lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CO)C5)ncc3F)cc2n1C(C)C
InChIKey: HLOKDQHOCMHLLI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 41.1 nM (pChEMBL 7.389999866485596)
Descriptors: MW 493.52, ALogP 3.68, HBA 8, HBD 2, PSA 109.06, QED 0.44
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3ccccc3o2)c(N2CCCCCC2)nc1N
InChIKey: FSPGYSVEHLETQR-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of factor 11a (unknown origin) using chromogenic L-pyroGlu-L-Pro-L-Arg-p-nitroaniline as substrate by fluorescence assay
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 393.45, ALogP 2.48, HBA 7, HBD 4, PSA 147.15, QED 0.39
Compound (SMILES): O=C(CCCCCCN1CCc2ccccc2C1)NO
InChIKey: LOEFBHPFPGYXOH-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant HDAC8 (unknown origin) expressed in Escherichia coli using fluor de Lys(R) as substrate pretreated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 276.38, ALogP 2.5, HBA 3, HBD 2, PSA 52.57, QED 0.46
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]cc(-c4ccncc4)c3c2)cnc1Cl)c1ccccc1F
InChIKey: ATRNPHJIZBECNS-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human full length His-tagged PI3K p110delta/p85alpha expressed in baculovirus expression system using PIP2/PS as substrate after 1 hr by ADP-Glo luminescence assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 479.92, ALogP 5.28, HBA 5, HBD 2, PSA 100.63, QED 0.33
Compound (SMILES): Cc1c2ccc(N(C)c3ccnc(Nc4ccc(C(=O)Nc5ccccc5N)cc4)n3)cc2nn1C
InChIKey: IPBGKKBBYNOXCG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using fluorogenic Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 478.56, ALogP 5.02, HBA 8, HBD 3, PSA 113.99, QED 0.29
Compound (SMILES): CNC(=O)c1cc(OCCCCN2CCN(c3nsc4ccccc34)CC2)ccn1
InChIKey: ILCIQMQWVOJQBG-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonistic activity at alpha-1A adrenergic receptor (unknown origin) after 10 mins by FLIPR assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 425.56, ALogP 3.03, HBA 7, HBD 1, PSA 70.59, QED 0.56
Compound (SMILES): Cc1cc(=O)oc2cc(OCc3cc[n+](Cc4ccc(Br)cc4)cc3)ccc12.[Br-]
InChIKey: IZFCERVBDMXUMX-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated for 6 mins followed by substrate addition measured up to 180 secs by Ellman's method
Measurement: IC50 = 217.5 nM (pChEMBL 6.659999847412109)
Descriptors: MW 437.31, ALogP 4.78, HBA 3, HBD 0, PSA 43.32, QED 0.33
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(CNC(=O)CN[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NC(C)=O)c1
InChIKey: WXRHOUDHPIZUCS-OUVSMADYSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of PGPH activity of human 26S proteasome using Z-LLE-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1632.1
Compound (SMILES): COc1ccccc1N1CCN(CCOCCOc2cc(C)cc(C)c2C)CC1.Cl.Cl
InChIKey: BKAPUHZAVMXBQP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from recombinant human 5-HT6 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 1540 nM (pChEMBL 5.809999942779541)
Descriptors: MW 398.55, ALogP 3.84, HBA 5, HBD 0, PSA 34.17, QED 0.6
Compound (SMILES): COc1ncc(-c2ccc3ncc(C(=O)NCCN4CCOCC4)n3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: AOFNYCXYCYLTJD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human PI3Kgamma expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate by HTRF colorimetric assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 572.59, ALogP 2.55, HBA 9, HBD 2, PSA 127.16, QED 0.31
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2c(Br)cc(Br)cn12)c1ccc(Cl)cc1
InChIKey: MEWSBNIVOLYKGU-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-4/beta-3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P63079
