lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1c[nH]c2nccc(-c3ccn(CN4CCOCC4)c3)c12
InChIKey: PSCIVEPEARWYTD-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LanthaScreen Kinase Activity Assay: In the assay, 1 nM LRRK2 WT or 250 pM LRRK2 G2019S kinase is incubated with the test compound (typically at 0 to 30 μM) for 30 minutes before the kinase reaction is initiated by addition of 1.3 mM ATP and 0.4 μM fluorescein-LRRKtide. The reaction mixture (20 μl total volume) is incubated for 2 hours at 30° C. before the reaction is terminated by addition of 10 mM EDTA and 1 nM terbium-labelled anti-phospho-LRRKtide antibody (final volume 20 μl). The mixture is further incubated for 30 minutes at RT. TR-FRET is measured by excitation of the terbium-donor with 340 nm light and subsequent (delay time 100 μs) measurement of terbium and fluorescein emission at 495 nm and 520 nm, respectively, over a time window of 1000 μs. The measurement is repeated 10 times for fluorescein and 10 times for terbium emission with a 2000 μs time window between repeats. TR-FRET measurements are performed on a Biomek Synergy plate. The TR-FRET signal is calculated as the emission-ratio at 520 nm over 495 nm.
Measurement: EC50 = 3868 nM (pChEMBL 5.409999847412109)
Descriptors: MW 307.36, ALogP 2.19, HBA 5, HBD 1, PSA 69.87, QED 0.81
Compound (SMILES): CO[C@H]1CC[C@H](n2c(=O)n(C)c3cnc4ccc(-c5ccc(OCCCN(C)C)nc5)cc4c32)C1
InChIKey: ZPOCWOPPQUMNCW-SFTDATJTSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Cellular Assay: Assay d) MDA-MB-468 cells (human breast adenocarcinoma ##ATCC HTB 132) were seeded at 1500 cells/well in 40 μl of DMEM containing 10% FBS and 1% glutamine into Greiner 384 well black flat-bottomed plates. Cell plates were incubated for 18 h in a 37° C. incubator before dosing with compounds of formula (I) in 100% DMSO using acoustic dispensing. Compounds were dosed in a 12 point concentration range into a randomised plate map. Control wells were generated either by dosing of 100% DMSO (max signal) or addition of a reference compound (a PI3K-β inhibitor) that completely eliminated the pAKT signal (min control). Plates were incubated, at 37° C. for 2 h, cells were then fixed by the addition of 10 μl of a 3.7% formaldehyde solution. After 30 minutes the plates were washed with PBS using a Tecan PW384 plate washer. Wells were blocked and cells permeabilised with the addition of 40 μl of PBS containing 0.5% Tween20 and 1% Marvel™ (dried milk powder) and incubated for 60 minutes at r.t. The plates were washed with PBS containing 0.5% (v/v) Tween20 and 20 μl rabbit anti-phospho AKT Ser473 (Cell Signalling Technologies, #3787) in same PBS-Tween+1% Marvel™ was added and incubated overnight at 4° C. Plates were washed 3 times with PBS 0.05% Tween 20 using a Tecan PW384. 20 μl of secondary antibody Alexa Fluor 488 anti-Rabbit (Molecular Probes, #A11008) diluted in PBS+0.05% Tween20 containing 1% Marvel™ was added to each well and incubated for 1 h at r.t. Plates were washed three times as before then 20 μl PBS added to each well and plates sealed with a black plate sealer. The plates were read on an Acumen plate reader as soon as possible, measuring green fluorescence after excitation with 488 nm laser.
