lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@@H](C)[C@@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: HXVUFUQHFFIAAD-CDFPPUFDSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of 125I-rat amylin from human AMY3R complex of CTR/RAMP3 expressed in Baby hamster kidney cell membrane incubated for 120 mins by SPA method
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 3952.41
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@H]5COCCO5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: SEOFRNNPVLILNV-HXOSKORISA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of Bcl-2 G101V mutant (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 864.04, ALogP 7.92, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): CN1CCN(C(c2cccnc2)c2nnnn2CCc2ccccc2)CC1
InChIKey: VGNIHZIDQKBDHQ-UHFFFAOYSA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31596
Assay: Positive allosteric modulation of EAAT2 in Sprague-Dawley rat microglial cells assessed as increase in glutamate uptake preincubated for 10 mins followed by 3-H-L-glutamate addition and measured after 10 mins by microplate scintillation counter analysis
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 363.47, ALogP 1.65, HBA 7, HBD 0, PSA 62.97, QED 0.66
Compound (SMILES): CCCC(=O)Nc1cc2c(Oc3ccc(NC(=O)CCCc4ccc(C)cc4)cc3F)ncnc2cc1OC
InChIKey: MTQNLQINVQTEEY-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal GST tagged human recombinant c-Met (956 to end residues) expressed in baculovirus infected Sf9 cells using Poly (4:1 Glu, Tyr) as substrate incubated for 60 mins in presence of ATP by ADP-Glo luminescent assay
Measurement: IC50 = 678.4 nM (pChEMBL 6.170000076293945)
Descriptors: MW 530.6, ALogP 6.58, HBA 6, HBD 2, PSA 102.44, QED 0.23
Compound (SMILES): COc1cc(NC(=O)c2cnc3ccccc3c2)c(C(=O)Nc2ccc(C3CCN(Cc4ccc5c(c4)OCO5)CC3)cc2)cc1OC
InChIKey: SOAPFLDMMJNCEM-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human Hepatocyte using Luciferin-IPA as substrate
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 644.73, ALogP 6.86, HBA 8, HBD 2, PSA 111.25, QED 0.18
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(-c3ccc(NC(=O)c4cc5ncccc5o4)cc3)cc2)n1
InChIKey: BKHWSLFWRLAKOI-RXFWQSSRSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of wildtype IDH1 (unknown origin) using DL-isocitrate as substrate incubated for 60 mins in presence of NADP by fluorescence microplate reader
Measurement: IC50 = 5720 nM (pChEMBL 5.239999771118164)
Descriptors: MW 562.63, ALogP 6.69, HBA 8, HBD 2, PSA 122.48, QED 0.21
Compound (SMILES): CC1(C)NC(=O)[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)CCCCNC(=O)C[C@H](C(=O)N2CCC[C@H]2C(N)=O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: KIGFSGWCFLVNJA-CEVYIAARSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO-K1 cells co-expressing G-alpha15 by calcium mobilization assay
Measurement: EC50 = 49.1 nM (pChEMBL 7.309999942779541)
Descriptors: MW 734.86, ALogP -0.98, HBA 9, HBD 8, PSA 255.15, QED 0.17
Compound (SMILES): COc1ccc(-n2cncc2-c2cc(C(C)C)c(O)cc2O)cc1
InChIKey: WLCDHTWEAIXCCB-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Binding affinity to human N-terminal his tagged Hsp90alpha (1 to 241 residues) expressed in Escherichia coli (DE3) strain assessed as dissociation constant by ITC method
Measurement: Kd = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 324.38, ALogP 4.08, HBA 5, HBD 2, PSA 67.51, QED 0.76
Compound (SMILES): COC(=O)[C@@H](CCSC)NC(=O)c1cn(CCCCCF)c2ccccc12
InChIKey: PRLIVMHPUVNUDJ-QGZVFWFLSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor stably transfected in AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 394.51, ALogP 3.81, HBA 5, HBD 1, PSA 60.33, QED 0.47
Compound (SMILES): Clc1ccc(Nc2nc3ccccc3c3nc(C4CCCCC4)sc23)cc1Cl
InChIKey: JZTBWOAWUOGGQF-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 19.05 nM (pChEMBL 7.71999979019165)
Descriptors: MW 428.39, ALogP 7.94, HBA 4, HBD 1, PSA 37.81, QED 0.36
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(=O)N2CCn3ncc(C(F)(F)F)c3C2)c2nc(C)c(C)nc21
InChIKey: TWLQKSJIDBZENC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 phosphorylation at Thr14 residue in human HCC1569 cells incubated for 6 hrs by Western blot analysis
