lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCn1nc(C2CC2)cc1Nc1nc(C(=O)NCCCOCCOCCOCCCNc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)nc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XEJMFVWHCPNMRS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 bromodomain 1 in human Ramos cells
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 946.03, ALogP 5.3, HBA 17, HBD 5, PSA 259.05, QED 0.04
Compound (SMILES): COc1cc(C2CC(c3cccc(-n4cnnn4)c3)=NN2)cc(OC)c1OC
InChIKey: CRIXUXNTLYDAIZ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 380.41, ALogP 2.13, HBA 9, HBD 1, PSA 95.68, QED 0.7
Compound (SMILES): CCCCOc1nc(N)c2[nH]c(=O)n(CCCCC3CCCCO3)c2n1
InChIKey: MFRCGVPWKBJJAF-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at TLR7 in cryopreserved human PBMC assessed as IFN-alpha production after 24 hrs by MSD assay
Measurement: EC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 363.46, ALogP 2.62, HBA 7, HBD 2, PSA 108.05, QED 0.66
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCC3CCNCC3)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: WRLIXNPBHOQWLQ-UHFFFAOYSA-M
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Inhibition of HIS-tagged recombinant Leishmania infantum TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 531.75, ALogP 4.27, HBA 7, HBD 2, PSA 81.87, QED 0.21
Compound (SMILES): COC(=O)c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)CC(C)(C)C)cc1
InChIKey: LUXKEEIMLQRZAH-CVEARBPZSA-N
Target: von Hippel-Lindau disease tumor suppressor (SINGLE PROTEIN), Homo sapiens
UniProt: P40337
Assay: Binding affinity to VHL E3 ligase (unknown origin) by fluorescence polarization (FP) assay
Measurement: IC50 = 53200 nM (pChEMBL 4.269999980926514)
Descriptors: MW 376.45, ALogP 1.49, HBA 5, HBD 2, PSA 95.94, QED 0.76
Compound (SMILES): O=C(Nc1cccnc1)c1ccnn2c(NCC3CC3)cnc12
InChIKey: HXAODWZKEDXMRG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of full length GST-tagged human recombinant GSK3-alpha using FL-KRREILSRRP[ps]ERYR-NH2 as substrate incubated for 20 hrs
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 308.35, ALogP 2.2, HBA 6, HBD 2, PSA 84.21, QED 0.75
Compound (SMILES): CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(Cc1cccc(OCC(=O)OC)c1)C(=O)CN1CCCCC1
InChIKey: OAGLFSGRIBUNSB-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 transfected in HEK293 cells assessed as induction of SEAP production incubated overnight by SEAP reporter gene based assay
Measurement: EC50 = 135.1 nM (pChEMBL 6.869999885559082)
Descriptors: MW 600.76, ALogP 4.97, HBA 9, HBD 1, PSA 115.81, QED 0.2
Compound (SMILES): Cn1cc(Nc2nc(NC3COC3)c3nc(CC#N)ccc3n2)cn1
InChIKey: GUMLSJFARGTKIB-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) in presence of ATP by enzymatic assay
Measurement: IC50 = 447 nM (pChEMBL 6.349999904632568)
Descriptors: MW 336.36, ALogP 1.38, HBA 9, HBD 2, PSA 113.57, QED 0.72
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cccnc3C)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: BLLJUCXNHUVEHL-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in human Jurkat cells assessed as inhibition constant incubated for 1 hr by HTRF assay
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 528.59, ALogP 3.81, HBA 8, HBD 3, PSA 126.49, QED 0.33
Compound (SMILES): O=C(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)N1CCCn2cccc2C1c1ccccc1
InChIKey: OLEDVGXMMNXDSS-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at TGR5 in human HEK293 cells assessed as increase in cAMP production
Measurement: EC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 452.4, ALogP 6.16, HBA 2, HBD 0, PSA 25.24, QED 0.43
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(C)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: BVVMGUQEMUEAHE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human N-terminal His6-tagged recombinant full-length PLK1 expressed in baculovirus infected Sf9 cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 474.57, ALogP 2.24, HBA 10, HBD 2, PSA 104.34, QED 0.45
Compound (SMILES): Cc1c(C2CC3(CNCCO3)C2)sc2[nH]c(-c3cn4ncnc4c4c3CCC4)c(C(C)C)c12
InChIKey: ZFTAKZHGZFJNOZ-DYNODNKPSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay
Measurement: EC50 = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 461.64, ALogP 5.1, HBA 6, HBD 2, PSA 67.24, QED 0.45