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 475.59, ALogP 4.02, HBA 8, HBD 0, PSA 74.41, QED 0.36
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(CN4CCOCC4)cc3)cc3c2C(C)CN3C2CCCC2)c(=O)[nH]1
InChIKey: QHNITKGBPYIHKK-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of human EZH2 Y641F mutant using histone H3 as substrate after 1 hr in presence of 3H-SAM by filter paper detection analysis
Measurement: IC50 = 902 nM (pChEMBL 6.039999961853027)
Descriptors: MW 554.74, ALogP 5.29, HBA 5, HBD 2, PSA 77.67, QED 0.42
Compound (SMILES): NC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: WCGABIDAIIRVAW-MGCOHNPYSA-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 = 180 nM (pChEMBL 6.75)
Descriptors: MW 270.34, ALogP 1.84, HBA 5, HBD 2, PSA 84.89, QED 0.74
Compound (SMILES): COc1cc(OC)cc(N(C/C=C\c2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MCUVUHFGOBRXMR-SREVYHEPSA-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 508.58, ALogP 5.3, HBA 9, HBD 0, PSA 87.42, QED 0.27
Compound (SMILES): COc1cc(F)c2c(C(=O)OCC34CCN(CC3)CC4)c[nH]c2c1
InChIKey: YPPSEWNWWBLHPK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 332.38, ALogP 2.96, HBA 4, HBD 1, PSA 54.56, QED 0.87
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2cc1NC(=O)/C=C/CN1CCCC1
InChIKey: NYCRPERPKUAEHF-DHZHZOJOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 547.66, ALogP 5.76, HBA 8, HBD 2, PSA 97.2, QED 0.21
Compound (SMILES): CCOC(=O)N[C@H]1CC[C@@H](CCN2CCN(c3nsc4ccccc34)CC2)CC1
InChIKey: BYJLEOXPONSXOY-HDICACEKSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from recombinant human 5-HT2A receptor expressed in HEK293 cell membranes after 60 mins by scintillation counting method
Measurement: Ki = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 416.59, ALogP 4.11, HBA 6, HBD 1, PSA 57.7, QED 0.77
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(N2CCOCC2)n1
InChIKey: ZHMULGIXCIACTQ-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
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 518.43, ALogP 5.56, HBA 9, HBD 1, PSA 81.63, QED 0.34
Compound (SMILES): Cc1ccc(OCCN(C)C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: LZYYNJHSXYSINQ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 619.68, ALogP 6.98, HBA 8, HBD 2, PSA 96.68, QED 0.17
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: LUDUMCCMFRYVOR-ZYELEKFWSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Inhibition of anti-CXCR4 PE antibody clone 12G5 binding to CXCR4 in human CCRF-CEM cells preincubated for 30 mins followed by anti-CXCR4 PE antibody clone 12G5 addition measured after 30 mins by flow cytometric method
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 942.14, ALogP -2.09, HBA 12, HBD 14, PSA 364.8, QED 0.03
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2cnccn2)CN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: FYUUGCZPBDIVNB-JTQLQIEISA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human recombinant P2X7 expressed in 1321N1 cells assessed as inhibition of BzATP-induced calcium mobilization after 30 mins by calcium-4 staining based FLIPR assay
Measurement: IC50 = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 422.8, ALogP 3.32, HBA 6, HBD 0, PSA 76.8, QED 0.63
Compound (SMILES): Cc1cccc2cc([C@H](C)Nc3ncnc4[nH]cc(Br)c34)n(C3CC3)c(=O)c12
InChIKey: RHAFIPJCZAUEQH-LBPRGKRZSA-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 < 100 nM (pChEMBL 7)
Descriptors: MW 438.33, ALogP 4.85, HBA 5, HBD 2, PSA 75.6, QED 0.48
Compound (SMILES): COc1cc(OC)cc(N(CCNC2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CZKFBZFMVHZPQK-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 472.59, ALogP 4.72, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4COCc4ccc(Cl)c(Cl)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: WDFSHXFIISIKKK-SETZDUAMSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Binding Assay: Binding assay of certain compounds of this invention to the opioid receptor was determine using radioligand binding assay (screening and dose-displacement).