Assay: Displacement of [3H]EBOB from rat GABA-A receptor alpha4beta3 expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting analysis
Measurement: IC50 = 1860 nM (pChEMBL 5.730000019073486)
Descriptors: MW 511.63, ALogP 6.49, HBA 4, HBD 1, PSA 46.4, QED 0.34
Compound (SMILES): c1ccc(Cc2ccnc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: BCRYOGOFXLRJPN-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-DOI from recombinant human 5HT2CR transfected in human HEK293 cells incubated for 45 mins by radioligand binding assay
Measurement: Ki = 0.2512 nM (pChEMBL 9.600000381469727)
Descriptors: MW 279.39, ALogP 2.4, HBA 3, HBD 1, PSA 28.16, QED 0.91
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C)C1CCCC1
InChIKey: WSYPLKHNBQOYMW-UFWKXQSMSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 1340 nM (pChEMBL 5.869999885559082)
Descriptors: MW 833.08, ALogP 0.82, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): Cc1[nH]c(C(=O)NC/C=C/c2c[nH]c(N)n2)cc1Br
InChIKey: JEHHUBJAINFZKG-NSCUHMNNSA-N
Target: Potassium voltage-gated channel subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22459
Assay: Inhibition of human Kv1.4 expressed in CHO cells at -80 mV holding potential by whole cell automated patch clamp method
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 324.18, ALogP 1.83, HBA 3, HBD 4, PSA 99.59, QED 0.69
Compound (SMILES): c1cc(CC2CCC2)c2c(n1)N1CCNC[C@H]1CC2
InChIKey: WDUJNEUBVHIQQH-CQSZACIVSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-DOI from recombinant human 5HT2AR transfected in human HEK293 cells incubated for 45 mins by radioligand binding assay
Measurement: Ki = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 257.38, ALogP 2.15, HBA 3, HBD 1, PSA 28.16, QED 0.88
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)C=C(CF)OC(N)=N1
InChIKey: ORHZQSYKGHHDOP-IBGZPJMESA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate after 15 mins in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 383.36, ALogP 2.76, HBA 6, HBD 2, PSA 113.39, QED 0.84
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cccc2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C
InChIKey: USVNOCZPGCZLRG-OLDVANGTSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 905.15, ALogP 2.03, HBA 9, HBD 6, PSA 226.66, QED 0.11
Compound (SMILES): NC(=O)CC1CN(S(=O)(=O)c2ccc(F)cc2)c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2S1
InChIKey: KBDBIOMGAWEQRR-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 2820 nM (pChEMBL 5.550000190734863)
Descriptors: MW 532.46, ALogP 3.68, HBA 5, HBD 2, PSA 100.7, QED 0.57
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1nc(C)nc(-c3cccc4ncc(C)cc34)c12
InChIKey: HCPVNQUKSHCVCO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay
Measurement: Ki = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 449.51, ALogP 6.22, HBA 6, HBD 1, PSA 89.72, QED 0.34
Compound (SMILES): CC(C)(O)CNC(=O)C[C@@H]1CN(S(=O)(=O)c2ccc(F)cc2)c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2S1
InChIKey: XUCORPNQMQOUMD-OAHLLOKOSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at GAL4-tagged human LXRbeta assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 604.57, ALogP 4.08, HBA 6, HBD 3, PSA 106.94, QED 0.41
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](N)CC(=O)O)C(=O)N[C@@H](Cc2ccc(I)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)O
InChIKey: FAZKACLBWZFQSM-RWKAWOQZSA-N
Target: Urotensin-2 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P49684
Assay: Agonist activity at UT receptor in Sprague-Dawley rat thoracic aortic ring assessed as induction of contraction