Compound (SMILES): CC(C)(O)C12CC(C1)N(c1cc(-n3ncc4ccc(C5(C#N)CC5)cc43)ncn1)C2
InChIKey: JCFAEVGLSCFNOD-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of GST20-tagged human LRRK2 G2019S mutant using LRRKtide peptide preincubated for 15 mins followed by substrate addition and measured after 90 mins by TR-FRET assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 400.49, ALogP 3.11, HBA 7, HBD 1, PSA 90.86, QED 0.72
Compound (SMILES): O=C(Nc1nc2cc(C(F)(F)F)ccc2[nH]1)C1CC1c1ccccc1
InChIKey: FWLLGFWJIGDNEX-UHFFFAOYSA-N
Target: Lysophosphatidic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBW0
Assay: Inhibition of LPA2 receptor (unknown origin)
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 345.32, ALogP 4.32, HBA 2, HBD 2, PSA 57.78, QED 0.74
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C(C)=O)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: HHLHKPYGNVLWFW-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: ASV & NPG EGFR Exon 20 Insertion Mutations: A compound's ability in selectively inhibiting EGFR exon 20 insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 20 insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions NPG (H773_V774insNPG) or ASV (V769_D770insASV), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR exon 20 insertions (named Ba/F3-EGFR-Exon20-NPG or Ba/F3-EGFR-Exon20-ASV) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds were determined as follows: BaF3-EGFR-Exon20 cells (NPG or ASV) seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega) This assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives. Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 613.72, ALogP 5.2, HBA 11, HBD 2, PSA 130.92, QED 0.16
Compound (SMILES): O=C(OCc1cc(Cl)cc(Cl)c1)N1CCN(C2CN(C(=O)c3ccc4c(c3)B(O)OC4)C2)CC1
InChIKey: PSAPYVMRXXTWPF-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human recombinant ATX
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 504.18
Compound (SMILES): Cc1ccc2cccc(S(=O)(=O)Nc3ccccc3C#Cc3ccc(C(=O)O)nc3)c2n1
InChIKey: PMLXPQSQGBRBFW-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Binding affinity to full-length C-terminal GFP-tagged human MCT4 incubated for 1 hrs by fluorescence cross-correlation spectroscopy analysis
Measurement: IC50 = 579 nM (pChEMBL 6.239999771118164)
Descriptors: MW 443.48, ALogP 3.84, HBA 5, HBD 2, PSA 109.25, QED 0.46
Compound (SMILES): Cc1c(NC(=O)c2nc3c(s2)CNCC3)cccc1-c1cccc2[nH]ncc12
InChIKey: KKTYFCMSPIVBTR-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 389.48, ALogP 3.89, HBA 5, HBD 3, PSA 82.7, QED 0.5
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CCCl)[C@@H]1CCC2=O
InChIKey: QKXHIGCQJRMURJ-VDWQKOAOSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 7998.34 nM (pChEMBL 5.099999904632568)
Descriptors: MW 334.89, ALogP 4.7, HBA 2, HBD 0, PSA 34.14, QED 0.69
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3nnc(-c4ccc5[nH]ccc5c4)s3)C3CCN2CC3)c1
InChIKey: ADPGBLDMLCUZBX-RTWAWAEBSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Binding affinity to alpha7 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 11.1 nM (pChEMBL 7.960000038146973)
Descriptors: MW 417.54, ALogP 4.17, HBA 6, HBD 1, PSA 66.93, QED 0.53
Compound (SMILES): C[C@@H]1[C@H](O)[C@@H](CSCCCNC(=N)NCCCC[C@@H](N)C(N)=O)O[C@H]1n1cnc2c(N)ncnc21
InChIKey: HWGPUBUWBOCZRP-JWCPYIQLSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Inhibition of human PRMT1 by fluorescence-based SAHH-coupled assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 508.65, ALogP -0.48, HBA 11, HBD 7, PSA 216.1, QED 0.1
Compound (SMILES): COc1ccc2c(c1)c(CC(=O)NC(=S)Nc1ccc(Cl)cc1)c(C)n2C(=O)c1ccc(Cl)cc1
InChIKey: CKVDXPYUDXZVST-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX-2 colorimetric enzyme immunoassay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 526.45, ALogP 6.01, HBA 5, HBD 2, PSA 72.36, QED 0.31
Compound (SMILES): COc1ccc(C(=O)Nc2nc(NC(=O)c3ccccc3)nn2-c2ccccc2)cc1
InChIKey: MYEJFECSKROJSO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase inhibitor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P38936
Assay: Inhibition of p21 (unknown origin)
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 413.44, ALogP 3.78, HBA 6, HBD 2, PSA 98.14, QED 0.5
Compound (SMILES): CC(C)OP(=O)(OC(C)C)C(Cc1cc(C2CCCCC2)nc(C(C)(C)C)c1)P(=O)(OC(C)C)OC(C)C
