lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2nc(NCCCN(C)C)nc(OC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: GMIMRINGJXMLEA-UHFFFAOYSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O60341
Assay: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay
Measurement: Kd = 2849 nM (pChEMBL 5.539999961853027)
Descriptors: MW 479.63, ALogP 4.05, HBA 8, HBD 1, PSA 71.98, QED 0.41
Compound (SMILES): O=C(c1ccc(CNCCO)cc1)N1CCc2c(-c3cccc4[nH]ccc34)cccc21
InChIKey: NBJSQXLBXDZCQN-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of Tag2-PD1/Tag1-PD-L1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 and measured after 2 hrs by HTRF analysis
Measurement: IC50 = 635.2 nM (pChEMBL 6.199999809265137)
Descriptors: MW 411.51, ALogP 4.12, HBA 3, HBD 3, PSA 68.36, QED 0.42
Compound (SMILES): O=C(c1ccc(CNCCO)cc1)N1CCc2c(-c3ccc4nccnc4c3)cccc21
InChIKey: GYYYLZJASNTPRD-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of Tag2-PD1/Tag1-PD-L1 (unknown origin) protein-protein interaction preincubated for 15 mins followed by addition of anti-Tag1-Eu3+ and anti-Tag2-XL665 and measured after 2 hrs by HTRF analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 424.5, ALogP 3.58, HBA 5, HBD 2, PSA 78.35, QED 0.46
Compound (SMILES): O=C(NCCCCCCCCCCO)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: XITLYMQUBWKORI-GIUVAWJUSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60603
Assay: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 949.21, ALogP 6.31, HBA 7, HBD 5, PSA 177.25, QED 0.06
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C(F)(F)F)c1
InChIKey: IIPVCRYVHLVYPM-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK3 in human primary T-cells assessed as reduction of IL-2 stimulated STAT5 phosphorylation preincubated for 1 hr followed by IL-2 stimulation for 15 mins by FACS method
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 431.37, ALogP 4.73, HBA 7, HBD 3, PSA 105.07, QED 0.42
Compound (SMILES): COc1cc(CC(=O)Nc2cc([C@H]3CC[C@@H](OC(=O)NC(C)C)C3)[nH]n2)ccn1
InChIKey: JFXBJZCDBBMRSA-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length recombinant C-terminal 6His-tagged CDK2/N-terminal GST-tagged cyclin E1 expressed in baculovirus-infected Sf21 cells using 5-FAM- QSPKKG peptide as substrate preincubated with enzyme and ATP for 30 mins followed by substrate addition and measured after 20 hrs by fluorescence- based microfluidic mobility shift assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 401.47, ALogP 2.77, HBA 6, HBD 3, PSA 118.23, QED 0.66
Compound (SMILES): C=C/C(C)=C/C[C@]1(C)[C@H](C)C[C@H](OC)[C@]23C(=C[C@@H](OC(C)=O)C[C@@H]12)[C@@H](OC(C)=O)O[C@H]3OC(C)=O
InChIKey: OOURVAPLSNHOBV-FPGBBJPCSA-N
Target: GABA-A receptor; alpha-1/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Positive allosteric modulation of GABAA alpha1beta2gamma2 receptor (unknown origin) stably expressed in CHO cells assessed as activation of GABA-induced response in presence of GABA by FLIPR assay
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 490.59, ALogP 4.24, HBA 8, HBD 0, PSA 97.36, QED 0.23
Compound (SMILES): CC[C@](C)(O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: ABAMKJIAQACLMF-MBOCNQOASA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2A receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by whole cell patch clamp method
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 416.69, ALogP 6.89, HBA 2, HBD 2, PSA 40.46, QED 0.48
Compound (SMILES): COCC(=O)N[C@H]1Cc2ccccc2[C@H]1Nc1ncnc2c1nnn2[C@@H]1C[C@@H](COS(N)(=O)=O)[C@@H](O)C1
InChIKey: UHZSMEDUPPKHQT-KQRABZDBSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in NEDD8-Ubcl2 adduct formation incubated for 2 hrs in presence of L-glutathione and ATP by HTRF assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 532.58, ALogP -0.41, HBA 12, HBD 4, PSA 196.47, QED 0.28
Compound (SMILES): CC(C)(Oc1cccc(N2CCC[C@@H](C(=O)N(Cc3ccc(-c4cnc5[nH]ccc5c4)cc3)C3CC3)C2)c1)C(=O)N1CCNCC1.Cl
InChIKey: DIQXSVIGXRCFGM-XXIQNXCHSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P35222
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-N-terminal biotinylated human BCL9 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 620.8, ALogP 5.23, HBA 6, HBD 2, PSA 93.8, QED 0.27
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c2OC(c2ccccc2I)CC3=O)[C@@H](O)C1