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 1187.15
Compound (SMILES): COc1ccc(CCN2CCC(CCc3cccc(OCCF)c3)CC2)cc1.Cl
InChIKey: OHGHLCACOHENEN-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]dopamine uptake at VMAT2 in rat striatal synaptic vesicles by scintillation spectrometry
Measurement: Ki = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 385.52, ALogP 4.93, HBA 3, HBD 0, PSA 21.7, QED 0.58
Compound (SMILES): Cc1cc(-n2cc3c(n2)CN(C(=O)c2cc(C#N)ccc2N2CCC(F)(F)CC2)C3)ccn1
InChIKey: NPWVAYJGBWTJEG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.48, ALogP 3.84, HBA 6, HBD 0, PSA 78.05, QED 0.61
Compound (SMILES): CC(C(=O)NCCCCOc1ccc(S(N)(=O)=O)cc1)c1ccc(-c2ccccc2)c(F)c1
InChIKey: SXZXSKWFAQMQAO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 94.1 nM (pChEMBL 7.03000020980835)
Descriptors: MW 470.57, ALogP 4.22, HBA 4, HBD 2, PSA 98.49, QED 0.43
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccc(NC(=O)COCc3ccccc3)cc2)n1
InChIKey: WBBROFIVWCOOIW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 3620 nM (pChEMBL 5.440000057220459)
Descriptors: MW 589.1, ALogP 5.58, HBA 9, HBD 2, PSA 101.08, QED 0.23
Compound (SMILES): OC(Cn1cnnn1)(c1ccc(F)cc1F)C(F)(F)c1ccc(-c2ccc(OCC(F)(F)F)cc2)cn1
InChIKey: IDUYJRXRDSPPRC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins with substrate followed by NADPH addition measured after 15 mins by LC/MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 527.4, ALogP 4.63, HBA 7, HBD 1, PSA 85.95, QED 0.34
Compound (SMILES): N#Cc1ccc(-c2cnc3ccc(-c4ccc(C(=O)N5CCOCC5)cc4)cn23)cc1
InChIKey: FWRFPHJSGLYXTD-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of N-terminal GST-fused human full length recombinant MNK1 (1 to 424 residues) expressed in baculovirus-infected Sf21 cells using TATKSGSTTKNR as substrate preincubated with enzyme and substrate for 10 mins followed by ATP addition and measured after 40 mins by ADP-glo luminescence assay
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 408.46, ALogP 4.01, HBA 5, HBD 0, PSA 70.63, QED 0.51
Compound (SMILES): CC(C)CCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CN)C(=O)N[C@@H](CC1CCCC1)C(=O)N1CCC[C@H]1c1nc(-c2ccccc2)cn1CC1CCCCC1)C(C)C
InChIKey: VDSRTRLFYMNHAU-XTJUCFOSSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Displacement of N-Flu-DOT1L from MBP-tagged AF9 (unknown origin) (487 to 568 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 829.14, ALogP 5.87, HBA 8, HBD 4, PSA 171.76, QED 0.15
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)C(C)OC(CS(C)(=O)=O)CN3S(C)(=O)=O
InChIKey: PCQOPPOYJPHFQB-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 4a NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 524.59, ALogP 2.87, HBA 7, HBD 1, PSA 122.99, QED 0.54
Compound (SMILES): CC(C)N1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)CC6)n3)nc2)CC1
InChIKey: JEUQWNQSQIEFOJ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 518.62, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.39
Compound (SMILES): COc1cc(C(N)=O)nc(-c2cccc(C#C[C@]3(O)CCN(C)C3=O)c2)c1
InChIKey: LQSHXYHWYGKAMX-FQEVSTJZSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) expressed in HEK293 cells harboring NFkB-Luc assessed as reduction in NFkB signal after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 365.39, ALogP 0.8, HBA 5, HBD 2, PSA 105.75, QED 0.78
Compound (SMILES): Cc1cc(Nc2ccc3ccccc3c2)ccc1C(=O)Nc1cn(C(C)C)c(=O)n(C2(C(=O)N[C@H]3CC(=O)OC3O)CC2)c1=O
InChIKey: BTGMTHBOODBMHN-SUHMBNCMSA-N
Target: Caspase-6 (SINGLE PROTEIN), Homo sapiens
UniProt: P55212
