lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=[N+]([O-])/C=C/c1ccc(Oc2ccccc2)cc1
InChIKey: NCOKGFBCWSFFLL-ZHACJKMWSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Antagonist activity at human TLR4 in HEK-Blue hTLR4 cells assessed as inhibition of LPS-induced receptor activation preincubated with LPS followed by compound addition and measured 24 hrs by Quanti-Blue based SEAP reporter gene assay
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 241.25, ALogP 3.73, HBA 3, HBD 0, PSA 52.37, QED 0.61
Compound (SMILES): CC(C)(C)OC(=O)N1C[C@@H](n2cc(-c3ccc4nc(N)sc4n3)nn2)C[C@H]1C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1
InChIKey: AZCFXTPLBWULJY-DJJJIMSYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 667.22 nM (pChEMBL 6.179999828338623)
Descriptors: MW 609.03, ALogP 5.39, HBA 10, HBD 2, PSA 141.15, QED 0.31
Compound (SMILES): NCCn1ncc2c(NCc3ccccc3[N+](=O)[O-])cc(C(F)(F)F)cc21
InChIKey: FMRBGLMTFBVHNE-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of N-terminal hexa-histidine tagged human IDO1 (12 to 403 residues) expressed in Escherichia coli Transetta (DE3) using L-tryptophan as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 30 to 60 mins by microplate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 379.34, ALogP 3.53, HBA 6, HBD 2, PSA 99.01, QED 0.5
Compound (SMILES): N#Cc1ccc(C[C@@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCc3ccccc3C2)cc1
InChIKey: TVFMIWUEXKUQEY-XMMPIXPASA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at human FPR2 transfected in human HL-60 cells assessed as increase in calcium mobilization measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 442.49, ALogP 4.02, HBA 3, HBD 2, PSA 85.23, QED 0.63
Compound (SMILES): CCN(CC)C(=O)c1ccc2c(c1)nc(Cc1ccc(OC(=O)NCCCCCCN3CCc4ccccc4C3)cc1)n2CCC(C)C
InChIKey: YBILVISNRAVIPV-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate preincubated for 20 mins followed by substrate addition and measured every 30 sec for 3 mins by DTNB-based UV analysis
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 651.9, ALogP 7.86, HBA 6, HBD 1, PSA 79.7, QED 0.12
Compound (SMILES): COc1ccc(-c2cn3ccc(N(C)C)cc3n2)cc1
InChIKey: JEZWQOJTHNHFCJ-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 preincubated with compound for 1 hrs followed by CL264 addition and measured next day by SEAP-based spectrophotometry assay
Measurement: IC50 = 6740 nM (pChEMBL 5.170000076293945)
Descriptors: MW 267.33, ALogP 3.08, HBA 4, HBD 0, PSA 29.77, QED 0.73
Compound (SMILES): CC(C)(C)c1nc(C23CCC(CN(C(=O)C45CC(F)(C4)C5)c4cccc(-c5nc(C6CC6)no5)c4)(CC2)CC3)no1
InChIKey: KMWDADSUZQXCTH-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 559.69, ALogP 6.81, HBA 7, HBD 0, PSA 98.15, QED 0.31
Compound (SMILES): O=C1/C(=C\c2ccc(O)c(CN3CCN(c4ccccc4F)CC3)c2)Cc2ccccc21
InChIKey: AJFKJKLXJPRZJE-QNGOZBTKSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometry based esterase assay
Measurement: Ki = 51.1 nM (pChEMBL 7.289999961853027)
Descriptors: MW 428.51, ALogP 4.68, HBA 4, HBD 1, PSA 43.78, QED 0.61
Compound (SMILES): CNC(=O)c1cncc(-c2cnc3cc(-c4cnn(C)c4)c(OC(C)C)nn23)c1
InChIKey: IBACXGSAIWIMHV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human FGFR1 using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 365 nM (pChEMBL 6.440000057220459)
Descriptors: MW 391.44, ALogP 2.34, HBA 8, HBD 1, PSA 99.23, QED 0.56
Compound (SMILES): COc1ccc(C2(C(=O)Nc3ccn(-c4cncc(F)c4)n3)CC2)cc1
InChIKey: RYPRBAVEWVOKQH-UHFFFAOYSA-N
Target: Very long chain fatty acid elongase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BW60
Assay: Inhibition of ELOVL1 in human HEK2936E cells assessed as reduction of C26:0 LPC synthesis incubated for 48 hrs by cellular assay
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 352.37, ALogP 3.09, HBA 5, HBD 1, PSA 69.04, QED 0.77
Compound (SMILES): CCOC(=O)c1nc(-c2ccc(OC)cc2)oc1C
InChIKey: DAFRLXQGMZPMLA-UHFFFAOYSA-N
Target: RISC-loading complex subunit TARBP2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15633
Assay: Binding affinity to human recombinant TRBP by SPR assay
Measurement: Kd = 10.42 nM (pChEMBL 7.980000019073486)
Descriptors: MW 261.28, ALogP 2.84, HBA 5, HBD 0, PSA 61.56, QED 0.79
Compound (SMILES): Cl.O=C1Nc2ccc(I)cc2/C1=C1/Nc2ccccc2/C1=N\OCC(=O)N1CCNCC1
InChIKey: IDHNHRXOFNBMQL-WCFRLSLOSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 = 0.45 nM (pChEMBL 9.350000381469727)
Descriptors: MW 529.34, ALogP 2.23, HBA 6, HBD 3, PSA 95.06, QED 0.32
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@H](NC(=O)[C@@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-UBHSHLNASA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 4752 nM (pChEMBL 5.320000171661377)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): CCCC[Si](C)(C)c1cc(O)c(C2CCCC2)c(OC)c1
InChIKey: WKVNYGJWBHBRPZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from recombinant human CB2 receptor expressed in CHO cells assessed as inhibition constant incubated for 120 mins by radioligand binding assay
Measurement: Ki = 903.14 nM (pChEMBL 6.039999961853027)
Descriptors: MW 306.52
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)N6CCC(N)CC6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: DPGZANBIVHEAKV-KTQFYHDFSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Mus musculus
UniProt: Q61503
Assay: Inhibition of mouse CD73 assessed as reduction in inorganic phosphate release upon substrate hydrolysis using AMP/ATP as substrate incubated for 1 hr followed by substrate addition and measured after 2 hrs by malachite green reagent based colorimetric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 582.87, ALogP 7.66, HBA 4, HBD 2, PSA 92.86, QED 0.33
Compound (SMILES): COc1ccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)c(O)c1
InChIKey: POCNIPUWZPJPSF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 8.318 nM (pChEMBL 8.079999923706055)
Descriptors: MW 328.8, ALogP 3.77, HBA 3, HBD 3, PSA 57.28, QED 0.67
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(I)cc3)nc3ccccc3c2[nH]1
InChIKey: PMLCQIVFRJHHRF-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Inhibition of human TPSO receptor expressed in human HEK293T cell membrane incubated for 90 mins by radioligand binding assay
Measurement: Ki = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 484.39, ALogP 7.14, HBA 3, HBD 2, PSA 53.6, QED 0.27
Compound (SMILES): Cc1onc(-c2ccc(F)cc2)c1COc1ccc2c(n1)CCN(Cc1ccco1)C2=O
InChIKey: MAOSDNFFDKNYFB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells stably at -80 mV holding potential by automated patch clamp method
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 433.44, ALogP 4.55, HBA 6, HBD 0, PSA 81.6, QED 0.44
Compound (SMILES): O=C1N(C2CCCCC2)CC[C@]12C[C@@H](O)CN2Cc1ccc(-c2ccc(F)cc2)nc1
InChIKey: SONDFPMZDUEEPA-RDGATRHJSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of 11beta-HSD1 in human PBMC cells using 3H-cortisone as substrate assessed as conversion of cortisone to cortisol by ELISA
Measurement: IC50 > 37 nM (pChEMBL 7.432000160217285)
Descriptors: MW 423.53, ALogP 3.76, HBA 4, HBD 1, PSA 56.67, QED 0.81
Compound (SMILES): COc1cc(Nc2ncc(OCc3c(F)c(OC)cc(OC)c3F)cn2)ccc1N1CCC(N2CCN(C)CC2)CC1
InChIKey: SYBLMCUTGSQYDI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of wild type N-terminal GST tagged FGFR3 (436 to 806 residues) (unknown origin) expressed in sf21 insect cells preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by off-chip mobility shift assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 584.67, ALogP 4.32, HBA 10, HBD 1, PSA 84.45, QED 0.37
Compound (SMILES): CC(C)(C)CNC(=S)Nc1ccc2c(c1)CCN2Cc1ccc(N=O)cc1
InChIKey: WPRKZXRSIVTSOS-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX in human PMNL assessed as reduction in all-trans isomers of LTB4 and 5-HETE formation preincubated for 15 mins followed by A23187 addition and measured after 10 mins by RP-HPLC analysis
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 382.53, ALogP 4.98, HBA 4, HBD 2, PSA 56.73, QED 0.56
Compound (SMILES): Cc1ccc(-c2c(CN3CCOCC3)nc3scc(C(=O)NN)n23)cc1
InChIKey: MSIRVCGEZTUEOG-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human HER2 incubated for 40 to 45 mins and measured after 15 mins by Kinase-Glo Max assay
Measurement: IC50 = 357 nM (pChEMBL 6.449999809265137)
Descriptors: MW 371.47, ALogP 1.81, HBA 7, HBD 2, PSA 84.89, QED 0.42
Compound (SMILES): Nc1nc(N)nc(NCCCCN2CCN(c3cccc(Cl)c3Cl)CC2)n1
InChIKey: ZHPOMVVVPOMELJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor expressed in CHO-K1 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 411.34, ALogP 2.36, HBA 8, HBD 3, PSA 109.22, QED 0.6
Compound (SMILES): Cc1ncc(CC(=O)Nc2cc([C@H]3CC[C@@H](OC(=O)NC(C)C)C3)[nH]n2)s1
InChIKey: UUPJXVBCBPIVKZ-QWHCGFSZSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of NanoLuc-fused CDK2 (unknown origin) expressed in 293-NB2 cells incubated for 2 hrs in presence of tracer K10 by NanoBRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 391.5, ALogP 3.13, HBA 6, HBD 3, PSA 109, QED 0.7
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCCCCC(=O)NO)c4)nc3c2)c1
InChIKey: NWFDFAGWBLMYBX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin)
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 544.66, ALogP 5.51, HBA 9, HBD 2, PSA 114.63, QED 0.12
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@@H]1CCc2ccccc21