Measurement: IC50 = 289 nM (pChEMBL 6.539999961853027)
Descriptors: MW 499.5, ALogP 3.81, HBA 8, HBD 2, PSA 115.09, QED 0.43
Compound (SMILES): CNc1ncc2cc(-c3ccc(-c4cccc(C)n4)cc3Cl)c(=O)n(CCCCCN)c2n1
InChIKey: WLVXFJRANPEJSA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 24 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6E0
Assay: Inhibition of MST3 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay
Measurement: EC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 462.99, ALogP 4.65, HBA 7, HBD 2, PSA 98.72, QED 0.37
Compound (SMILES): CC12CC3CC(C)(C1)CC(NC(=O)Nc1ccc(C(=O)NCCCCCCC(=O)NO)cc1)(C3)C2
InChIKey: LICDGBVIDDVNJZ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human HDAC2 using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence based assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 484.64, ALogP 4.74, HBA 4, HBD 5, PSA 119.56, QED 0.19
Compound (SMILES): CCN1C(=O)N([C@H]2CC[C@H](C(F)(F)F)CC2)C(=O)C12CCN(CC1CCOCC1)CC2
InChIKey: MVFPHXKJIJZYOY-IYARVYRRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by whole cell patch clamp recording
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 445.53, ALogP 3.65, HBA 4, HBD 0, PSA 53.09, QED 0.62
Compound (SMILES): Cl.O=C(CCc1ccccc1)N(c1ccccc1)C1CCN(CCc2ccccc2)CC1
InChIKey: XYWXONNRLDYVBU-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]NTI from DOR (unknown origin) expressed in CHO cell membrane assessed as inhibition constant incubated for 1.5 hrs by scintillation counter method
Measurement: Ki = 6595 nM (pChEMBL 5.179999828338623)
Descriptors: MW 412.58, ALogP 5.36, HBA 2, HBD 0, PSA 23.55, QED 0.5
Compound (SMILES): COc1ccc2c(c1)N(CCN(C)C)/C(=C/C(C)=O)S2.O=C(O)/C=C/C(=O)O
InChIKey: SDNZQQUMVZIGGM-XAYIRVKOSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at recombinant human 5-HT2A expressed in CHO-K1 cells assessed as inhibition of alpha-Me-5-HT induced increase in IP1 accumulation incubated for 60 mins by HTRF ASSAY
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 292.4, ALogP 2.6, HBA 5, HBD 0, PSA 32.78, QED 0.78
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2cccc(Nc3ccc4c(-c5cn[nH]c5)n[nH]c4c3)c2)n(-c2ccccc2F)n1
InChIKey: YGUHZTGUYHUMMF-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of wild type TRKB (unknown origin) using TK peptide as substrate incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 549.61, ALogP 6.96, HBA 6, HBD 5, PSA 128.34, QED 0.15
Compound (SMILES): CC(C)N[C@H]1Cc2cc(Cl)ccc2-n2c(nnc2[C@H]2CC[C@H](Oc3ccccn3)CC2)C1
InChIKey: JUAQZCVTUKRQRY-YYWHXJBOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells at -80 mV holding potential incubated for 7 to 10 mins by automated patch clamp method
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 452, ALogP 4.89, HBA 6, HBD 1, PSA 64.86, QED 0.6
Compound (SMILES): CC(C)(C)c1cc(C(=O)Nc2cccc(S(N)(=O)=O)c2)n(Cc2ccccc2)n1
InChIKey: DBMVDPKUTSNRBM-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62968
Assay: Inhibition of rat neuronal Nav1.8 by patch clamp electrophysiology
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 412.52, ALogP 3.13, HBA 5, HBD 2, PSA 107.08, QED 0.67
Compound (SMILES): COc1cc(NC(=O)c2cc(=O)c3ccccc3o2)c(C(=O)Nc2ccc(N3CCN(Cc4cccc(-n5cncn5)c4)CC3)cc2)cc1OC
InChIKey: YXMWQNCYIYYFRA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human Hepatocyte using Luciferin-IPA as substrate
Measurement: IC50 = 475 nM (pChEMBL 6.320000171661377)
Descriptors: MW 685.74, ALogP 5.22, HBA 11, HBD 2, PSA 144.06, QED 0.2
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCOc2ccc(N(CC(F)(F)F)S(=O)(=O)C3CC4OC3C(c3ccc(-n5ccnc5)cc3)=C4c3ccc(O)cc3)cc2)C(C)(C)C)cc1
InChIKey: PLAVXXXKWALXPD-LVBUJRILSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of recombinant human aromatase using ARO substrate/NADP+ mixture by fluorescence assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 1124.32
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: LIZHNINWBCQRGY-QJMUSDNHSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P32214
Assay: Agonist activity at rat AMY3R complex of CTR/RAMP3 expressed in Baby hamster kidney cells incubated for 3 hrs by cAMP assay
Measurement: EC50 = 0.262 nM (pChEMBL 9.579999923706055)
Descriptors: MW 3970.43
Compound (SMILES): NS(=O)(=O)c1ccc(COc2ccc3cc(C(=O)O)c(=O)oc3c2)cc1
