lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cc(Cl)c(O)c([N+](=O)[O-])c2)c1
InChIKey: SPIZPABAPBQRSM-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB E129A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 436.81, ALogP 5.64, HBA 6, HBD 2, PSA 126.7, QED 0.31
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)COCc2ccccc2)n1
InChIKey: YTBZQGYFOZNNDW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 589.1, ALogP 5.58, HBA 9, HBD 2, PSA 101.08, QED 0.23
Compound (SMILES): CC(C(=O)NCCCOc1ccc(S(N)(=O)=O)cc1)c1cccc(C(=O)c2ccccc2)c1
InChIKey: LCMKFYRXIFBJTQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 catalytic domain incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 466.56, ALogP 3.25, HBA 5, HBD 2, PSA 115.56, QED 0.35
Compound (SMILES): CCCCC/C=C\[C@@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NCCO
InChIKey: HPZWGIGIINAFKI-QUMJFYJXSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from human CB2 receptor expressed in HEK293 cell membranes in absence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 361.57, ALogP 5.49, HBA 2, HBD 2, PSA 49.33, QED 0.28
Compound (SMILES): CC(C)OC(=O)N1CCC(CCCCCOc2ccc(C(=O)N(C)C)cc2)CC1
InChIKey: BLGZCKKNXGGFSV-UHFFFAOYSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in HEK293 cells assessed as increase in intracellular cAMP level after 30 mins
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 404.55, ALogP 4.58, HBA 4, HBD 0, PSA 59.08, QED 0.57
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)CC(C)C6)n3)nc2)CC1
InChIKey: ZZBUMHLUAAJMOY-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 504.59, ALogP 4.24, HBA 8, HBD 1, PSA 75, QED 0.42
Compound (SMILES): O=C(O)CCC(=O)N(C1CC1)[C@H]1c2ccccc2N(C(=O)c2ccc(OC(F)(F)F)cc2)[C@H]2CC[C@H]21
InChIKey: BWTYCMYHBBZDDQ-IZIIKQMZSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity at CRTh2 in human whole blood assessed as inhibition of DK-PGD2-induced eosinophils shape change preincubated for 10 mins followed by DK-PGD2 addition measured after 4 mins by flow cytometry
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 502.49, ALogP 4.92, HBA 4, HBD 1, PSA 87.15, QED 0.58
Compound (SMILES): CCCCC/C=C\C/C=C\C/C=C\[C@H](C)/C=C\CCCC(=O)N[C@H](C)CO
InChIKey: SKCZBQSPGJHKOX-OCJZLHTRSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Agonist activity at rat CB1 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins
Measurement: EC50 = 28.4 nM (pChEMBL 7.550000190734863)
Descriptors: MW 375.6, ALogP 5.88, HBA 2, HBD 2, PSA 49.33, QED 0.26
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NCc3ccccc3)c12
InChIKey: NCTWOUCSFCSFJN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 349.44, ALogP 3.35, HBA 5, HBD 3, PSA 92.93, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCCCCCCC(=O)N[C@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: PJDKVHXZLHUPET-QUSBNXTPSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Agonist activity at Galphaq-Rluc2/Gbeta1/GFP10-Ggamma1 fused human NTS1 expressed in CHO-K1 cell membranes assessed as Galphaq activation after 5 mins by BRET assay
Measurement: EC50 = 166.2 nM (pChEMBL 6.78000020980835)
Descriptors: MW 783.02, ALogP 3.62, HBA 8, HBD 7, PSA 220.26, QED 0.11
Compound (SMILES): COCCN1CCc2nc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)ccc2C1
InChIKey: ROMAHJZEHBXJSU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 1094 nM (pChEMBL 5.960000038146973)
Descriptors: MW 493.56, ALogP 4.8, HBA 8, HBD 1, PSA 80.99, QED 0.4
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(OCC(=O)NCc4ccccc4)cc3)[nH]c2c1=O
