC) conjugate and a europium (Eu) labeled antibody directed against phosphorylated-BAD (S112). Excitation of Eu by a high energy laser light (337 nm) leads to a transfer of energy to the APC molecule, and results in an emission at 665 nm. The fluorescence is directly proportional to the amount of phosphorylated BAD peptide present in the reaction. Compounds were prepared in DMSO by conducting 3-fold serial dilutions to give a 10-point dosing curve having a high dose of 1 μM. A reference compound was included on each assay plate in order to validate that plate; on one plate of every assay run, two additional reference compounds were included. The final buffer conditions were as follows: 60 mM Hepes, pH 7.0, 0.05% BSA, 2 mM DTT. Incubations were carried out at RT (22° C.) for 2 h for Pim-1, 1 hour and 30 min for Pim-3, and 45 min for Pim-2. The reaction was stopped by the addition of 3 mM EDTA, and fluorescence was measured by an HTRF® Rubystar microplate reader.
Measurement: IC50 = 17.8 nM (pChEMBL 7.75)
Descriptors: MW 367.45, ALogP 4.67, HBA 2, HBD 2, PSA 57.78, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C[Si](C)(C)C)c4)nc3c2)c1
InChIKey: VVKVBFYAFWGFSV-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 487.68
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(C#N)ccc3C#N)CC2)C1
InChIKey: JOGNOKZDYQQWGP-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 533.57, ALogP 3.54, HBA 8, HBD 1, PSA 141.42, QED 0.41
Compound (SMILES): Cc1cc2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2cc1O
InChIKey: FXGCQUWMOXWKQZ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.39, ALogP 2.82, HBA 4, HBD 2, PSA 65.56, QED 0.86
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3c(F)cccn23)n1
InChIKey: WTYLEWGEAKNPLB-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 811.89, ALogP 6.43, HBA 11, HBD 2, PSA 137.3, QED 0.16
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(C(F)(F)F)c(F)c3)CC2)C1
InChIKey: AJXWDVYAVCKCDI-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 552.54, ALogP 4.21, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): COc1cc(C2CCN(C3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VMVAXVQCRBDHOB-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 760.86, ALogP 8.35, HBA 9, HBD 2, PSA 99.92, QED 0.14
Compound (SMILES): N#CCC(=O)N1CCCC(c2ncn3cnc4[nH]ccc4c23)C1
InChIKey: RVHXGUCJVOYTRJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
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 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 308.35, ALogP 1.83, HBA 5, HBD 1, PSA 90.08, QED 0.78
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccccc1)C(=O)NCCCCC[N+](C)(C)C
InChIKey: FCUVIHIUNUOUJE-FMYROPPKSA-O
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 580.79, ALogP 3.06, HBA 4, HBD 4, PSA 116.4, QED 0.17
Compound (SMILES): Cc1ccccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: BSVJKUPXZKILRQ-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 > 10 nM (pChEMBL 8)
Descriptors: MW 495.59, ALogP 3.75, HBA 7, HBD 2, PSA 118.76, QED 0.44
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: JBBAETKDVUXXJY-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 821.95, ALogP 6.37, HBA 12, HBD 2, PSA 137.3, QED 0.14
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MLUFVERLBQGOEV-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 = 6025.6 nM (pChEMBL 5.21999979019165)
Descriptors: MW 419.49, ALogP 3.57, HBA 8, HBD 1, PSA 85.53, QED 0.47
Compound (SMILES): C=CC(=O)Nc1ccc(NS(=O)(=O)c2cccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)c2)cc1
InChIKey: JQBQAGHSJMBPSH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha (R108 to N1068 residues) expressed in mammalian expression system incubated for 60 mins by ADAPTA assay
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 569.65, ALogP 4.81, HBA 8, HBD 3, PSA 136.63, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)no2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HGOIJUTXACYYTH-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 = 5754.4 nM (pChEMBL 5.239999771118164)
Descriptors: MW 456.51, ALogP 4.68, HBA 9, HBD 0, PSA 91.33, QED 0.35
Compound (SMILES): FC(F)(F)c1ccc(NC2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: UPKMVHXRBQYWBB-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 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 400.41, ALogP 4.76, HBA 5, HBD 2, PSA 70.9, QED 0.52
Compound (SMILES): c1ccc(NC2=NC[C@@]3(CN4CCC3CC4)O2)nc1
InChIKey: NWOGQPOGFKBIMN-AWEZNQCLSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Antagonist activity at human 5-HT3A expressed in HEK293 cells assessed as reduction in acetylcholine-induced activity preincubated for 30 mins followed by addition of acetylcholine measured for 2 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 258.32, ALogP 1.34, HBA 5, HBD 1, PSA 49.75, QED 0.83
Compound (SMILES): CCOc1ccc(C[C@@H](NC(=O)c2sccc2N)C(=O)N[C@@H](Cc2cscn2)C(=O)NCc2ccc(CN)cc2)cc1
InChIKey: HDDOGAGGUYGJLQ-FTJBHMTQSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Enzyme Assay: Human serine protease enzymes plasmin, thrombin, trypsin, Factor Xa and Factor XIIa were assayed for enzymatic activity using an appropriate fluorogenic substrate. Protease activity was measured by monitoring the accumulation of liberated fluorescence from the substrate over 5 minutes. The linear rate of fluorescence increase per minute was expressed as percentage (%) activity. The Km for the cleavage of each substrate was determined by standard transformation of the Michaelis-Menten equation.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.77, ALogP 3.03, HBA 9, HBD 5, PSA 161.46, QED 0.15