InChIKey: BKYUUBOSZSVARW-CHXHCODASA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Antagonist activity at N-terminal His-tagged XIAP-BIR3 domain (253 to 347 residues)(unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 679.77, ALogP 1.93, HBA 8, HBD 4, PSA 163.01, QED 0.22
Compound (SMILES): COc1cc2c(cc1OC)S(=O)(=O)C(F)(CC1CCN(Cc3cccc(F)c3)CC1)C2.Cl
InChIKey: KLVMGMIPBUAWCD-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 451.54, ALogP 4.14, HBA 5, HBD 0, PSA 55.84, QED 0.66
Compound (SMILES): CC(C)Oc1ccc(-c2cn(-c3ccc(CN4CC(C(=O)[O-])C4)cc3)nn2)cc1C(F)(F)F.[Na+]
InChIKey: XEQYOLZTLGVXCN-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 = 0.84 nM (pChEMBL 9.079999923706055)
Descriptors: MW 460.46, ALogP 4.26, HBA 6, HBD 1, PSA 80.48, QED 0.57
Compound (SMILES): Nc1cc(C(F)(F)F)c(-c2cc(N3CCOC(c4ccccc4)C3)nc(N3CCOCC3)n2)cn1
InChIKey: QTQLXWBKHCYYSY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 4035 nM (pChEMBL 5.389999866485596)
Descriptors: MW 486.5, ALogP 3.55, HBA 8, HBD 1, PSA 89.63, QED 0.6
Compound (SMILES): Cc1cccc(N(C)C(=O)[C@@H]2C[C@@H](O)CN2c2nc(C)cc(C(F)(F)F)c2C#N)c1
InChIKey: FAQDVYGMYVIYHD-QAPCUYQASA-N
Target: DNA polymerase theta (SINGLE PROTEIN), Homo sapiens
UniProt: O75417
Assay: Displacement of tracer from recombinant Tb-labeled DNA polymerase theta (unknown origin) assessed as end point Kd using DNA as substrate preincubated for 30 mins followed by compound addition for 2 hrs by HTRF assay
Measurement: Kd = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 418.42, ALogP 3.19, HBA 5, HBD 1, PSA 80.46, QED 0.83
Compound (SMILES): CCCCCCCCCCCCCCCCNC(=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: RVOIMCKZDXTQOS-YKAPJTMCSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
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 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 1017.37
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@]4(C)C(=O)c4ccc6ccccc6c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: XEIGWVZJLXNMIJ-LEKWGUGTSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from rat MOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 107 nM (pChEMBL 6.96999979019165)
Descriptors: MW 549.71, ALogP 6.35, HBA 5, HBD 0, PSA 48, QED 0.34
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4OCc4cccc(OC)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: BFRLXNXMJLTBAD-MDIPFLTBSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Inhibition of CA200645 binding to NanoLuc-fused human adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 407.38 nM (pChEMBL 6.389999866485596)
Descriptors: MW 512.57, ALogP 1.14, HBA 11, HBD 4, PSA 152.88, QED 0.33
Compound (SMILES): CCCCn1nc(C2CCN(CCCCc3c[nH]c4ccc(C#N)cc34)CC2)cc1-c1ccc(Oc2ccc(Cl)cc2)cc1
InChIKey: RIXQYBLJJICSQJ-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in human HEK293 cells
Measurement: IC50 = 1206 nM (pChEMBL 5.920000076293945)
Descriptors: MW 606.21, ALogP 9.35, HBA 5, HBD 1, PSA 69.87, QED 0.14
Compound (SMILES): O=C(N/N=C/c1ccc(N2CCCCC2)cc1)c1ccc(CN2CCC(CO)CC2)cc1
InChIKey: GJSXFHLPQQQFLU-OVVQPSECSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine as substrate preincubated for 10 mins followed by substrate addition by spectrophotometric based Ellman's method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 434.58, ALogP 3.65, HBA 5, HBD 2, PSA 68.17, QED 0.52
Compound (SMILES): NC(=O)c1cc2c(-c3ccc(C(=O)NC4CCOCC4)s3)cccc2s1
InChIKey: VXJOAFWNSFAWGV-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human DYRK1B incubated for 130 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 1104.5 nM (pChEMBL 5.960000038146973)
Descriptors: MW 386.5, ALogP 3.64, HBA 5, HBD 2, PSA 81.42, QED 0.72
Compound (SMILES): CCN(CC)c1ccc2c(-c3ccc(S(=O)(=O)NCCCCCC(=O)NCCNCCCC4(c5ccccc5)OC(C)(C)c5ccccc54)cc3S(=O)(=O)[O-])c3ccc(=[N+](CC)CC)cc-3oc2c1
InChIKey: RPQOVOZBHWXNBF-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23977
Assay: Displacement of [3H]-WIN 3542875 from DAT in Sprague-Dawley rat brain striatum incubated for 120 mins by radioligand binding assay
Measurement: Ki = 4870 nM (pChEMBL 5.309999942779541)
Descriptors: MW 978.29, ALogP 8.3, HBA 10, HBD 3, PSA 173.12, QED 0.02
Compound (SMILES): Cc1nc(N2CCC(C)(N)CC2)cc(=O)n1-c1cccc(Cl)c1Cl
InChIKey: HGAOJDKDTHZJNB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human SHP2 assessed as downregulation of PERK level in human KYSE520 cells incubated for 2 hrs by Alpha screen assay
Measurement: IC50 = 557 nM (pChEMBL 6.25)
Descriptors: MW 367.28, ALogP 3.17, HBA 5, HBD 1, PSA 64.15, QED 0.89
Compound (SMILES): CNC(=O)N(CCO)c1cc(-c2cnc(N)cc2C(F)(F)F)nc(N2CCOCC2)n1
InChIKey: TZOOJTPCLONHIL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 5865 nM (pChEMBL 5.230000019073486)
Descriptors: MW 441.41, ALogP 1.11, HBA 8, HBD 3, PSA 129.73, QED 0.63
