lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ncccn1
InChIKey: GQFVXGULVTUNMM-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 = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 472.95, ALogP 3.84, HBA 6, HBD 1, PSA 101.49, QED 0.6
Compound (SMILES): CCCCOc1ccc(CCC(=O)N2CCN(c3ccc(O)cc3)CC2)cc1
InChIKey: ANKCAVFAEXIRFY-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 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 382.5, ALogP 3.85, HBA 4, HBD 1, PSA 53.01, QED 0.7
Compound (SMILES): COc1ccc(Nc2ncnc3c2cnn3-c2ccc(Cl)cc2C)cc1Cl
InChIKey: RNJQSVZFLIHBSM-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P78356
Assay: Inhibition of recombinant PI5P4Kbeta (unknown origin) expressed in Escherichia coli BL21(DE3) by ADP-Glo reagent based assay
Measurement: IC50 > 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 400.27, ALogP 5.18, HBA 6, HBD 1, PSA 64.86, QED 0.51
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: CDRHMFVWJYVLGL-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: P39051
Assay: Inhibition of HIS-tagged recombinant Trypanosoma brucei TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 26900 nM (pChEMBL 4.570000171661377)
Descriptors: MW 546.72, ALogP 3.29, HBA 7, HBD 2, PSA 102.18, QED 0.2
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSC(C(=O)NC(C)C(N)=O)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NC(=O)C(C(C)O)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(C)NC(=O)C2CCCN2C(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(CCCNC(=N)N)NC1=O
InChIKey: SJBURJCQSMMNIC-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using Z-GGR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1879.19
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: NAUMQOWVCNOPGB-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin)
Measurement: IC50 = 492 nM (pChEMBL 6.309999942779541)
Descriptors: MW 547.41, ALogP 5.54, HBA 7, HBD 1, PSA 85.81, QED 0.31
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5c(F)cccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: WXVYORSFYSHIOF-ZDUSSCGKSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Positive allosteric modulation of human mGluR3
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.4, ALogP 2.88, HBA 7, HBD 0, PSA 74.51, QED 0.64
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(N)=O
InChIKey: IOIVYVYLDQJIMW-ONFFMKDPSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 457.51, ALogP -1.67, HBA 8, HBD 5, PSA 203.27, QED 0.18
Compound (SMILES): CSc1c(C#N)c(=O)c2ccc(F)cc2n1-c1c(Cl)cccc1Cl
InChIKey: AWQZXHDLUBADMM-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily KQT member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51787
Assay: Inhibition of recombinant human KCNQ1
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 379.24, ALogP 5.03, HBA 4, HBD 0, PSA 45.79, QED 0.59
Compound (SMILES): Cc1ccc(-c2ccnc(Nc3ccc(N4CCN(C)CC4)c(C(F)(F)F)c3)n2)cc1
InChIKey: JGQOMJGZCRMYPO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 427.47, ALogP 4.97, HBA 5, HBD 1, PSA 44.29, QED 0.64
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-SVBPBHIXSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc2[nH]c(=O)n(C3CCN(Cc4ccc(-c5[nH]c(=O)c(C)nc5-c5ccccc5)cc4)CC3)c2c1
InChIKey: CGWRGCGZPRWFTG-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Binding affinity to N-terminal His6-tagged TEV protease fused wild-type AKT1 (2 to 446 residues) (unknown origin) expressed in Sf9 cells assessed as inhibition constant
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 560.66, ALogP 5.02, HBA 6, HBD 3, PSA 115.88, QED 0.24
Compound (SMILES): CC(C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: NSIQQHYATFPGEC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells harboring harboring EGFR L858R/T790M double mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 537.65, ALogP 2.96, HBA 12, HBD 2, PSA 143.95, QED 0.34
Compound (SMILES): O=c1c(Cl)c(COc2cccc(Cl)c2C2CC2)[nH]c2nc(-c3ccccc3)nn12