InChIKey: YQNDSSWLPSRYLJ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from recombinant human adenosine A3 receptor expressed in CHO cell membranes after 45 mins by liquid scintillation counting method
Measurement: Ki = 266 nM (pChEMBL 6.579999923706055)
Descriptors: MW 433.47, ALogP 2.19, HBA 6, HBD 3, PSA 121.87, QED 0.39
Compound (SMILES): CCN1CCN(c2ccc(-c3nn(CC4CCCC4)c4nc(NC)ncc34)cn2)CC1
InChIKey: CXNXNSYZZDJASK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild-type human partial length FLT3 (V592 to Y969 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 420.57, ALogP 3.26, HBA 8, HBD 1, PSA 75, QED 0.66
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2c(Br)cc(Br)cn12)c1ccc(OCCCCF)cc1
InChIKey: IMXMASNCRRZFJZ-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-3/gamma-2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P18508
Assay: Displacement of [3H]EBOB from rat GABA-A receptor alpha6beta3gamma2 expressed in HEK293 cell membranes after 90 mins in presence of GABA by liquid scintillation counting analysis
Measurement: IC50 = 1280 nM (pChEMBL 5.889999866485596)
Descriptors: MW 567.28, ALogP 6.97, HBA 5, HBD 1, PSA 55.63, QED 0.23
Compound (SMILES): CC(=O)N1c2ccc(-c3cnc(C(N)=O)nc3)cc2N(Cc2ccccc2CO)C[C@@H]1C1CC1
InChIKey: JVAKWUYUZCOCKR-XMMPIXPASA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of BRD3 BD1 (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 457.53, ALogP 2.89, HBA 6, HBD 2, PSA 112.65, QED 0.59
Compound (SMILES): CCOc1c(OC)cc(/C=C/C(=O)c2ccncc2)cc1OC
InChIKey: DRSHJEXKZDUEMK-AATRIKPKSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 expressed in HEK293 cells using 7-ethoxyresorufin as substrate pretreated for 30 mins followed by substrate addition measured for 60 mins by fluorescence assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 313.35, ALogP 3.39, HBA 5, HBD 0, PSA 57.65, QED 0.58
Compound (SMILES): N#Cc1ccc(-c2cnc3cnc(-c4ccc(C(=O)N5CCOCC5)cc4)cn23)cc1
InChIKey: DKRBCZRLAIEHLG-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: In Vitro Kinase Assay: MNK1 and MNK2 inhibitor activity was determined using recombinant kinase domains expressed in E. coli. MNK1 and MNK2 were expressed as GST fusion proteins and the GST tag was removed using PreScission protease. After concentration to 10-15 mg/ml the proteins were flash frozen in liquid nitrogen and stored at −80° C. MNK1 and MNK2 were activated using recombinant ERK2 which was activated using a constitutively active mutant of MEK1, both ERK2 and MEK1 were expressed in E. coli as N-terminally his tagged proteins. Recombinant ERK2 was activated by incubating 11.3 μM of the kinase with 1 μM MEK1 and 100 μM ATP. This reaction mixture was then used immediately for the activation of the MNKs. The activation of the MNK1 was performed by incubating 5.0 μM of MNK1 with 0.3 μM of activated ERK2 and 500 μM ATP at 30° C. for 6 hours. The activation of MNK2 was performed by incubating 50 μM of MNK2 with 3.0 μM of activated ERK2 and 500 μM ATP at 30° C. for 2 hours. The activated MNKs were stored at −20° C. until required for assay.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 409.45, ALogP 3.41, HBA 6, HBD 0, PSA 83.52, QED 0.52
Compound (SMILES): CCC1CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(CC)CC6)cn5)ncc4F)cc3n21
InChIKey: DSSKUVUQTGKPGW-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 518.62, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.37
Compound (SMILES): N#CC1(c2ccccc2)CCN(c2c(C(=O)N3CCN(C(=O)C4CC4)CC3)cnc3ccc(F)cc23)CC1
InChIKey: FOUWVAHUAQGPHA-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of 100 nM paclitaxel-mediated cytotoxicity after 4 days by CellTiter-Glo assay
