lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: QELHXZVXMWGTPU-KUVZEKDXSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.045 nM (pChEMBL 10.350000381469727)
Descriptors: MW 3654.14
Compound (SMILES): CCN(CC)[C@@H](C(=O)N1C[C@H](F)C[C@H]1c1ncc(-c2ccc3c(ccc4oc5cc(-c6cnc([C@@H]7C[C@@H](F)CN7C(=O)[C@@H](c7ccccc7)N(CC)CC)[nH]6)ccc5c(=O)c43)c2)[nH]1)c1ccccc1
InChIKey: KVGZMEGPCWHQJL-JTSNZIGCSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2b assessed as decrease in viral replication
Measurement: EC50 = 797 nM (pChEMBL 6.099999904632568)
Descriptors: MW 931.1, ALogP 10.27, HBA 8, HBD 2, PSA 134.67, QED 0.08
Compound (SMILES): CC1OC2(CCN(CCc3ccccc3)CC2)CN(c2ccccc2Cl)C1=O
InChIKey: BLXCYXQUSIEXTF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in channel current at -80 mV holding potential by whole cell patch clamp assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 398.93, ALogP 4.17, HBA 3, HBD 0, PSA 32.78, QED 0.77
Compound (SMILES): CCCN(CCCCCc1ccc(O)c(OC)c1)[C@H]1CCc2nc(N)sc2C1
InChIKey: PXPHOMJZPNVWMG-KRWDZBQOSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3 dopamine receptor expressed in CHO cells by [35S]GTPgammaS binding assay
Measurement: EC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 403.59, ALogP 4.42, HBA 6, HBD 2, PSA 71.61, QED 0.57
Compound (SMILES): COc1ccc(S(=O)(=O)N(CC(C)C)C[C@H](O)[C@@H](Cc2ccccc2)n2cc(COC(=O)N[C@H]3c4ccccc4C[C@H]3O)nn2)cc1
InChIKey: MEWAZRJLRMEJDV-FYZVQMPESA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV-1 protease V82A mutant
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 663.8, ALogP 3.66, HBA 10, HBD 3, PSA 156.11, QED 0.18
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CCCCNC(=O)c1cc2ccccc2[nH]1
InChIKey: CTDCQQXDSZWWIE-HRAATJIYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293 cell membranes measured after 60 mins by scintillation counting method
Measurement: Ki = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 407.52, ALogP 3.12, HBA 5, HBD 3, PSA 96.27, QED 0.52
Compound (SMILES): CN(Cc1ccccc1)c1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)CP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: NRCRRUYZIFHEBT-SCFUHWHPSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P21588
Assay: Inhibition of recombinant rat CD73 expressed in Sf9 cells using [2,8-3H]-AMP as substrate incubated for 25 mins by scintillation counting method
Measurement: Ki = 0.746 nM (pChEMBL 9.130000114440918)
Descriptors: MW 563.83, ALogP 1.07, HBA 11, HBD 5, PSA 200.59, QED 0.18
Compound (SMILES): O=C(Nc1nccs1)[C@@H](c1cc(F)ccc1O)N1Cc2ccccc2C1=O
InChIKey: YTUFHOKUFOQRDF-MRXNPFEDSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) expressed in mouse Ba/F3 cells assessed as reduction in cell growth incubated for 72 hrs in presence of 1 ug/ml Cetuximab by celltiter-glo luminescent cell viability assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 383.4, ALogP 3.32, HBA 5, HBD 2, PSA 82.53, QED 0.72
Compound (SMILES): COc1nc(N[C@@H](C)c2cc3cc(Cl)c(C4CC4)cc3[nH]c2=O)ncc1C#N
InChIKey: IQGRWPVZOSEPGO-JTQLQIEISA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 395.85, ALogP 3.9, HBA 6, HBD 2, PSA 103.69, QED 0.68
Compound (SMILES): CCn1cncc1-c1c[nH]c2ccc(Cl)cc12
InChIKey: VJPJWNIYTXLISE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human recombinant 5-HT7B receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 245.71, ALogP 3.7, HBA 2, HBD 1, PSA 33.61, QED 0.73
Compound (SMILES): Nc1nc(C(=O)NNC(=S)Nc2ccc(Cl)cc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: ZJHRZQQMZWMFRX-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 = 21.9 nM (pChEMBL 7.659999847412109)
Descriptors: MW 466.94, ALogP 0.78, HBA 8, HBD 5, PSA 170.05, QED 0.28
Compound (SMILES): O=c1oc2ccccc2c2nn(CN3CCN(S(=O)(=O)c4ccc(C(F)(F)F)cc4)CC3)cc12
InChIKey: ZRIRLWBZGKNIFV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs in presence of ATP by fluorescence polarization assay
Measurement: IC50 = 7510 nM (pChEMBL 5.119999885559082)
Descriptors: MW 492.48, ALogP 3.13, HBA 7, HBD 0, PSA 88.65, QED 0.41
Compound (SMILES): CN(C)Cc1ccc2nc3n(c(=O)c2c1)-c1ccc(F)cc1C3=O
InChIKey: QEMBAUOTJNSDTQ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells assessed as reduction in kynurenine production incubated for 18 hrs
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 323.33, ALogP 2.13, HBA 5, HBD 0, PSA 55.2, QED 0.57
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc(CNC(=O)c3ccc4nc(N)sc4c3)cc2)CC1