Compound (SMILES): C[C@@]1(c2nc(NC(=O)c3ccc(C#N)cn3)ccc2F)CS(=O)(=O)[C@](C)(CF)C(=N)N1
InChIKey: GNWNOQLLBKOHTC-RBUKOAKNSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) expressed in HEK293 cells expressing human APP with Swedish and London familial AD mutation
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 448.46, ALogP 1.68, HBA 7, HBD 3, PSA 148.69, QED 0.64
Compound (SMILES): COc1cc(CCNCc2ccccc2OC)c(OC)cc1C#N
InChIKey: QBJWOIWLBRLGKZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor transfected in HEK293T cells assessed as mini Galphaq recruitment measured for 2 hrs by luminescent assay
Measurement: EC50 = 6.71 nM (pChEMBL 8.170000076293945)
Descriptors: MW 326.4, ALogP 2.92, HBA 5, HBD 1, PSA 63.51, QED 0.76
Compound (SMILES): Cc1ccc(NC(=O)CCc2cccc(-c3cnc4[nH]ccc4c3)c2)cc1
InChIKey: JCKVLPHXLBKZSF-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 in human HCT-116 cells transfected with TOPFlash luciferase reporter plasmid assessed as reduction in TCF/LEF transcriptional activity
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 355.44, ALogP 5.11, HBA 2, HBD 2, PSA 57.78, QED 0.52
Compound (SMILES): CC(C)CN1CCN(Cc2ccc(-c3ccnc(Nc4cnn(CCO)c4)n3)cc2Cl)C(=O)C1
InChIKey: FYMDYCDZAGVLOG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of pBTK in human whole blood
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 484, ALogP 3.03, HBA 8, HBD 2, PSA 99.41, QED 0.48
Compound (SMILES): COC(=O)C1CN(Cc2ccc(C3=NOC(c4ccccc4)C3)cc2)C1
InChIKey: OQHRDXNTCGJJMD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 350.42, ALogP 3.16, HBA 5, HBD 0, PSA 51.13, QED 0.78
Compound (SMILES): CCCCCCNC(=O)C(=O)[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H]1[C@@H]2[C@H](CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)C2(C)C
InChIKey: HSBNQSWJQGVJAD-SQHJXKMMSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of eGFP fused SARS-CoV2 main protease transfected in HEK293T/17 cells incubated for 72 hrs by fluorescence based flow cytometry analysis
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 632.85, ALogP 2.26, HBA 6, HBD 5, PSA 165.81, QED 0.15
Compound (SMILES): N#Cc1cccnc1N1CCN(CCCOc2ccc3c(c2)NC(=O)CC3)CC1
InChIKey: VZLAEFHZBRUVDC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor expressed in CHO-K1 cells measured after 1.5 hrs by Microbeta plate reader method
Measurement: Ki = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 391.48, ALogP 2.43, HBA 6, HBD 1, PSA 81.49, QED 0.76
Compound (SMILES): O[C@@H](CN1[C@@H]2CC[C@H]1C/C(=C\c1ccccc1)C2)c1ccc(F)cc1
InChIKey: LOHGGNVLXAIIFN-LGNPHWTCSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-DTG from sigma 2 receptor in rat liver membrane measured after 120 mins by microbeta counting analysis
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 337.44, ALogP 4.57, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(CCc5ccc(C(=O)NO)cc5)c4)nc3c2)c1
InChIKey: SFYGBVJAWPTPMZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin)
Measurement: IC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 595.7, ALogP 5.01, HBA 10, HBD 3, PSA 126.66, QED 0.13
Compound (SMILES): Cc1cc(C(=O)NCc2ccc(CN)cc2)c(C)n1Cc1cccc(-c2cccnc2)n1
InChIKey: PBAAHHAGMWJRRK-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: KLK1 assay: KLK1 inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stürzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human KLK1 (Callbiochem) was incubated at 37° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.54, ALogP 4, HBA 5, HBD 2, PSA 85.83, QED 0.47
Compound (SMILES): Cl.NCOc1ccc2ccccc2c1
InChIKey: USGQEAKPJRVVHY-UHFFFAOYSA-N
Target: Alanine--glyoxylate aminotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21549
Assay: Inhibition of recombinant wild type His-tagged AGT (unknown origin) expressed in Escherichia coli BL21 assessed as inhibition constant using L-alanine and glyoxylate as a substrate in presence of PLP
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 173.21, ALogP 2.13, HBA 2, HBD 1, PSA 35.25, QED 0.71
Compound (SMILES): O=C1CSc2cc(OCCc3ccccc3)ccc2N1
InChIKey: YZRSTIHEDHFFHE-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using using kynuramine as substrate assessed as inhibition of 4-hydroxyquinoline formation incubated for 20 mins by fluorescence spectrophotometric analysis
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 285.37, ALogP 3.35, HBA 3, HBD 1, PSA 38.33, QED 0.94
Compound (SMILES): Cc1ccc(C(=O)N(CCCNC(=O)CCCCCCCCN2CCN(S(=O)(=O)c3ccc(NC(=S)NCc4cccnc4)cc3)CC2)[C@@H](c2nc3cc(Cl)ccc3c(=O)n2Cc2ccccc2)C(C)C)cc1
InChIKey: LZCAADBODOWVEZ-OIVUAWODSA-N
Target: Microtubule-associated protein 1 light chain 3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ8