InChIKey: BOAUYYANDYPVOX-UHFFFAOYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Induction of HMGCR degradation in HEK293 cells incubated for 4 hrs by luciferase based assay
Measurement: EC50 = 598 nM (pChEMBL 6.21999979019165)
Descriptors: MW 573.69, ALogP 9.38, HBA 7, HBD 0, PSA 83.95, QED 0.22
Compound (SMILES): CCOP(=O)(OCC)C(NC(=O)c1cc(-c2ccsc2)n(-c2ccc(S(N)(=O)=O)cc2)n1)c1ccccc1OC
InChIKey: VMRNULJRRJOOJG-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 604.65, ALogP 4.95, HBA 10, HBD 2, PSA 151.84, QED 0.22
Compound (SMILES): CC(C)(C)C1CCC(c2cc(C(=O)N3CCC(Oc4cc(N5CCNCC5)ccc4Cl)CC3)ccc2O[C@H]2CCNC2)CC1.Cl.Cl
InChIKey: LPYGBCRUPYRXDI-IDPPSCOXSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)/N-terminal biotinylated human BCL9 HD2 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 623.28, ALogP 6.49, HBA 6, HBD 2, PSA 66.07, QED 0.37
Compound (SMILES): CCCN(CCc1cc(O)c(CCN(CCC)[C@H]2CCc3nc(N)sc3C2)cc1O)[C@H]1CCc2nc(N)sc2C1
InChIKey: WLQPRUMGPAOCRW-VXKWHMMOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]-spiroperidol from rat D2L receptor expressed in HEK293 cells assessed as inhibition constant by Cheng-Prusoff equation analysis
Measurement: Ki = 54.7 nM (pChEMBL 7.260000228881836)
Descriptors: MW 584.86, ALogP 4.8, HBA 10, HBD 4, PSA 124.76, QED 0.22
Compound (SMILES): O=S(=O)([O-])OC[C@@H]1O[C@H](O[C@H]2[C@H](OS(=O)(=O)[O-])[C@H](OS(=O)(=O)[O-])[C@@H](O[C@H]3[C@H](OS(=O)(=O)[O-])[C@H](OS(=O)(=O)[O-])[C@@H](OS(=O)(=O)[O-])O[C@@H]3COS(=O)(=O)[O-])O[C@H]2COS(=O)(=O)[O-])[C@@H](OS(=O)(=O)[O-])[C@@H](OS(=O)(=O)[O-])[C@@H]1O[C@H]1O[C@@H](COS(=O)(=O)[O-])[C@@H](OS(=O)(=O)[O-])[C@H](OS(=O)(=O)[O-])[C@@H]1OS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
InChIKey: RHKKFRZLJMEYJD-JIDQTGHFSA-A
Target: Heparanase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y251
Assay: Inhibition of heparanase (unknown origin) incubated for 18 hrs by fondaparinux assay
Measurement: IC50 = 416 nM (pChEMBL 6.380000114440918)
Descriptors: MW 1787.48
Compound (SMILES): O=C(NO)c1ccc(CN2CC(=O)N(Cc3cccc(Cl)c3)[C@H](Cc3ccccc3)C2=O)cc1
InChIKey: GUNBRUHPJCKSKN-HSZRJFAPSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 8550 nM (pChEMBL 5.070000171661377)
Descriptors: MW 477.95, ALogP 3.44, HBA 4, HBD 2, PSA 89.95, QED 0.4
Compound (SMILES): CNCC1Cc2cc(F)cc(-c3ccc(Cl)cc3Cl)c2O1
InChIKey: LYHHUZTWGZOEKQ-UHFFFAOYSA-N
Target: Aquaporin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29972
Assay: Inhibition of human AQP1 water channel expressed in CHO cells incubated for 10 mins by FLIPR Tetra assay
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 326.2, ALogP 4.32, HBA 2, HBD 1, PSA 21.26, QED 0.91
Compound (SMILES): O=C(N[C@H]1CCNC1=O)c1cnc2nc(C3CC3)c(Cl)cc2c1
InChIKey: QSQHSIMHBOHOJE-LBPRGKRZSA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O60760
Assay: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 330.78, ALogP 1.78, HBA 4, HBD 2, PSA 83.98, QED 0.9
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)CC1
InChIKey: CTYFJJGDZUXTIC-RRPNLBNLSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L
Measurement: IC50 = 45940 nM (pChEMBL 4.340000152587891)
Descriptors: MW 602.68, ALogP 3.67, HBA 7, HBD 2, PSA 105.9, QED 0.33
Compound (SMILES): CC(=O)N1CCC(c2cc3c(N[C@H](C)c4cccc(C(F)(F)F)c4C)ncnc3n(C)c2=O)CC1
InChIKey: LPEJCOUGTBYZQU-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of 6His-tagged SOS1 (unknown origin) mediated GST-tagged KRAS G12D activation preincubated for 15 mins followed by KRAS G12D addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 487.53, ALogP 4.55, HBA 6, HBD 1, PSA 80.12, QED 0.58
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(C5CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: IBFWZLVKHAJJDH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of human N-terminal His6-tagged recombinant full-length PLK1 expressed in baculovirus infected Sf9 cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 528.66, ALogP 3.82, HBA 10, HBD 2, PSA 104.34, QED 0.39
Compound (SMILES): CCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1)C(=O)C(=O)NCc1ccccn1
InChIKey: PLVWMBFPIAQRHK-VXKWHMMOSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS CoV-2 Main protease expressed in Escherichia coli BL21(DE3) by FRET analysis