Measurement: EC50 = 1930 nM (pChEMBL 5.710000038146973)
Descriptors: MW 511.6, ALogP 4.13, HBA 5, HBD 0, PSA 80.54, QED 0.53
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)c2)cc1
InChIKey: OLERVUUNEGIAOP-LFYBBSHMSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using RHKKAc peptide as substrate
Measurement: IC50 = 751 nM (pChEMBL 6.119999885559082)
Descriptors: MW 476.51, ALogP 3.64, HBA 7, HBD 2, PSA 114.7, QED 0.18
Compound (SMILES): C[C@H](/C=C\C/C=C\C/C=C\CCCC(=O)NC1CC1)/C=C\CCCCCN=[N+]=[N-]
InChIKey: IPUZYSOVMUVCPW-YJTVTXQSSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Agonist activity at rat CB1 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins
Measurement: EC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 398.6, ALogP 6.95, HBA 2, HBD 1, PSA 77.86, QED 0.09
Compound (SMILES): O=S(=O)(Oc1cccc(C(F)(F)F)c1)C1CC2OC1C(c1ccc(/C=C/c3cc(O)cc(O)c3)cc1)=C2c1ccc(O)cc1
InChIKey: NUIRMNFDTYWLJF-SNAWJCMRSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at human ERbeta expressed in HEK293T cells after 24 hrs by ERE-based dual luciferase reporter gene assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 622.62, ALogP 6.85, HBA 7, HBD 3, PSA 113.29, QED 0.15
Compound (SMILES): CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1
InChIKey: ZHRPTNIIEOQLIM-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 443.5, ALogP 3.36, HBA 6, HBD 0, PSA 81.5, QED 0.6
Compound (SMILES): CS[C@@]1(C(=O)Nc2ccc3[nH]nc(-c4ccc(OC(C)C)nc4)c3c2)CCN(CC(=O)N2CC=C(c3ccc(-c4ncn(C)n4)cc3)CC2)C1
InChIKey: KPQQGHGDBBJGFA-QNGWXLTQSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin) co-incubated with substrate
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 691.86, ALogP 5.27, HBA 10, HBD 2, PSA 134.16, QED 0.2
Compound (SMILES): COc1cc2c(cc1-n1cnc3ccc(-c4ccnc5[nH]ccc45)cc31)CNC2
InChIKey: RFUHKEPWGZUNBG-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 381.44, ALogP 4.18, HBA 5, HBD 2, PSA 67.76, QED 0.49
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccc(NC(=O)CO)cc2)n1
InChIKey: WVUXKGMCPCJLAI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2740 nM (pChEMBL 5.559999942779541)
Descriptors: MW 498.97, ALogP 3.36, HBA 9, HBD 3, PSA 112.08, QED 0.43
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(P(=O)(O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: VANCCRKYBVXGLS-NHCUHLMSSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 553.55, ALogP 2.77, HBA 7, HBD 5, PSA 178.64, QED 0.05
Compound (SMILES): CC(Cc1cccc(-n2c(C(N)=O)cc3ccc(OC(F)(F)F)cc32)c1)C(=O)O
InChIKey: YBZZMPQWPYBANH-UHFFFAOYSA-N
Target: Phospholipase A2 group V (SINGLE PROTEIN), Homo sapiens
UniProt: P39877
Assay: Inhibition of sPLA2-5 (unknown origin) using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 406.36, ALogP 3.89, HBA 4, HBD 2, PSA 94.55, QED 0.65
Compound (SMILES): CC(C)(O)CNC(=O)CC1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: WKDNXLPZDBZVOG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Spa Binding Assay: The binding of potential ligands to RORγ is measured by competition with [3H] 25-hydroxycholesterol using a scintillation proximity assay (SPA) binding assay. The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromotography. 50 nM RORγ (A262-S507) is incubated with test compound at varying concentrations for 15 min at room temperature in PBS buffer containing 0.5% fatty acid free BSA. 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 15 min. 4 mg/mL of Ysi Copper HIS-TAG SPA Beads (Perkin Elmer) are added, and the mixture is incubated for 30 min. The reaction is read on a MicroBeta Trilux scintillation plate reader (Perkin Elmer).