InChIKey: NVPGIFLCJMRJOV-FWGPOVQZSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4/Cyclin D1 (unknown origin)
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 495.31, ALogP 3.19, HBA 6, HBD 3, PSA 90.23, QED 0.56
Compound (SMILES): CN(C)c1ccc(-c2nc3cc(F)ccc3[nH]2)cc1
InChIKey: ALWZHAOGGMSYPG-UHFFFAOYSA-N
Target: TCF4-CTNNB1 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P35222
Assay: Inhibition of beta catenin/Tcf4 (unknown origin) protein protein interaction measured after 24 hrs by TOP-flash luciferase reporter gene assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 255.3, ALogP 3.44, HBA 2, HBD 1, PSA 31.92, QED 0.76
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnn2C)c2c(n1)c(-c1ccn[nH]1)nn2C
InChIKey: AIRFZNQGDRBDOC-LLVKDONJSA-N
Target: ATR/ATRIP (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13535
Assay: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 379.43, ALogP 1.38, HBA 9, HBD 1, PSA 102.57, QED 0.57
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NC(=O)c4ccc5c(c4)OCCO5)CO3)c2n1
InChIKey: FGJQMRKSDIRTPZ-AXMJJZENSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P20831
Assay: Inhibition of Staphylococcus aureus DNA gyrase supercoiling activity incubated for 25 min by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 485.47, ALogP 1.62, HBA 9, HBD 2, PSA 121.26, QED 0.54
Compound (SMILES): C[C@@H]1COC[C@H]2COc3c(nc(-c4ccnc5[nH]ccc45)nc3C3(S(C)(=N)=O)CC3)N21
InChIKey: DTDLHHWBDQLEOL-QZVKVLMASA-N
Target: ATR/ATRIP (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13535
Assay: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 440.53, ALogP 2.67, HBA 8, HBD 2, PSA 117.08, QED 0.64
Compound (SMILES): CN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: RBMBLJOYIGVBNO-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin A (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 = 676 nM (pChEMBL 6.170000076293945)
Descriptors: MW 433.49, ALogP 2.46, HBA 7, HBD 2, PSA 86.28, QED 0.65
Compound (SMILES): CC(C)(C)OC(=O)CCOCCOCCOCCNC(=O)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: UCSKZVBAXKEGAR-ACZCQCEDSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9QUN7
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 1053.27
Compound (SMILES): CC(C)(C)OC(=O)NCCCCCCCCCCCCNC(=O)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: VVBYPFKBQKBKMS-OGGLDSASSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9QUN7
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 1076.39
Compound (SMILES): CC[C@@](C)(O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: ABAMKJIAQACLMF-JEPZXVLISA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2B receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by whole cell patch clamp method
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 416.69, ALogP 6.89, HBA 2, HBD 2, PSA 40.46, QED 0.48
Compound (SMILES): Nc1nc2ccc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(F)c(F)c5)C4)nn3)nc2s1
InChIKey: DDQYAVSQXTUITB-BONVTDFDSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 1589.62 nM (pChEMBL 5.800000190734863)
Descriptors: MW 442.46, ALogP 2.35, HBA 9, HBD 3, PSA 123.64, QED 0.44
Compound (SMILES): CC(C)(C)Oc1ccc(C(=O)OCCCCCCCCCCCCNC(=O)[C@@H]2CN(C(=O)c3ccc(C(=O)N4C[C@@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)[C@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)C4)cc3)C[C@H]2C(=O)N[C@H]2C[C@@H]2c2ccccc2)cc1
InChIKey: RNRLAOOGPXLMDG-PWYWENMFSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9QUN7
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 1153.48
Compound (SMILES): O=C(Nc1nc2ccc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(Cl)c(C(F)(F)F)c5)C4)nn3)nc2s1)C1CC1
InChIKey: TYVQJCSBHJOJCN-UGSOOPFHSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 109.91 nM (pChEMBL 6.960000038146973)
Descriptors: MW 576.99, ALogP 4.51, HBA 9, HBD 3, PSA 126.72, QED 0.31
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc(Cl)c(Sc5cnc(N6CCC7(CC6)CO[C@@H](C)[C@H]7N)cn5)n4)ncc3F)cc2n1C(C)C
InChIKey: ZOCBTZIMNNTWDS-YVGXBJCXSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of recombinant N-terminal GST/His6-fusion tagged human CDK4/Cyclin D3 expressed in Sf9 insect cells using 5-FAM-IPTSPITTTYFFFKKK as substrate preincubated for 10 mins followed by substrate addition and incubated for 3 hrs in presence of ATP by caliper mobility shift analysis
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 693.23, ALogP 6.73, HBA 12, HBD 2, PSA 132.79, QED 0.19