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 482.58, ALogP 2.89, HBA 6, HBD 3, PSA 126.49, QED 0.38
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccccc2C#Cc2ccc(C(=O)O)cc2)c(C)c1C
InChIKey: SGEZOSSQJLHFCS-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human MDA-MB-231 cells assessed as inhibition of lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 435.5, ALogP 4.21, HBA 4, HBD 2, PSA 92.7, QED 0.59
Compound (SMILES): CN1CCCCCN[C@@H](Cc2ccc(Cl)cc2)CC(=O)N[C@H]2CCc3ccccc3N(CC(=O)N[C@H](Cc3ccc(Cl)c(Cl)c3)CC1=O)C2=O
InChIKey: QSVKLXVZKQEZQJ-VATRQPNGSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Binding affinity to N-terminal his6-tagged human recombinant Mcl-1 expressed in Escherichia coli assessed as dissociation constant by SPR analysis
Measurement: Kd = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 741.16, ALogP 5.76, HBA 5, HBD 3, PSA 110.85, QED 0.32
Compound (SMILES): CC(C)(C)C1CCC(c2cc(C(=O)N3CCC(Oc4cc(N5CCNCC5)cc(F)c4F)CC3)ccc2O[C@H]2CCNC2)CC1.Cl.Cl
InChIKey: CTMZMCRCOXTORC-WKAXZJORSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)/N-terminal biotinylated human BCL9 HD2 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 624.82, ALogP 6.12, HBA 6, HBD 2, PSA 66.07, QED 0.39
Compound (SMILES): Nc1nc(Cl)cc(Oc2ccc3c(C(=O)Nc4cccc(C(F)(F)F)c4)cccc3c2)n1
InChIKey: LVCPXLQPUCRFEF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGF-induced human VEGFR2 autophosphorylation transfected in CHO cells measured after 2 hrs by chemiluminescence assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 458.83, ALogP 5.93, HBA 5, HBD 2, PSA 90.13, QED 0.37
Compound (SMILES): C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC=C5C[C@@H](O)C[C@@H](O[C@@H]6O[C@H](C)[C@H](O)[C@H](O[C@@H]7OC[C@@H](O)[C@H](O)[C@H]7O)[C@H]6O[C@@H]6O[C@@H](C)[C@H](O)[C@@H](O)[C@H]6O)[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C
InChIKey: FHKHGNFKBPFJCB-LYLKFOBISA-N
Target: Solute carrier family 22 member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O15245
Assay: Inhibition of OCT1(unknown origin)-mediated ASP+ uptake in HEK293 cells expressing OCT1 using ASP+ as substrate incubated for 5 mins
Measurement: IC50 = 41280 nM (pChEMBL 4.380000114440918)
Descriptors: MW 855.03, ALogP 0.85, HBA 16, HBD 8, PSA 235.68, QED 0.17
Compound (SMILES): O=C(CNc1cc(F)cc(C(F)(F)F)c1)N1CCC[C@@H](Nc2ncnc3[nH]ccc23)C1
InChIKey: YKJARMJWOWCALV-CQSZACIVSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of unphosphorylated BTK (unknown origin) in the presence of ATP by FRET assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 436.41, ALogP 3.63, HBA 5, HBD 3, PSA 85.94, QED 0.53
Compound (SMILES): COc1cc2c(cc1OC)C(=O)/C(=C/c1ccc(OCCN3CCCCC3)cc1)C2
InChIKey: WVGABZRHRYHCCO-XSFVSMFZSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AchE by Ellman's method
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 407.51, ALogP 4.39, HBA 5, HBD 0, PSA 48, QED 0.64
Compound (SMILES): Cc1ccc(Nc2nc(N)nc(COc3cc(N4CCCC4=O)cc(C(C)(C)C)c3)n2)cc1Cl
InChIKey: VTISBYJHFANBST-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at N-terminal FLAG tagged human FFAR4 transfected in African green monkey COS-7 cells assessed as accumulation of inositol phosphate incubated for 90 mins by TopCount NXT counter based analysis
Measurement: EC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 481, ALogP 5.16, HBA 7, HBD 2, PSA 106.26, QED 0.5
Compound (SMILES): CNC(=O)c1nn(C)cc1NC(=O)c1ccc2cnc(NCCN)nn12.O=C(O)C(F)(F)F
InChIKey: NDPMJBVZEKVFHD-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of human GST-tagged IRAK4 incubated for 30 mins in presence of ATP by fluorescent polarization assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 357.38, ALogP -0.55, HBA 9, HBD 4, PSA 144.26, QED 0.46
Compound (SMILES): C=CC(=O)Nc1ccc(-n2nc(C(C)C)c(-c3c(C)ccc4[nH]ncc34)c2C)c(F)c1
InChIKey: DKNNJRNFDCLOQZ-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in ERK phosphorylation incubated for 6 hrs by MSD assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 417.49, ALogP 5.42, HBA 4, HBD 2, PSA 75.6, QED 0.43
Compound (SMILES): Cc1nc2ccccc2n1-c1cnnc(Nc2ccc(OC(F)F)cc2)n1
InChIKey: GKNDXGKBTJRVSQ-UHFFFAOYSA-N
Target: Polycomb complex protein BMI-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35226
Assay: Inhibition of BMI1 (unknown origin) by ELISA assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 368.35, ALogP 3.86, HBA 7, HBD 1, PSA 77.75, QED 0.58