InChIKey: LUDBUNFYCFJHHY-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 452.54, ALogP 2.83, HBA 7, HBD 2, PSA 114.62, QED 0.58
Compound (SMILES): NCc1ccc(S(=O)(=O)c2cccc3ccccc23)s1
InChIKey: OEQAIWGPRVSJAU-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 303.41, ALogP 3.19, HBA 4, HBD 1, PSA 60.16, QED 0.81
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: QJKKKFYLHKLADL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-stimulated adenylyl cyclase activity by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 372.39, ALogP 2.25, HBA 7, HBD 2, PSA 107.31, QED 0.53
Compound (SMILES): CC(=O)N1N=C(c2ccc(Cl)c(Cl)c2)CC1c1cccc(OS(N)(=O)=O)c1
InChIKey: DHDFHJSTIPECRH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 85.2 nM (pChEMBL 7.070000171661377)
Descriptors: MW 428.3, ALogP 3.27, HBA 5, HBD 1, PSA 102.06, QED 0.81
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)cc4)ncn3CCO)nn12
InChIKey: AIQZOKCURJAIIL-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of TGFBR1 in TGFbeta-stimulated human NHLF cells assessed as reduction in SMAD2 nuclear translocation
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 348.34, ALogP 2.26, HBA 7, HBD 1, PSA 92.03, QED 0.61
Compound (SMILES): CC(C)CCCc1ccc2cc(C(=O)O)ccc2c1
InChIKey: ZQLORCYRMVILSV-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, NMDA 2C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14957
Assay: Positive allosteric modulation of GluN2C receptor (unknown origin) expressed in xenopus laevis oocytes assessed as increase in glycine-induced channel current by two electrode voltage clamp method
Measurement: EC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 256.34, ALogP 4.52, HBA 1, HBD 1, PSA 37.3, QED 0.85
Compound (SMILES): O=C(N[C@H]1CCc2cc(F)cc(F)c2NC1=O)c1n[nH]c(Cc2ccccc2)n1
InChIKey: ATQAGKAMBISZQM-HNNXBMFYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIP1 in human neutrophils assessed as inhibition of TNF-alpha/QVD-Oph/RMT5265-stimulated necroptosis by measuring cellular ATP levels measured at 21 hrs post stimulation by cell-Titer Glo luminescent cell viability assay
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 397.39, ALogP 2.36, HBA 4, HBD 3, PSA 99.77, QED 0.63
Compound (SMILES): CC(C)NCC(O)COc1ccccc1CCCSCC(=O)NCCOCCOCCNC(=O)CCCCCC1(C)C(/C=C/C=C/C=C2/N(CCCS(=O)(=O)O)c3ccc(S(=O)(=O)O)cc3C2(C)C)=[N+](CCCS(=O)(=O)[O-])c2ccc(S(=O)(=O)O)cc21
InChIKey: HXUGFTSAFCNATL-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Antagonist activity at human recombinant beta2 adrenoreceptor expressed in CHOK1 cells incubated for 30 mins by HTRF
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 1312.68
Compound (SMILES): Cc1cc(N2CC(C(=O)O)CC2=O)c(Cl)c(C)c1S(N)(=O)=O
InChIKey: PXKOFARYUUHCAL-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant full length N-terminal His6x-tagged human CA5B expressed in Escherichia coli Rosetta 2 (DE3) by DSF-based fluorescence thermal shift assay
Measurement: Kd = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 346.79, ALogP 1.04, HBA 4, HBD 2, PSA 117.77, QED 0.85
Compound (SMILES): Cc1cc(F)cc(C)c1Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NC34CC(C3)C4)cc12
InChIKey: RYTVXECKOUJGIF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: TR-FRET Assay: Compound dilution series were prepared in DMSO via an approximately 3-fold serial dilution. Compound dilutions were added directly into white, low-volume assay plates (Perkin Elmer Proxiplate 384 Plus#6008280) using a Labcyte Echo in conjunction with Labcyte Access and Thermo Multidrop CombinL robotics. Compounds were then suspended in eight microliters (μL) of assay buffer (20 mM Sodium Phosphate, pH 6.0, 50 mM NaCl, 1 mM Ethylenediaminetetraacetic acid disodium salt dihydrate, 0.01% Triton X-100, 1 mM DL-Dithiothreitol) containing His-tagged bromodomain, Europium-conjugated anti-His antibody (Invitrogen PV5596) and Alexa-647-conjugated probe.The final concentration of 1× assay mixture contained 2% DMSO, 12 nM His tagged BRD4 (BDI_K57-E168) and 100 nM probe or 4 nM His tagged BRD4 (BDII_E352-M457) and 30 nM probe, and 1 nM Europium-conjugated anti-His-tag antibody, and compound concentrations in the range of: 49.02 μM-0.61 nM or 0.98 μM-0.15 nM.After a one-hour equilibration at room temperature, TR-FRET ratios were determined using an Envision multilabel plate reader (Ex 340, Em 495/520).