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cn([C@@H]3CN[C@H](C(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)C3)nn2)cn1
InChIKey: QDXRELOFIZDHGS-YOEHRIQHSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 139.64 nM (pChEMBL 6.860000133514404)
Descriptors: MW 505.89, ALogP 3.68, HBA 7, HBD 3, PSA 113.83, QED 0.44
Compound (SMILES): O=C(NCCCCCCCCCCO)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: XITLYMQUBWKORI-GIUVAWJUSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9QUN7
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 949.21, ALogP 6.31, HBA 7, HBD 5, PSA 177.25, QED 0.06
Compound (SMILES): C=C/C(C)=C/C[C@]1(C)[C@H](C)C[C@H](OC)[C@]23C(=C[C@@H](OC(C)=O)C[C@@H]12)[C@@H](OC(C)=O)O[C@H]3OC(C)=O
InChIKey: OOURVAPLSNHOBV-FPGBBJPCSA-N
Target: GABA-A receptor; alpha-1/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Positive allosteric modulation of recombinant GABAA alpha1beta2gamma2 receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as potentiation of GABA-induced chloride current at -70 mV holding potential in presence of GABA EC3 to 7 by two-microelectrode voltage-clamp assay
Measurement: EC50 = 43600 nM (pChEMBL 4.360000133514404)
Descriptors: MW 490.59, ALogP 4.24, HBA 8, HBD 0, PSA 97.36, QED 0.23
Compound (SMILES): Cc1nc(N2CCN(C)CC2C)ccc1Nc1nc(N)c(C(=O)c2c(Cl)cccc2Cl)s1
InChIKey: VPDSZVYUHWYXCW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 491.45, ALogP 4.85, HBA 8, HBD 2, PSA 87.38, QED 0.49
Compound (SMILES): CC[C@](C)(O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@](C)(O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: ABAMKJIAQACLMF-MBOCNQOASA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Positive allosteric modulation of recombinant human GluN1/GluN2B receptor stably expressed in HEK293 cells assessed as increase in glycine/L-glutamate-induced channel current at -70 mV holding potential by whole cell patch clamp method
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 416.69, ALogP 6.89, HBA 2, HBD 2, PSA 40.46, QED 0.48
Compound (SMILES): CC(C)(Oc1cccc(N2CCC[C@@H](C(=O)N(Cc3ccc(-c4cnc5[nH]ccc5c4)cc3)C3CC3)C2)c1)C(=O)N1CCNCC1.Cl
InChIKey: DIQXSVIGXRCFGM-XXIQNXCHSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P35222
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-N-terminal biotinylated human BCL9 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: Ki = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 620.8, ALogP 5.23, HBA 6, HBD 2, PSA 93.8, QED 0.27
Compound (SMILES): COc1ccc2ncc(F)c(C[C@H](O)[C@H]3OC[C@H](NC(=O)c4ccc5c(c4)OCCO5)CO3)c2n1
InChIKey: FGJQMRKSDIRTPZ-AXMJJZENSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1U9
Assay: Inhibition of Staphylococcus aureus DNA topoisomerase 4 decatenation activity using kDNA as substrate incubated for 10 to 20 min by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 485.47, ALogP 1.62, HBA 9, HBD 2, PSA 121.26, QED 0.54
Compound (SMILES): COc1ccc(C2=NN(c3ccccn3)C(=O)C2)cc1
InChIKey: DXWBEIPEDHYRHM-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD-1/PD-L1 interaction in CHO-K1 cells transfected with PD-1-YFP/SHP-2-CFP and measured by FRET assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 267.29, ALogP 2.23, HBA 4, HBD 0, PSA 54.79, QED 0.86
Compound (SMILES): CN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: RBMBLJOYIGVBNO-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4/cyclin-D3 (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 433.49, ALogP 2.46, HBA 7, HBD 2, PSA 86.28, QED 0.65
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4c(F)cccc4C(F)(F)F)s3)cc2)CC1
InChIKey: QVZIQCVGMKXLJK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 479.5, ALogP 4.61, HBA 7, HBD 2, PSA 74.49, QED 0.41
Compound (SMILES): COc1cc(CC(=O)Nc2cc([C@H]3CC[C@@H](OC(=O)NC(C)C)C3)[nH]n2)ccn1
InChIKey: JFXBJZCDBBMRSA-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Biochemical Assay: The purpose of CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 full length catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2, CPC Scientific, Sunnyvale, Calif.) (SEQ ID NO:1). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Wild-type CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Matl enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (±inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA.