Compound (SMILES): CC(C)(O)[C@@H](NC(=O)C1(C(F)(F)F)CCCCC1)C(=O)Nc1nnc(Cc2ccc(C#N)cc2)s1
InChIKey: OROCEINYIZEWEB-KRWDZBQOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 21 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK80
Assay: Inhibition of human full length USP21 using Btn-Ahx-PNIRFLD-K(Ubi)-LPQQT-GD-amide as substrate preincubated for 15 to 20 mins followed by substrate addition and measured after 25 mins by HTRF assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 509.55, ALogP 3.71, HBA 7, HBD 3, PSA 128, QED 0.52
Compound (SMILES): Clc1cc(Nc2nc(-c3nccs3)cs2)cc(Cl)c1Cl
InChIKey: KHOPUVQYPHBWKK-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 7.452 nM (pChEMBL 8.130000114440918)
Descriptors: MW 362.69, ALogP 5.97, HBA 5, HBD 1, PSA 37.81, QED 0.58
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CCn1cc(CNC(=O)c2cc3ccccc3[nH]2)nn1
InChIKey: ZCKIEICGPWNFBV-KSFYIVLOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-(R)-(+)7-OH-DPAT from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 13500 nM (pChEMBL 4.869999885559082)
Descriptors: MW 460.54, ALogP 2.13, HBA 8, HBD 3, PSA 126.98, QED 0.39
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cnn(C)c5)ccc4n3)cn2)CC1
InChIKey: WGMWEVJCHUDPID-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) in presence of ATP by enzymatic assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 459.56, ALogP 3.56, HBA 10, HBD 1, PSA 98.81, QED 0.47
Compound (SMILES): N=C(N)NCCC[C@@H](N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1C[C@H](O)C[C@H]1C(=O)NCC(=O)N[C@@H](Cc1cccs1)C(=O)N[C@@H](CO)C(=O)N[C@@H]1Cc2ccccc2CN(CC(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C1=O
InChIKey: BSEBJMALANNKSB-ABNZPDLFSA-N
Target: B2 bradykinin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30411
Assay: Antagonist potency at B2 bradykinin receptor (unknown origin)
Measurement: Kd = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 1210.39
Compound (SMILES): O=C(NC1CCNCC1)c1cc2c(NC(=O)c3c(Cl)cccc3Cl)ccnc2[nH]1
InChIKey: LJRSRJRCXIJFJO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/Cyclin E1 (unknown origin) assessed as inhibition of substrate peptide phosphorylation using eIF4E-binding protein 1 as peptide substrate incubated for 4 hrs in presence of ATP by Lance Ultra HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 432.31, ALogP 3.6, HBA 4, HBD 4, PSA 98.91, QED 0.51
Compound (SMILES): O=C(Nc1cncc(-c2ccccc2F)c1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: DCGYJAQAXSBBMF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): CCCC(=O)c1sc(-c2cccc(F)c2)nc1O
InChIKey: CSBIPFKLSRWESZ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in ethyl 4-methoxy-2-phenylthiazole-5-carboxylate induced Ca2+ efflux preincubated for 5 mins followed by ethyl 4-methoxy-2-phenylthiazole-5-carboxylate addition and measured for 3 mins by FLIPR assay
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 265.31, ALogP 3.64, HBA 4, HBD 1, PSA 50.19, QED 0.86
Compound (SMILES): O=C1C2Cc3c([nH]c4ccccc34)[C@@H](c3ccc4c(c3)OCO4)N2C(=O)CN1CCC1CCN(Cc2ccccc2)CC1
InChIKey: KVANOXIAOYTXBY-VWERDZHISA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin)
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 576.7, ALogP 4.88, HBA 5, HBD 1, PSA 78.11, QED 0.35
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccccc2)S(=O)(=O)c2ccc3ccccc3c2)cc1O
InChIKey: WGIGWPOXLUWDBM-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 11395 nM (pChEMBL 4.940000057220459)
Descriptors: MW 433.49, ALogP 4.64, HBA 4, HBD 2, PSA 94.91, QED 0.46
Compound (SMILES): CC1c2nnc(C(F)(F)F)n2CCN1C(=O)C[C@H](N)Cc1cc(F)c(F)cc1F.Cl
InChIKey: QYXSQTCNDFEYSX-JDXSOMNQSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP-4 (unknown origin)
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 421.35, ALogP 2.58, HBA 5, HBD 1, PSA 77.04, QED 0.61
Compound (SMILES): Cc1cncc2cccc(S(=O)(=O)N3CCNCC[C@@H]3C)c12
InChIKey: MXHZTZIKTRBFFS-ZDUSSCGKSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of ROCK1 (unknown origin)
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 319.43, ALogP 1.92, HBA 4, HBD 1, PSA 62.3, QED 0.92
Compound (SMILES): CCOC(=O)COc1cccc(CN(CCCn2c(CCOC)nc3c(N)nc4ccccc4c32)C(=O)CN(CC)CC)c1OC