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 529.61, ALogP 5.59, HBA 5, HBD 3, PSA 96.35, QED 0.3
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(-c3ccc4c(c3)OCO4)ccc2=O)cc1
InChIKey: QZVFUKMYOBSKKZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human cytosolic CA 1 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 99 nM (pChEMBL 7)
Descriptors: MW 371.37, ALogP 1.28, HBA 7, HBD 1, PSA 113.51, QED 0.74
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNC(=O)CCCCC3CCSS3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: PSDRVKSUMXGOJT-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cells assessed as inhibition of NECA-stimulated adenylyl cyclase activity by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 577.74, ALogP 4.29, HBA 10, HBD 3, PSA 136.41, QED 0.18
Compound (SMILES): Cc1cnc2c(N)c(C(=O)NC[C@@H](C)c3ccc(N4CC5CCC(C4)N5)c(C#N)c3)sc2n1
InChIKey: IUDBVIYRVHSGCE-NLNFPOJYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 μL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 μM filtered. Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 μM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub-Rh110 Ubiquitin-Rhodamine 110, R&D Systems # U-555) concentration was 25 nM with [Ub-Rh110]<<Km. 3 μL of 2× enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 μL of 2×Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 μL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 461.6, ALogP 2.93, HBA 8, HBD 3, PSA 119.96, QED 0.53
Compound (SMILES): CNC(=O)N(C)C1CCCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)C1
InChIKey: XCCRZELLYCPWQG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 519.68, ALogP 3.91, HBA 7, HBD 2, PSA 89.62, QED 0.42
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc(-c2ccccn2)cc1)CC1CC1c1cccc(F)c1.Cl
InChIKey: LQZJZNZEYCNJGG-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D4 receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 2222 nM (pChEMBL 5.650000095367432)
Descriptors: MW 459.61, ALogP 5.91, HBA 3, HBD 1, PSA 45.23, QED 0.34
Compound (SMILES): CN(C)S(=O)(=O)Nc1cccc(-c2ccc3c(NC(=O)C4CC4)n[nH]c3c2)c1
InChIKey: GXQWWDBZTZLIAJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: O75716
Assay: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assay
Measurement: Ki = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 399.48, ALogP 2.8, HBA 4, HBD 3, PSA 107.19, QED 0.59
Compound (SMILES): COc1cc(C2CCCN(C)C2)ccc1Nc1ncc2c(n1)-c1ccc(C)cc1NC(=O)N2
InChIKey: NGRVWRKSYIUGNZ-UHFFFAOYSA-N
Target: Activated CDC42 kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07912
Assay: Inhibition of tracer 236 binding to recombinant human GST-tagged TNK2 (110 to 476 residues) expressed in baculovirus expression system incubated for 60 mins by by Lanthascreen assay
Measurement: IC50 = 364 nM (pChEMBL 6.440000057220459)
Descriptors: MW 444.54, ALogP 4.97, HBA 6, HBD 3, PSA 91.41, QED 0.53
Compound (SMILES): COC1CCN(c2nc(NCC(=O)O)c(C(=O)Nc3ccc4ccccc4c3)s2)C1
InChIKey: FEDBAJDLXMUXPQ-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13526
Assay: Inhibition of N-terminal His tagged human Pin1 expressed in Escherichia coli BL21 (DE3) using Suc-Ala-Glu-Pro-Phe-4-nitroanilide as substrate preincubated with enzyme for 10 mins followed by substrate addition by UV-Vis spectrophotometer analysis
Measurement: IC50 = 7150 nM (pChEMBL 5.150000095367432)
Descriptors: MW 426.5, ALogP 3.27, HBA 7, HBD 3, PSA 103.79, QED 0.53
Compound (SMILES): O=C(c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1)N1CCCCC1
InChIKey: CQDXHMWJWCDKSB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/cyclin D1 (unknown origin)
Measurement: IC50 = 861 nM (pChEMBL 6.070000171661377)
Descriptors: MW 474.61, ALogP 3.72, HBA 8, HBD 2, PSA 91.21, QED 0.58