Measurement: Ki = 0.64 nM (pChEMBL 9.1899995803833)
Descriptors: MW 401.47, ALogP 2.77, HBA 6, HBD 3, PSA 118.23, QED 0.66
Compound (SMILES): C=C/C(C)=C/C[C@]1(C)[C@H](C)C[C@H](OC)[C@]23C(=C[C@@H](OC(C)=O)C[C@@H]12)[C@@H](OC(C)=O)O[C@H]3OC(C)=O
InChIKey: OOURVAPLSNHOBV-FPGBBJPCSA-N
Target: GABA-A receptor; GABA-A site (alpha1/beta2 interface) (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Positive allosteric modulation of recombinant GABAA alpha1beta2 receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as potentiation of GABA-induced chloride current at -70 mV holding potential in presence of GABA EC3 to 7 by two-microelectrode voltage-clamp assay
Measurement: EC50 = 57600 nM (pChEMBL 4.239999771118164)
Descriptors: MW 490.59, ALogP 4.24, HBA 8, HBD 0, PSA 97.36, QED 0.23
Compound (SMILES): Cc1nc(N2CCN(C)CC2C)ccc1Nc1nc(N)c(C(=O)c2c(Cl)cccc2Cl)s1
InChIKey: VPDSZVYUHWYXCW-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition of human recombinant full length GST-tagged CDK6/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 498 nM (pChEMBL 6.300000190734863)
Descriptors: MW 491.45, ALogP 4.85, HBA 8, HBD 2, PSA 87.38, QED 0.49
Compound (SMILES): CN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: RBMBLJOYIGVBNO-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 433.49, ALogP 2.46, HBA 7, HBD 2, PSA 86.28, QED 0.65
Compound (SMILES): CCCCNc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: LDLJTALPLRVDBD-IDTAVKCVSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Agonist activity at human P2X2R/P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 691.83 nM (pChEMBL 6.159999847412109)
Descriptors: MW 563.29, ALogP 0, HBA 14, HBD 7, PSA 265.14, QED 0.13
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4c(F)cccc4C(F)(F)F)s3)cc2)CC1
InChIKey: QVZIQCVGMKXLJK-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition of human recombinant full length GST-tagged CDK6/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 479.5, ALogP 4.61, HBA 7, HBD 2, PSA 74.49, QED 0.41
Compound (SMILES): Cc1c(COc2ccc(CNCCCCCCC(=O)NO)c(F)c2)cccc1-c1ccccc1
InChIKey: KUCRNNAFMQPIED-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PDL1 interaction (unknown origin) in by HTRF assay
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 464.58, ALogP 5.93, HBA 4, HBD 3, PSA 70.59, QED 0.17
Compound (SMILES): Cc1nc(N2CCN(C)CC2C)ccc1Nc1nc(N)c(C(=O)c2c(Cl)cccc2Cl)s1
InChIKey: VPDSZVYUHWYXCW-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of human recombinant full length His-tagged CDK9/Cyclin T1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 491.45, ALogP 4.85, HBA 8, HBD 2, PSA 87.38, QED 0.49
Compound (SMILES): COC1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CCC(c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-SIYOEGHHSA-N
Target: Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q16204
Assay: Inhibition of recombinant CCDC6-RET (unknown origin) incubated for 120 mins by Perkin Elmer electrophoretic mobility shift platform method
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CN1CCc2cc(-c3nc(Nc4ccc(N5CCNCC5)cn4)ncc3F)ccc2C1=O
InChIKey: RBMBLJOYIGVBNO-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) in presence of ATP by time resolved-FRET assay
Measurement: IC50 = 1038 nM (pChEMBL 5.980000019073486)
Descriptors: MW 433.49, ALogP 2.46, HBA 7, HBD 2, PSA 86.28, QED 0.65
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4c(F)cccc4C(F)(F)F)s3)cc2)CC1
InChIKey: QVZIQCVGMKXLJK-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of human recombinant full length His-tagged CDK9/Cyclin T1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 479.5, ALogP 4.61, HBA 7, HBD 2, PSA 74.49, QED 0.41
Compound (SMILES): COC1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CCC(c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-SIYOEGHHSA-N
Target: Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P33176
Assay: Inhibition of KIF5B-RET (unknown origin) assessed as inhibition of RET autophosphorylation expressed in mouse BaF3 cells
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: ZOUHWHPRPDJDQE-HNNXBMFYSA-N
Target: JAK1/JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK1/JAK2/TYK2 signalling in human whole blood assessed as inhibition of IL-6 stimulated STAT1 phosphorylation in CD4+ lymphocytes preincubated for 1 hr followed by IL-6 stimulation and incubated for 20 mins by flow cytometry analysis
Measurement: IC50 = 125.9 nM (pChEMBL 6.900000095367432)
Descriptors: MW 429.47, ALogP 3.22, HBA 5, HBD 1, PSA 79.6, QED 0.81
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: ZOUHWHPRPDJDQE-HNNXBMFYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK3 signalling in human whole blood assessed as inhibition of IL-2 stimulated STAT5 phosphorylation in CD4+ lymphocytes preincubated for 1 hr followed by IL-2 stimulation and incubated for 20 mins by flow cytometry analysis
