lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccc(C)cc1
InChIKey: ZMRYYAYXNFIDRW-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of TNF-alpha induced NF-kappaB signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 485.01, ALogP 5.36, HBA 4, HBD 1, PSA 75.71, QED 0.53
Compound (SMILES): Cc1c(Oc2ccc(CN)cc2F)ccc2c1B(O)OC2
InChIKey: ZCITXZXBLWIHHP-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of GST-tagged ROCK2 (5 to 554 residues) (unknown origin) using S6-peptide as substrate preincubated for 15 mins followed by 33P-ATP addition and measured after 120 mins by scintillation counter analysis
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 287.1
Compound (SMILES): O=C(NO)c1ccc(Cn2cnc(-c3ccccc3)n2)nc1
InChIKey: YVLUDPFAHVPIBZ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using fluorogenic substrate measured after 30 mins
Measurement: IC50 = 431 nM (pChEMBL 6.369999885559082)
Descriptors: MW 295.3, ALogP 1.51, HBA 6, HBD 2, PSA 92.93, QED 0.56
Compound (SMILES): C=CCOC(=O)/N=c1\oc2cc(N(CC)CC)ccc2cc1-c1nc2ccccc2s1
InChIKey: HBWNDXAVUPAAIJ-ROMGYVFFSA-N
Target: Kelch-like ECH-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14145
Assay: Binding affinity to human KEAP1 by fluorescence based assay
Measurement: Kd = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 433.53, ALogP 5.78, HBA 6, HBD 0, PSA 67.93, QED 0.36
Compound (SMILES): CCc1nc(C)nn1CC(=O)N1CCN(c2sc(C(F)(F)F)nc2-c2cnc(C(F)(F)F)nc2)C[C@H]1C
InChIKey: AIPQYPCEXRVEFE-LLVKDONJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG stably expressed in CHO cells at -80 mV holding voltage by automated QPatch electrophysiological assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 548.52, ALogP 3.84, HBA 9, HBD 0, PSA 92.93, QED 0.45
Compound (SMILES): N#Cc1cn(CCCc2ccccc2)c2c(N3CCN(CCc4c[nH]c5ccccc45)CC3)ncnc12
InChIKey: YKKLHDHOUSXZOO-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 in human NCI-H69AR cells incubated for 180 mins in presence of daunorubicin by flow cytometry analysis
Measurement: IC50 = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 489.63, ALogP 4.78, HBA 6, HBD 1, PSA 76.77, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)CC1
InChIKey: LNJMXIZSFNEQQF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA analysis
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 432.48, ALogP 3.08, HBA 7, HBD 2, PSA 123.04, QED 0.48
Compound (SMILES): Cc1cc(OCc2nc(N)nc(NCCc3ccccc3C)n2)cc(N2CCCC2=O)c1
InChIKey: QWIJRJAWIYYATJ-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at N-terminal FLAG tagged human FFAR4 transfected in African green monkey COS-7 cells assessed as accumulation of inositol phosphate incubated for 90 mins by TopCount NXT counter based analysis
Measurement: EC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 432.53, ALogP 3.43, HBA 7, HBD 2, PSA 106.26, QED 0.56
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(Cl)cc23)CC1
InChIKey: GKMJDDGKJJWAFL-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 373.83, ALogP 4.76, HBA 3, HBD 1, PSA 42.15, QED 0.7
Compound (SMILES): CCCC[C@@H](C)[C@@H]1CC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](C)C(=O)N[C@H]([C@@H](C)CC)C(=O)O1
InChIKey: VEELKRGSLCNVAR-AWIGMLKBSA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75908
Assay: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrs
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 487.64, ALogP 2.89, HBA 5, HBD 3, PSA 113.6, QED 0.49
Compound (SMILES): Cn1nccc1NC(=O)Nc1ccc(-c2nc(-c3ccc(CN4CCN(S(C)(=O)=O)CC4)s3)nc(N3CCOCC3)n2)cc1
InChIKey: VXFIQWFKZBLWIN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) by kinase-glo luminescent assay
Measurement: IC50 = 571.23 nM (pChEMBL 6.239999771118164)