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 570.56, ALogP 6.44, HBA 5, HBD 0, PSA 40.16, QED 0.37
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OCC1CN(C)CCO1
InChIKey: WWKIMALVSPDSCC-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human N-terminal GST His6-tagged thrombin cleavage site-fused ErbB2 kinase domain (Q679 to V1255 residues) expressed in baculovirus infected insect Sf9 cells using biotinylated poly-EY as substrate after 60 mins by alphascreen assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 511.78, ALogP 4.65, HBA 7, HBD 1, PSA 68.74, QED 0.48
Compound (SMILES): C=CC(=O)Nc1cccc(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)c1
InChIKey: DWCINJSURHVICU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells preincubated for 1 hr followed by Biotin-AVLESEEELYSSARQ-NH2 substrate addition in presence of ATP and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 479.54, ALogP 4.97, HBA 6, HBD 3, PSA 111.27, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C(N)=O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YXAFWGPKAAKJHB-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 519.57, ALogP 3.73, HBA 9, HBD 1, PSA 121.28, QED 0.32
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(CCN5CCNCC5)c4)nc3c2)c1
InChIKey: KYDPEBSICGOHJT-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 = 7762.47 nM (pChEMBL 5.110000133514404)
Descriptors: MW 570.72, ALogP 4.52, HBA 11, HBD 1, PSA 93.46, QED 0.26
Compound (SMILES): CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@H]4NCC(=O)N(C)C)no2)cc1C#N.Cl
InChIKey: IANYXLDHLUODAK-ZMBIFBSDSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 expressed in bla TANGO U2OS cells assessed as inhibition of cAMP formation preincubated for 4 hrs followed by FRET-based beta-lactamase fluorescent substrate addition measured after 2 hrs
Measurement: EC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 445.52, ALogP 3.73, HBA 7, HBD 1, PSA 104.28, QED 0.59
Compound (SMILES): COc1cc(OC)cc(N(CCn2cccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XPKLWQVCOXZZKV-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 455.52, ALogP 4.08, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): CCc1ccc(/N=C2\S/C(=C\c3ccnc(Nc4ccc(C(=O)O)cn4)c3)C(=O)N2C)cc1
InChIKey: ZJQWORQRPDYKRS-KGQWDEOMSA-N
Target: Death-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIK4
Assay: Binding affinity to human DAPK2 expressed in Escherichia coli BL21 cells incubated for 1 hr by active site directed binding competition assay
Measurement: Kd = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 459.53, ALogP 4.71, HBA 7, HBD 2, PSA 107.78, QED 0.51
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cccc(-c2cnc3[nH]cc(Cl)c3c2)c1
InChIKey: QLAKLVIXUIVHNO-QPJJXVBHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 354.84, ALogP 3.94, HBA 3, HBD 2, PSA 61.02, QED 0.68
Compound (SMILES): CCOC(=O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: YVNMVJWJGAAQLE-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 447.5, ALogP 3.75, HBA 9, HBD 0, PSA 91.6, QED 0.38
Compound (SMILES): NC/C(=C/F)COc1ccc(C(N)=O)cc1
InChIKey: CUIDJRZBPVHOGV-YVMONPNESA-N
Target: Diamine oxidase [copper-containing] (SINGLE PROTEIN), Homo sapiens
UniProt: P19801
Assay: DAO Inhibition Assay: Recombinant human DAO (2.4 μg/mL) was used as source of DAO enzyme activities. The assay was performed as described in the method for human SSAO/VAP-1 (Example 5) except the substrate used was 200 μM putrescine, and the control wells contained 10 μM aminoguanidine instead of Mofegiline: Briefly, in a standard 96 well plate assay 50 μL of purified human SSAO/VAP-1 (0.25 μg/mL) in 0.1 M NaPO4 buffer (pH 7.4) was added into each well. Test compounds were dissolved in DMSO and tested in a Concentration Response Curve (CRC) with 4-9 data points, typically in the micromolar or nanomolar range after incubation with human SSAO/VAP-1 for 30 min at 37 °C. After 30 min incubation, 50 μL of the reaction mixture containing 600 μM benzylamine (Sigma Aldrich), 120 μM Amplex Red (Sigma Aldrich) and 1.5 U/mL horseradish peroxidase (Sigma Aldrich) prepared in 0.1 M NaPO4 buffer (pH 7.4) were added to the corresponding well. The fluorescence unit (RFU) was read every 2.5 min for 30 min at 37 °C. excitation 565 nm and emission 590 (Optima; BMG labtech). The slope of the kinetics for each well was calculated using MARS data analysis software (BMG labtech) and this value was used to deduce the IC50 value (Dotmatics).