InChIKey: SAEYJRKCVGBDQH-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 80.5 nM (pChEMBL 7.090000152587891)
Descriptors: MW 375.36, ALogP 1.72, HBA 6, HBD 2, PSA 136.9, QED 0.65
Compound (SMILES): COc1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: REJCPQNUOGQCEV-KDXMTYKHSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 850.01, ALogP 7.82, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): CNc1ncc2cc(-c3ccc(-c4cccc(C)n4)cc3Cl)c(=O)n(CCCCN)c2n1
InChIKey: YASIXTGDNNJPQS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 24 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6E0
Assay: Inhibition of MST3 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 448.96, ALogP 4.26, HBA 7, HBD 2, PSA 98.72, QED 0.41
Compound (SMILES): CCCC(CCC)c1nc2c(Sc3ccc(Cl)c(Cl)c3)nc3ccccc3c2[nH]1
InChIKey: DHFLPHOXYLLQRZ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 26.92 nM (pChEMBL 7.570000171661377)
Descriptors: MW 444.43, ALogP 8.25, HBA 3, HBD 1, PSA 41.57, QED 0.31
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: QIOJJWFYYSCRGM-HGXDQEOYSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P32214
Assay: Agonist activity at rat AMY3R complex of CTR/RAMP3 expressed in Baby hamster kidney cells incubated for 3 hrs by cAMP assay
Measurement: EC50 = 0.643 nM (pChEMBL 9.1899995803833)
Descriptors: MW 3929.33
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(C(=O)NO)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: ZVFTUAXFCXJYHK-LBPRGKRZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length N-terminal GST-tagged human recombinant HDAC6 (1 to 1215 residues) preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 83.7 nM (pChEMBL 7.079999923706055)
Descriptors: MW 514.47, ALogP 0.25, HBA 10, HBD 4, PSA 165.67, QED 0.21
Compound (SMILES): Cc1nn(C(C)c2nn(-c3ccncc3)c3cc(Cl)ccc23)c2ncnc(N)c12
InChIKey: GXOALVFPYNWGHO-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2:PS as substrate measured after 1 hrs in presence of by ADP-Glo Kinase assay
Measurement: IC50 = 2043 nM (pChEMBL 5.690000057220459)
Descriptors: MW 404.87, ALogP 3.71, HBA 8, HBD 1, PSA 100.33, QED 0.49
Compound (SMILES): Cc1cccc(CC2(C(=O)N[C@H]3CCNC[C@@H]3F)CC2)c1
InChIKey: OKTCRDVAYVVPPY-GJZGRUSLSA-N
Target: Somatostatin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30872
Assay: Displacement of [125I]somatostatin from human SSTR1 expressed in CHO-K1 cell membrane incubated for 60 mins by microbeta scintillation counter analysis
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 290.38, ALogP 2.13, HBA 2, HBD 2, PSA 41.13, QED 0.89
Compound (SMILES): CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: BAEZCMHLDJIEPF-KFVILGJFSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Antagonist activity at C-terminal HA-tagged human MC3-R stably expressed in HEK293 cells co-expressing GScAMP22P cAMP reporter assessed as inhibition of alpha-MSH induced cAMP production by cell based luminescence assay
Measurement: IC50 = 102.33 nM (pChEMBL 6.989999771118164)
Descriptors: MW 1233.45
Compound (SMILES): OCCSc1nnc(-c2ccc3c(c2)nc(CN2CCC(c4cccc(OCc5ccc(Cl)cc5F)n4)CC2)n3C[C@@H]2CCO2)[nH]1
InChIKey: DTTYCGQUIAGABO-VWLOTQADSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at GLP-1R (unknown origin) transfected in HEK293 cells assessed as beta-arrestin2 recruitment incubated for 5 mins by Envision multiplate reader analysis
Measurement: EC50 = 581 nM (pChEMBL 6.239999771118164)
Descriptors: MW 664.21, ALogP 5.84, HBA 10, HBD 2, PSA 114.21, QED 0.16
Compound (SMILES): NC(=O)[C@H]1CCCCN1C(=O)[C@H]1CC(=O)NCCCC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1
InChIKey: QIMGNSRYFCYLDZ-XPLNXOJDSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO-K1 cells co-expressing G-alpha15 by calcium mobilization assay
Measurement: EC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 720.83, ALogP -1.37, HBA 9, HBD 8, PSA 255.15, QED 0.16
Compound (SMILES): CS(=N)(=O)c1ccccc1-c1ccc(N2CC[C@@H](NC(=O)Nc3ccc(Cl)cc3F)C2=O)c(F)c1F
InChIKey: NPUMXUOJSKGMFM-CUQPBNISSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays: A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 fluorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 536.96, ALogP 5.39, HBA 4, HBD 3, PSA 102.36, QED 0.41