InChIKey: HGXDDSUVIVWHNN-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of BODIPY 500/510 C4 from human FABP4 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 427.29, ALogP 4.85, HBA 5, HBD 1, PSA 72.28, QED 0.49
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccccc2C#Cc2ccc(C(=O)O)nc2)c2ncccc12
InChIKey: GKBULVNTEXLKJY-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human SNU-398 cells assessed as inhibition of lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 459.48, ALogP 3.54, HBA 6, HBD 2, PSA 118.48, QED 0.44
Compound (SMILES): O=C1CC2Cc3ccsc3C2=NN1CCCCN1CCN(Cc2ccccc2)CC1
InChIKey: NYFCTSGIAUTTNF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 538 nM (pChEMBL 6.269999980926514)
Descriptors: MW 422.6, ALogP 3.45, HBA 5, HBD 0, PSA 39.15, QED 0.64
Compound (SMILES): C=CCn1c(=O)c2cnc(Nc3ccc4c(c3)CNCC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: WOBLPQMIMKNCIR-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Wee1 Binding Assay: Wee 1 kinase was determined by using Flurorescence Resonance Energy Transfer (FRET) assay. In 384-well plates, Wee1 kinase (2 nM final concentration) was mixed with AlexaFluor labeled tracer 178 (50 nM final concentration, Kd=24 nM), Eu-anti-GST antibody (2 nM final concentration) and then inhibitor (0.003 to 10 micromolar) in a final volume of 16 μl kinase buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA). The plate was shaken for 30 seconds, incubated for 60 min at RT, and recorded on fluorescence plate reader.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 485.59, ALogP 3.52, HBA 9, HBD 3, PSA 109.89, QED 0.36
Compound (SMILES): COC1CCN(c2nccc(Nc3cc4c(cn3)c(C(N)=O)cn4C(C)C)n2)CC1
InChIKey: GBQZWJZYHRNIFT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR del (746 to 750) mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 323 nM (pChEMBL 6.489999771118164)
Descriptors: MW 409.49, ALogP 2.86, HBA 8, HBD 2, PSA 111.19, QED 0.64
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2Cl)CCC1(O)c1cccc(O)c1
InChIKey: VZKYGOFDBBGOOF-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(N)=O)c2C#N)cc1
InChIKey: KIWBVAQAICXQKZ-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 436.52, ALogP 4.9, HBA 5, HBD 1, PSA 101.89, QED 0.44
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3cc(OC)c(C)c(OC)c3)nn21
InChIKey: ZEIZIRVZVXALHM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 21.9 nM (pChEMBL 7.659999847412109)
Descriptors: MW 461.52, ALogP 3.5, HBA 7, HBD 3, PSA 120.5, QED 0.46
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): O=C(O)c1ccc(N(C2CCCC2)S(=O)(=O)c2ccc3ccccc3c2)cc1O
InChIKey: DJNCDDPHSXBDHZ-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 1911 nM (pChEMBL 5.71999979019165)
Descriptors: MW 411.48, ALogP 4.38, HBA 4, HBD 2, PSA 94.91, QED 0.65
Compound (SMILES): c1ccc(COC2CCN(Cc3cn4ccccc4n3)CC2)nc1
InChIKey: VUGZNXOHTNGPHN-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 2290.87 nM (pChEMBL 5.639999866485596)
Descriptors: MW 322.41, ALogP 2.91, HBA 5, HBD 0, PSA 42.66, QED 0.72
Compound (SMILES): CN(C)c1cccc2c(S(=O)(=O)N[C@H](C(=O)Nc3ccc(C(=O)NO)cc3)c3ccccc3)cccc12
InChIKey: QXIIXGYKPYLMDY-VWLOTQADSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 365.9 nM (pChEMBL 6.440000057220459)
Descriptors: MW 518.6, ALogP 3.68, HBA 6, HBD 4, PSA 127.84, QED 0.21
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-SZAHLOSFSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 639.8, ALogP 3.83, HBA 8, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): O=C(CCCCCCNCc1ccc([N+](=O)[O-])cc1)NO
InChIKey: BNOSPXWJXXMXQF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 295.34, ALogP 2.14, HBA 5, HBD 3, PSA 104.5, QED 0.27
Compound (SMILES): NC(=O)c1ccccc1-c1ccc(N2CCC[C@@H](NC(=O)Nc3ccc(C(F)(F)F)cc3)C2=O)cc1
InChIKey: PURUWPLYNJDKEY-JOCHJYFZSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: cAMP Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays. A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 flurorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm.