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 586.53, ALogP 3.93, HBA 5, HBD 3, PSA 106.94, QED 0.43
Compound (SMILES): COc1ccc2cc(C(C)C(=O)Nc3ccc(S(N)(=O)=O)cc3)ccc2c1
InChIKey: AMYIARUUMISUFR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 28.5 nM (pChEMBL 7.539999961853027)
Descriptors: MW 384.46, ALogP 3.24, HBA 4, HBD 2, PSA 98.49, QED 0.71
Compound (SMILES): COc1cc(/C=C/C(=O)c2ccncc2)cc(OC)c1
InChIKey: FSJSMAUYGXKRCX-ONEGZZNKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in yeast microsomal membranes using dibenzylfluorescein as substrate measured after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 269.3, ALogP 2.99, HBA 4, HBD 0, PSA 48.42, QED 0.62
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)[C@H](C)O[C@H](CS(C)(=O)=O)CN3S(C)(=O)=O
InChIKey: PCQOPPOYJPHFQB-BBRMVZONSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 4a NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 524.59, ALogP 2.87, HBA 7, HBD 1, PSA 122.99, QED 0.54
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: DOQIAUOAJLSPND-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 480.5, ALogP 3.77, HBA 6, HBD 0, PSA 85.16, QED 0.44
Compound (SMILES): C[C@@H]1SC(c2ccco2)=N[C@H]1CO
InChIKey: FLXRMDBEHARLHW-BQBZGAKWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 197.26, ALogP 1.52, HBA 4, HBD 1, PSA 45.73, QED 0.78
Compound (SMILES): C=CC(=O)N1CCN(c2ncnc3c(F)c(-c4c(O)cccc4F)c(Cl)cc23)CC1
InChIKey: ZRPZPNYZFSJUPA-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Covalent binding affinity to KRAS G12C mutant at Cys12 residue in human NCI-H358 cells assessed as reduction of log2 H/L ratio for tryptic peptide LVVVGACGVGK incubated for 4 hrs followed by cell lysis and subsequently labelled with light thiol probe N-((S)-18-iodo-11-isopropyl-10,13,17-trioxo-3,6-dioxa-9,12,16-triazaoctadecyl)-6-((4R,5S)-5-methyl-2-oxoimidazolidin-4-yl)hexanamide and heavy thiol probe 4 for 1 hr under dark conditions followed by tryptic digestion for overnight and measured by discovery ABPP based nano LC-MS/MS analysis
Measurement: IC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 430.84, ALogP 3.77, HBA 5, HBD 1, PSA 69.56, QED 0.64
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]ccc3c2)cnc1Cl)c1ccccc1
InChIKey: CXQCIWGEISYBCY-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human full length His-tagged PI3K p110delta/p85alpha expressed in baculovirus expression system using PIP2/PS as substrate after 1 hr by ADP-Glo luminescence assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 384.85, ALogP 4.08, HBA 4, HBD 2, PSA 87.74, QED 0.52
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCNCC4)nc3)nn(CC3OCCO3)c2n1
InChIKey: GFFVAKKFWQHFLB-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild-type human partial length FLT3 (V592 to Y969 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 396.46, ALogP 0.71, HBA 10, HBD 2, PSA 102.25, QED 0.65
Compound (SMILES): CC(C)Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1
InChIKey: NXVTZWGZZGMQMN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 391.41, ALogP 3.22, HBA 6, HBD 0, PSA 84.04, QED 0.68
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3S(=O)(=O)c3ccc(/C=C/C(=O)NO)cc3)c2)cc1
InChIKey: SLQMIYBDKPSYGO-YIXHJXPBSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using RHKKAc peptide as substrate
Measurement: IC50 = 848 nM (pChEMBL 6.070000171661377)
Descriptors: MW 476.51, ALogP 3.64, HBA 7, HBD 2, PSA 114.7, QED 0.18
Compound (SMILES): O=c1n(-c2ccc(C(F)(F)C(O)(Cn3cnnn3)c3ccc(F)cc3F)nc2)cnn1C1CCCCC1
InChIKey: BIFOHTJWLVLXNQ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 10 mins with substrate followed by NADPH addition measured after 15 mins by LC/MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 518.48, ALogP 2.88, HBA 10, HBD 1, PSA 116.54, QED 0.37