Compound (SMILES): COc1ccc2c(c1[C@@H]1C[C@H]1CN)CCO2.O=C(O)C(F)(F)F
InChIKey: YUQSQXVZLGSUAI-KXNXZCPBSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5-HT2C receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 19.5 nM (pChEMBL 7.710000038146973)
Descriptors: MW 219.28, ALogP 1.69, HBA 3, HBD 1, PSA 44.48, QED 0.84
Compound (SMILES): CC(C)n1c(=O)c(-c2c(F)cc(NS(=O)(=O)Cc3ccc(F)cc3)cc2F)cc2cnc(N[C@H]3CC[C@H](N(C)C)CC3)nc21
InChIKey: KXRGJOFBTUDTEE-HCGLCNNCSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of human His-tagged IRE1alpha expressed in Sf9 insect cells preincubated for 1 hr followed by Alexa fluor 647-labeled probe addition and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 0.08 nM (pChEMBL 10.100000381469727)
Descriptors: MW 628.72, ALogP 5.68, HBA 8, HBD 2, PSA 109.22, QED 0.25
Compound (SMILES): C=C1CCN2Cc3ccc(OC)cc3[C@H]3CCCC[C@]32C1
InChIKey: BTHSSTHWHHWWSB-MOPGFXCFSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Binding affinity to sigma-1 receptor (unknown origin)
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 283.42, ALogP 4.26, HBA 2, HBD 0, PSA 12.47, QED 0.71
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C3CCOCC3)cc2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: GMYGLPNVIWASPQ-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT3 SH2 domain (unknown origin) preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 = 2070 nM (pChEMBL 5.679999828338623)
Descriptors: MW 655.6, ALogP 4.1, HBA 7, HBD 3, PSA 136.48, QED 0.11
Compound (SMILES): CC(C)OP(=O)(COCCOc1nsc(/N=C/N(C)C)n1)OC(C)C
InChIKey: VRQKBYSWBFDCCQ-OQLLNIDSSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK3beta using GSK3 peptide as substrate preincubated for 15 mins followed by ATP addition and measured after 90 mins by ADP-Glo kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.43, ALogP 3.16, HBA 9, HBD 0, PSA 95.37, QED 0.23
Compound (SMILES): COc1ccc2c(CC(=O)N[C@@H](CC(=O)O)C(=O)O[C@@H]3CC[C@@]4(C)[C@H](CC[C@@H]5[C@@H]4CC[C@]4(C)[C@@H]([C@H](C)CCC(=O)OCCOCCOCCOCCOCCN=[N+]=[N-])CC[C@@H]54)C3)cc(=O)oc2c1
InChIKey: HQUDTVGKCFNIBD-YBDDYKLVSA-N
Target: Beta-galactoside alpha-2,6-sialyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15907
Assay: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 953.14, ALogP 7.21, HBA 14, HBD 2, PSA 244.12, QED 0.02
Compound (SMILES): O=c1[nH]c2ccccc2c2cc(-c3ccccc3)cc(Nc3ccc(F)cc3)c12
InChIKey: QZMJHHPSBSMFHP-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of recombinant human MMP2 (110 to 452 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in yeast expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 98000 nM (pChEMBL 4.010000228881836)
Descriptors: MW 380.42, ALogP 6.23, HBA 2, HBD 2, PSA 44.89, QED 0.36
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCC#Cc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O
InChIKey: VRFWWVRYDNNKHQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of N-terminal His6-tagged recombinant human GSK3beta H350L mutant expressed in baculovirus infected Sf21 cells using GSM as substrate incubated for 30 mins in presence of ATP by Kinase-Glo luminescent assay
Measurement: IC50 = 294.7 nM (pChEMBL 6.53000020980835)
Descriptors: MW 626.69, ALogP 2.88, HBA 9, HBD 3, PSA 159.69, QED 0.19
Compound (SMILES): COc1ccc(CC(=O)NC(=N)N[C@H](CC(C)C)C(=O)Nc2cc(S(N)(=O)=O)ccc2C)cc1OC.O=C(O)C(F)(F)F
InChIKey: QCHXODUHLNFTSE-FSRHSHDFSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human liver Cathepsin D preincubated for 10 mins followed by substrate addition and further incubated for 2 hrs in dark by fluorimetric analysis
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 519.62, ALogP 1.9, HBA 7, HBD 5, PSA 172.7, QED 0.24
Compound (SMILES): COc1cc2onc(C)c2cc1NS(=O)(=O)c1ccccc1Cl