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 496.49, ALogP 4.79, HBA 3, HBD 3, PSA 104.53, QED 0.47
Compound (SMILES): O=C1CCc2cc(OCCN3CCCC3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of full length human ALDH1A2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): Cc1cccc2c(C(=O)N3CCN(Cc4ccc(C(=O)NO)cc4)CC3)c[nH]c12
InChIKey: LOYLSJNIQXFWSL-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using fluorogenic peptide RHKKAc-AMC as substrate by fluorescence-based assay
Measurement: IC50 = 1850 nM (pChEMBL 5.730000019073486)
Descriptors: MW 392.46, ALogP 2.55, HBA 4, HBD 3, PSA 88.67, QED 0.47
Compound (SMILES): CCC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1C
InChIKey: YKDZIFFKQUNVHH-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 2 subunit 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P20042
Assay: Inhibition of eIF2beta phosphorylation in human HCT-116 cells
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 375.44, ALogP 3.58, HBA 7, HBD 3, PSA 107.14, QED 0.61
Compound (SMILES): N#Cc1nc2c(nc1C#N)-c1ccc(O)cc1C2=O
InChIKey: WWMOLNPIOMEHFL-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of USP8 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 248.2, ALogP 1.14, HBA 6, HBD 1, PSA 110.66, QED 0.64
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: UUXMKUDVTHMKFM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 478.68, ALogP 7.2, HBA 5, HBD 1, PSA 54.7, QED 0.16
Compound (SMILES): Cc1onc(-c2ccccc2)c1C=CCCCCCNC(=O)CS
InChIKey: IUTMTBXLLAOWGT-UHFFFAOYSA-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 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 344.48, ALogP 4.27, HBA 4, HBD 2, PSA 55.13, QED 0.53
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cn1)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: CZIDGRDZSFIUHX-UHFFFAOYSA-N
Target: CTP synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U2N0
Assay: Inhibition of rat CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 512.54, ALogP 3.83, HBA 8, HBD 2, PSA 126.83, QED 0.49
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCN(c3cccnc3)CC2C(=O)NO)cc1
InChIKey: LHPNKVRYCBRQPZ-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 using Mca-Pro-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 20 to 30 mins by fluorescence microplate reader analysis
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 392.44, ALogP 0.48, HBA 7, HBD 2, PSA 112.07, QED 0.56
Compound (SMILES): O=C(NC1CC1)c1nc2cccnn2c1-c1cc(F)c(Cl)c(F)c1
InChIKey: GYZISZRYVGZYRR-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Scintillation Proximity Assay (SPA): The PDE4A3, PDE4B1, PDE4C1 and PDE4D3 assays use the Scintillation Proximity Assay (SPA) technology to measure the inhibition of human recombinant PDE4A1, PDE4B3, PDE4C1, and PDE4D3 enzyme activity by compounds in vitro. The PDE4A1, PDE4B3, PDE4C1, and PDE4D3 assays are run in parallel using identical parameters, except for the concentration of enzyme (80 pM PDE4A3, 40 pM PDE4B3, 40 pM PDE4C1 and 10 pM PDE4D). The assays are performed in a 384-well format with 50 uL assay buffer (50 mM TRIS pH7.5; 1.3 mM MgCl2; 0.01% Brij) containing enough PDE4A3, PDE4B1, PDE4C1, and PDE4D to convert 20% of substrate (1 μM cAMP consisting of 20 nM 3H-cAMP+980 uM cold cAMP) and a range of inhibitors. Reactions are incubated for 30 min at 25° C. The addition of 20 uL of 8 mg/ml yitrium silicate SPA beads (Perkin Elmer) stops the reaction. The plates are sealed (TopSeal, Perkin Elmer) and the beads are allowed to settle for 8 hrs, after which they are read on the Trilux Microbeta overnight.