Assay: Inhibition of human recombinant caspase-6 using Ac-VEID-AMC as substrate at Km after 20 mins by fluorescence assay
Measurement: IC50 > 9999 nM (pChEMBL 5)
Descriptors: MW 611.66, ALogP 3.29, HBA 10, HBD 4, PSA 160.76, QED 0.22
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCN(S(=O)(=O)c2ccccc2[N+](=O)[O-])CCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: TVMJNXHHEYHGGK-HVJTVJTHSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]Tyr3-neurotensin from human NTS1 receptor expressed in CHOK1 cell membranes after 60 mins by gamma counting analysis
Measurement: Ki = 328 nM (pChEMBL 6.480000019073486)
Descriptors: MW 998.21, ALogP 2.38, HBA 13, HBD 8, PSA 326.8, QED 0.05
Compound (SMILES): CCOc1cc(/C=C/C(=O)c2ccncc2)cc(OCC)c1OCC
InChIKey: FTGTZPWFFDGBNS-BQYQJAHWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in yeast microsomal membranes using dibenzylfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 341.41, ALogP 4.17, HBA 5, HBD 0, PSA 57.65, QED 0.51
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(=O)n(C)c2)c1)c1cccc(Cl)c1
InChIKey: GKXKDDYZHCNTKR-LOSJGSFVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Antagonist activity at glucocorticoid receptor (unknown origin) expressed in human ChaGoK1 cells assessed as inhibition of dexamethasone induced transactivation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: IC50 = 324 nM (pChEMBL 6.489999771118164)
Descriptors: MW 528.99, ALogP 5.29, HBA 6, HBD 1, PSA 78.15, QED 0.34
Compound (SMILES): Cc1ccc(NC(=O)CSc2nc3ccccc3n2S(=O)(=O)c2cc(C)cc(C)c2)cc1
InChIKey: HAIANVFPDPKFTL-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase Y188L mutant in HIV1 infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 > 3130 nM (pChEMBL 5.504000186920166)
Descriptors: MW 465.6, ALogP 4.93, HBA 6, HBD 1, PSA 81.06, QED 0.41
Compound (SMILES): C[C@H]1COCCN1c1nc(-c2cnc(N)cc2F)cc(C2(S(C)(=O)=O)CC2)n1
InChIKey: LBIPJQHFIZPQHA-NSHDSACASA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST-tagged mTOR catalytic domain (1360 to 2549 residues) expressed in baculovirus expression system using GFP-4EBP1 as substrate measured after 1 hr by Lathascreen method
Measurement: IC50 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 407.47, ALogP 1.52, HBA 8, HBD 1, PSA 111.3, QED 0.81
Compound (SMILES): C=CC(=O)N[C@@H]1Cn2c(c(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1=C
InChIKey: KJRVCMVPIKELBC-LJQANCHMSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of recombinant human TEC using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 423.48, ALogP 4.17, HBA 6, HBD 2, PSA 95.06, QED 0.47
Compound (SMILES): COC(=O)c1ccc(OCc2oc(-c3cccc(OC)c3)nc2C)cc1
InChIKey: SYFIGKNOBXITNY-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Antagonist activity at CMV-fused RXRalpha-LBD-GAL4-DBD (unknown origin) expressed in HEK293T cells assessed as inhibition of bexarotene-induced receptor transactivation after 16 hrs by bright-Glo luciferase reporter gene assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 353.37, ALogP 4.02, HBA 6, HBD 0, PSA 70.79, QED 0.62
Compound (SMILES): CCN[C@@H]1CCC=C(c2ccc(F)cc2)[C@H]1CNc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl.Cl
InChIKey: IEXCIAKIMAWIDV-IUFJOMBNSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 14100 nM (pChEMBL 4.849999904632568)
Descriptors: MW 539.07, ALogP 5.76, HBA 6, HBD 3, PSA 83.12, QED 0.32
Compound (SMILES): Cc1c2ccc(N(C)c3ccnc(Nc4ccc(C(=O)NCCCCCCC(=O)NO)cc4)n3)cc2nn1C
InChIKey: PSNSRJNHZPJVJH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of VEGFR-1 (unknown origin) after 40 mins by kinase-Glo assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 530.63, ALogP 4.37, HBA 9, HBD 4, PSA 137.3, QED 0.12