Descriptors: MW 638.78, ALogP 2.56, HBA 12, HBD 2, PSA 150.71, QED 0.29
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5ccccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: PAGHJJMXITYTPR-AWEZNQCLSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Positive allosteric modulation of rat mGluR7
Measurement: EC50 = 263.03 nM (pChEMBL 6.579999923706055)
Descriptors: MW 391.41, ALogP 2.74, HBA 7, HBD 0, PSA 74.51, QED 0.66
Compound (SMILES): CCn1nnc(-c2sc(-c3ccccc3O)nc2O)n1
InChIKey: FMWAGGMQECABRZ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in cold stimulated Ca2+ efflux preincubated for 5 mins followed by cold stimulation and measured for 3 mins
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 289.32, ALogP 1.89, HBA 8, HBD 2, PSA 96.95, QED 0.76
Compound (SMILES): O=C(CN(Cc1ccc(Cl)cc1)C(=O)c1cc2ccccc2[nH]1)NC1CCCCC1
InChIKey: CRTGTKRROZUQTQ-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding affinity to human MDM2 assessed as dissociation constant
Measurement: Ki = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 423.94, ALogP 4.91, HBA 2, HBD 2, PSA 65.2, QED 0.59
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)O[C@@H](C)C(C)(C)C)nc2C2(CCC(F)(F)CC2)C1(C)C
InChIKey: BQJACMMFLPJGCR-ZDUSSCGKSA-N
Target: Thyrotropin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P16473
Assay: Antagonist activity at human TSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 438.52, ALogP 5.05, HBA 5, HBD 1, PSA 84.42, QED 0.7
Compound (SMILES): CCN(CC)c1ccc(/C=C2\C(=O)N(C3CCCCC3)C(=S)N2C)cc1
InChIKey: MTAXOQPARRPELE-XDJHFCHBSA-N
Target: NADPH oxidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04839
Assay: Inhibition of human NOX2 assessed as reduction in ROS production using lucigenin as substrate in presence of NADPH by chemiluminescence based microplate reader analysis
Measurement: IC50 = 5660 nM (pChEMBL 5.25)
Descriptors: MW 371.55, ALogP 4.27, HBA 3, HBD 0, PSA 26.79, QED 0.57
Compound (SMILES): Cc1ccncc1-c1cccc2c1OCCN2c1ccccc1
InChIKey: COHFJQPPHXIADS-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 302.38, ALogP 4.59, HBA 3, HBD 0, PSA 25.36, QED 0.69
Compound (SMILES): Cn1cc(Nc2nc(NC3CCOCC3)c3nc(CC#N)ccc3n2)cn1
InChIKey: MWCZZMKIONRYDB-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) phosphorylation by cell based assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 364.41, ALogP 2.16, HBA 9, HBD 2, PSA 113.57, QED 0.71
Compound (SMILES): COc1cccc(-n2ncc3c(-c4cnccc4C)ccnc32)c1
InChIKey: KQVWYTLYAHUHRC-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 316.36, ALogP 3.8, HBA 5, HBD 0, PSA 52.83, QED 0.58
Compound (SMILES): COC(=O)c1cc2c(cn1)[nH]c1ccc(NCc3ccccc3)cc12
InChIKey: JTYYMOMTGZSRFM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Binding affinity to human recombinant GABAA alpha2 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 331.38, ALogP 4.11, HBA 4, HBD 2, PSA 67.01, QED 0.55
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)CC1
InChIKey: GYHRANYJOBNLHW-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 447.96, ALogP 5, HBA 3, HBD 1, PSA 35.58, QED 0.7
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NCC(N)=O
InChIKey: YJKNBYBEJYUUHW-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 11400 nM (pChEMBL 4.940000057220459)
Descriptors: MW 441.89, ALogP 4.02, HBA 5, HBD 3, PSA 110, QED 0.51
Compound (SMILES): CC(C)N1Cc2cc(F)ccc2OCC(C)(C)NC(=O)c2cnc3ccc1nn23
InChIKey: WCSITSBWFOSTLO-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin)
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 397.45, ALogP 3.18, HBA 6, HBD 1, PSA 71.76, QED 0.68
Compound (SMILES): COc1ccc2[nH]c3c(c2c1)N=CN(CCCN(C)C1CCCCC1)C3