Assay: Binding affinity to LC3B (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd = 993 nM (pChEMBL 6)
Descriptors: MW 1046.8
Compound (SMILES): Cc1cccc(Cc2c(C)nc3c(C(=O)N4CCN(c5cccc(C(F)(F)F)c5)CC4)cnn3c2C)c1
InChIKey: HSNCWUMANMRRHE-UHFFFAOYSA-N
Target: RuvB-like 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y230
Assay: Inhibition of full length recombinant His6 tagged human RUVBL2 expressed in Escherichia coli Rosetta cells incubated for 70 mins in presence of ATP by ATPase assay
Measurement: IC50 > 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 507.56, ALogP 5.23, HBA 5, HBD 0, PSA 53.74, QED 0.38
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(Oc4cc5nncn5cn4)c(C)c3)c2cc1NC(=O)/C(F)=C\[C@H]1CCCN1C
InChIKey: BQKAPRHCWWQTIM-PDEZOQIOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type human N-terminal GST tagged EGFR (669 to 1210 residues) expressed in Sf21 insect cells incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 = 86.33 nM (pChEMBL 7.059999942779541)
Descriptors: MW 583.63, ALogP 5.2, HBA 11, HBD 2, PSA 131.69, QED 0.22
Compound (SMILES): COC(=O)C1CCN(C(=O)c2cccc(NCc3cnc4nc(N)nc(N)c4n3)c2)CC1
InChIKey: WZBPRUPXHZYYIT-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of recombinant Leishmania major PTR1 expressed in Escherichia coli BL21 (DE3) cells using H2B as substrate in presence of cytochrome c and NADPH by envision multilabel reader
Measurement: IC50 = 1690 nM (pChEMBL 5.769999980926514)
Descriptors: MW 436.48, ALogP 1.22, HBA 10, HBD 3, PSA 162.24, QED 0.5
Compound (SMILES): O=C1NCc2nc(-c3c(F)cccc3F)cc(Nc3ccc(C(=O)N4CCOCC4)cn3)c21
InChIKey: BEMLAJCOGNIHCJ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Tyk2 & JAK2 Caliper Assay: The caliper machine employs an off chip mobility shift assay to detect phosphorylated peptide substrates from kinase assays, using microfluidics technology. The assays are carried out at ATP concentration equivalent to the ATP Km, and at 1 mM ATP. Compounds are serially diluted in DMSO then further diluted in assay buffer (25 mM HEPES, pH 7.5, 0.01% Brij-35, 0.01% Triton, 0.5 mM EGTA). 5 ul of diluted compound was added into wells first, then 10 ul of enzyme mix was added into wells, followed by 10 uL of substrate mix (peptide and ATP in 10 mM MgCl2) to start reaction. Reaction was incubated at 28° C. for 25 min and then added 25 ul stop buffer (100 mM HEPES, 0.015% Brij-35, 50 mM EDTA), followed by reading with Caliper. JAK2 at 1 nM final concentration and TYK2 at 9.75 nM are from Carna, and substrates used are ATP at 20 and 16 uM, respectively. JAK2 assay uses peptide 22 and TYK2 uses peptide 30 (Caliper), each at 3 uM.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 451.43, ALogP 2.88, HBA 6, HBD 2, PSA 96.45, QED 0.63
Compound (SMILES): CC(=O)N1CCC[C@@H](Oc2ccc(-c3ccn[nH]3)nc2)C1
InChIKey: BGXFGYZGXIXTCT-CYBMUJFWSA-N
Target: Cytochrome P450 4F2 (SINGLE PROTEIN), Homo sapiens
UniProt: P78329
Assay: Inhibition of human recombinant CYP4F2 using Luciferin-4F2/3 as substrate incubated for 60 mins in presence of NADPH regenerating system by luminescence based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 286.33, ALogP 1.86, HBA 4, HBD 1, PSA 71.11, QED 0.93
Compound (SMILES): O=C(COc1ccc(-c2ccccc2)cc1)NCC1CCN(Cc2ccccc2)CC1
InChIKey: OTKIZSHLVPXZAG-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE by Ellman's spectrophotometric method
Measurement: IC50 = 5580 nM (pChEMBL 5.25)
Descriptors: MW 414.55, ALogP 4.76, HBA 3, HBD 1, PSA 41.57, QED 0.58
Compound (SMILES): Cc1ccc(-c2nc(N)nc3c2cnn3Cc2ccc(C(=O)NO)cc2)o1
InChIKey: KYNXYBJKGKYGER-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using trypsin and LGK(Ac)-AMC as substrates incubated for 1 hr and measured by fluorescence assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 364.37, ALogP 2.14, HBA 8, HBD 3, PSA 132.09, QED 0.37
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4ccsc4)nc3)ncc2Cl)c1
InChIKey: CMLIHNXRVQWYBQ-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 = 159.6 nM (pChEMBL 6.800000190734863)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): CCOc1ccc(C(=O)Cc2ncc(C(=O)N(C)CCCOc3ccc([N+](=O)[O-])cc3)cn2)cc1
InChIKey: GDRNTAGWOJVGBL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE (unknown origin) using butyrylthiocholine iodide as substrate by DTNB reagent based Ellman's method
Measurement: IC50 = 6660 nM (pChEMBL 5.179999828338623)
Descriptors: MW 478.51, ALogP 3.75, HBA 8, HBD 0, PSA 124.76, QED 0.17
Compound (SMILES): Oc1cccc2[nH]cc(C[C@H]3CCCN3)c12
InChIKey: PVFAYAZDVYXQFR-SNVBAGLBSA-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: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 216.28, ALogP 2.17, HBA 2, HBD 3, PSA 48.05, QED 0.72