Compound (SMILES): Cc1cc(CC(=O)Nc2ccn(Cc3ccc(C#N)cn3)n2)ccc1OC(F)(F)F
InChIKey: GJKURPNQOJQXPQ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 using testosterone as substrate preincubated for 30 mins
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 415.38, ALogP 3.59, HBA 6, HBD 1, PSA 92.83, QED 0.66
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(C(=O)NO)s4)ccc3OCC)nc12
InChIKey: NGFDENLSEDFSFN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length human recombinant C-terminal FLAG/His-tagged HDAC1 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 4 hrs fluorescence assay
Measurement: IC50 = 841 nM (pChEMBL 6.079999923706055)
Descriptors: MW 467.55, ALogP 3.45, HBA 8, HBD 3, PSA 122.13, QED 0.27
Compound (SMILES): O=S(=O)(NC1CCN(CC(O)COc2ccccc2-c2ccccc2)CC1)c1cccc(Cl)c1
InChIKey: JFHVZERFQKQSFW-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-Raclopride from human dopamine D2L receptor expressed in HEK293 or CHO-K1 cells after 1 hr by microbeta counting analysis
Measurement: Ki = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 501.05, ALogP 4.19, HBA 5, HBD 2, PSA 78.87, QED 0.46
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCC2)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: ZWTUZOQCWSYYNO-AGEXMYHWSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 888, ALogP -0.31, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCCCOc1ccc(C2=N[C@@H](CO)[C@H](C)S2)cc1
InChIKey: VJHCELMTVAQBMD-FZMZJTMJSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 279.41, ALogP 3.11, HBA 4, HBD 1, PSA 41.82, QED 0.81
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CN)C(N)=O
InChIKey: GBWDHKBLRMDDCK-DKTXOJPGSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of human 26S proteasome using Boc-LRR-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1323.6
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: SFAJGGFDBDWTMC-BAGYTPMASA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 632.67, ALogP 2.63, HBA 9, HBD 6, PSA 224.81, QED 0.04
Compound (SMILES): Cc1nn(C)c2nc(NNC(=O)Nc3cc(Cl)nc(OCC4CC4)c3)cc(C(C)C)c12
InChIKey: KATYKXXGQBFJLO-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Displacement of [32P]S1P from recombinant human S1PR5 expressed in cell membranes pretreated for 30 mins followed by [32P]S1P addition measured after 60 mins by scintillation counting method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 443.94, ALogP 4.39, HBA 7, HBD 3, PSA 105.99, QED 0.37
Compound (SMILES): CCC(=C(c1ccc(OCCN2CCCCCC2)cc1)c1ccc(OCCN2CCCCCC2)cc1)c1cccc(C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)c1
InChIKey: SBODERJBBPEJRV-ASNOGBRRSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of human 26S proteasome using Boc-LRR-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 1916.42
Compound (SMILES): COc1cc(NC(C(=O)c2c[nH]c3ccccc23)c2ccccc2)cc(OC)c1
InChIKey: RUOUETBOFZRKGX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 386.45, ALogP 5.22, HBA 4, HBD 2, PSA 63.35, QED 0.43
Compound (SMILES): Cc1cc(-n2cc3c(n2)CN(C(=O)c2cc(C#N)ccc2-c2cccc(F)c2)C3)ccn1
InChIKey: YIXNGZTVLPLRHN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.45, ALogP 4.41, HBA 5, HBD 0, PSA 74.81, QED 0.49
Compound (SMILES): C[C@@H]1SC(c2ccccc2O)=N[C@H]1Cc1c[nH]cn1
InChIKey: YSCNOWHLCXMNDZ-CABZTGNLSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from human 5-HT2C receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 273.36, ALogP 2.61, HBA 4, HBD 2, PSA 61.27, QED 0.9
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4cnc(N)nc4)cn3n2)CC1