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 224.24, ALogP 0.98, HBA 3, HBD 2, PSA 78.34, QED 0.78
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3cc4ccccc4o3)CC2)C1
InChIKey: NDRFHXUVPHBSHC-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 492.59, ALogP 4.16, HBA 8, HBD 1, PSA 102.8, QED 0.38
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3C)ncnc2cc1OCC1CN(C)CCO1
InChIKey: JRGYGHIKWBYTFJ-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 7.300000190734863)
Descriptors: MW 463.37, ALogP 4.71, HBA 7, HBD 1, PSA 68.74, QED 0.57
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(OC([2H])([2H])[2H])cc(N(CCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MLUFVERLBQGOEV-XERRXZQWSA-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 419.49, ALogP 3.57, HBA 8, HBD 1, PSA 85.53, QED 0.47
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3cncs3)c2c(=O)n1-c1ccccc1
InChIKey: VLBCDBMQYLNSLY-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition Assays: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110δ/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration of 10 or 100 μM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 531.6, ALogP 3.96, HBA 9, HBD 2, PSA 120.2, QED 0.33
Compound (SMILES): CN1CCN(C/C=C/C(=O)Nc2cc3c(Nc4ccc(Cc5ccccn5)cc4)ncnc3cn2)CC1
InChIKey: NBXCNCMWLZADMG-GQCTYLIASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 494.6, ALogP 3.5, HBA 8, HBD 2, PSA 99.17, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(Cc2cn(CCO)nn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KFKMPCWDJDVUQL-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 = 8128.31 nM (pChEMBL 5.090000152587891)
Descriptors: MW 486.54, ALogP 2.97, HBA 11, HBD 1, PSA 116.24, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNC(C)(C)CF)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SXYFYNVZTYNDKV-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 = 7762.47 nM (pChEMBL 5.110000133514404)
Descriptors: MW 492.6, ALogP 4.91, HBA 8, HBD 1, PSA 77.33, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC[C@H]2CC#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: QDLMCOSRVJITKF-FTBISJDPSA-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 511.63, ALogP 4.95, HBA 9, HBD 0, PSA 92.33, QED 0.3
Compound (SMILES): COc1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1OCC1CN(C)C(C)(C)CO1
InChIKey: LTSCIXSOBYGHLC-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 495.38, ALogP 5.32, HBA 7, HBD 1, PSA 68.74, QED 0.46
Compound (SMILES): O=c1cc(NC2CCN(S(=O)(=O)C(F)(F)F)CC2)c2cc(C(c3ccc(Cl)cc3)c3nccs3)ccc2[nH]1
InChIKey: NLIJQLLYUVUMPM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using (S)-mephenytoin as substrate after 10 to 30 mins by LC/MS analysis
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 583.06, ALogP 5.54, HBA 6, HBD 2, PSA 95.16, QED 0.31
Compound (SMILES): COc1cc(-c2cccc(OC(F)F)c2)c(F)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
InChIKey: ANRNNOYJCDFVSP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Reversible inhibition of CYP3A4 in human liver microsomes using midazolam as substrate in presence of NADPH
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 557.51, ALogP 5.2, HBA 8, HBD 1, PSA 112.66, QED 0.28
Compound (SMILES): CN1CCN(C/C=C/C(=O)Nc2cc3c(Nc4ccc(F)c(Cl)c4)ncnc3cn2)CC1
InChIKey: QSGIGRAFESHIBA-NSCUHMNNSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA
Measurement: IC50 = 2420 nM (pChEMBL 5.619999885559082)
Descriptors: MW 455.93, ALogP 3.3, HBA 7, HBD 2, PSA 86.28, QED 0.55