InChIKey: BBGBTOPSYUIPQM-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Binding affinity to tau (unknown origin)
Measurement: Kd = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 354.5, ALogP 4.31, HBA 4, HBD 1, PSA 43.86, QED 0.84
Compound (SMILES): C[C@]12CCC(=O)C=C1C(=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
InChIKey: PJMNEPMSGCRSRC-IEVKOWOJSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase (unknown origin)
Measurement: IC50 = 279.9 nM (pChEMBL 6.550000190734863)
Descriptors: MW 300.4, ALogP 3.27, HBA 3, HBD 0, PSA 51.21, QED 0.69
Compound (SMILES): COc1ccc2c(ccn2-c2c(Cl)cc(-n3nc(C#N)c(=O)[nH]c3=O)cc2Cl)c1
InChIKey: OQEIQUOAQQFLAI-UHFFFAOYSA-N
Target: Thyroid hormone receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10828
Assay: Agonist activity at human THRbeta transfected in Huh7 cells co-transfected with luciferase reporter plasmid assessed as reduction in luciferase activity incubated for 16 hrs by Steady-Glo luciferase assay
Measurement: EC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 428.24, ALogP 3.05, HBA 7, HBD 1, PSA 105.7, QED 0.54
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): CC(N[C@H]1CC[C@H](NC(=O)c2cnc3nc(C4CC4)ccc3c2)CC1)C(F)F
InChIKey: ZXOJWLAQYIYEHC-ZWNDMSQQSA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35543
Assay: Inhibition of H-PGDS in rat RBL cells assessed as reduction in A23187-induced PGD2 production pretreated for 30 mins followed by A23187 addition for 30 mins by RapidFire Mass spectrometry
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 388.46, ALogP 3.79, HBA 4, HBD 2, PSA 66.91, QED 0.79
Compound (SMILES): CC(C)Oc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: PPBVLCXRMSVIEI-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant
Measurement: Ki = 461.3 nM (pChEMBL 6.340000152587891)
Descriptors: MW 475.52, ALogP 3.03, HBA 8, HBD 1, PSA 142.07, QED 0.51
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccc(Cl)cc3)cc2)nc2cnccc12)C(N)=O
InChIKey: KFUPSHPLPAHYAR-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 1490 nM (pChEMBL 5.829999923706055)
Descriptors: MW 441.92, ALogP 5.16, HBA 5, HBD 2, PSA 104.69, QED 0.43
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: ATFCNLVUGGJYEX-DHRBKSIMSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as Ki by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 936 nM (pChEMBL 6.03000020980835)
Descriptors: MW 701.8, ALogP -0.95, HBA 10, HBD 6, PSA 252.68, QED 0.09
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(Cl)c(O)c(C(N)=O)c3)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: FRJRUCNOMGJHID-AWEZNQCLSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 27.8 nM (pChEMBL 7.559999942779541)
Descriptors: MW 599.48, ALogP 2.69, HBA 10, HBD 3, PSA 151.61, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2ccc(O)cc2O3)c([N+](=O)[O-])c1
InChIKey: WYRAOTGCFPPQHI-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 433.44, ALogP 1.95, HBA 8, HBD 2, PSA 153.07, QED 0.55
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1C/C=C1\CCC(CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: HFPHPWOFSUNVRW-QIBJJAHESA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylscopolamine from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 7920 nM (pChEMBL 5.099999904632568)
Descriptors: MW 459.59, ALogP 4.06, HBA 5, HBD 3, PSA 96.27, QED 0.48
Compound (SMILES): Cc1onc(-c2ccccc2)c1COCCCCCNC(=O)C(C)S
InChIKey: SXOJHTOVXGQVDN-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 362.5, ALogP 3.77, HBA 5, HBD 2, PSA 64.36, QED 0.5
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)OCC(C)C)nc2C2(CCCCC2)C1(C)C
InChIKey: UOMXYCDNPJDTQB-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 374.49, ALogP 4.03, HBA 5, HBD 1, PSA 84.42, QED 0.86