InChIKey: XEBRAMSBPJUGET-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST-tagged mTOR catalytic domain (1360 to 2549 residues) expressed in baculovirus expression system by AlexaFluor647-labeled kinase tracer 314 based LanthaScreen assay
Measurement: Ki = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 473.56, ALogP -0.32, HBA 11, HBD 1, PSA 135.08, QED 0.53
Compound (SMILES): O=S(=O)(Oc1ccccc1Cl)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: CQDCBCLWITTXGG-AATRIKPKSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at human ERalpha expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: IC50 = 166 nM (pChEMBL 6.78000020980835)
Descriptors: MW 589.07, ALogP 6.49, HBA 7, HBD 3, PSA 113.29, QED 0.17
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)CO)n1
InChIKey: BQBNPQXFWWIVER-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 4180 nM (pChEMBL 5.380000114440918)
Descriptors: MW 498.97, ALogP 3.36, HBA 9, HBD 3, PSA 112.08, QED 0.43
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cccc(O)c2)c1
InChIKey: HDBQZCCNZOGXEE-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB R136A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 357.37, ALogP 5.08, HBA 4, HBD 2, PSA 83.56, QED 0.53
Compound (SMILES): CCC(SC1=Nc2ccccc2C2=NC(C(C)CC)C(=O)N12)C(=O)Nc1ccccc1C
InChIKey: HTFJGDBBWXQQCN-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of 100 nM paclitaxel-mediated cytotoxicity after 4 days by CellTiter-Glo assay
Measurement: EC50 = 2220 nM (pChEMBL 5.650000095367432)
Descriptors: MW 448.59, ALogP 5.15, HBA 5, HBD 1, PSA 74.13, QED 0.66
Compound (SMILES): CC(C)Cc1ccc(C(C)C(=O)NCCCOc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: UBWFOFQYWMLOHJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 418.56, ALogP 3.22, HBA 4, HBD 2, PSA 98.49, QED 0.58
Compound (SMILES): CCOC(=O)c1c(C)oc2cc(OCc3ccccc3)c(OCc3oc4cc(OCC5CCCCC5)c(OS(=O)(=O)[O-])cc4c3C(=O)OCC)cc12.[Na+]
InChIKey: RVIRXUKDYXNKEW-UHFFFAOYSA-M
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using spectrozyme TH as substrate pretreated for 10 mins followed by substrate addition measured in presence of 15 uM exosite 1 competitor hirudine peptide by spectrophotometric method
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 736.79, ALogP 8.14, HBA 12, HBD 1, PSA 170.17, QED 0.08
Compound (SMILES): CC(C)(CO)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc(Cl)cn3)c2)c2cnc(N)nc21
InChIKey: BPIWZDNVMQQBQX-UHFFFAOYSA-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 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 479.93, ALogP 2.6, HBA 9, HBD 3, PSA 148.91, QED 0.34
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN(C)C)C5)ncc3F)cc2n1C(C)C
InChIKey: SSVSKCKWUAPYHI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 913 nM (pChEMBL 6.039999961853027)
Descriptors: MW 520.59, ALogP 4.25, HBA 8, HBD 1, PSA 92.07, QED 0.41
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)CC6)n3)nc2)CC1
InChIKey: YCANTYAOGZQCIG-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 504.59, ALogP 4.55, HBA 8, HBD 1, PSA 75, QED 0.41
Compound (SMILES): O=C(Cc1ccc(Cl)c(Cl)c1)N1CCOC2CNCC(N3CCCC3)C21
InChIKey: JMSHYBARLFGBPR-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma2 receptor in Sprague-Dawley rat liver membranes after 120 mins by scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 398.33, ALogP 2.2, HBA 4, HBD 1, PSA 44.81, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(OCCNC(=O)Cc2ccccc2Nc2c(Cl)cccc2Cl)cc1
InChIKey: VNIROKIVWRXGRV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 57.6 nM (pChEMBL 7.239999771118164)
Descriptors: MW 494.4, ALogP 4.12, HBA 5, HBD 3, PSA 110.52, QED 0.39