Compound (SMILES): CC1(O)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: UMXGNCKYCWSYMP-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 PTP domain (237 to 535 residues) using DiFMUP as substrate preincubated for 30 mins and followed by substrate addition and measured by microplate reader method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 353.25, ALogP 3.38, HBA 5, HBD 2, PSA 75.27, QED 0.87
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOCCNC(=O)c2ccc(-c3ccc(N4CCN(C)CC4)c(NC(=O)c4c[nH]c(=O)cc4C(F)(F)F)c3)cc2)C(C)(C)C)cc1
InChIKey: CTQDFWAQIJZIMB-UOHLUGTHSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Displacement of N-(4'-((17-(5,5-difluoro-7-(1H-pyrrol-2-yl)-5H-5l4,6l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-3-yl)-15-oxo-4,7,10-trioxa-14-azaheptadecyl)carbamoyl)-4-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-3-yl)-6-hydroxy-4-(trifluoromethyl)nicotinamide tracer from N-/C-terminal NanoLuc-fused full-length WDR5 (unknown origin) transfected in HEK293T cell lysate incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 5210 nM (pChEMBL 5.28000020980835)
Descriptors: MW 1072.22
Compound (SMILES): CCS(=O)(=O)Nc1ccc(Oc2ccc(F)cc2F)c(-c2cn(C)c(=O)c3cc(-c4ccc(CCCO)cc4)oc23)c1
InChIKey: RSAOOLVJUIXUJO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of C-terminal His6-tagged BRD4 BD2 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay
Measurement: IC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 594.64, ALogP 6.22, HBA 7, HBD 2, PSA 110.77, QED 0.2
Compound (SMILES): O=c1[nH]c(CSC2CCNCC2)nc2cc(NC3CCCC3)cc(F)c12
InChIKey: YZDTVOCBHYWUNM-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Enzymatic Inhibition Assay: Enzymatic inhibition of PARP14 was measured using a dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) monitoring the auto-modification of PARP14 by biotinylated nicotinamide adenine dinucleotide (biotin-NAD). 1 μL of a dose response curve of each test compound was spotted in 384-well nickel-coated white microplates (Thermo) using a Mosquito (TTP Labtech). Reactions were performed in a 50 μL volume by adding 40 μL of PARP14 in assay buffer (20 mM HEPES pH==8, 100 mM NaCl, 0.1% bovine serum albumin, 2 mM DTT and 0.002%0 Tween20), incubating with test compound at 25° C. for 30 min, then adding 10 μL of biotin-NAD (Biolog). The final concentrations of PARP14 and biotin-NAD are 50 nM and 3 μM, respectively. Reactions proceeded at 25° C. for 3 h, then were quenched with 5 μL of 10 mM unmodified nicotinamide adenine dinucleotide (Sigma-Aldrich). The quenched reactions were washed 3 times with 100 μL of TBST wash buffer (50 mM Tris-HCl, 150 mM NaCl and 0.1% Tween20). Next, to the washed and dried plate was added 25 μL of DELFIA Europium-N1 streptavidin (Perkin Elmer) diluted in DELFIA assay buffer (Perkin Elmer). After a 30 min incubation at 25° C., the plate was washed 5 times with TBST wash buffer. Finally, 25 μL of DELFIA enhancement solution was added. After a 5 min incubation the plate was read on an Envision platereader equipped with a LANCE/DELFIA top mirror (Perkin Elmer) using excitation of 340 nm and emission of 615 nm to measure the amount of Europium present in each well, informing on the amount of biotin-NAD that was transferred in the automodification reaction.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 376.5, ALogP 3.4, HBA 5, HBD 3, PSA 69.81, QED 0.75
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: MNMRRFAISKIFMJ-SLHDEKGNSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Inhibition of CA200645 binding to NanoLuc-fused human adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 468.51, ALogP 0.99, HBA 10, HBD 4, PSA 143.65, QED 0.4
Compound (SMILES): O=C(O)c1ccc(SC2=NS(=O)(=O)c3ccccc32)cc1
InChIKey: LABKIXIZKCQJOX-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition of human erythrocytes pyruvate kinase
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 319.36, ALogP 2.63, HBA 4, HBD 1, PSA 83.8, QED 0.92
Compound (SMILES): C[C@H](c1cccc2ccccc12)N1CCC(C(=O)NCC2CCN(C)CC2)CC1
InChIKey: IBBYCYRKKJABQD-LJQANCHMSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of full-length SARS-CoV-2 PLpro expressed in Escherichia coli BL21(DE3) using Ub-Rho as substrate incubated for 5 mins by enzymatic assay
Measurement: IC50 = 2160 nM (pChEMBL 5.670000076293945)
Descriptors: MW 393.58, ALogP 4.07, HBA 3, HBD 1, PSA 35.58, QED 0.83
Compound (SMILES): CCS(=O)(=O)Cc1ccc(Oc2ccc(F)cc2F)c(-c2cn(C)c(=O)c3cc(-c4cc(C)c(OCCO)c(C)c4)oc23)c1
InChIKey: PPAPUDIDCDAFEO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of C-terminal His6-tagged BRD4 BD2 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 623.67, ALogP 6.46, HBA 8, HBD 1, PSA 107.97, QED 0.19