Compound (SMILES): CC[C@](C)(N)c1ccnc(Nc2cc3cc(-c4cnnn4C)nc(N)c3cn2)c1
InChIKey: DDYHLDIRRCTDLO-FQEVSTJZSA-N
Target: Serine/threonine-protein kinase greatwall (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GX5
Assay: Inhibition of MASTL in human MDA-MB-231 cells assessed as reduction in ENSA phosphorylation incubated for 1 hr by sandwich ELISA
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 389.47, ALogP 2.73, HBA 9, HBD 3, PSA 133.45, QED 0.47
Compound (SMILES): C=CC(=O)N1CC(Oc2cc3c(-c4c[nH]nc4-c4cccc(OC)c4)ncnc3cc2OC)C1
InChIKey: NRNQPLOTQBCINB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wildtype EGFR (unknown origin) phosphorylation transfected in human NCI-H2073 cells preincubated for 2 hrs followed by EGF stimulation for 10 mins by HTRF assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 457.49, ALogP 3.48, HBA 7, HBD 1, PSA 102.46, QED 0.42
Compound (SMILES): C/C(=N/O)c1cc2ccc(OCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: DRTMYTUADOXNIZ-JAIQZWGSSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 397.3 nM (pChEMBL 6.400000095367432)
Descriptors: MW 388.4, ALogP 2.22, HBA 7, HBD 2, PSA 132.19, QED 0.3
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cc(NC3CCN(C(=O)OC(C)(C)C)CC3)c(=O)n(C)c2)cc2c1ccn2C(C)(c1ccccn1)c1ccccn1
InChIKey: MAXHXZXXHPTGFC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of N-terminal his6-tagged human BRD4 BD1 (44 to 168 residues) expressed in Escherichia coli Rossetta BL21 (DE3) cells incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 297.9 nM (pChEMBL 6.53000020980835)
Descriptors: MW 711.89, ALogP 6.18, HBA 10, HBD 2, PSA 140.45, QED 0.18
Compound (SMILES): Nc1nc2ccc(C(=O)N3CCN(C(=O)/C=C/c4ccc(Br)cc4)CC3)cc2s1
InChIKey: YVICAZJLKUSZMU-FPYGCLRLSA-N
Target: G-protein coupled receptor 183 (SINGLE PROTEIN), Homo sapiens
UniProt: P32249
Assay: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells assessed as reversal of 7alpha,25-Dihydroxycholesterol induced cAMP reduction incubated for 30 mins by Glosensor cAMP assay
Measurement: IC50 = 0.82 nM (pChEMBL 9.09000015258789)
Descriptors: MW 471.38, ALogP 3.64, HBA 5, HBD 1, PSA 79.53, QED 0.59
Compound (SMILES): O=C(NCCC1CCN(Cc2ccccc2)CC1)c1c[nH]c2ccccc12
InChIKey: RVZBUEBWSLHLKO-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 incubated for 2 hrs by FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 361.49, ALogP 4.2, HBA 2, HBD 2, PSA 48.13, QED 0.69
Compound (SMILES): COC(=O)[C@H](CC(C)C)NC(=O)c1cn(CCCCCF)c2ccccc12
InChIKey: TZVABTORJKXCKT-SFHVURJKSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor stably transfected in AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 7.079 nM (pChEMBL 8.149999618530273)
Descriptors: MW 376.47, ALogP 4.1, HBA 4, HBD 1, PSA 60.33, QED 0.5
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(C#CCCCCCCCNC(=O)OC(C)(C)C)cc3)nc3ccccc3c2[nH]1
InChIKey: KQTJUJIRBPZXIR-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 595.83, ALogP 9.76, HBA 5, HBD 3, PSA 91.93, QED 0.1
Compound (SMILES): C[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O
InChIKey: GTORYCSJDNNQSH-DEUCSSKNSA-N
Target: Methylcytosine dioxygenase TET2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6N021
Assay: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis
Measurement: IC50 ~ 10000 nM (pChEMBL 5)
Descriptors: MW 1731.96
Compound (SMILES): O=C1c2c(ccc(O)c2O)CN1Cc1ccc(O)c(O)c1
InChIKey: IOWJXPQRBSDASB-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase L (SINGLE PROTEIN), Bunyavirus La Crosse
UniProt: A5HC98
Assay: Inhibition of N-terminal His-tagged LACV cap-ENDO expressed in Escherichia coli BL21 Gold (DE3) using 6-FAM/BHQ-1-labeled 12mer poly(A) ssRNA as substrate preincubated for 15 mins followed by substrate addition measured for 20 mins by FRET assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 287.27, ALogP 1.66, HBA 5, HBD 4, PSA 101.23, QED 0.63
Compound (SMILES): COc1cc(-c2cn(C)c(=O)c3cnccc23)cc(Cl)c1CN1CCC(C2CCN(C(=O)c3ccc(NC4CCC(=O)NC4=O)cc3C(F)(F)F)CC2)CC1
InChIKey: GJLBGLYQUJCSAH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 779.26, ALogP 6.26, HBA 9, HBD 2, PSA 125.87, QED 0.2
Compound (SMILES): O=C1c2c(ccc(O)c2O)CN1CCc1ccc(O)cc1