Measurement: IC50 = 157.4 nM (pChEMBL 6.800000190734863)
Descriptors: MW 429.47, ALogP 3.22, HBA 5, HBD 1, PSA 79.6, QED 0.81
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: ZOUHWHPRPDJDQE-HNNXBMFYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 signalling in human whole blood assessed as inhibition of IFN-alpha stimulated STAT1 phosphorylation in CD4+ lymphocytes preincubated for 1 hr followed by IFN-alpha stimulation and incubated for 20 mins by flow cytometry analysis
Measurement: IC50 = 59.6 nM (pChEMBL 7.21999979019165)
Descriptors: MW 429.47, ALogP 3.22, HBA 5, HBD 1, PSA 79.6, QED 0.81
Compound (SMILES): COc1cc2c(cc1Nc1ncc(C(N)=O)c(Nc3ccccc3N3CCOC3=O)n1)CN(C)CC2
InChIKey: SAMRXAVMDVDUHT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin) using SLP76 as substrate incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 489.54, ALogP 3.02, HBA 9, HBD 3, PSA 134.94, QED 0.46
Compound (SMILES): CNC(=O)C(C)N(CC(c1ccccc1)c1ccncc1)C(=O)c1cc(C)c(=O)n(C)c1
InChIKey: ADTAYZYOXMLYGV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-tagged BRD4 BD1/BD2 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 432.52, ALogP 2.5, HBA 5, HBD 1, PSA 84.3, QED 0.62
Compound (SMILES): CC12CC3CC(C)(C1)CC(NC(=O)CCCC(=O)NC1CCCCC1)(C3)C2
InChIKey: QCXHQMVOXZCMHB-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH using PHOME as substrate measured after 10 mins by fluorescent based assay
Measurement: IC50 = 1588.5 nM (pChEMBL 5.800000190734863)
Descriptors: MW 374.57, ALogP 4.47, HBA 2, HBD 2, PSA 58.2, QED 0.72
Compound (SMILES): CC(=O)N1CCN(c2ccc3c(c2)CCN(S(=O)(=O)N(C)Cc2c(F)cccc2Cl)C3)C[C@H]1C
InChIKey: PSPKETIBTXFNCY-QGZVFWFLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Agonist activity at europium-labeled human RORgammat LBD assessed as induction of XL665-labeled co-activator SRC1 recruitment incubated for 1 hr by dual FRET assay
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 509.05, ALogP 3.27, HBA 4, HBD 0, PSA 64.17, QED 0.62
Compound (SMILES): Cn1c(SCc2ccc(C(=O)Nc3ccccc3N)cc2)nnc1-c1ccncc1
InChIKey: WLXGJQWKDBCQOO-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human full-length recombinant HDAC1 preincubated for 5 mins followed by HDAC substrate addition and further incubated for 45 mins by fluorescence microplate reader assay
Measurement: IC50 = 7640 nM (pChEMBL 5.119999885559082)
Descriptors: MW 416.51, ALogP 4, HBA 7, HBD 2, PSA 98.72, QED 0.36
Compound (SMILES): CC(C)(C)NC(=O)c1c2c(nn1-c1cnccn1)CC1CCC2O1
InChIKey: MONALPJXLGOEDL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis
Measurement: EC50 = 1650 nM (pChEMBL 5.78000020980835)
Descriptors: MW 327.39, ALogP 1.97, HBA 6, HBD 1, PSA 81.93, QED 0.91
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)C(c1ccccc1)N(Cc1ncc(-c3ccccc3)o1)C(=O)N2C
InChIKey: UTFQVYVRUDUFMR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4-BD1 (unknown origin) preincubated for 15 mins followed by substrate addition and measured after 1 hr
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 490.56, ALogP 6.77, HBA 5, HBD 0, PSA 75.61, QED 0.27
Compound (SMILES): Cc1nccc(-n2ncc3c2CCN(C(C)C(=O)Nc2ccc(Cl)cc2)C3)n1
InChIKey: PBQFXLZHNQKTKY-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells assessed as production of N-formylkynurenine using tryptophan as substrate in presence of inactivated fetal bovine serum
Measurement: IC50 = 1052 nM (pChEMBL 5.980000019073486)
Descriptors: MW 396.88, ALogP 3.01, HBA 6, HBD 1, PSA 75.94, QED 0.73
Compound (SMILES): CCC(=O)N[C@H]1CC[C@@H](n2c(=O)cc(C)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)CC1
InChIKey: BZFRLXSVKCBWHB-OYRHEFFESA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Binding affinity to wild-type human partial length TTK (N505 to V798 residues) expressed in bacterial expression system by active site-directed competition binding based Kinomescan method
Measurement: Kd = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 533.68, ALogP 3.61, HBA 9, HBD 2, PSA 104.62, QED 0.47
Compound (SMILES): O=C(OCCn1c([N+](=O)[O-])cnc1/C=C/c1ccc2ccccc2c1)c1nccc2ccccc12
InChIKey: JQXXDQRITGHFBH-ZRDIBKRKSA-N
Target: Telomerase reverse transcriptase (SINGLE PROTEIN), Homo sapiens
UniProt: O14746
Assay: Inhibition of telomerase in human SGC-7901 cell extract by TRAP assay
Measurement: IC50 = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 464.48, ALogP 5.52, HBA 7, HBD 0, PSA 100.15, QED 0.18