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4cccc(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: WAYSVGLDKMEZLH-KRWDZBQOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin)
Measurement: IC50 = 0.112 nM (pChEMBL 9.949999809265137)
Descriptors: MW 512.97, ALogP 4.89, HBA 7, HBD 1, PSA 85.81, QED 0.45
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCN5CCCCCC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: BHNAORVEXRBMID-YOGXEWEVSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 464.74, ALogP 6.65, HBA 3, HBD 0, PSA 15.71, QED 0.44
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51617
Assay: Inhibition of IRAK1 (unknown origin) in presence of 25 uM ATP
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): C[C@@H]1C[C@@H](O)c2ncnc(N3CCN(C(=O)[C@H](CNCCCCCCCCCCCc4cccc5c4CN(C4CCC(=O)NC4=O)C5=O)c4ccc(Cl)cc4)CC3)c21
InChIKey: VLYIIJVXJVEICJ-CZUNFGTBSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of Akt3 (unknown origin)
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 812.46, ALogP 6.21, HBA 9, HBD 3, PSA 148.07, QED 0.1
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccc(F)cc3)cc2)nc2cnccc12)C(N)=O
InChIKey: CQZXCWWMMNVIFZ-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 425.47, ALogP 4.65, HBA 5, HBD 2, PSA 104.69, QED 0.47
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(-c5ccccc5F)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: CYDYWAYVIILVQJ-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 554.63, ALogP 3.83, HBA 10, HBD 2, PSA 104.34, QED 0.33
Compound (SMILES): C/C=C/n1c(=O)c2cnc(Nc3ccc(CN4CCOCC4)cc3)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: XGBGLGGARORZSJ-UUILKARUSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 501.59, ALogP 3.27, HBA 10, HBD 2, PSA 110.33, QED 0.4
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@H](C)C2)c1
InChIKey: HVXGLCUTIOCPRK-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): Cc1cnc(Nc2ccc(N3CCN(C)CC3)c(F)c2)nc1Nc1ccc(S(=O)(=O)NC(C)(C)C)cc1
InChIKey: GYLQBOZRIDQRRF-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by 33P-ATP radiolabeled assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 527.67, ALogP 4.24, HBA 8, HBD 3, PSA 102.49, QED 0.42
Compound (SMILES): CC1(C)c2ccccc2N(Cc2ccc(C(=O)NO)cc2)C1c1ccncc1
InChIKey: WOTUHAJNRNHMHC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using FLUOR DE LYS fluorometric substrate pre-incubated for 15 mins and followed by substrate addition and measured after 60 mins by microplate reader assay
Measurement: IC50 = 4640 nM (pChEMBL 5.329999923706055)
Descriptors: MW 373.46, ALogP 4.24, HBA 4, HBD 2, PSA 65.46, QED 0.53
Compound (SMILES): CC1=CC(C)=[N+]2C1=C(c1ccc(OCCn3cc(CCCOc4cc(C(=O)O)nc5c(C)c6nc(C(=O)O)cc(O)c6cc45)nn3)cc1)c1nc(C)cn1[B-]2(F)F
InChIKey: KHEPRHNLTBJKJD-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at GPR-35 in human HT-29 cells assessed as desensitization of zaprinast induced DMR response incubated for 1 hr followed by zaprinast stimulation in presence of ML-145
Measurement: IC50 = 1034.1 nM (pChEMBL 5.989999771118164)
Descriptors: MW 776.57
Compound (SMILES): O=c1ccc2c(N3CCCN(CCCCOc4ccc5ccnn5c4)CC3)ccc(O)c2[nH]1
InChIKey: RGAXRFLOVCZZNS-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor assessed as increase in cAMP accumulation
Measurement: EC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 447.54, ALogP 3.25, HBA 7, HBD 2, PSA 86.1, QED 0.42
Compound (SMILES): C#CCOc1cccc2oc(=O)ccc12
InChIKey: XWFITGVIMAVRMA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Mixed type inhibition of CYP3A4 (unknown origin)
Measurement: Ki = 46600 nM (pChEMBL 4.329999923706055)
Descriptors: MW 200.19, ALogP 1.8, HBA 3, HBD 0, PSA 39.44, QED 0.55