InChIKey: RVHMHWHBWHJEQK-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase L (SINGLE PROTEIN), Bunyavirus La Crosse
UniProt: A5HC98
Assay: Inhibition of N-terminal His-tagged LACV cap-ENDO expressed in Escherichia coli BL21 Gold (DE3) using 6-FAM/BHQ-1-labeled 12mer poly(A) ssRNA as substrate preincubated for 15 mins followed by substrate addition measured for 20 mins by FRET assay
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 285.3, ALogP 2, HBA 4, HBD 3, PSA 81, QED 0.75
Compound (SMILES): O=S(=O)(Cc1ccccc1)Nc1c(F)cc(Oc2ncccc2-c2ccnc(N[C@@H]3CNC[C@H](F)C3)n2)c(F)c1F
InChIKey: RBOAUACOQMQNBF-MSOLQXFVSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of His-tagged IRE1alpha (G547 to L977 residues) (unknown origin) expressed in Sf9 cells preincubated with anti-His Europium labeled antibody for 1 hr prior to compound addition followed by tracer 236 addition and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 588.59, ALogP 4.8, HBA 8, HBD 3, PSA 118.13, QED 0.19
Compound (SMILES): COc1cc(NC(=O)c2cc(=O)c3ccccc3o2)c(C(=O)Nc2ccc(N3CCN(Cc4ccc5c(c4)OCO5)CC3)cc2)cc1OC
InChIKey: GSSBJWZIIJMIQY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human Hepatocyte using Luciferin-IPA as substrate
Measurement: IC50 = 4655 nM (pChEMBL 5.329999923706055)
Descriptors: MW 662.7, ALogP 5.37, HBA 10, HBD 2, PSA 131.81, QED 0.21
Compound (SMILES): Cc1cc(C)cc(Nc2nccc(-c3cc(C(=O)N[C@H](C)CO)n(C)n3)n2)c1
InChIKey: RDZUOEOCBZLODC-CQSZACIVSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of LYN (unknown origin) incubated for 60 mins in presence of ATP by KinaseGlo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.45, ALogP 2.35, HBA 7, HBD 3, PSA 104.96, QED 0.61
Compound (SMILES): Cc1ccc([C@H](F)C(=O)N[C@H](c2ccc(C)c(OCC3(C#N)CC3)c2)[C@@H](C)C(=O)O)cc1
InChIKey: VXEWXCGZPAPUTJ-WTNAPCKOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.5, ALogP 4.57, HBA 4, HBD 2, PSA 99.42, QED 0.6
Compound (SMILES): O=C(O)CCCn1cccc1C(=O)c1ccccc1Cl
InChIKey: BCKGHIMESBAZDY-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane incubated for 90 mins by competition binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 291.73, ALogP 3.24, HBA 3, HBD 1, PSA 59.3, QED 0.83
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(-c2ccc(N3CCCC3c3ccccc3C3CC3)cc2F)cc1Oc1cnc2[nH]ccc2c1
InChIKey: JMPPAQAOUMVRMY-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X Fluorescence Polarization Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-xl protein with its ligand in an assay based on fluorescence polarization methodology. Recombinant human 2.7 nM Bcl-2/1.3 nM Bcl-xl protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 1 μM for Bcl-2 assay, and 10 μM or 1 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 ml potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK (FITC)INR-amide (1 nM for Bcl-2, 0.82 nM for Bcl-xl) was added to plate and further incubated at room temperature for 0.5 h. The FP signals (485 nm-520 nm-520 nm) were read on BMG PHERAstar FS or BMG PHERAstar FSX instalment. The inhibition percentage of Bcl-2/Bcl-xl interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the FP signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 830.94, ALogP 9.25, HBA 10, HBD 3, PSA 168.79, QED 0.08
Compound (SMILES): CC(C)c1ccc(-n2nc(-c3cc(F)ccc3OCCCC(=O)O)cc2-c2ccccc2Cl)cc1
InChIKey: XYNGYSZOLMCUGA-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Fluorescent Displacement Assay: A Nunc black plate was used as a 96-well plate for the purpose of measurement, and to each well was added 40 μL of sodium phosphate buffer and a sodium phosphate buffer solution of FABP3 (AVISCERA BIOSCIENCE) (250 nM, 25 μL), and for a blank, 25 μL of sodium phosphate buffer was added. To each well was added as a detection reagent, a 1,8-ANS (ALDRICH) solution (10 μM, ethanol/sodium phosphate buffer solution=1:4 v/v, 25 μL), and ethanol solutions of compounds diluted to different concentrations were added in an amount of 10 μL each (the final ethanol concentration was 15%). The plate was shaken for 10 sec. in the plate reader and incubated for 10 min. at room temperature. Then, it was subjected to fluorescent measurement at an excitation wavelength of 355 nm and a measurement wavelength of 460 nm. Used for measurement was ARVO X One by PerkinElmer Japan.