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5ccc(C(C)(C)C)cc5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: IWPTYZQLDWQHRK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Microfluidic Off-Chip Mobility Shift Assay Protocol for Potency Assessment Against BTK Enzyme: Briefly, 2.5× stocks of full-length human BTK (08-080) from CarnaBio USA, Inc., Natick, Mass., 1.6×ATP and appropriate kinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2; developed in-house) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM HEPES, pH 7.5, and 10 mM DTT. 5 uL of enzyme buffer and 7.5 uL of ATP/kinKDR peptide substrate mix were added to Matrix (#115304) 384-well, sterile, polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 27° C. Following the incubation period, reactions were stopped by adding 60 uL stop buffer consisting of 100 mM HEPES, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (Caliper Life Sciences, Mountain View, Calif.), 5% DMSO. Stopped reactions were monitored at −2 PSI, −3000 V/−700 V in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was measured by off-chip mobility shift assay measuring the charge/mass difference between substrate and product resulting from peptide phosphorilation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel. Switzerland).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 482.56, ALogP 5.39, HBA 5, HBD 2, PSA 88.49, QED 0.35
Compound (SMILES): COC(=O)c1cccc(COc2ccc(OC(F)(F)F)cc2)c1
InChIKey: RGPGMTZLSJWHOJ-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 10 pM of bilirubin by HTRF assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 326.27, ALogP 3.95, HBA 4, HBD 0, PSA 44.76, QED 0.78
Compound (SMILES): NC1(c2ccc(-c3cc(C(=O)O)cc(-n4cc(-c5ccc(C(F)(F)F)cc5)nn4)c3)cc2)CCC1
InChIKey: XLRPTLXQOCJDBN-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of fluorescent antagonist binding to human P2Y14 receptor expressed in CHO cells preincubated with compound for 30 mins followed by fluorescent antagonist addition and measured after 30 mins by flow cytometry analysis
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 478.47, ALogP 5.66, HBA 5, HBD 2, PSA 94.03, QED 0.39
Compound (SMILES): N[C@H](CC(=O)O)Cn1nnc(-c2ccc(Oc3nc4ccccc4s3)cc2)n1
InChIKey: WOCAXANSPDAXAZ-GFCCVEGCSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of recombinant full length N-terminal His6-tagged LTA4H (unknown origin) expressed in Escherichia coli BL21 DE3 cells at enzyme concentration 9 nM using Arg-AMC as substrate preincubated for 15 mins followed by substrate addition and measured every 10 mins for 300 mins by fluorescence based assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 396.43, ALogP 2.54, HBA 9, HBD 2, PSA 129.04, QED 0.49
Compound (SMILES): COc1ccc2c3c([nH]c2c1)[C@H](CC(C)C)N1C[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@@H]1C3
InChIKey: YFJZAFDYUVYHMH-SSKFGXFMSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) transfected in HEK293/R2 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 455.6, ALogP 4.11, HBA 5, HBD 2, PSA 83.66, QED 0.64
Compound (SMILES): Cc1n[nH]c2ncc(-c3cc(N[C@@H](CO)c4ccccc4)cnc3Cl)cc12
InChIKey: VSIAIRQSYURWTI-SFHVURJKSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) incubated for 2 hrs in presence of ATP by FRET based LANCE assay
Measurement: IC50 = 20.75 nM (pChEMBL 7.679999828338623)
Descriptors: MW 379.85, ALogP 4.13, HBA 5, HBD 3, PSA 86.72, QED 0.45
Compound (SMILES): Cc1c(NC(=O)CCN2CCN(C)CC2)c[nH]c1/C=C1\C(=O)Nc2ccc(F)cc21
InChIKey: XQFSSEZMJGLXCA-ATVHPVEESA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) incubated for 30 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 411.48, ALogP 2.53, HBA 4, HBD 3, PSA 80.47, QED 0.66
Compound (SMILES): CCCCc1[nH]c(=O)c(-c2nnc(Cc3ccccc3Cl)o2)c(O)c1-c1c(OC)cccc1OC
InChIKey: AVIGKSFGMUYBAV-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Intracellular cAMP Accumulation Assay: HEK293 cells stably expressing human APJ receptor were used to assess the activity of compounds. Cultured cells were detached and resuspended in the cAMP Homogeneous Time-Resolved Fluorescence (HTRF) assay buffer (Cisbio cat; #62AM4PEJ). The assay was performed in 384-well assay plates (Perkin-Elmer; cat #6008289) according to assay protocol provided by the manufacturer. Serial dilutions of a compound together with assay buffer containing 0.2 nM IBMX and 2 μM forskolin were added to each well containing 5,000 cells and incubated for 30 minutes at room temperature. Subsequently, cAMP D2 reagent was added in the lysis buffer followed by the EuK antibody (Cisbio; cat #62AM4PEJ) and incubated for 60 min. The fluorescence emission ratio was measured using fluorometer. The intracellular cAMP concentrations (compound-stimulated inhibition of forskolin-mediated cAMP production) were calculated by extrapolation from a standard curve using known cAMP concentrations. The EC50 values were obtained by fitting the data to a sigmoidal concentration-response curve with variable slope. The maximal achievable inhibition of forskolin-induced cAMP levels (Ymax) for each compound was expressed as relative percentage of inhibition attained using pyroglutamated apelin-13 ((Pyr1)apelin-13) peptide, which was set to 100%.The examples disclosed below were tested in the APJ in vitro assays described above and were found having human APJ cyclic AMP (hcAMP) activity. The EC50 value of each compound is presented at the end of the example description.