Compound (SMILES): COc1ccc2c(c1)c(CC(=O)NCCCCOc1ccc(S(N)(=O)=O)cc1)c(C)n2C(=O)c1ccc(Cl)cc1
InChIKey: OWXCNNFFXOOPBZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 584.09, ALogP 4.47, HBA 7, HBD 2, PSA 129.72, QED 0.25
Compound (SMILES): O=C(Nc1nccs1)C(c1cc(F)ccc1O)N1Cc2ccccc2C1=O
InChIKey: YTUFHOKUFOQRDF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) phosphorylation expressed in mouse BaF3 cells measured after 4 hrs by HTRF assay
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 383.4, ALogP 3.32, HBA 5, HBD 2, PSA 82.53, QED 0.72
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(N=[N+]=[N-])c2)n1
InChIKey: GHORRHODUODRLJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 4670 nM (pChEMBL 5.329999923706055)
Descriptors: MW 466.93, ALogP 5.37, HBA 8, HBD 1, PSA 111.51, QED 0.28
Compound (SMILES): COc1ccc(-c2ccc(S(=O)(=O)c3ccccc3C3CCC(=O)N(O)C3=O)cc2)cc1
InChIKey: OEAKPCGGFWRJFX-UHFFFAOYSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human MMP-14 catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 3 hrs followed by substrate addition measured every 10 secs for 15 mins by fluorometric assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 451.5, ALogP 3.82, HBA 6, HBD 1, PSA 100.98, QED 0.47
Compound (SMILES): Nc1nc2[nH]c(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)nc3)cc2c(=O)[nH]1
InChIKey: FSOJIOKMUXQEMI-HNNXBMFYSA-N
Target: Folate receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P14207
Assay: Binding affinity to human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs in presence of folic acid by Cell-Titer Blue assay
Measurement: IC50 = 471 nM (pChEMBL 6.329999923706055)
Descriptors: MW 456.46, ALogP 0.84, HBA 7, HBD 6, PSA 204.15, QED 0.23
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(C(=O)NO)o4)ccc3OCC)nc12
InChIKey: QUKABWAMCFBWDF-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of full length human recombinant N-terminal GST-tagged PDE5A1 expressed in baculovirus infected sf9 cells using cGMP as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 451.48, ALogP 2.98, HBA 8, HBD 3, PSA 135.27, QED 0.28
Compound (SMILES): CN1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)C[C@@H]1CC1CCCCC1
InChIKey: OWOKBMMSSDNFQM-ZEQRLZLVSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Human CHIT1 Activity Assay: An enzymatic assay with recombinant human CHIT1 was used in order to establish inhibitory activity of the compounds (Boot et al., 2001, JBC: 276). The assay was run in the 96-well plate format, each reaction in the total volume of 100 μL. 4-methylumbelliferyl β-D-N,N′,N″-triacetylchitotriose was used as a substrate for the enzyme. Upon hydrolysis by CHIT1, the substrate releases 4-methylumbelliferyl (4MU) that, when ionized in basic pH, emits fluorescence at 460 nm.Briefly, 40 μL of a substrate was added to each well, followed by 10 μL of compound dilution and 50 μL of CHIT1 recombinant enzyme solution. The reaction was carried out in citrate buffer, pH 5.2, in the dark, at 37° C. for 60 minutes with shaking. After that time the reaction was stopped by adding 195 μL of Stop Solution (pH 10.5) to each well. The fluorescence of the reaction product was measured in Perkin Elmer Envision fluorescent plate reader at an excitation wavelength of 355 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 486.11, ALogP 4.21, HBA 6, HBD 2, PSA 77.31, QED 0.64
Compound (SMILES): CCS(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: AFSFDOMLBGCXCS-ZDUSSCGKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.49, ALogP 3.69, HBA 7, HBD 0, PSA 94.39, QED 0.47
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCCCNCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: PQGTYTDFCQZYJB-WZVSLAMBSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]Tyr3-neurotensin from human NTS1 receptor expressed in CHOK1 cell membranes after 60 mins by gamma counting analysis