Compound (SMILES): CC(C)=CCN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: VOKSWYLNZZRQPF-MDASCCDHSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane assessed as inhibition constant measured after 120 mins by scintillation counting method
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 285.43, ALogP 3.88, HBA 2, HBD 1, PSA 23.47, QED 0.83
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCNCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: POIIDLJXIAHDFT-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 1002.76
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3ccccc3)ccc21
InChIKey: HHCZFHVWMCIUJH-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 3830 nM (pChEMBL 5.420000076293945)
Descriptors: MW 382.44, ALogP 3.67, HBA 4, HBD 1, PSA 79.62, QED 0.75
Compound (SMILES): CCCCS(=O)(=O)N(c1ccc2c(c1)CCCN2C(=O)c1ccco1)S(=O)(=O)CCCC
InChIKey: NHKIBQLDANKHOI-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 2840 nM (pChEMBL 5.550000190734863)
Descriptors: MW 482.62, ALogP 3.94, HBA 6, HBD 0, PSA 104.97, QED 0.51
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(N(S(=O)(=O)c3ccc(F)cc3)S(=O)(=O)c3ccc(F)cc3)ccc21
InChIKey: IVEAXCPKMHOTQU-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 558.58, ALogP 4.74, HBA 6, HBD 0, PSA 104.97, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(Cl)c(OC)c4)nn32)CC1
InChIKey: BCPNJXKITYKKCV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 551 nM (pChEMBL 6.260000228881836)
Descriptors: MW 473.96, ALogP 3.1, HBA 7, HBD 2, PSA 111.71, QED 0.62
Compound (SMILES): O=C(Nc1ccc(-c2n[nH]c(=O)c3ccccc23)cc1)N1CCc2ccccc21
InChIKey: XTIYMUSBVIPTLM-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 382.42, ALogP 4.18, HBA 3, HBD 2, PSA 78.09, QED 0.55
Compound (SMILES): C=CC(=O)N1CCCCCCCn2cc(c3ccccc32)-c2ccnc(n2)Nc2cc1ccc2OC
InChIKey: DGNRLSVNVHHACI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant (unknown origin)
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 481.6, ALogP 6.33, HBA 6, HBD 1, PSA 72.28, QED 0.34
Compound (SMILES): O=C(NO)c1ccc(CN2CC(=O)N(Cc3ccccc3)[C@H](Cc3ccccc3)C2=O)cc1
InChIKey: VFVKMAGFYMKRQA-HSZRJFAPSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 443.5, ALogP 2.79, HBA 4, HBD 2, PSA 89.95, QED 0.43
Compound (SMILES): Clc1ccc(Nc2nc(-c3nccs3)cs2)cc1
InChIKey: JRUQTPLCBLNIGX-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 118.7 nM (pChEMBL 6.929999828338623)
Descriptors: MW 293.8, ALogP 4.66, HBA 5, HBD 1, PSA 37.81, QED 0.76
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(-c5ccccc5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: TWYAUJSGFHQKSM-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 536.64, ALogP 3.69, HBA 10, HBD 2, PSA 104.34, QED 0.34
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n([C@H]5C=CCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: LZTPSBCGWGMOMP-QFIPXVFZSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 526.65, ALogP 3.59, HBA 10, HBD 2, PSA 104.34, QED 0.37
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCN(C(=O)CCCCCCCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: AOIZISCRIVNZJJ-XWJFFXCMSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Displacement of [3H-SAM] from full-length EZH2 (2 to 746 residues) (unknown origin) using a core histone substrate
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 1154.53
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2ccc(OCCO)cc2O3)c([N+](=O)[O-])c1
InChIKey: KDHNWXMBKLGVCS-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 0.47 nM (pChEMBL 9.329999923706055)
Descriptors: MW 477.5, ALogP 1.62, HBA 9, HBD 2, PSA 162.3, QED 0.46
Compound (SMILES): CCCCN(CCCC)c1cc(NC(=O)c2nnn(-c3cc(OC)ccc3OC)c2C)cc(C(C)(C)C)c1