Measurement: Kd = 1128 nM (pChEMBL 5.949999809265137)
Descriptors: MW 492.98, ALogP 7.37, HBA 4, HBD 1, PSA 64.35, QED 0.25
Compound (SMILES): COc1ncc(-c2cc(OC3CCOCC3)c3ncnc(C)c3c2)cc1/N=N\c1ccccc1F
InChIKey: KOVMNYOKQJCSAR-MVJHLKBCSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) preincubated for 30 sec under shaking condition followed by 15 mins incubation at 25 degreeC and measured after 60 mins of substrate addition (compound prepared in presence of 365 nm UV light irradiation) by ADP-Glo reagent based assay
Measurement: IC50 = 3.55 nM (pChEMBL 8.449999809265137)
Descriptors: MW 473.51, ALogP 6.12, HBA 8, HBD 0, PSA 91.08, QED 0.31
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(-c2ccc(N3CCCCC3c3ccccc3)cc2)cc1Oc1cnc2[nH]ccc2c1
InChIKey: JEEVMACECLXEOG-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Bcl-2/Bcl-X Fluorescence Polarization Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-xl protein with its ligand in an assay based on fluorescence polarization methodology. Recombinant human 2.7 nM Bcl-2/1.3 nM Bcl-xl protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 1 μM for Bcl-2 assay, and 10 μM or 1 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 ml potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK (FITC)INR-amide (1 nM for Bcl-2, 0.82 nM for Bcl-xl) was added to plate and further incubated at room temperature for 0.5 h. The FP signals (485 nm-520 nm-520 nm) were read on BMG PHERAstar FS or BMG PHERAstar FSX instalment. The inhibition percentage of Bcl-2/Bcl-xl interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the FP signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 786.91, ALogP 8.62, HBA 10, HBD 3, PSA 168.79, QED 0.08
Compound (SMILES): O=C(c1ccc(-c2ccc3ncc(-c4cc5ccccc5o4)n3c2)cc1)N1CCNCC1
InChIKey: LXNUFRAUJVQQOV-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay
Measurement: IC50 = 364.1 nM (pChEMBL 6.440000057220459)
Descriptors: MW 422.49, ALogP 4.46, HBA 5, HBD 1, PSA 62.78, QED 0.47
Compound (SMILES): CCCC(CC)c1nc2c(Nc3ccc(I)cc3)nc3ccccc3c2[nH]1
InChIKey: PRUMEFLIDJLGTG-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 470.36, ALogP 6.75, HBA 3, HBD 2, PSA 53.6, QED 0.31
Compound (SMILES): C=C1C(=O)[C@]23[C@H](O)[C@H]1CC[C@H]2[C@]12C=CCC(C)(C)[C@H]1[C@H](O)[C@@]3(OCCC(=O)O)OC2
InChIKey: NFWAITKLWZRIGK-DMXDCXNVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 418.49, ALogP 1.68, HBA 6, HBD 3, PSA 113.29, QED 0.47
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCN(C)CC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: OIWLSGNPKAUJJL-QLKFWGTOSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of Bcl-2 G101V mutant (unknown origin) using (Ac-GQVGRQLAIIGDK (FITC) INR-amide) as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 875.11, ALogP 8.85, HBA 11, HBD 3, PSA 166.04, QED 0.08
Compound (SMILES): Nc1ccnc2cc(C(=O)Nc3ccccc3)[nH]c12
InChIKey: ZVXQROOOFBQYEM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 phosphatase-only domain (unknown origin) catalytic activity
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 252.28, ALogP 2.4, HBA 3, HBD 3, PSA 83.8, QED 0.65
Compound (SMILES): COc1cc(Nc2nccc(-c3cc(C(=O)N(C)[C@@H](C)CN4CCC4)n(C)n3)n2)cc(OC)c1
InChIKey: DLDBILXNGCZRLQ-INIZCTEOSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Mus musculus
UniProt: P48025
Assay: Inhibition of SYK in IL-3 stimulated mouse BaF3-TEL/SYK cells
Measurement: IC50 = 5170 nM (pChEMBL 5.289999961853027)
Descriptors: MW 465.56, ALogP 2.8, HBA 9, HBD 1, PSA 97.64, QED 0.52