InChIKey: VHKZECWRWBZSQV-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 transfected in HEK293 cells assessed as induction of SEAP production incubated overnight by SEAP reporter gene based assay
Measurement: EC50 = 95.7 nM (pChEMBL 7.019999980926514)
Descriptors: MW 634.78, ALogP 4.07, HBA 11, HBD 1, PSA 134.27, QED 0.16
Compound (SMILES): O=C(O)c1cccc(-c2nc(N3[C@@H]4CC[C@H]3C[C@@H](OCc3c(-c5c(Cl)cccc5Cl)noc3C3CC3)C4)no2)n1
InChIKey: XGNRESDUIUGQQG-FVQHAEBGSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR (unknown origin)
Measurement: EC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 582.44, ALogP 6.39, HBA 9, HBD 1, PSA 127.61, QED 0.25
Compound (SMILES): CC#CC(=O)Nc1ccc(Oc2ccc(NC(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)c(C)c2)cn1
InChIKey: LZLPOZLPCFKHGA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant His-tagged human FGFR4 (781 to 1338 residues) expressed in insect cells incubated for 1 hr by caliper mobility shift assay
Measurement: IC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 580.61, ALogP 5.55, HBA 6, HBD 3, PSA 98.83, QED 0.32
Compound (SMILES): Cc1nn(C)c2ccc(N(Cc3ccc(F)cc3)C(=O)NCCCn3cncc3C)cc12
InChIKey: OQTAXPXFMBBVCF-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 434.52, ALogP 4.33, HBA 5, HBD 1, PSA 67.98, QED 0.44
Compound (SMILES): NC(=O)N1N=C(c2ccc(Cl)cc2)CC1c1cn(-c2ccccc2)nc1-c1ccc(F)cc1
InChIKey: QFPGXHUSRVMYNK-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2 using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 459.91, ALogP 5.56, HBA 4, HBD 1, PSA 76.51, QED 0.43
Compound (SMILES): NC[C@H]1O[C@@H](O[C@@H](C#Cc2cccc(C(=O)O)c2)[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H]1O
InChIKey: TXDTZQLBZPHJLH-YGJJZIGLSA-N
Target: Phospho-N-acetylmuramoyl-pentapeptide-transferase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0C1R8
Assay: Inhibition of Staphylococcus aureus MraY using UDP-MurNAc-dansylpentapeptide as substrate incubated for 3 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 519.46, ALogP -3.3, HBA 12, HBD 7, PSA 226.79, QED 0.19
Compound (SMILES): O=C(Nc1ccc2c(c1)C(=O)CC2)c1nnc(Sc2c(Cl)cncc2Cl)s1
InChIKey: AFYZZFSFDVZKMP-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-EKL as substrate
Measurement: EC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 437.33, ALogP 4.77, HBA 7, HBD 1, PSA 84.84, QED 0.63
Compound (SMILES): O=[N+]([O-])c1cc(CNCCCNC2CCCCC2)ccc1CNCCCNC1CCCCC1
InChIKey: FRYAFEXWCVGVPH-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Binding affinity to CXCR4 (unknown origin) expressed in CHO cells incubated for 40 mins by competitive binding assay method
Measurement: IC50 = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 459.68, ALogP 4.4, HBA 6, HBD 4, PSA 91.26, QED 0.18
Compound (SMILES): CN1CCC[C@H]1Cc1c[nH]c2cccc(OCc3ccccc3)c12
InChIKey: FQTZZHAWEBFBAW-SFHVURJKSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: i. Prepare the assay buffer following the table below;Reagent ConcentrationTris 50 mMCaCl2  4 mMBSA 0.1% (w/v)Adjust pH to 7.4 followed by 0.2 μM sterile filtrationii. Preparation of 8 doses of reference and exemplary test compounds starting from 10 mM stock solution as requested by 5-fold serial dilutions with 100%;iii. Prepare (v/v) DMSO: a. Add 50 μl/well of 0.5% (v/v) PEI to UniFilter-96 GF/B plates. Seal the plates and incubate at 4° C. for 3 hrs; b. After incubation, wash the plates 3 times with ice-cold wash buffer (50 mM Tris, pH7.4);iv. Preparation of assay plates: a. Dilute cell membrane with assay buffer and add 330 μl/well to 96 round deep well plates to reach a concentration of 20 μg/well; b. Prepare 8 concentrations of reference or exemplary test compounds and add 110 μl/well to 96 round deep well plates; c. Dilute [3H]-ketanserin with assay buffer to 5 nM (5× final concentration) and add 110 μl/well to 96 round deep well plates.v. Centrifuge the plate at 1000 rpm for 30 secs and then agitate at 600 rpm, R.T. for 5 min.vi. Seal the plates and incubate the plate at 27° C. for 90 min.vii. Stop the incubation by vacuum filtration onto GF/B filter plates followed by 4 times washing with ice-cold wash buffer (50 mM Tris, pH7.4).vii. Dry the plates at 37° C. for 45 min.ix. Seal the filter plates and add 40 μl/well of scintillation cocktail.x. Read the plate by using a Microbeta2 microplate counter.