Measurement: Ki = 903 nM (pChEMBL 6.039999961853027)
Descriptors: MW 841.11, ALogP 2.15, HBA 10, HBD 9, PSA 258.31, QED 0.1
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: ODSFZEXVNOIJHI-ILOBPARPSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 916.06, ALogP 0.47, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Cn2cnc3ccccc32)c(SCCc2ccccc2)cc1Cl
InChIKey: JFFJZAFZPSZSOW-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human N-terminal His-tagged carbonic anhydrase 7 (3 to 264 residues) expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 9.73 nM (pChEMBL 8.010000228881836)
Descriptors: MW 486.02, ALogP 4.55, HBA 6, HBD 1, PSA 95.05, QED 0.29
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@H]1c1ccc(F)cc1
InChIKey: ZYKGPZCLGUYTEM-AZUAARDMSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Mus musculus
UniProt: Q8BRU6
Assay: Inhibition of VMAT2 in C57Bl/6J mouse striatal membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 8 mins
Measurement: IC50 = 24.7 nM (pChEMBL 7.610000133514404)
Descriptors: MW 439.49, ALogP 2.5, HBA 6, HBD 1, PSA 84.4, QED 0.6
Compound (SMILES): Cc1cc(-n2cc3c(n2)CN(C(=O)c2cc(C#N)ccc2O[C@@H](C)C(F)(F)F)C3)ccn1
InChIKey: FEFVMUCXYVUBPN-AWEZNQCLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 441.41, ALogP 3.93, HBA 6, HBD 0, PSA 84.04, QED 0.61
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCCOCCNC(=O)C[C@@H]2N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc32)C(C)(C)C)cc1
InChIKey: PQOGZKGXGLHDGS-QQRWPDCKSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 BD2 domain (unknown origin)
Measurement: Kd = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 986.66, ALogP 6.53, HBA 14, HBD 4, PSA 202.26, QED 0.07
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(NC(=O)CCO)c2)n1
InChIKey: REJGYEAFJGXQCJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 513, ALogP 3.75, HBA 9, HBD 3, PSA 112.08, QED 0.39
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)N[C@H]1CC[C@H](Oc2ccc(C(=O)OCc3ccccc3)cc2)CC1
InChIKey: IEOQZCMTPHDRLT-SAIGFBBZSA-N
Target: Liver carboxylesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23141
Assay: Inhibition of human carboxylesterase 1 expressed in baculovirus system using CMNA substrate by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.53, ALogP 6.45, HBA 5, HBD 2, PSA 85.89, QED 0.33
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4cccc(OC)c4F)cc3)c3cncc(OC)c32)C1
InChIKey: LLRUOFRCNQYKAO-LJQANCHMSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Kinases Assay : Btk kinase activity was determined using a homogenous time resolved fluorescence (HTRF) methodology. Measurements were performed in a reaction volume of 15 μL using 384-well assay plates. Kinase enzyme, inhibitor, ATP and 1 μM peptide substrate were incubated in a reaction buffer compose of Hepes50 mM (pH7.0), NaN3 0.02%, BSA 0.01%, Orthocanadate 0.1 mM. After one hour, the kinase reaction was quenched by the addition of E t-labeled antibody and XL-665 in 1×Detection buffer containing 60 mM EDTA (Cisbio), and the mixture was allowed to incubate for one hour. The HTRF signal was measured on a multimode plate reader (EnVision Multilabel Reader, Perkin Elmer) with an excitation wavelength (λEx) of 330 nm and detection wavelengths (λEm) of 615 and 665 nm. Activity was determined by the ratio of the fluorescence at 665 nm to that at 615 nm. For each compound, enzyme activity as measured at various concentrations of compound, Negative control reactions were performed in the absence of inhibitor in two replicates and eight no enzyme controls were used to determine baseline fluorescence levels. IC50s were obtained according to the equation:Y=100/(1+10{circumflex over ( )}((Log IC50−X)*HillSlope)).For BTK assay, [ATP]=80 μM, BTK=3.4 nM.For LYN assay, [ATP]=20 μM, LYN=0.12 n M. For LCK assay, [ATP]=20 μM, LCK=0.2 nM. For BLK assay, [ATP]=20 μM, BLK=0.6 n M.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 502.55, ALogP 5.4, HBA 7, HBD 0, PSA 78.71, QED 0.32