Compound (SMILES): CC(O)(C#Cc1cc2n(n1)CCCN2c1ccnc(NC23CC(C2)C3)n1)c1nccs1
InChIKey: FCEPJTGIGMKUJU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) incubated 30 to 60 mins by ADP-Glo Kinase assay
Measurement: IC50 = 5.39 nM (pChEMBL 8.270000457763672)
Descriptors: MW 433.54, ALogP 2.9, HBA 9, HBD 2, PSA 91.99, QED 0.61
Compound (SMILES): Cl.Fc1ccc([C@@H]2C[C@H]2NCc2cn(-c3ccc(-c4ccccc4)cc3)nn2)cc1F
InChIKey: GSWPDHFALHBKFJ-NXCGSPNESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAO-B (unknown origin) assessed as luminescent signal by MAO-Glo-assay
Measurement: IC50 = 371 nM (pChEMBL 6.429999828338623)
Descriptors: MW 402.45, ALogP 4.86, HBA 4, HBD 1, PSA 42.74, QED 0.5
Compound (SMILES): C#CC(=O)NCCn1cc(-c2ncnc3cc(OC)c(OC)cc23)c(-c2cccc(OC)c2)n1
InChIKey: DBFHHKASHGEKCJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wildtype EGFR (unknown origin) phosphorylation transfected in human NCI-H2073 cells preincubated for 2 hrs followed by EGF stimulation for 10 mins by HTRF assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 457.49, ALogP 2.94, HBA 8, HBD 1, PSA 100.39, QED 0.41
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(C#CCCCCCCCCCN=[N+]=[N-])cc3)nc3ccccc3c2[nH]1
InChIKey: GJHNVXHWGLIYBQ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 15.14 nM (pChEMBL 7.820000171661377)
Descriptors: MW 549.77, ALogP 10.32, HBA 4, HBD 2, PSA 102.36, QED 0.05
Compound (SMILES): C=C(c1ccccc1)c1ccc(C(F)(F)P(=O)(O)O)c2c1oc1ccccc12
InChIKey: FABFVSJJDHFUMQ-UHFFFAOYSA-N
Target: Dual specificity protein phosphatase 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q9ESS0
Assay: Inhibition of mouse MKP-5 (320 to 647 residues) expressed in Escherichia coli BL21(DE3) using DiFMUP as substrate incubated for 10 mins by fluorescence based assay
Measurement: IC50 = 4720 nM (pChEMBL 5.329999923706055)
Descriptors: MW 400.32, ALogP 5.87, HBA 2, HBD 2, PSA 70.67, QED 0.42
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3cccc(I)c3)nc3ccccc3c2[nH]1
InChIKey: XTAFYATXKXYDKO-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 10 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.16 to 8.37 No_unit)
Measurement: EC50 = 34.67 nM (pChEMBL 7.460000038146973)
Descriptors: MW 484.39, ALogP 7.14, HBA 3, HBD 2, PSA 53.6, QED 0.27
Compound (SMILES): CCOc1cccc2cc(/C(C)=N/Nc3nc(-c4ccc(F)cc4)cs3)c(=O)oc12
InChIKey: VMQNBXUTTXEJJP-DHRITJCHSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 6 hrs by phenol red staining based stopped flow CO2 hydrase assay
Measurement: Ki = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 423.47, ALogP 5.29, HBA 7, HBD 1, PSA 76.72, QED 0.26
Compound (SMILES): C=CC(=O)Nc1ccccc1Nc1cc2c(C)nc(-c3c(Cl)c(OC)cc(OC)c3Cl)cc2cn1
InChIKey: BKZCLQWUBOUWAM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) by Z'-LYTE kinase assay
Measurement: IC50 = 3270 nM (pChEMBL 5.489999771118164)
Descriptors: MW 509.39, ALogP 6.8, HBA 6, HBD 2, PSA 85.37, QED 0.27
Compound (SMILES): CCCNNC(=O)CCCCCCNC(=O)c1cc2cnccc2[nH]1
InChIKey: BADMYFPDYIWLBR-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis
Measurement: IC50 = 2.97 nM (pChEMBL 8.529999732971191)
Descriptors: MW 345.45, ALogP 2.27, HBA 4, HBD 4, PSA 98.91, QED 0.37
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(-c3cnn(CCCCCCC(=O)NO)c3)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: NKUPYUFUIQRZCX-FQEVSTJZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length N-terminal GST-tagged human recombinant HDAC6 (1 to 1215 residues) preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 664.69, ALogP 2.45, HBA 12, HBD 4, PSA 183.49, QED 0.1