Measurement: EC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 320.44, ALogP 4.38, HBA 2, HBD 1, PSA 28.26, QED 0.76
Compound (SMILES): Cc1ccc(-c2ccc3cc(OC[C@H](O)CF)ccc3n2)cn1
InChIKey: FBXCMFBJUZVBJS-OAHLLOKOSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 59.3 nM (pChEMBL 7.230000019073486)
Descriptors: MW 312.34, ALogP 3.31, HBA 4, HBD 1, PSA 55.24, QED 0.79
Compound (SMILES): CCOC(=O)Nc1nc2ccc(-c3cc(Cc4n[nH]c(=O)c5ccccc45)ccc3F)cc2[nH]1
InChIKey: DCSUGHIXMFUMOQ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin)
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 457.47, ALogP 4.76, HBA 5, HBD 3, PSA 112.76, QED 0.35
Compound (SMILES): O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)cc2)CC1
InChIKey: WCAGCKMTLAATQU-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor extracted from HEK293 cell membrane assessed as inhibition constant incubated for 1 hrs by radioligand competitive binding based scintillation counter analysis
Measurement: Ki = 2454.71 nM (pChEMBL 5.610000133514404)
Descriptors: MW 383.92, ALogP 3.83, HBA 3, HBD 0, PSA 26.79, QED 0.78
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-c3noc(-c4ccc(OCCF)c(C(F)(F)F)c4)n3)cc2)C1
InChIKey: GBHNMMILYUXCPU-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 465.4, ALogP 4.29, HBA 6, HBD 1, PSA 88.69, QED 0.5
Compound (SMILES): CCC(CC)(NC(=O)c1ccc(N2CC(OC)C2)c(OC[C@H]2C[C@@H]2CO)n1)C(=O)OCCCF
InChIKey: XHLLTWSYWBSEOC-IAGOWNOFSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Radioligand Binding Assay: The affinity of the compounds of the invention for cannabinoid CB1 receptors was determined using recommended amounts of membrane preparations (PerkinElmer) of human embryonic kidney (HEK) cells expressing the human CNR1 or CNR2 receptors in conjunction with 1.5 or 2.6 nM [3H]-CP-55,940 (Perkin Elmer) as radioligand, respectively. Binding was performed in binding buffer (50 mM Tris, 5 mM MgCl2, 2.5 mM EDTA, and 0.5% (wt/vol) fatty acid free BSA, pH 7.4 for CB1 receptor and 50 mM Tris, 5 mM MgCl2, 2.5 mM EGTA, and 0.1% (wt/vol) fatty acid free BSA, pH 7.4 for CB2 receptor) in a total volume of 0.2 ml for 1 h at 30Â° C. shaking. The reaction was terminated by rapid filtration through microfiltration plates coated with 0.5% polyethylenimine (UniFilter GFB filter plate; Packard). Bound radioactivity was analyzed for Ki using nonlinear regression analysis (Activity Base, ID Business Solution, Limited), with the Kd values for [3H]CP55,940 determined from saturation experiments. The compounds of formula (I) show an excellent affinity for the CB2 receptor.