Measurement: IC50 < 0.488 nM (pChEMBL 9.312000274658203)
Descriptors: MW 348.74, ALogP 3.22, HBA 4, HBD 1, PSA 59.29, QED 0.74
Compound (SMILES): O=C(NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO)c1cccc(C(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1
InChIKey: LJOOWNHZCTUDSG-XRSDMRJBSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 expressed in CHO cells using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 1232.62
Compound (SMILES): COc1ccc(C(c2c(-c3ccccc3)n(O)c3ccccc23)N2CCN(C)CC2)cc1
InChIKey: BBAJRFXAJHAPJE-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Inhibition of Bfl-1 (unknown origin) incubated for 30 min by fluorescence polarization assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 427.55, ALogP 4.89, HBA 5, HBD 1, PSA 40.87, QED 0.46
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-RRPNLBNLSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): CC1(C)c2ccccc2N(Cc2ccc(C(=O)NO)cc2)C1c1cccnc1
InChIKey: HGCZGYHCBRKJNB-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of C-terminal His-tagged recombinant human HDAC3 (1 to 428 residues) expressed in baculovirus infected Sf9 insect cells co-expressing NCOR2 using a fluorogenic substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by fluorescence based assay
Measurement: IC50 = 5871 nM (pChEMBL 5.230000019073486)
Descriptors: MW 373.46, ALogP 4.24, HBA 4, HBD 2, PSA 65.46, QED 0.53
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccnc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: UWDRPHXOMMPVSE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 448.88, ALogP 4.71, HBA 6, HBD 1, PSA 57.18, QED 0.58
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(O)c4)cc23)CC1
InChIKey: ZTBPVQXPLLMZGW-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Agonist activity at human SST3 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(ccn2-c2ccnc(N)n2)cn1
InChIKey: ISYRCGISNANONJ-KRWDZBQOSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin)
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 307.36, ALogP 1.91, HBA 6, HBD 2, PSA 89.85, QED 0.71
Compound (SMILES): Cc1ccc(S(=O)(=O)O)cc1.Cc1ccsc1C(=O)Nc1cc(CN2CCN(C(=O)CO)CC2)ccc1/C=C/c1n[nH]c2ccccc12
InChIKey: SIJKXSMUXNJNQM-HRNDJLQDSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora B kinase expressed in MDA-MB-231 cells
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 515.64, ALogP 3.99, HBA 6, HBD 3, PSA 101.56, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccccc4)n3)cc2C(F)(F)F)CC1
InChIKey: CWFRZEJQFAQELA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 413.45, ALogP 4.66, HBA 5, HBD 1, PSA 44.29, QED 0.67
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCN1CCN(Cc2ccccc2)CC1
InChIKey: BNGICRROXYSOFL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 5110 nM (pChEMBL 5.289999961853027)
Descriptors: MW 408.57, ALogP 3.06, HBA 5, HBD 0, PSA 39.15, QED 0.76
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-KAYWLYCHSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(Cl)c(Br)c(Cl)c4)nn32)CC1
InChIKey: SXKQCOANBPFCHG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 74.8 nM (pChEMBL 7.130000114440918)
Descriptors: MW 527.25, ALogP 4.5, HBA 5, HBD 2, PSA 93.25, QED 0.45
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1Cc1ccc(CN2CCN(Cc3ccccc3)CC2)cc1
InChIKey: FMHFUABJEGMXDA-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 484.67, ALogP 4.76, HBA 5, HBD 0, PSA 39.15, QED 0.51
Compound (SMILES): Cc1ccc(-c2ccc3c(C)n[nH]c3c2)c2c1[C@@H](N(C)C(=O)c1ncccc1C(F)F)CCC2