Compound (SMILES): CC1(C)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: QEQUHVRIJFFOKD-LMOJIFKQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 875.99, ALogP -0.46, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1ccc(-c2ccccc2)cc1
InChIKey: FHKFHTMCQMFFEY-AOYPEHQESA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]DOI from human 5HT2A receptor expressed in HEK293 cell membranes
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 497.6, ALogP 4.03, HBA 6, HBD 1, PSA 84.4, QED 0.39
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(-n2cc(-c3cncnc3)c3nc(N(C)C4CCN(CC)CC4)ccc32)c1F
InChIKey: AEJACXAFHXBVHF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Binding affinity to DNA-tagged BRAF (unknown origin) V600E mutant by KINOMEscan assay
Measurement: Kd = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 569.68, ALogP 4.83, HBA 8, HBD 1, PSA 96.25, QED 0.31
Compound (SMILES): NCCCNC(=O)c1ccc(-c2cc(C(=O)O)cc(-n3cc(-c4ccc(C(F)(F)F)cc4)nn3)c2)s1
InChIKey: VYXSDIPOJBFWHQ-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-DADLE from human delta opioid receptor expressed in HEK293 cells after 90 mins by scintillation counting method
Measurement: Ki = 941 nM (pChEMBL 6.03000020980835)
Descriptors: MW 515.52, ALogP 4.46, HBA 7, HBD 3, PSA 123.13, QED 0.3
Compound (SMILES): COc1cccc(/C=C/C(=O)c2ccncc2)c1
InChIKey: SMEDYRIIZMHYEO-AATRIKPKSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 expressed in HEK293 cells using 7-ethoxyresorufin as substrate pretreated for 30 mins followed by substrate addition measured for 60 mins by fluorescence assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 239.27, ALogP 2.99, HBA 3, HBD 0, PSA 39.19, QED 0.61
Compound (SMILES): CC1(C)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: YSZTVMQFORZYJG-LUKCZKMGSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 839.96, ALogP -1.22, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]nc(-c4ccncc4)c3c2)cnc1Cl)c1ccccc1
InChIKey: JNQFWBSHMGXTQX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 7.37 nM (pChEMBL 8.130000114440918)
Descriptors: MW 462.92, ALogP 4.54, HBA 6, HBD 2, PSA 113.52, QED 0.37
Compound (SMILES): Cc1cc(OCCCN2CCN(c3ccccc3)CC2)ccc1Cl.Cl.Cl
InChIKey: RTHQQMXOILOELC-UHFFFAOYSA-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 liquid scintillation counting method
Measurement: Ki = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 344.89, ALogP 4.24, HBA 3, HBD 0, PSA 15.71, QED 0.73
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2ccccn12)c1ccc(Cl)cc1
InChIKey: AZKMWHRDICVYEI-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-4/beta-1/delta (PROTEIN COMPLEX), Homo sapiens
UniProt: O14764
Assay: Positive allosteric modulation of human recombinant alpha4beta1delta GABAA receptor expressed in delta-HEK cells assessed as potentiation of GABA-induced response in presence of GABA EC20 by FMP assay
Measurement: EC50 = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 353.83, ALogP 4.97, HBA 4, HBD 1, PSA 46.4, QED 0.56
Compound (SMILES): Fc1ccc(Cc2ccnc3c2CC[C@@H]2CNCCN32)cc1
InChIKey: PUZQIEAXLJCDIM-MRXNPFEDSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant 5-HT2B receptor (unknown origin) expressed in HEK293 cells assessed as increase in [3H]-inositol phosphate accumulation by scintillation counting method
Measurement: EC50 = 307 nM (pChEMBL 6.510000228881836)
Descriptors: MW 297.38, ALogP 2.54, HBA 3, HBD 1, PSA 28.16, QED 0.92
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(CC(=O)NO)cc4)ccc3OCC)nc12
InChIKey: AFVWNFJXGSIJSF-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 475.55, ALogP 3.31, HBA 7, HBD 3, PSA 122.13, QED 0.25