InChIKey: RVANWEJRMUQPDF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of HYSGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH binding to recombinant human His6-tagged BRD4 bromodomain 1 (N44 to E168 residues) expressed in Escherichia coli BL21 (DE3) cells measured after 2 hrs by Alphascreen assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 352.8, ALogP 3.6, HBA 5, HBD 1, PSA 81.43, QED 0.78
Compound (SMILES): O=C1NC(=O)C(=Cc2cn(-c3ccccc3)nc2-c2ccccc2)C(=O)N1
InChIKey: WOGISSLYRYBUMU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Displacement of 5-carboxyfluorescein-labeled PBD-binding peptide from PLk1 PBD (unknown origin) expressed in bacterial expression system incubated for 10 mins by fluorescence polarization assay
Measurement: IC50 = 32170 nM (pChEMBL 4.489999771118164)
Descriptors: MW 358.36, ALogP 2.29, HBA 5, HBD 2, PSA 93.09, QED 0.55
Compound (SMILES): Cc1ccc(C(=O)N2CCC(Nc3ncnc4[nH]ncc34)CC2)cc1
InChIKey: BKZMBKARUPDQST-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PAK 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13153
Assay: Inhibition of PAK1 (unknown origin) using lipid substrate measured after 40 mins by ADP-glo kinase assay
Measurement: IC50 = 39450 nM (pChEMBL 4.400000095367432)
Descriptors: MW 336.4, ALogP 2.38, HBA 5, HBD 2, PSA 86.8, QED 0.77
Compound (SMILES): CCOC(=O)c1cccc(-c2ccc3[nH]ccc3c2)c1
InChIKey: RLSLCADIEOFGDD-UHFFFAOYSA-N
Target: Patatin-like phospholipase domain-containing protein 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BJ56
Assay: Inhibition of murine ATGL expressed in COS-7 cells
Measurement: IC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 265.31, ALogP 4.01, HBA 2, HBD 1, PSA 42.09, QED 0.73
Compound (SMILES): Cc1ccc(-c2nc3cc(C(F)(F)F)ccc3[nH]2)cc1
InChIKey: VSFGHBSOJPEFRU-UHFFFAOYSA-N
Target: Neuropeptides B/W receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48145
Assay: Antagonist activity at human NPBWR1 assessed as inhibition of agonist-induced cAMP accumulation by cAMP assay
Measurement: IC50 = 791 nM (pChEMBL 6.099999904632568)
Descriptors: MW 276.26, ALogP 4.56, HBA 1, HBD 1, PSA 28.68, QED 0.69
Compound (SMILES): O=C(O)c1cc(C2=CCCCC2)ccc1O
InChIKey: ALKWOVJIFRPBQJ-UHFFFAOYSA-N
Target: 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDX5
Assay: Inhibition of human ACMSD using ACMS substrate by spectrometry
Measurement: IC50 = 27100 nM (pChEMBL 4.570000171661377)
Descriptors: MW 218.25, ALogP 3.05, HBA 2, HBD 2, PSA 57.53, QED 0.8
Compound (SMILES): CCCn1c(=O)c2ccccc2n2c(=S)n(CC(=O)c3ccccc3)nc12
InChIKey: VEIFQCWXUBNKKM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of biotin-Ahx-CETFDPPLHSpTAI-NH2 binding to recombinant human full-length HA-EGFP-tagged Plk1 PBD expressed in HEK293A cells preincubated for 30 mins followed by biotin-Ahx-CETFDPPLHSpTAI-NH2 addition and measured after 1 hr by 3,3',5,5'-tetramethylbenzidine substrate based ELISA
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 378.46, ALogP 3.47, HBA 7, HBD 0, PSA 61.3, QED 0.39
Compound (SMILES): COc1cc(NC2(c3cccc(Cl)c3)C(=O)N(C(C)(C)C)C(=O)C2=Cc2ccccc2)cc(OC)c1OC
InChIKey: DZTIBENBOYDOHT-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]Nalpha-methylhistamine from recombinant human histamine H3 receptor stably transfected in HEK-293T cells membrane incubated for 90 mins by scintillation counting method
Measurement: Ki = 3200 nM (pChEMBL 5.5)
Descriptors: MW 535.04, ALogP 5.92, HBA 6, HBD 1, PSA 77.1, QED 0.3
Compound (SMILES): CC(C)(C)CC(=O)N[C@@H](CS(=O)(=O)N1CCN(c2ccccn2)CC1)C(=O)NC1(C#N)CC1
InChIKey: SJKOGFYCCHOYII-KRWDZBQOSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of Cathepsin S in human Raji cells assessed as increase in Lip10 accumulation after 24 hrs by SDS-PAGE analysis
Measurement: EC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 476.6, ALogP 0.63, HBA 7, HBD 2, PSA 135.5, QED 0.56