InChIKey: ZGVMLURVURNUQI-QHCPKHFHSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of his-tagged c-MET D1228V mutant (1050 to 1346 residues) (unknown origin) by ADP-glo assay
Measurement: IC50 = 10980 nM (pChEMBL 4.960000038146973)
Descriptors: MW 460.53, ALogP 6.33, HBA 3, HBD 1, PSA 61.88, QED 0.39
Compound (SMILES): CCOC(=O)c1nn(-c2ccccc2)cc1CN(C)[C@@H]1CCSC1
InChIKey: CDDSADAPSRSSJF-MRXNPFEDSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at D4R (unknown origin) by camp reporter assay
Measurement: EC50 = 10800 nM (pChEMBL 4.96999979019165)
Descriptors: MW 345.47, ALogP 2.99, HBA 6, HBD 0, PSA 47.36, QED 0.75
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCCNC(=O)C(C)S
InChIKey: HAKJNBQITNLGKA-UHFFFAOYSA-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 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 356.49, ALogP 4, HBA 4, HBD 2, PSA 55.13, QED 0.45
Compound (SMILES): CCCN(CCc1ccc(CCN(CCC)[C@H]2CCc3c(O)cccc3C2)cc1)[C@@H]1CCc2cc(O)c(O)cc2C1
InChIKey: FWACCHRUKMDWQL-ZWXJPIIXSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3 receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by Perkin elmer analysis
Measurement: EC50 = 0.86 nM (pChEMBL 9.069999694824219)
Descriptors: MW 556.79, ALogP 6.43, HBA 5, HBD 3, PSA 67.17, QED 0.22
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cncnc5)ccc4n3)cn2)CC1
InChIKey: QQIQOMIKWUAMAA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) in presence of 25 uM ATP
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 457.54, ALogP 3.62, HBA 10, HBD 1, PSA 106.77, QED 0.46
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C)c2)n1
InChIKey: QYMHHIWJCCQYPU-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.47, ALogP 5.09, HBA 5, HBD 2, PSA 71.42, QED 0.42
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(OC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: OYXCACHCXKHEOC-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 1025.6
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3cccc5ccccc35)C4=O)nn2)cc1
InChIKey: MWWVNAOGVSRMHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 25.31 nM (pChEMBL 7.599999904632568)
Descriptors: MW 553.56, ALogP 3.23, HBA 9, HBD 1, PSA 154.55, QED 0.25
Compound (SMILES): COc1ccc(/C(=N\O)N2CCN(c3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: MMEGVAXNSOBAQE-CZIZESTLSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 390.46, ALogP 1.3, HBA 6, HBD 2, PSA 108.46, QED 0.35
Compound (SMILES): COc1cc(/C=C/C(=O)[N-]S(=O)(=O)c2ccc(-n3nc(C(F)(F)F)cc3-c3ccc(C)cc3)cc2)ccc1[O-].[Na+].[Na+]
InChIKey: NMSJRWUGJMSTET-UHFFFAOYSA-L
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin)
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 557.55, ALogP 5.1, HBA 7, HBD 2, PSA 110.52, QED 0.31
Compound (SMILES): CC#CCOc1ccc2cc(C(O)(c3ccc(Br)cc3)c3cccnc3)oc2c1
InChIKey: GZWXDDIEDPOAKI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate by LC-MS/MS analysis
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 448.32, ALogP 5.28, HBA 4, HBD 1, PSA 55.49, QED 0.42
Compound (SMILES): CC(C)n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: DABVJURXDMIZKX-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 365.46, ALogP 1.21, HBA 7, HBD 1, PSA 97.19, QED 0.87
Compound (SMILES): O=C1NC(NC2CCCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: HJEKFRDOAYXXRU-DHDCSXOGSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells using myelin basic protein as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 340.45, ALogP 3.44, HBA 5, HBD 2, PSA 66.38, QED 0.65
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: QAMABQFUDMLHGO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 450.62, ALogP 6.42, HBA 5, HBD 1, PSA 54.7, QED 0.21