InChIKey: RWUAIBBERCZABS-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 521.71, ALogP 6.55, HBA 7, HBD 1, PSA 81.51, QED 0.29
Compound (SMILES): CNC(=O)c1cc(COC(=O)c2ccc3c(c2)c(COc2ccc4[nH]ccc4c2)cn3S(C)(=O)=O)cc(=O)[nH]1
InChIKey: VJTGCTYUJTUPBS-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of human recombinant His6 tagged SENP1 catalytic domain expressed in Escherichia coli BL21 (DE3) using SUMO2-AMC as substrate incubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 548.58, ALogP 2.91, HBA 8, HBD 3, PSA 152.35, QED 0.25
Compound (SMILES): Nc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)N[C@H]1CCN(c2cccc(Cl)c2)C1
InChIKey: QZVBCPBEJSYHNK-QFIPXVFZSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibitory Activity Assay: KLK1 inhibitory activity in vitro was determined using standard published methods. Human KLK1 (Callbiochem) was incubated at 25° 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 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 503.01, ALogP 3.39, HBA 7, HBD 2, PSA 98.18, QED 0.4
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)[C@@H](C)n2nnnc2N1C
InChIKey: BVMAEXVWFIGNKQ-SECBINFHSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 324.35, ALogP 1.47, HBA 7, HBD 2, PSA 104.62, QED 0.74
Compound (SMILES): COc1ccc(S(=O)(=O)N2CC(C)(C)C(CCSCc3ccccc3)C2C(=O)NO)cc1
InChIKey: APCLVQAXJIHPKK-UHFFFAOYSA-N
Target: Interstitial collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P03956
Assay: Inhibition of human MMP1 using Dnp-Pro-Cha-Gly-Cys(Me)-His-Ala-Lys(Nma)-NH2 substrate by fluorimetric analysis
Measurement: IC50 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 478.64, ALogP 3.54, HBA 6, HBD 2, PSA 95.94, QED 0.33
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: JGOIBENTSQHWDQ-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 973.71, ALogP 14.06, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) in presence of ATP
Measurement: IC50 = 2233 nM (pChEMBL 5.650000095367432)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51
Compound (SMILES): C=CC(=O)N1CCc2ccc(N3C(=O)CCc4cnc5ccc(-c6cnn(C)c6)cc5c43)cc21
InChIKey: JVOWSKQMJFOGDZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 4310 nM (pChEMBL 5.369999885559082)
Descriptors: MW 449.51, ALogP 4.32, HBA 5, HBD 0, PSA 71.33, QED 0.44
Compound (SMILES): CC(=O)Nc1cc(Oc2ccc(NC(=O)Cc3ccccc3C(F)(F)F)cc2)ncn1
InChIKey: PFGNOYJAWUKCEW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 430.39, ALogP 4.43, HBA 5, HBD 2, PSA 93.21, QED 0.6
Compound (SMILES): CC1(C)SSC[C@@H](C(N)=O)NC(=O)[C@H]1NC(=O)[C@H](CC1CCCCC1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1
InChIKey: NWRSEICSTMDHPZ-BTVYXRGWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 954.19, ALogP -3.4, HBA 13, HBD 15, PSA 413.68, QED 0.02
Compound (SMILES): O=c1[nH]n2c(=O)c3ccccc3nc2/c1=C/c1ccc(Br)cc1
InChIKey: QXOHUUUSFJPFTN-LCYFTJDESA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin) by fluorescence based analysis
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 368.19, ALogP 1.85, HBA 4, HBD 1, PSA 67.23, QED 0.56
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(OC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: QJBDLOQOXGQJTD-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 959.69, ALogP 13.82, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): O=S(=O)(Nc1nccs1)c1cc(Cl)c(NCCCCNC[C@H]2CCCN2)cc1F
InChIKey: ANLDPIQLMLMNRA-CYBMUJFWSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 at voltage yielding 20% channel inactivation by manual patch-clamp assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 462.02, ALogP 3.27, HBA 7, HBD 4, PSA 95.15, QED 0.38
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NC[C@H](C)O