Compound (SMILES): CCOc1cc(N2CCC(N3CCN(CC(F)F)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: PYJDXWHQSYUUTM-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 793.87, ALogP 7.98, HBA 10, HBD 2, PSA 103.16, QED 0.12
Compound (SMILES): COc1cc(OC)cc(N(CCNS(C)(=O)=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YZRSMWKLOJZVAD-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 482.57, ALogP 2.73, HBA 9, HBD 1, PSA 111.47, QED 0.39
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(C(=O)NCCCCCCn2cccc(O)c2=S)c(F)c1
InChIKey: HYXAHECMTOFOFP-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 659.73, ALogP 6.86, HBA 7, HBD 2, PSA 101.6, QED 0.14
Compound (SMILES): CC#CC(=O)N[C@H]1CC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1
InChIKey: PTPSYWCHGKIOKO-BGYRXZFFSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 466.55, ALogP 4.49, HBA 7, HBD 2, PSA 107.95, QED 0.42
Compound (SMILES): CC(C)S(=O)(=O)c1ccccc1Nc1nc(N/N=C/c2ccc(F)cc2)ncc1Cl
InChIKey: STKCTXOVMCUJSB-BHGWPJFGSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using peptide as substrate after 60 mins by HTRF assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 447.92, ALogP 4.64, HBA 7, HBD 2, PSA 96.34, QED 0.4
Compound (SMILES): CS(=O)(=O)C1(c2nc(-c3cccc4[nH]ccc34)nc3c2OC[C@@H]2COCCN32)CCOCC1
InChIKey: DPGRLMCPNILHCM-HNNXBMFYSA-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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 470.55, ALogP 2.27, HBA 8, HBD 1, PSA 106.64, QED 0.62
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC(F)F
InChIKey: XHBINYIIFGVWSM-VNTMZGSJSA-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 558.76, ALogP 4.95, HBA 8, HBD 1, PSA 83.96, QED 0.44
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: SRWBBPJNBPSOFD-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 534.62, ALogP 5.68, HBA 9, HBD 0, PSA 87.42, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(CCCN)c4)nc3c2)c1.O=C(O)C(F)(F)F
InChIKey: FTLYVYRWTXLATF-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 = 9120.11 nM (pChEMBL 5.039999961853027)
Descriptors: MW 489.62, ALogP 4, HBA 9, HBD 2, PSA 103.35, QED 0.31
Compound (SMILES): c1cnc2c(N3CCN(CCCc4ccc(OCCCN5CCCCCC5)cc4)CC3)cccc2c1
InChIKey: XHHDACAEDLRJOJ-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 486.7, ALogP 5.63, HBA 5, HBD 0, PSA 31.84, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4cncnc4)cc23)c1F
InChIKey: PDZUTJYMOJFETL-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 457.46, ALogP 3.68, HBA 6, HBD 2, PSA 117.7, QED 0.41
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1O[C@H]1CO[C@H]2[C@@H]1OC[C@@H]2N1CCOCC1
InChIKey: UPTQFQIWDCTNMU-ZMUKGBGYSA-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 577.86, ALogP 4.04, HBA 9, HBD 1, PSA 87.2, QED 0.47
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3F)C2)nnc1-c1cccnc1
InChIKey: IKSPSLCLHNNQFS-XXBNENTESA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor expressed in CHO cell membranes after 90 mins in presence of quinelorane by [35S]-GTPgammaS binding assay
Measurement: Ki = 1.479 nM (pChEMBL 8.829999923706055)
Descriptors: MW 441.55, ALogP 4.52, HBA 6, HBD 0, PSA 46.84, QED 0.4
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(Br)cc4)cs3)cccc2n(C)c1=O
InChIKey: NIVMPNIOANBDGM-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 485.36, ALogP 3.3, HBA 7, HBD 1, PSA 85.99, QED 0.48
Compound (SMILES): CN(C)CCOc1ccc(Oc2ccccc2)cc1
InChIKey: INAQPAUETXGHJF-UHFFFAOYSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of human C-terminal his6-tagged/N-terminal T7 gene leader sequence-tagged LTA4H using L-arginine-7-amino-4-Methylcoumarine as substrate preincubated for 30 mins followed by substrate addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 257.33, ALogP 3.42, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): O=C(O)COC[C@H]1CC[C@@H](COC(=O)N(c2ccccc2)c2cccc(F)c2)CC1