Compound (SMILES): CCCCCCOc1cc(Cl)c2c(CCC(=O)O)c(C(=O)O)[nH]c2c1
InChIKey: ZFPCHYJCZVFAIV-UHFFFAOYSA-N
Target: Uracil nucleotide/cysteinyl leukotriene receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13304
Assay: Displacement of [3H]PSB-12150 from human GPR17 expressed in CHO cell membranes after 60 mins by liquid scintillation counting
Measurement: Ki = 13100 nM (pChEMBL 4.880000114440918)
Descriptors: MW 367.83, ALogP 4.5, HBA 3, HBD 3, PSA 99.62, QED 0.54
Compound (SMILES): CCN(CC)[C@@H](C)CNC(=O)c1cc(-c2cnn3ccc(-c4cccs4)nc23)nc(N2CC(OC)C2)c1
InChIKey: UCHOYOABTVPSLZ-SFHVURJKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 519.68, ALogP 3.81, HBA 9, HBD 1, PSA 87.89, QED 0.34
Compound (SMILES): CC1=C(CC(=O)NCCOc2ccc(S(N)(=O)=O)cc2)c2cc(F)ccc2/C1=C/c1ccc([S+](C)[O-])cc1
InChIKey: SKOXNUJTXFITBK-MFKUBSTISA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 554.67, ALogP 4.12, HBA 5, HBD 2, PSA 121.55, QED 0.3
Compound (SMILES): CCCCC/C=C\[C@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NC1CC1
InChIKey: QWOSQZCKUTULAW-VVFVXTANSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Agonist activity at rat CB1 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins
Measurement: EC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 357.58, ALogP 6.66, HBA 1, HBD 1, PSA 29.1, QED 0.26
Compound (SMILES): Cc1cc(COc2ccc(S(=O)(=O)N(C)C3(C(=O)NO)CN(C(=O)C(C)C)C3)cc2)c2ccccc2n1
InChIKey: BQDVTMRZPWSYOT-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Inhibition of ADAM10 (unknown origin)
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 526.62, ALogP 2.49, HBA 7, HBD 2, PSA 129.14, QED 0.34
Compound (SMILES): CC(C(=O)NCCCOc1ccc(S(N)(=O)=O)cc1)c1ccc(-c2ccccc2)c(F)c1
InChIKey: YKEULJQRBHWKDW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 43.3 nM (pChEMBL 7.360000133514404)
Descriptors: MW 456.54, ALogP 3.83, HBA 4, HBD 2, PSA 98.49, QED 0.48
Compound (SMILES): O=C(O)c1noc(-c2ccccc2)c1-c1cccc(-c2cc(Cl)c(O)c([N+](=O)[O-])c2)c1
InChIKey: SPIZPABAPBQRSM-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of Mycobacterium tuberculosis H37Rv His-tagged ptpB R136A mutant expressed in Escherichia coli BL21(DE3) using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 436.81, ALogP 5.64, HBA 6, HBD 2, PSA 126.7, QED 0.31
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(=O)COCc2ccccc2)n1
InChIKey: YTBZQGYFOZNNDW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 589.1, ALogP 5.58, HBA 9, HBD 2, PSA 101.08, QED 0.23
Compound (SMILES): CC(C(=O)NCCCOc1ccc(S(N)(=O)=O)cc1)c1cccc(C(=O)c2ccccc2)c1
InChIKey: LCMKFYRXIFBJTQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 466.56, ALogP 3.25, HBA 5, HBD 2, PSA 115.56, QED 0.35
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)NCc3ccccc3)c12
InChIKey: NCTWOUCSFCSFJN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 349.44, ALogP 3.35, HBA 5, HBD 3, PSA 92.93, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCCCCCCC(=O)N[C@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: PJDKVHXZLHUPET-QUSBNXTPSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]Tyr3-neurotensin from human NTS1 receptor expressed in CHOK1 cell membranes after 60 mins by gamma counting analysis
Measurement: Ki = 5600 nM (pChEMBL 5.25)
Descriptors: MW 783.02, ALogP 3.62, HBA 8, HBD 7, PSA 220.26, QED 0.11
Compound (SMILES): COCCN1CCc2nc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)ccc2C1
InChIKey: ROMAHJZEHBXJSU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 14.8 nM (pChEMBL 7.829999923706055)
Descriptors: MW 493.56, ALogP 4.8, HBA 8, HBD 1, PSA 80.99, QED 0.4
Compound (SMILES): CCN1CCN(c2ccc(-c3nn(CC4CCCC4)c4nc(NC)ncc34)cn2)CC1