InChIKey: JZVPITOQWJPGIA-AWEZNQCLSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human whole blood assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): CN(CC1(C(=O)NC23CC4CC(C2)CC(C(N)=O)(C4)C3)CC1)S(=O)(=O)c1ccccc1F
InChIKey: VEFHANPSESBAGN-UHFFFAOYSA-N
Target: Hydroxysteroid 11-beta dehydrogenase 1 (SINGLE PROTEIN), Macaca mulatta
UniProt: Q56D22
Assay: Inhibition of monkey 11beta-HSD1 in liver microsome incubated for 24 hrs by LC-MS analysis
Measurement: IC50 = 2.43 nM (pChEMBL 8.609999656677246)
Descriptors: MW 463.58, ALogP 2.17, HBA 4, HBD 2, PSA 109.57, QED 0.65
Compound (SMILES): Cc1onc(-c2ccccc2)c1COCCCCCNC(=O)[C@H](C)S
InChIKey: SXOJHTOVXGQVDN-HNNXBMFYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 362.5, ALogP 3.77, HBA 5, HBD 2, PSA 64.36, QED 0.5
Compound (SMILES): CC(C)n1nc(C(=O)NC2C3CN(CC4CCOCC4)CC32)c2ccccc21.O=C(O)C(=O)O
InChIKey: OLXNWUWZVKDKSX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 382.51, ALogP 2.7, HBA 5, HBD 1, PSA 59.39, QED 0.86
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-XMMPIXPASA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Inverse agonist activity at human GAL4-fused LXRalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)=CCc1c(O)ccc2c1O/C(=C\c1ccc(O)cc1)C2=O
InChIKey: FUXXTORAZIFFMU-WQRHYEAKSA-N
Target: Maltase-glucoamylase (SINGLE PROTEIN), Homo sapiens
UniProt: O43451
Assay: Inhibition of alpha-glucosidase (unknown origin)
Measurement: IC50 = 73800 nM (pChEMBL 4.130000114440918)
Descriptors: MW 322.36, ALogP 4.22, HBA 4, HBD 2, PSA 66.76, QED 0.66
Compound (SMILES): C[C@@H]1[C@@H]2Cc3ccccc3[C@]1(C)CCN2CCNc1ccccc1
InChIKey: VGBPBHGWCLWDSK-VOQZNFBZSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma 2 receptor (unknown origin) assessed as inhibition constant in presence of (+)-SKF10047 by radioligand binding assay
Measurement: Ki = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 320.48, ALogP 4.32, HBA 2, HBD 1, PSA 15.27, QED 0.9
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(N(S(=O)(=O)c3cc4ccccc4s3)S(=O)(=O)c3cc4ccccc4s3)ccc21
InChIKey: MKJYULNSRVBJSN-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 3190 nM (pChEMBL 5.5)
Descriptors: MW 634.78, ALogP 6.89, HBA 8, HBD 0, PSA 104.97, QED 0.2
Compound (SMILES): O=C(CCc1ccccc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: AHBHZZLUODBWMS-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 310.4, ALogP 2.67, HBA 3, HBD 1, PSA 43.78, QED 0.94
Compound (SMILES): O=c1cc(CNC[C@@H](CO)Cc2ccsc2)[nH]c2ccc(F)cc12
InChIKey: IPKYJQPHFTVWOU-ZDUSSCGKSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of 3H-N-Methylspiperone from DRD3 in human HEK293T cells membrane assessed as inhibition constant incubated for 2 hrs by radioligand competition assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 346.43, ALogP 2.67, HBA 4, HBD 3, PSA 65.12, QED 0.62
Compound (SMILES): Cc1ncc2c(=O)[nH]c(-c3ccc(C(C)(C)O)cc3)cn12
InChIKey: ZGHNBPCNVXEKGL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 283.33, ALogP 2.23, HBA 4, HBD 2, PSA 70.39, QED 0.76
Compound (SMILES): CCOC(=O)[C@]1(C)CCC[C@@]2(C)[C@@H]3CC[C@@]4(C)C[C@]3(CC[C@@H]21)C[C@H]4OC(=O)c1ccc(O)cc1
InChIKey: IHICFGKTMNVNGG-OFPBPYSDSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of CDC25B (unknown origin) by DAS-ELISA
Measurement: IC50 = 2340 nM (pChEMBL 5.630000114440918)
Descriptors: MW 468.63, ALogP 6.28, HBA 5, HBD 1, PSA 72.83, QED 0.53
Compound (SMILES): COc1cc(N2CCC(N(C)C)CC2)ccc1Nc1ncc(C(=O)OC(C)C)c(-c2c[nH]c3ccccc23)n1
InChIKey: PSTYPEHMIDKSSQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 10 mins by HTRF assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 528.66, ALogP 5.47, HBA 8, HBD 2, PSA 95.61, QED 0.29