Compound (SMILES): Cl.O=C(/C=C/c1ccco1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: FBKBGHFTDSIGLZ-KNPGKMNISA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]diprenorphine from human DOR expressed in CHO cells assessed as dissociation constant incubated for 1.5 hrs by radioligand binding assay
Measurement: Kd = 550.9 nM (pChEMBL 6.260000228881836)
Descriptors: MW 446.55, ALogP 3.04, HBA 5, HBD 2, PSA 74.94, QED 0.69
Compound (SMILES): Cc1ccc(S(=O)(=O)N[C@H](CCC(=O)NCC(C)C)C(=O)O)cc1
InChIKey: FPNCESYOAUSRJV-CQSZACIVSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of MMP-8 (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 356.44, ALogP 1.28, HBA 4, HBD 3, PSA 112.57, QED 0.62
Compound (SMILES): O=C1c2c(ccc(O)c2O)CN1Cc1ccc([N+](=O)[O-])cc1
InChIKey: AGABXQTYCAQROR-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase L (SINGLE PROTEIN), Bunyavirus La Crosse
UniProt: A5HC98
Assay: Inhibition of N-terminal His-tagged LACV cap-ENDO expressed in Escherichia coli BL21 Gold (DE3) using 6-FAM/BHQ-1-labeled 12mer poly(A) ssRNA as substrate preincubated for 15 mins followed by substrate addition measured for 20 mins by FRET assay
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 300.27, ALogP 2.16, HBA 5, HBD 2, PSA 103.91, QED 0.51
Compound (SMILES): O=C(Nc1ccc2c(c1)C=CS(=O)(=O)O2)c1ccc(F)c(S(=O)(=O)N2CCCCC2)c1
InChIKey: HATVZLVCIPCKFD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 30.6 nM (pChEMBL 7.510000228881836)
Descriptors: MW 466.51, ALogP 2.95, HBA 6, HBD 1, PSA 109.85, QED 0.69
Compound (SMILES): Clc1ccc(Nc2nc(-c3nc(-c4ccccc4)cs3)cs2)cc1
InChIKey: CCGQETNDZUSLTK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-O-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 3913.5 nM (pChEMBL 5.409999847412109)
Descriptors: MW 369.9, ALogP 6.33, HBA 5, HBD 1, PSA 37.81, QED 0.46
Compound (SMILES): C=CC(=O)N1CC[C@H](n2cc(-c3ccncc3)c(-c3cccc(NC(=O)c4ccc5c(c4)CN(C)C5=O)c3)n2)C1
InChIKey: ZRSILAUGDKDGPL-VWLOTQADSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR D770_N771insSVD mutant (unknown origin) phosphorylation transfected in human NCI-H2073 cells incubated for 2 hrs by HTRF assay
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 532.6, ALogP 4.41, HBA 6, HBD 1, PSA 100.43, QED 0.37
Compound (SMILES): CCN(CC)CCNC(=O)[C@H]1CC[C@H](NC(=O)c2cnc3nc2Nc2ccc(OC)c(c2)OC/C=C\CN3)CC1
InChIKey: HQMSWMADUGUYFF-SAGPEPNNSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by MCE assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 551.69, ALogP 3.34, HBA 9, HBD 4, PSA 129.74, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(NC(=O)c3cnc4nc3Nc3ccc(C#N)c(c3)OC/C=C\CN4)cc2)CC1
InChIKey: PHLXDZNTGVMWGX-IHWYPQMZSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by MCE assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 496.58, ALogP 3.46, HBA 9, HBD 3, PSA 118.44, QED 0.47
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](NC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCN2CCC(Cc3ccccc3)CC2)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: KQAFSYXROGCRFB-LKZWIQFFSA-N
Target: Neuropeptide FF receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ6
Assay: Displacement of [125I]-1DMeNPFF from human NPFFR1 expressed in CHO cell membrane incubated for 1 hr by Topcount counting method
Measurement: Ki = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 1056.33