Compound (SMILES): COc1cc(OC)c2c(N3CCSCC3)nc(-c3cc(C)c(OCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: VQCRICWGWXEAJW-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human His-tagged HDAC6 expressed in baculovirus infected insect cells using Ac-Leu-Gly-Lys(Ac)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 526.66, ALogP 4.54, HBA 9, HBD 2, PSA 106.04, QED 0.22
Compound (SMILES): NC(=O)C(SCc1cccc(C(F)(F)F)c1)C1CCCCC1
InChIKey: KLSAPBIHSLXFIK-UHFFFAOYSA-N
Target: Epoxide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07099
Assay: Inhibition of human mEH using CMNGC as substrate preincubated for 5 mins followed by substrate addition and measured at 30 secs interval for 10 mins by fluorescence assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 331.4, ALogP 4.37, HBA 2, HBD 1, PSA 43.09, QED 0.87
Compound (SMILES): Cn1cc(NC(=O)c2cnn3cccnc23)c(-c2cc(Cl)ccc2OC(F)F)n1
InChIKey: CJXPNZXEEPSZHK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 (866 to 1154 residues) expressed in baculovirus expression system using Tyr 06 as substrate incubated for 60 mins by Z'-lyte assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 418.79, ALogP 3.64, HBA 7, HBD 1, PSA 86.34, QED 0.53
Compound (SMILES): Nc1cc(COc2ccc3nc(NC4CCCCC4)sc3c2)ccn1
InChIKey: BATXRTAHHWFDOX-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of AlexaFluor-labeled tracer 236 binding to recombinant human His-tagged CSF1R (538 to 910 residues) preincubated for 20 mins followed by Eu-labeled anti-His antibody addition and measured after 90 mins by FRET based LanthaScreen assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 354.48, ALogP 4.6, HBA 6, HBD 2, PSA 73.06, QED 0.7
Compound (SMILES): CN(Cc1ccc2[nH]nc(/C=C/c3ccccn3)c2c1)c1cc(F)cc(F)c1
InChIKey: BNMXHZKBTHOMBT-SOFGYWHQSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TrkA (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 376.41, ALogP 5.04, HBA 3, HBD 1, PSA 44.81, QED 0.53
Compound (SMILES): O=C1NCCC12CCN(c1c(Cl)cncc1-c1cc3ccccc3o1)CC2
InChIKey: ILMHDRGZABQLEW-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of CDK8/cyclin C (unknown origin) using RBER-IRStide as substrate incubated for 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 381.86, ALogP 4.25, HBA 4, HBD 1, PSA 58.37, QED 0.72
Compound (SMILES): CN(C)CCCCOc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)c1cc([N+](=O)[O-])ccc1F
InChIKey: KBWLRDUIBCUUPC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST tagged EGFR L858R mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 570.98, ALogP 6.19, HBA 8, HBD 2, PSA 122.52, QED 0.12
Compound (SMILES): FC1(F)Oc2ccc(Nc3ncc(C(F)(F)F)c(NC4CC4)n3)cc2O1
InChIKey: ACIBBWPFHYLNQW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 374.27, ALogP 4.13, HBA 6, HBD 2, PSA 68.3, QED 0.78
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc([C@H](C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2)CC1
InChIKey: KSUPSBDNUMSNQO-HNNXBMFYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Biochemical Assay for CDK12 (Kd Determination): Kinase-tagged T7 phage strains were grown in parallel in 24-well blocks in an E. coli host derived from the BL21 strain. E. coli were grown to log-phase and infected with T7 phage from a frozen stock (multiplicity of infection=0.4) and incubated with shaking at 32° C. until lysis (90-150 minutes). The lysates were centrifuged (6,000×g) and filtered (0.2 μm) to remove cell debris. The remaining kinases were produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific phage binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 40× stocks in 100% DMSO and directly diluted into the assay. All reactions were performed in polypropylene 384-well plates in a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR.