InChIKey: CXNXNSYZZDJASK-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 420.57, ALogP 3.26, HBA 8, HBD 1, PSA 75, QED 0.66
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2c(Br)cc(Br)cn12)c1ccc(OCCCCF)cc1
InChIKey: IMXMASNCRRZFJZ-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-3/delta (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P18506
Assay: Displacement of [3H]EBOB from rat GABA-A receptor alpha6beta3delta expressed in HEK293 cell membranes after 90 mins in presence of GABA by liquid scintillation counting analysis
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 567.28, ALogP 6.97, HBA 5, HBD 1, PSA 55.63, QED 0.23
Compound (SMILES): CC(=O)N1c2ccc(-c3cnc(C(N)=O)nc3)cc2N(Cc2ccccc2CO)C[C@@H]1C1CC1
InChIKey: JVAKWUYUZCOCKR-XMMPIXPASA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of BRD3 BD2 (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 457.53, ALogP 2.89, HBA 6, HBD 2, PSA 112.65, QED 0.59
Compound (SMILES): CCOc1c(OC)cc(/C=C/C(=O)c2ccncc2)cc1OC
InChIKey: DRSHJEXKZDUEMK-AATRIKPKSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 expressed in HEK293 cells using 7-ethoxyresorufin as substrate pretreated for 30 mins followed by substrate addition measured for 60 mins by fluorescence assay
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 313.35, ALogP 3.39, HBA 5, HBD 0, PSA 57.65, QED 0.58
Compound (SMILES): N#Cc1ccc(-c2cnc3cnc(-c4ccc(C(=O)N5CCOCC5)cc4)cn23)cc1
InChIKey: DKRBCZRLAIEHLG-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: In Vitro Kinase Assay: MNK1 and MNK2 inhibitor activity was determined using recombinant kinase domains expressed in E. coli. MNK1 and MNK2 were expressed as GST fusion proteins and the GST tag was removed using PreScission protease. After concentration to 10-15 mg/ml the proteins were flash frozen in liquid nitrogen and stored at −80° C. MNK1 and MNK2 were activated using recombinant ERK2 which was activated using a constitutively active mutant of MEK1, both ERK2 and MEK1 were expressed in E. coli as N-terminally his tagged proteins. Recombinant ERK2 was activated by incubating 11.3 μM of the kinase with 1 μM MEK1 and 100 μM ATP. This reaction mixture was then used immediately for the activation of the MNKs. The activation of the MNK1 was performed by incubating 5.0 μM of MNK1 with 0.3 μM of activated ERK2 and 500 μM ATP at 30° C. for 6 hours. The activation of MNK2 was performed by incubating 50 μM of MNK2 with 3.0 μM of activated ERK2 and 500 μM ATP at 30° C. for 2 hours. The activated MNKs were stored at −20° C. until required for assay.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 409.45, ALogP 3.41, HBA 6, HBD 0, PSA 83.52, QED 0.52
Compound (SMILES): COc1ccc(C(=O)c2ccc3c(ccn3S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)c2)cc1
InChIKey: OLERVUUNEGIAOP-LFYBBSHMSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human HDAC10 using RHKKAc peptide as substrate
Measurement: IC50 = 5890 nM (pChEMBL 5.230000019073486)
Descriptors: MW 476.51, ALogP 3.64, HBA 7, HBD 2, PSA 114.7, QED 0.18
Compound (SMILES): CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1
InChIKey: ZHRPTNIIEOQLIM-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 443.5, ALogP 3.36, HBA 6, HBD 0, PSA 81.5, QED 0.6
Compound (SMILES): CS[C@@]1(C(=O)Nc2ccc3[nH]nc(-c4ccc(OC(C)C)nc4)c3c2)CCN(CC(=O)N2CC=C(c3ccc(-c4ncn(C)n4)cc3)CC2)C1
InChIKey: KPQQGHGDBBJGFA-QNGWXLTQSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin) preincubated followed by substrate addition
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 691.86, ALogP 5.27, HBA 10, HBD 2, PSA 134.16, QED 0.2
Compound (SMILES): COc1cc2c(cc1-n1cnc3ccc(-c4ccnc5[nH]ccc45)cc31)CNC2
InChIKey: RFUHKEPWGZUNBG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 381.44, ALogP 4.18, HBA 5, HBD 2, PSA 67.76, QED 0.49