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 481.57, ALogP 2.12, HBA 8, HBD 2, PSA 110.22, QED 0.31
Compound (SMILES): COc1ccc(/C=C/C(=O)c2cc(I)c(Cl)cc2O)cc1
InChIKey: QLCWXMQTECDEPJ-QPJJXVBHSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin)
Measurement: IC50 = 13.82 nM (pChEMBL 7.860000133514404)
Descriptors: MW 414.63, ALogP 4.55, HBA 3, HBD 1, PSA 46.53, QED 0.45
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(-c5ccccn5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: GLVMCPYFBLZASU-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human full length GST-tagged WEE1 expressed in insect cells incubated for 15 mins followed by ATP addition by ADP Glo luminescent assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 537.63, ALogP 3.08, HBA 11, HBD 2, PSA 117.23, QED 0.34
Compound (SMILES): Cc1onc(-c2ccccc2)c1/C=C/CCCCCNC(=O)CS
InChIKey: IUTMTBXLLAOWGT-XYOKQWHBSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 344.48, ALogP 4.27, HBA 4, HBD 2, PSA 55.13, QED 0.53
Compound (SMILES): O=C(COc1ccc(Cl)cc1)Nc1nonc1NC(=O)COc1ccc(Cl)cc1
InChIKey: LFJYDFPHTVHUPV-UHFFFAOYSA-N
Target: Sentrin-specific protease 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC62
Assay: Inhibition of SENP2 (unknown origin)
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 437.24, ALogP 3.41, HBA 7, HBD 2, PSA 115.58, QED 0.55
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc2c(ccn2-c2ccccc2)c1
InChIKey: KXMNTAAQVMYDJJ-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q56A07
Assay: Inhibition of mouse Nav1.7/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 314.37, ALogP 2.32, HBA 4, HBD 1, PSA 68.17, QED 0.81
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(C)c(C)c(C)c4)nn32)CC1
InChIKey: FLLXVDVLNOYACV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 2458 nM (pChEMBL 5.610000133514404)
Descriptors: MW 421.55, ALogP 3.36, HBA 5, HBD 2, PSA 93.25, QED 0.74
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCCCN1CCN(Cc2ccccc2)CC1
InChIKey: DXQPJYSXJVUZSK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor expressed in HEK cell membrane incubated for 120 mins by microplate beta scintillation counting analysis
Measurement: Ki = 496 nM (pChEMBL 6.300000190734863)
Descriptors: MW 436.63, ALogP 3.84, HBA 5, HBD 0, PSA 39.15, QED 0.62
Compound (SMILES): CCNC(=O)C1=CC2C(c3cc(C(C)(C)O)ccc3Oc3c(C)cc(F)cc3C)=CN(C)C(=O)C2N1
InChIKey: KWRBIGNTVLPSMJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 BD2 (unknown origin) assessed as dissociation constant by ITC analysis
Measurement: Kd = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 493.58, ALogP 3.88, HBA 5, HBD 3, PSA 90.9, QED 0.57
Compound (SMILES): CCOc1ccc(F)c(N2CC[C@@H](Oc3ccc(N4CC(C)(C)C[C@@H]4CC(=O)O)cc3)[C@H](C)C2)c1
InChIKey: HJSFLAWFGNKFEC-BNIKKZEQSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Positive allosteric modulation of human GPR40 by calcium based FLIPR analysis
Measurement: EC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 484.61, ALogP 5.6, HBA 5, HBD 1, PSA 62.24, QED 0.53
Compound (SMILES): C#CCCCCCCN1CCC(COC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1
InChIKey: KQCRPVVAJACIHG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 489.01, ALogP 7.13, HBA 3, HBD 1, PSA 41.57, QED 0.29
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc5ccccc5c4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: TXPWCFRRRKKLCN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Disruption of HIS-FLAG-tagged recombinant Leishmania infantum TryR dimerization expressed in Escherichia coli Rossetta BL21 (DE3) cells incubated for 16 hrs by ELISA analysis
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 596.78, ALogP 4.44, HBA 7, HBD 2, PSA 102.18, QED 0.15
Compound (SMILES): C[C@]12CCC(=O)C=C1C=C(CCc1ccc([N+](=O)[O-])cc1)[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
InChIKey: ZPVDGPIFJNHZML-CVSNDOPFSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 95.06 nM (pChEMBL 7.019999980926514)
Descriptors: MW 433.55, ALogP 5.77, HBA 4, HBD 0, PSA 77.28, QED 0.45
Compound (SMILES): CCN(C)C(=O)Oc1ccc2c(c1)C=CC(C)N(C)C2CCOc1ccc([N+](=O)[O-])cc1
InChIKey: AHKYADRRQAQSLQ-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 439.51, ALogP 4.9, HBA 6, HBD 0, PSA 85.15, QED 0.45
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(C)c3)cc2)nc2cnccc12)C(N)=O
InChIKey: SGGAMBTYCITZTQ-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 10 uM ATP by HTRF assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 421.5, ALogP 4.82, HBA 5, HBD 2, PSA 104.69, QED 0.46
Compound (SMILES): COc1ccc([C@H](C)NC(=O)c2sc3nnc(C)c(C)c3c2N)cc1F
InChIKey: RKUJNYIUSSLNNZ-JTQLQIEISA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulator activity at human M4 receptor expressed in CHO cells co-expressing Gqi5 in presence of EC20 concentration of acetylcholine by calcium mobilization assay
Measurement: EC50 = 512.86 nM (pChEMBL 6.289999961853027)
Descriptors: MW 374.44, ALogP 3.53, HBA 6, HBD 2, PSA 90.13, QED 0.73
Compound (SMILES): Oc1cc(-c2ncc3c(N4CCC[C@]5(CCO5)C4)nc(OC[C@@]45CCCN4C[C@H](F)C5)nc3c2F)c2c(Cl)c(F)ccc2c1
InChIKey: HJZNAFKAHVFVRU-YYAADSQRSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of N-terminal His-tagged GDP-bound KRAS G12D mutant (1 to 169 residues) (unknown origin) assessed as inhibition of SOS mediated nucleotide exchange preincubated for 2 hrs followed by addition of SOS protein and unlabeled GTP measured after 30 mins by Alphascreen assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 626.08, ALogP 6.2, HBA 8, HBD 1, PSA 83.84, QED 0.28