Compound (SMILES): Cc1ccc(C2CCN(c3ccc(Nc4nccc(-c5ccc(C(=O)NCC#N)cc5)n4)cc3)CC2)o1
InChIKey: RCIYSHDQTFGLIG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 kinase domain
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 492.58, ALogP 5.43, HBA 7, HBD 2, PSA 107.08, QED 0.33
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(F)nc1
InChIKey: PGZQEUGRRIQARD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 41.4 nM (pChEMBL 7.380000114440918)
Descriptors: MW 394.41, ALogP 4.96, HBA 5, HBD 1, PSA 72.28, QED 0.42
Compound (SMILES): Cc1nc(NC(=O)c2cccc(-c3cnn(C)c3)n2)cc(N2CC[C@@H](C(C)(C)O)C2)n1
InChIKey: UPSNQHGCEYRORJ-MRXNPFEDSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in human SH-SY5Y cells assessed as inhibition of tetracycline induced LRRK2 phosphorylation at Ser935 residue incubated for 90 mins by MSD assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 421.51, ALogP 2.43, HBA 8, HBD 2, PSA 109.06, QED 0.65
Compound (SMILES): COc1ccc(CC(=O)N(C)C2CCCc3ccc(NS(=O)(=O)c4cc(-c5cccc(C(=O)N(C)C)c5)ccc4OC)cc32)cc1
InChIKey: AUBQSRXATQWTBD-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at OX2R (unknown origin)
Measurement: EC50 = 3.63 nM (pChEMBL 8.4399995803833)
Descriptors: MW 641.79, ALogP 5.95, HBA 6, HBD 1, PSA 105.25, QED 0.23
Compound (SMILES): Cc1ccc(Cc2c(C)nc3c(C(=O)N4CCN(c5cccc(C(F)F)c5)CC4)cnn3c2C)cc1
InChIKey: VZCOXLXBAKYLKQ-UHFFFAOYSA-N
Target: RuvB-like 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y230
Assay: Inhibition of full length recombinant His6 tagged human RUVBL2 expressed in Escherichia coli Rosetta cells incubated for 70 mins in presence of ATP by ATPase assay
Measurement: IC50 > 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 489.57, ALogP 5.15, HBA 5, HBD 0, PSA 53.74, QED 0.39
Compound (SMILES): C[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCC[C@@H]2[C@@H](O)C1CCCC1
InChIKey: NLRXGPDDNSKSQO-NHTMILBNSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P06536
Assay: Agonist activity at glucocorticoid receptor in rat INS-1 832/13 cells transfected with 3XGRE-promoter luciferase plasmid construct assessed as induction of receptor transactivation by luciferase reporter gene assay
Measurement: EC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 380.51, ALogP 5.31, HBA 3, HBD 1, PSA 38.05, QED 0.78
Compound (SMILES): CCCNNC(=O)c1cnc(N2CCN(Cc3c[nH]c4ccccc34)CC2)nc1
InChIKey: MAEKVVCEBJELGT-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human HDAC2 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 393.5, ALogP 1.92, HBA 6, HBD 3, PSA 89.18, QED 0.42
Compound (SMILES): N#Cc1ccc2c(Nc3ccc4[nH]nc(-c5ccncc5)c4c3)cccc2c1
InChIKey: AZGKLZGDJGQVGI-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full length LRRK2 G2019S mutant (unknown origin) by LRRKtide Adapta assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 361.41, ALogP 5.39, HBA 4, HBD 2, PSA 77.39, QED 0.45
Compound (SMILES): O=C(Nc1ccccc1F)[C@]12ON=C(c3cccnc3)[C@H]1[C@@H]1CC[C@H]2C1
InChIKey: LLPCNDHJBQJHHT-CIEYIMOZSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in Chinese hamster V79 MZh cells using [14C]-deoxycorticosteron as substrate measured after 6 hrs by phosphoimager analysis
Measurement: IC50 = 135 nM (pChEMBL 6.869999885559082)
Descriptors: MW 351.38, ALogP 3.38, HBA 4, HBD 1, PSA 63.58, QED 0.92
Compound (SMILES): COc1cc2c(C)nnc(N[C@H](C)c3cccc(C(F)(F)F)c3C)c2cc1OC
InChIKey: SUSQYYGPLOUGJB-GFCCVEGCSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: HTRF Displacement Assay: Table 21: This Example illustrates that exemplary compounds of the present invention bind to SOS1 and prevent a labeled tracer ligand from occupying the SOS1 binding site. The ability of a compound of Formula (I) to bind to SOS1 was measured using a HTRF displacement assay. A recombinant human SOS1 polypeptide (corresponding to amino acids 564-1049, expressed in E. Coli with N-terminal StrepII-TEV, C-terminal His-tag. MW=60.59 kDa) was incubated with an exemplary compound of Formula (I) (in a DMSO stock solution) in buffer (25 mM HEPES pH 7.5, 25 mM NaCl, 1 mM DTT, 0.01% Brij 35, 0.02% BSA, 0.1% DMSO). After a 15-minute incubation at room temperature, a solution comprised of a custom-made Cy5 labelled tracer and MAb Anti-6HIS Tb cryptate Gold (Cisbio 61HI2TLA) in buffer was added to the solution containing the SOS1 polypeptide and exemplary compound of Formula (I). After a 1-hour incubation at room temperature, the HTRF signal was measured using Envision plate reader (Perkin Elmer) according to the manufacturer's instructions. Excitation was from over a range of 245-395 nm, and emission 1 was detected at (657.5-672.5) nm and emission 2 detected at (606.5-623.5) nm. The HTRF ratio was calculated using the formula: [emission 1/emission 2]*10000.