Compound (SMILES): CC1C(=O)N(C)CCN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: OJGOVIODTPNPDG-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (100 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 100 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73
Compound (SMILES): O=C1NCCN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)C1C(=O)NCc1ccccc1
InChIKey: WJBZDMXLXHXOQF-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 7.586 nM (pChEMBL 8.119999885559082)
Descriptors: MW 532.47, ALogP 2.54, HBA 5, HBD 2, PSA 84.99, QED 0.51
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(C(F)(F)F)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: HCKWZGBREFFBGT-KRWDZBQOSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta 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 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 528, ALogP 5.58, HBA 6, HBD 1, PSA 65.9, QED 0.41
Compound (SMILES): Cc1cn(-c2ccc(Cl)cc2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: YUQSIOIGTXTCOF-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 362.84, ALogP 3.28, HBA 4, HBD 1, PSA 68.17, QED 0.78
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCN5CCCC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: HBHOBCZCVGHUSQ-MASCHLQQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 23.1 nM (pChEMBL 7.639999866485596)
Descriptors: MW 422.66, ALogP 5.48, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): COc1ccc2c(c1)CN(c1nccc(Nc3ccc4[nH]ncc4c3)n1)C2
InChIKey: SWHUIIODYNUMNO-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Rho-kinase inhibition assay for ROC2 and ROCK1: Dose response curves for Rho-kinase inhibition were derived from a Invitrogen Z′-LYTE Kinase Assay Kit (Invitrogen catalog number PV3793). Purified active ROCK1 and ROCK2 were obtained from Invitrogen (catalog numbers ROCK1, PV3691 and ROCK2, PV3759). The kit components include a coumarin and fluorescein labeled peptide based on myosin light chain 2 (KKRPQRRYSNVF), a proprietary protease containing development reagent and a proprietary Stop buffer used to terminate the development reaction. The inhibitory activities of compounds are measured according to the manufactures protocol. Briefly, decreasing concentrations of test compounds or the known ROCK inhibitor Y-27963, are added, from 10 uM to 2.56×10−5 uM to reaction buffer containing 50 mM HEPES pH 7.5, 10 mM MgCl2, 5 mM EGTA, and 0.05% Brij-35 and of ROCK1 at 0.18 ug/mL or ROCK2 at 0.8 ug/mL in assay dilution buffer. This mixture is overlayed into a white 96-well half area plate and the reaction is initiated with the addition of 5 uM ATP for ROCK1 or 12 uM ATP for ROCK2. The assay proceeds at room temperature for 1 hour followed by the addition of development reagent, and further incubation for 1 hour at room temperature. STOP reagent is then added and the reaction and immediately the coumarin and fluorescein emission signals are read on a Tecan Infinite M1000 fluorescence plate reader (excitation: 400 nm; emission 445 and 520 nm, respectively). By comparing the emission ratios of the test samples against control samples, percent phosphorylation values are calculated and the concentration of inhibitor that produces ½ inhibition of kinase activity (IC50) is determined using Prism. Table 1 provides IC50 concentrations for compounds of the above examples. Several of the compounds also demonstrated activity in a preliminary assay that measured inhibition of myosin light chain phosphorylation (pMLC). For compounds marked ND, activity was not determinable under the test conditions employed.