Compound (SMILES): CN(C)C[C@H]1C2CCC(c3ccccc3)(C2)[C@H]1O
InChIKey: HGNFUCJMHJYHIN-ZTTSNEECSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Binding affinity to thrombin cleavable N-terminal 6His tagged and 13C-IVLM labeled human KDM4A tandem TUDOR domain (897 to 1011 residues) expressed in Escherichia coli BL21(DE3)-T1R assessed as apparent Kd for H3(1-10)K4me3 peptide at 1 mM by ITC method (Rvb = 5.2 +/- 0.3 uM)
Measurement: Kd = 22700 nM (pChEMBL 4.639999866485596)
Descriptors: MW 245.37, ALogP 2.28, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O
InChIKey: VPDBSKOWEPRFMT-DZCXQCEKSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of trypsin-like activity of human 26S proteasome using Boc-LRR-MCA as substrate measured for 1 hr by fluorescence assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 1366.62
Compound (SMILES): COC(=O)CNC(=O)NCc1ccc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)cc1C
InChIKey: XOYDUGXEXIVUAJ-UHFFFAOYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Antagonist activity at human OTR expressed in HEK cells assessed as inhibition of OT-induced intracellular calcium flux incubated for 45 mins by Indo1-AM dye based fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 462.51, ALogP 2.6, HBA 7, HBD 3, PSA 117.59, QED 0.5
Compound (SMILES): CC(C)C[C@H]1CN(C2CCN(c3n[nH]c(N)n3)CC2)[C@@H](Cc2ccc(Cl)cc2)CN1C
InChIKey: RCGRIXXPKNDBJW-SFTDATJTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: ERG Channel Binding Assay: Fluorescence polarization assay based on the principle of fluorescence polarization where a red-shifted fluorescent tracer is displaced from the hERG channel by compounds that bind to the channel was used to establish the binding of the compounds to hERG channel. Briefly, the compounds in serial dilutions were incubated with a membrane fraction containing hERG channel protein and a high-affinity red fluorescent hERG channel ligand in black 384-well plate. The reaction was incubated for 4 h at room temperature followed by the measurement of the fluorescence polarization using Tecan Spark multimode plate reader at excitation wavelength of 535 nm and emission wavelength 590 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 446.04, ALogP 3.28, HBA 6, HBD 2, PSA 77.31, QED 0.71
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4cnc(N)nc4)c(Cl)n3n2)CC1
InChIKey: NOCRVEDBMWCMTR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST-tagged mTOR catalytic domain (1360 to 2549 residues) expressed in baculovirus expression system by AlexaFluor647-labeled kinase tracer 314 based LanthaScreen assay
Measurement: Ki = 5410 nM (pChEMBL 5.269999980926514)
Descriptors: MW 508.01, ALogP 0.34, HBA 11, HBD 1, PSA 135.08, QED 0.51
Compound (SMILES): CC(C)(O)[C@H](F)CNC(=O)C[C@@H]1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: FQWMGYJHFABALZ-FXAWDEMLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Spa Binding Assay: The binding of potential ligands to RORγ is measured by competition with [3H] 25-hydroxycholesterol using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromotography. 50 nM RORγ (A262-S507) is incubated with test compound at varying concentrations for 15 min at room temperature in PBS buffer containing 0.5% fatty acid free BSA. 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 15 min. 4 mg/mL of Ysi Copper HIS-TAG SPA Beads (Perkin Elmer) are added, and the mixture is incubated for 30 min. The reaction is read on a MicroBeta Trilux scintillation plate reader (Perkin Elmer).
Measurement: IC50 = 22.1 nM (pChEMBL 7.659999847412109)
Descriptors: MW 618.54, ALogP 4.26, HBA 5, HBD 3, PSA 106.94, QED 0.38