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 405.42, ALogP 5.46, HBA 5, HBD 1, PSA 56.27, QED 0.61
Compound (SMILES): CN(CCOc1ccc(C2NC(=O)N(C)C3=C2C(=O)c2ccccc23)cc1)CCC(Oc1ccc(C(F)(F)F)cc1)c1ccccc1
InChIKey: NHDHRDAKCPYZAP-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to human recombinant ERbeta by competitive fluorometric binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 641.69, ALogP 7.53, HBA 5, HBD 1, PSA 71.11, QED 0.18
Compound (SMILES): COc1ccc(-c2cccc(S(=O)(=O)N[C@@H](Cc3cccc(C(=N)N)c3)C(=O)N3CCN(C(=O)C4CCCCC4)CC3)c2)c(OC)c1
InChIKey: LNNWDFRSVZFSAT-HKBQPEDESA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Binding affinity to bovine thrombin assessed as inhibition constant using tosyl-Gly-Pro-Arg-AMC as substrate
Measurement: Ki = 414 nM (pChEMBL 6.380000114440918)
Descriptors: MW 661.83, ALogP 3.8, HBA 7, HBD 3, PSA 155.12, QED 0.21
Compound (SMILES): C=CC(=O)N1CCC[C@@H](NC(=O)c2sc3nccc4c3c2NC(=O)N4c2cnc(OC(C)C)cc2C)C1
InChIKey: KKABTGLLFMGRGR-MRXNPFEDSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: TBD: TBD
Measurement: IC50 = 7.94 nM (pChEMBL 8.100000381469727)
Descriptors: MW 520.62, ALogP 4.38, HBA 7, HBD 2, PSA 116.76, QED 0.47
Compound (SMILES): C[N+]1(C)CCC(Oc2ccc(/C=C/c3ccccc3)cc2)CC1.[I-]
InChIKey: DZSIDBQMKNPWAK-HRNDJLQDSA-M
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]-epibatidine from human alpha3beta4 nAChR expressed in SH-EP1 cells membrane assessed as inhibition constant preincubated for 5 mins followed by overnight incubation with [3H]-epibatidine by gamma liquid scintilation counting analysis
Measurement: Ki = 368 nM (pChEMBL 6.429999828338623)
Descriptors: MW 308.45, ALogP 4.47, HBA 1, HBD 0, PSA 9.23, QED 0.6
Compound (SMILES): Cc1ccc(-c2nc(N)nc3c2cnn3Cc2ccc(C(=O)Nc3ccccc3N)cc2)o1
InChIKey: HXEWOCGXCBSYAD-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using trypsin and LGK(Ac)-AMC as substrates incubated for 1 hr and measured by fluorescence assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 439.48, ALogP 3.86, HBA 8, HBD 3, PSA 137.88, QED 0.35
Compound (SMILES): COc1ccc2cc(-c3cccc(OCc4ccc(OCC(=O)O)c(F)c4)c3)ccc2c1
InChIKey: RPUMWGCDRJLYGW-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human PPARdelta measured by dual luciferase reporter gene assay
Measurement: EC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 432.45, ALogP 5.7, HBA 4, HBD 1, PSA 64.99, QED 0.39
Compound (SMILES): Cn1ncc(-c2cc(C(F)F)c3c(=O)[nH]nc(CN)c3c2)c1-c1sc2ccccc2c1C#N
InChIKey: RSTICELGAGSITL-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 methyltransferase activity in human HCT-116 cells expressing wild type MTAP assessed as inhibition of PRMT5-mediated SDMA modification level incubated for 96 hrs by In-cell Western analysis
Measurement: IC50 = 759 nM (pChEMBL 6.119999885559082)
Descriptors: MW 462.49, ALogP 4.47, HBA 7, HBD 2, PSA 113.38, QED 0.41
Compound (SMILES): O=C(Nc1nccs1)C(c1ncn2c1CCC2)N1Cc2ccc(C#Cc3cccnc3)cc2C1=O
InChIKey: NNRWAFNZNOEGGS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) phosphorylation expressed in mouse BaF3 cells measured after 4 hrs by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 480.55, ALogP 3.42, HBA 7, HBD 1, PSA 93.01, QED 0.45
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)N2CCC(c3ccncc3)CC2)c1
InChIKey: TUPUYLLHTGZRRB-OAHLLOKOSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay
Measurement: IC50 = 52800 nM (pChEMBL 4.28000020980835)
Descriptors: MW 339.44, ALogP 3.74, HBA 3, HBD 1, PSA 54.46, QED 0.92