InChIKey: UMQLASXGJFGXFL-HDICACEKSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Agonist activity at IP receptor in human primary platelets assessed as inhibition of ADP-induced platelet aggregation
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 415.46, ALogP 5.01, HBA 4, HBD 1, PSA 76.07, QED 0.66
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(F)c(-c4nccs4)c3)CC2)C1
InChIKey: VVYVGDLVYMCRNH-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 567.65, ALogP 4.31, HBA 9, HBD 1, PSA 119.62, QED 0.32
Compound (SMILES): COc1cc(CCN2CCN(C)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC(C)C)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VNOHWDYBGWYKHY-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 732.84, ALogP 7.32, HBA 10, HBD 2, PSA 109.15, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CNC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JWSLDBSDJDFRSK-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 470.53, ALogP 2.52, HBA 9, HBD 2, PSA 97.56, QED 0.42
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3)C2)n1C
InChIKey: XRDPJIJIWYVCKW-GCJKJVERSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 57.5 nM (pChEMBL 7.239999771118164)
Descriptors: MW 427.55, ALogP 4.28, HBA 7, HBD 0, PSA 59.98, QED 0.41
Compound (SMILES): CC1(C)C(=O)[C@H](C/C=C\CCCC(=O)O)[C@@H](/C=C/C(O)Cc2cc3ccccc3s2)[C@@H]1O
InChIKey: VJYUXEQWPPXOLL-FKUDPLTMSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding: HEK-293 cells stably expressing the human or feline FP receptor, or EP1, EP2, EP3, or EP4 receptors were washed with TME buffer, scraped from the bottom of the flasks, and homogenized for 30 sec using a Brinkman PT 10/35 polytron. TME buffer was added to achieve a final 40 ml volume in the centrifuge tubes (the composition of TME is 100 mM TRIS base, 20 mM MgCl2, 2M EDTA; 10 N HCl is added to achieve a pH of 7.4).The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4 C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2 (5 nM) were performed in a 100 ul volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 456.6, ALogP 4.76, HBA 5, HBD 3, PSA 94.83, QED 0.35
Compound (SMILES): CCOc1ccc(-c2nc(-c3cccc4c3CCC4NCCO)no2)cc1OCC
InChIKey: NUIKTBLZSPQGCP-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 expressed in bla TANGO U2OS cells assessed as inhibition of cAMP formation preincubated for 4 hrs followed by FRET-based beta-lactamase fluorescent substrate addition measured after 2 hrs
Measurement: EC50 = 135.94 nM (pChEMBL 6.869999885559082)
Descriptors: MW 409.49, ALogP 3.77, HBA 7, HBD 2, PSA 89.64, QED 0.56
Compound (SMILES): c1cc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)[nH]n1
InChIKey: TUYBDYWGOHKMRU-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 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 322.38, ALogP 1.71, HBA 6, HBD 2, PSA 90.79, QED 0.6
Compound (SMILES): O=C(C1c2ncn(-c3ccccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl)N1CCC1
InChIKey: HMDZQNVGVILYNN-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat 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 μl 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 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 489.89, ALogP 3.91, HBA 5, HBD 0, PSA 71.33, QED 0.56
Compound (SMILES): COC1CCC(OC)C(NC(=O)CN2CCN(Cc3ccc4c(c3)OCO4)CC2)C1
InChIKey: AOKPSAUXHJHABU-UHFFFAOYSA-N
Target: Beta-glucuronidase (SINGLE PROTEIN), Homo sapiens
UniProt: P08236
Assay: Inhibition of beta-glucuronidase (unknown origin)
Measurement: IC50 = 6430 nM (pChEMBL 5.190000057220459)
Descriptors: MW 419.52, ALogP 1.23, HBA 7, HBD 1, PSA 72.5, QED 0.71
Compound (SMILES): Fc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: LYEFGGREPUFIPO-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 350.4, ALogP 3.12, HBA 5, HBD 1, PSA 62.11, QED 0.62
Compound (SMILES): COc1cc2c(Nc3ccc(F)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2CO1
InChIKey: AFHNMWQBLLGGSP-KBPBESRZSA-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 7.300000190734863)
Descriptors: MW 476.91, ALogP 4.56, HBA 7, HBD 1, PSA 68.74, QED 0.52