Measurement: Kd = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 390.49, ALogP 3.83, HBA 3, HBD 2, PSA 78.09, QED 0.74
Compound (SMILES): Cc1c(C#N)c2nc(C(C)C)cn2c2nc(Nc3ccc(N4CCNCC4)cc3)ncc12
InChIKey: DJZJBAJKDQXEMV-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full-length N-terminal GST-fused CDK4 (1 to 303 residues)/GST-tagged CyclinD3 (1 to 292 residues) expressed in baculovirus expression system using ULight-elF4E-binding protein 1 peptide as substrate measured after 30 mins by LANCE assay
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 426.53, ALogP 3.73, HBA 8, HBD 2, PSA 94.17, QED 0.51
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccccc4F)CC3)cc2C1=O
InChIKey: JSYJUUGAOMCCSL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]spiperone from D2 receptor in rat striatum measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 117.2 nM (pChEMBL 6.929999828338623)
Descriptors: MW 397.49, ALogP 3.04, HBA 4, HBD 0, PSA 36.02, QED 0.7
Compound (SMILES): Cc1ccc(NC(=O)Nc2nc(Nc3ccccc3)cc(Sc3c[nH]c4ccccc34)n2)cc1
InChIKey: JLEQASLQEOSHCX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human N-terminal GST tagged VEGFR2 expressed in Sf9 insect cells using Poly- (Glu4:Tyr)-biotin substrate incubated for 45 mins by Kinase Glo Plus Luminescence kinase assay
Measurement: IC50 = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 466.57, ALogP 6.81, HBA 5, HBD 4, PSA 94.73, QED 0.21
Compound (SMILES): COc1cc2c(=O)c3c4ccc(C#N)cc4[nH]c3n(C(C)C)c2c(F)c1N1CCC(N2CCOCC2)CC1
InChIKey: AQWSSLUSWIRCGY-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058-1620 amino acids) expressed Sf9 cells pre-incubated for 30 mins before addition of Ulight-CKKSRGDYMTMQIG substrate and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 517.61, ALogP 4.54, HBA 7, HBD 1, PSA 86.52, QED 0.43
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: CLPNUAZARXELSV-XIJWKTHWSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Displacement of [125I] [NIe75, Tyr77]Pyr-apelin-13 from YFP-tagged human APJ receptor expressed in HEK293 cell membranes incubated for 1 hr by gamma counting based Cheng-Prusoff equation analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 838.97, ALogP -2.56, HBA 11, HBD 11, PSA 331.15, QED 0.04
Compound (SMILES): O=C(c1ccccc1)N1CCC[C@H](c2ccnc3ncnn23)C1
InChIKey: HDUMATANBDEZEU-AWEZNQCLSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of 6xHis-tagged human recombinant PDE2A expressed in Sf9 cells in presence of [3H]-cGMP and cGMP incubated for 40 mins by scintillation counting method
Measurement: IC50 = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 307.36, ALogP 2.14, HBA 5, HBD 0, PSA 63.39, QED 0.73
Compound (SMILES): Nc1nc2cc(C3CCNCC3)ccn2c1-c1ccc(O)cc1
InChIKey: QLLUGWVQQIMUDR-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of recombinant full length USP7 (unknown origin) using di-ubiquitin as substrate by fluorescence based assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 308.39, ALogP 2.76, HBA 5, HBD 3, PSA 75.58, QED 0.68
Compound (SMILES): COc1nc2nn(CC(=O)N[C@@H](C)c3ccc(Cl)c(F)c3)c(=O)n2cc1C
InChIKey: OXRGZEJMRGXAAC-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 393.81, ALogP 1.88, HBA 7, HBD 1, PSA 90.52, QED 0.71
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)C2CCN(CCC(F)(F)F)CC2)c2ccccc12
InChIKey: DOXCPKIQRWLNFN-GOSISDBHSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of wild-type EZH2 in PRC2 complex (unknown origin) using RKQLATKAARK(Me3)SAPATGGVKKP-NH2 peptide substrate preincubated for 30 mins followed by addition of [3H]-SAM measured after 2 hrs by Topcount scintillation proximity assay
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 532.61, ALogP 5.11, HBA 5, HBD 2, PSA 79.36, QED 0.42
Compound (SMILES): Cc1nc(CN2CCC[C@H]2c2ncccc2C)c(C#N)c(N2CCN(C)CC2)n1
InChIKey: CFMSLWSGIBOXIG-FQEVSTJZSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 391.52, ALogP 2.45, HBA 7, HBD 0, PSA 72.18, QED 0.79
Compound (SMILES): CC(=O)N[C@@H](CS)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1csc2ccccc12)C(=O)N1CCCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)C(C)(C)C)[C@@H](C)O)C(C)(C)S
InChIKey: UKVWVEOVBSSJJF-ZMHOLRAJSA-N
Target: Golgi-associated PDZ and coiled-coil motif-containing protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HD26
Assay: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 1645.07