Measurement: IC50 = 434 nM (pChEMBL 6.360000133514404)
Descriptors: MW 358.41, ALogP 3.63, HBA 6, HBD 2, PSA 78.96, QED 0.58
Compound (SMILES): COc1cccc(Cc2cc(C)nn([C@@H](C)C(=O)Nc3ccc(Cl)cc3)c2=O)c1
InChIKey: JQMCPEBDJPMQGI-HNNXBMFYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at human recombinant FPR2 stably transfected in Flp-In-CHO cells assessed as ERK1/2 phosphorylation incubated for 1 hr by Alphascreen fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.89, ALogP 4, HBA 5, HBD 1, PSA 73.22, QED 0.66
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-RRPNLBNLSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)CC1
InChIKey: CTYFJJGDZUXTIC-SXOMAYOGSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 602.68, ALogP 3.67, HBA 7, HBD 2, PSA 105.9, QED 0.33
Compound (SMILES): Cc1cn(-c2cncc(C(F)(F)F)c2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc12
InChIKey: AQAQROFTSRFYID-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 441.41, ALogP 3.71, HBA 5, HBD 1, PSA 81.06, QED 0.63
Compound (SMILES): CC(C)=CCc1ccc(O)c(C(=O)c2c(O)cc(C)cc2C(=O)C(C)C)c1O
InChIKey: YYPXPFQWFRXFCA-UHFFFAOYSA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Chlorocebus aethiops
UniProt: O77759
Assay: Inhibition of african green monkey SAOT2 in CHO cells assessed as reduction cholesteryl ester synthesis
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 382.46, ALogP 4.69, HBA 5, HBD 3, PSA 94.83, QED 0.5
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-SXOMAYOGSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: WWKQQRVQGOUIMX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 2360 nM (pChEMBL 5.630000114440918)
Descriptors: MW 436.6, ALogP 6.03, HBA 5, HBD 1, PSA 54.7, QED 0.25
Compound (SMILES): COCCCC(=O)N(C)CCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: FKEYBQUXJBIQQC-GNAFDRTKSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 511.07, ALogP 3.99, HBA 6, HBD 0, PSA 67.67, QED 0.36
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc(C)[nH]c2c1=O
InChIKey: POICMTYCJMMADL-ONEGZZNKSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 391.47, ALogP 3.35, HBA 4, HBD 1, PSA 67.33, QED 0.69
Compound (SMILES): O=C1NCCc2c1cnn2-c1ccnc(Cc2cc(F)cc(C(F)(F)F)c2)c1
InChIKey: VASPFLVEEOBQOS-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 by automated patch-clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.34, ALogP 3.3, HBA 4, HBD 1, PSA 59.81, QED 0.7
Compound (SMILES): COc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: HRRLKCWFIQQCIC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 1557 nM (pChEMBL 5.809999942779541)
Descriptors: MW 447.47, ALogP 2.26, HBA 8, HBD 1, PSA 142.07, QED 0.56
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3ncccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: HENRITOGWFFGGA-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of MAP4K2 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 464 nM (pChEMBL 6.329999923706055)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): COc1ccc(CNCCCCCCC(=O)NO)cc1OC
InChIKey: IQGSZEFWMXKAJG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 310.39, ALogP 2.25, HBA 5, HBD 3, PSA 79.82, QED 0.33
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: RXAZQWJCOUIOPS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HER2 Exon 20 YVMA Insertion Mutation: A compound's ability in selectively inhibiting Her2 exon 20 YVMA insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with Her2 Exon20 YVMA insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions YVMA (A775_G776ins YVMA), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing Her2 Exon20 YVMA insertions (named Ba/F3-Her2 Exon20 YVMA) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-Her2 Exon20 YVMA cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 557.66, ALogP 4.3, HBA 10, HBD 2, PSA 113.85, QED 0.21
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)c1csc(Nc2ccccc2)n1
InChIKey: CYVGSDYVNUNREA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 335.39, ALogP 4.02, HBA 5, HBD 3, PSA 82.7, QED 0.53