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 495.96, ALogP 5.4, HBA 7, HBD 2, PSA 110.47, QED 0.32
Compound (SMILES): COc1cc(/C=C/c2ccc(OCC(=O)NCc3ccccc3)cc2)c(-c2cnn[nH]2)c(OC)c1
InChIKey: SKRAJWWCDIUBQP-DHZHZOJOSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 inflammasome activation in LPS-stimulated mouse bone marrow-derived macrophages assessed as reduction in IL-1beta secretion preincubated for 30 mins followed by nigericin addition and measured after 30 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 470.53, ALogP 4.35, HBA 6, HBD 2, PSA 98.36, QED 0.33
Compound (SMILES): Nc1nc(-c2ccc(C(F)(F)F)cc2)cn2c1nc1ccccc12
InChIKey: VOPZXIDBNQYFKE-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-ZM241385 from human recombinant A2A receptor expressed in human HEK293 cell membrane preincubated for 5 mins and measured after 1.5 hrs by radioligand competition binding assay
Measurement: IC50 = 26.5 nM (pChEMBL 7.579999923706055)
Descriptors: MW 328.3, ALogP 4.15, HBA 4, HBD 1, PSA 56.21, QED 0.57
Compound (SMILES): Cc1nc(C(c2ccc(-c3ccc4cccc(F)c4c3)[nH]c2=O)C(C)C)[nH]c1C
InChIKey: OAXHMKKTZXRFJZ-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Displacement of [3H]PGE2 from human EP3 receptor expressed in CHO cells by radioligand competition binding assay
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 389.47, ALogP 5.46, HBA 2, HBD 2, PSA 61.54, QED 0.49
Compound (SMILES): Cc1c(N2CC[C@@H](C3(N)CC3)C2)c(F)cc2cc(C(=O)O)c(=O)n(C3CC3)c12
InChIKey: WJCZHUWTEKABIV-CYBMUJFWSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks patch clamp electrophysiology method
Measurement: IC50 = 92000 nM (pChEMBL 4.039999961853027)
Descriptors: MW 385.44, ALogP 2.8, HBA 5, HBD 2, PSA 88.56, QED 0.84
Compound (SMILES): CCn1c(CO)nn(-c2nc(OC(C)C(F)(F)F)c3c(Oc4c(F)cccc4Cl)nccc3c2F)c1=O
InChIKey: DCRUWTKENYEOJH-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH using dihydroorotate as substrate and CoQ6 as co-substrate by DCIP dye based spectrophotometry analysis
Measurement: IC50 = 0.59 nM (pChEMBL 9.229999542236328)
Descriptors: MW 545.85, ALogP 4.54, HBA 9, HBD 1, PSA 104.29, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(c2cnn3c(C(N)=O)c(-c4ccc(Oc5ccccc5F)cc4)[nH]c23)CC1
InChIKey: AVZDBQQUVXGEJK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full-length N-terminal GST tagged BTK (1 to 659 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 473.51, ALogP 4.25, HBA 5, HBD 2, PSA 105.72, QED 0.41
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCN2CCN(C)CC2)CC(=O)NC2CCC2)nn1C1CCCC1.Cl.Cl
InChIKey: FTFWYGDDBLDONQ-IFUPQEAVSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 40 mins by TR-FRET assay
Measurement: EC50 = 721 nM (pChEMBL 6.139999866485596)
Descriptors: MW 566.75, ALogP 3.48, HBA 8, HBD 2, PSA 100.96, QED 0.41
Compound (SMILES): COc1ccc(CNC2CC23CCc2ccccc23)c(Cl)c1OC
InChIKey: OSDYMFLVMKNLNC-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human LSD1 (172 to 852 residues) using Bio-H3K4me2 (1 to 24 residues) as substrate incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 343.85, ALogP 4.1, HBA 3, HBD 1, PSA 30.49, QED 0.89
Compound (SMILES): CCOc1ccc(OCC)c(-n2c3c(cc(-c4nc(-c5ccc(Cl)cc5)cs4)c2=O)C(=O)CC(C)(C)C3)c1
InChIKey: WXFPXDNGMSQBHL-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 549.09, ALogP 7.23, HBA 7, HBD 0, PSA 70.42, QED 0.24
Compound (SMILES): CCOC(=O)C1CCC(c2ccccc2)N1C(=O)c1cn(CCCNC(=O)C(F)(F)F)nn1
InChIKey: CDBJJPCFZVVCER-UHFFFAOYSA-N
Target: Thymidylate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P04818
Assay: Inhibition of thymidylate synthase (unknown origin)
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 467.45, ALogP 2.26, HBA 7, HBD 1, PSA 106.42, QED 0.47
Compound (SMILES): O=C(O)c1ccc(-c2ccnc(Nc3ccccc3)n2)cc1C1CCCC1
InChIKey: GZYIVQMHOULGOR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RR4
Assay: Inhibition of human CAMKK2 using CAMKKtide as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 359.43, ALogP 5.24, HBA 4, HBD 2, PSA 75.11, QED 0.65
Compound (SMILES): COc1cccc2oc(=S)[nH]c12
InChIKey: KNQYHNDFKVAMEI-UHFFFAOYSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human chymotrypsin-like beta 5i subunit of iCP using suc-LLVY-AMC as flurogenic substrate for 90 mins by fluorescence-based assay