Compound (SMILES): CO[C@@]12CC[C@H](N[C@H](C)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: ZDYOGHURRMOUMQ-VGDGPHSYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from mu opioid receptor in rat brain membranes incubated for 45 mins by liquid scintillation counting method
Measurement: Ki = 0.69 nM (pChEMBL 9.15999984741211)
Descriptors: MW 388.46, ALogP 1.26, HBA 6, HBD 3, PSA 91.26, QED 0.72
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CC(F)(F)F)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: HJZVCQVBPMDUMS-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 475.5, ALogP 4.7, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): Cn1cc(-c2ccccc2Oc2ccccc2)c2cc(C(=O)NCCCCCC(=O)NO)[nH]c2c1=O
InChIKey: XBNRWYDSWFHTJI-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) by fluorescence based assay
Measurement: IC50 = 44.4 nM (pChEMBL 7.349999904632568)
Descriptors: MW 488.54, ALogP 4.12, HBA 6, HBD 4, PSA 125.45, QED 0.15
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(CC(=O)N(C)C)CC2
InChIKey: HUTGSNJLUXEPLW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 573.12, ALogP 4.25, HBA 9, HBD 2, PSA 116.76, QED 0.39
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CCCCNC(=O)CC[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccccc2)NC1=O)[C@@H](C)CC
InChIKey: HBSYOUCAUKPLME-AFUKFTIKSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of recombinant human 10His-tagged eIF4E expressed in Escherichia coli BL21 (DE3) cells by catalytic enzyme-linked click chemistry assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 1766.18
Compound (SMILES): O=C(CN1C(=O)C(=O)c2ccccc21)Nc1ccc(-c2nc3ccccc3s2)cc1
InChIKey: UUJOJUOHYLWIBT-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human MAGL using 4-Nitrophenylacetate as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 413.46, ALogP 4.13, HBA 5, HBD 1, PSA 79.37, QED 0.51
Compound (SMILES): Cc1nn(-c2ccccn2)c2c1C(=O)CC(C)C2Br
InChIKey: NNSABVCGYBNBQX-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human N-terminal GST-tagged CDK2 (1 to 298 residues)/Cyclin A (174 to 432 residues) expressed in Escherichia coli Turner (DE3) cells assessed as reduction in ADP formation using PKTPKKAKKL as substrate by resorufin dye based fluorescence assay
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 320.19, ALogP 3.23, HBA 4, HBD 0, PSA 47.78, QED 0.76
Compound (SMILES): COc1cc2ncnc(Nc3ccc(NC(=O)c4ccc(I)cc4)cc3)c2cc1OC
InChIKey: NVNZPCHLHXUHOZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) by caliper mobility shift assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 526.33, ALogP 5.25, HBA 6, HBD 2, PSA 85.37, QED 0.33
Compound (SMILES): CC(C)(COC(=O)CCC(=O)OC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]1O)[C@@H](O)C(=O)NCCC(=O)NCCS
InChIKey: DFNKSCRPOZETMX-MTKRSLOGSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of recombinant Aurora A (unknown origin) using myelin basic protein as substrate incubated for 30 mins in presence or absence of DTT by [gamma-33P]-ATP based radioactive filter binding assay
Measurement: IC50 = 83000 nM (pChEMBL 4.079999923706055)
Descriptors: MW 627.68, ALogP -2.17, HBA 16, HBD 7, PSA 250.34, QED 0.08
Compound (SMILES): CCC1(O)CCCN(c2nc3nc(N4CCOCC4)oc3cc2NC(=O)c2coc(-c3ccnc(C)c3)n2)C1
InChIKey: QXLAWCPTQRLVMN-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length N-terminal His6-tagged human IRAK4 expressed in baculovirus infected sf9 cells using biotinylated histone H3 as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 533.59, ALogP 3.41, HBA 11, HBD 2, PSA 142.88, QED 0.38
Compound (SMILES): CCN(C)C(=O)Oc1ccc(/C=C/C(=O)N2CCc3ccccc3C2)cc1
InChIKey: MWFZYRJWHFSLOE-JLHYYAGUSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A
Measurement: IC50 = 97300 nM (pChEMBL 4.010000228881836)
Descriptors: MW 364.45, ALogP 3.74, HBA 3, HBD 0, PSA 49.85, QED 0.78
Compound (SMILES): CCn1cc(NC(=O)NCc2ccc(F)cc2)c2cc(NC(=O)c3ccc(CN4CCN(C)CC4)cc3)ccc21
InChIKey: LSYPGHFZZMKGHD-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of glycosylated human ATX using FS-3 as substrate preincubated for 45 mins followed by substrate addition and measured every 1 min for 30 mins by fluorescence microplate reader assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 542.66, ALogP 5.12, HBA 5, HBD 3, PSA 81.64, QED 0.29
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccccc2Cl)cc1
InChIKey: GJBRFDMGNAWWCF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 359.1 nM (pChEMBL 6.449999809265137)
Descriptors: MW 432.91, ALogP 1.55, HBA 5, HBD 4, PSA 147.46, QED 0.52