Measurement: IC50 = 81000 nM (pChEMBL 4.090000152587891)
Descriptors: MW 181.22, ALogP 2.5, HBA 3, HBD 1, PSA 38.16, QED 0.69
Compound (SMILES): CCNC(=O)c1ccc(OCc2ccc(OC)cc2)c(-c2cn(C)nn2)c1
InChIKey: FHMNHTWKYVWIBK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD1 Y97A mutant (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 366.42, ALogP 2.82, HBA 6, HBD 1, PSA 78.27, QED 0.7
Compound (SMILES): CCOP(=O)(/C=C/[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO[C@H]1O[C@@H]2O[C@@]3(C)CC[C@H]4[C@H](C)CC[C@@H]([C@H]1C)[C@@]24OO3)NC(=O)OCc1ccccc1)c1ccccc1)OCC
InChIKey: NICUQVPQDBOIPE-UPHPAZROSA-N
Target: Falcipain 2 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9N6S8
Assay: Inhibition of recombinant Plasmodium falciparum falcipain-2 expressed in Escherichia coli M15 assessed as reduction in free AMC release using Z-FR-AMC as a substrate measured over 30 mins by fluorometric assay
Measurement: IC50 = 3380 nM (pChEMBL 5.46999979019165)
Descriptors: MW 869.99, ALogP 7.67, HBA 12, HBD 3, PSA 178.21, QED 0.09
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5cc(C(C)(C)C)no5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: GUHXRVDXLVSTPU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Microfluidic Off-Chip Mobility Shift Assay Protocol for Potency Assessment Against BTK Enzyme: Briefly, 2.5× stocks of full-length human BTK (08-080) from CarnaBio USA, Inc., Natick, Mass., 1.6×ATP and appropriate kinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2; developed in-house) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM HEPES, pH 7.5, and 10 mM DTT. 5 uL of enzyme buffer and 7.5 uL of ATP/kinKDR peptide substrate mix were added to Matrix (#115304) 384-well, sterile, polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 27° C. Following the incubation period, reactions were stopped by adding 60 uL stop buffer consisting of 100 mM HEPES, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (Caliper Life Sciences, Mountain View, Calif.), 5% DMSO. Stopped reactions were monitored at −2 PSI, −3000 V/−700 V in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was measured by off-chip mobility shift assay measuring the charge/mass difference between substrate and product resulting from peptide phosphorilation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel. Switzerland).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 473.51, ALogP 4.38, HBA 7, HBD 2, PSA 114.52, QED 0.39
Compound (SMILES): COc1cc2c(N(C)C)nc(NCCCN3CCN(C)CC3)nc2cc1OCCCN1CCCC1
InChIKey: UEWDFXQJMZDJJE-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 expressed in HEK-blue-HTLR7 cells assessed as inhibition of CL264-induced NFkappaB activation measured after 24 hrs by secreted alkaline phosphatase reporter assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 485.68, ALogP 2.62, HBA 9, HBD 1, PSA 69.23, QED 0.46
Compound (SMILES): COc1ccccc1CCC(C)(C)NCC(O)c1ccc(O)c2[nH]c(=O)ccc12.Cl
InChIKey: HTKRSABNJNLJSC-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation
Measurement: EC50 = 2.042 nM (pChEMBL 8.6899995803833)
Descriptors: MW 396.49, ALogP 3.28, HBA 5, HBD 4, PSA 94.58, QED 0.47
Compound (SMILES): Cc1ccc(NC(=O)c2cn(C)c3ccccc3c2=O)cc1C
InChIKey: YRVYFKJFMSHLMJ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using kynuramine as substrate measured for 30 mins by fluorescence spectrophotometric assay
Measurement: IC50 = 82300 nM (pChEMBL 4.079999923706055)
Descriptors: MW 306.37, ALogP 3.41, HBA 3, HBD 1, PSA 51.1, QED 0.79
Compound (SMILES): CC(=O)Oc1cccc(Cc2ccnc(N3CCc4c(C(N)=O)cccc43)c2)c1
InChIKey: IIYAYBPEQMEOMW-UHFFFAOYSA-N
Target: G-protein coupled receptor 52 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T5
Assay: Agonist activity at GPR52 (unknown origin) expressed in CHO-K1 or HEK293 cells assessed as intracellular cAMP accumulation incubated for 1 hr by HTRF assay
Measurement: EC50 = 21.4 nM (pChEMBL 7.670000076293945)
Descriptors: MW 387.44, ALogP 3.39, HBA 5, HBD 1, PSA 85.52, QED 0.54
Compound (SMILES): Cc1cccc(-c2cnc(NC3CCN(CCCN)CC3)c3[nH]c(=O)c(C)cc23)c1
InChIKey: UHIMQYINBSDFQT-UHFFFAOYSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Inhibition of TAF1 bromodomain 2 (unknown origin) by TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.55, ALogP 3.43, HBA 5, HBD 3, PSA 87.04, QED 0.58