lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(O)c1ccc(-c2ccc(N3CCN(c4ncnc5c4ncn5[C@@H]4O[C@H](CO)[C@@H](O)[C@H]4O)CC3)cc2)cc1
InChIKey: SNEFWXMHHMDRJR-ZYWWQZICSA-N
Target: Adenosine kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P55263
Assay: Inhibition of recombinant human adenosine kinase expressed in Escherichia coli BL21 (DE3) using adenosine as substrate in presence of ATP and PEP by pyruvate kinase-lactate dehydrogenase-coupled UV-vis spectrophotometric assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 546.63, ALogP 1.66, HBA 11, HBD 4, PSA 140.23, QED 0.28
Compound (SMILES): COc1cccc(C2CN(C(=O)C[C@@H]3CCN(C#N)C3)C2)c1F
InChIKey: OBYZNAAMRLKAHI-LBPRGKRZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). A Excitation 540 nm; A Emission 590 nm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 317.36, ALogP 1.95, HBA 4, HBD 0, PSA 56.57, QED 0.8
Compound (SMILES): Cc1ccc(CN2CCN(c3nc4cc(N)ccc4o3)CC2)cc1
InChIKey: PGHDPQWRVZUOFI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition and measured for 1 min by DTNB reagent-based spectrophotometric analysis
Measurement: IC50 = 5186 nM (pChEMBL 5.289999961853027)
Descriptors: MW 322.41, ALogP 3.04, HBA 5, HBD 1, PSA 58.53, QED 0.75
Compound (SMILES): CC1(CC(=O)O)CSC(N)=N1
InChIKey: MYVSODDNRXNIOO-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18507
Assay: Agonist activity at recombinant human GABA-A alpha5beta2gamma2S receptor transiently expressed in human tsA201 cells incubated for 30 mins and measured up to 90 secs by FMP dye based FLIPR membrane potential blue assay
Measurement: EC50 = 4466.84 nM (pChEMBL 5.349999904632568)
Descriptors: MW 174.22, ALogP 0.28, HBA 4, HBD 2, PSA 75.68, QED 0.63
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC)cc3OCCO)nc2N1C1CCCC1
InChIKey: PGHXJQMSVOKZRE-GOSISDBHSA-N
Target: Serine/threonine-protein kinase PLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYY3
Assay: Inhibition of recombinant full length human GST-tagged PLK2 expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 195.9 nM (pChEMBL 6.710000038146973)
Descriptors: MW 468.56, ALogP 2.45, HBA 8, HBD 3, PSA 119.92, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccc(CNc2cc(Nc3ccc(N4CCOCC4)cc3)ncn2)cc1
InChIKey: ZPJZUNKZSHRLML-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and further incubated for 30 mins and subsequently measured after 1 hr by HTRF assay
Measurement: IC50 = 916 nM (pChEMBL 6.039999961853027)
Descriptors: MW 430.51, ALogP 3.79, HBA 7, HBD 3, PSA 91.41, QED 0.47
Compound (SMILES): C#CCN(CC#C)CCc1ccc(S(N)(=O)=O)cc1
InChIKey: REAJNGQFHWZSAP-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 276.36, ALogP 0.44, HBA 3, HBD 1, PSA 63.4, QED 0.77
Compound (SMILES): CCn1c(C(O)(c2ccccc2)c2ccccc2)nc2ccc(C(=O)Nc3nc(C)c[nH]3)cc21
InChIKey: ALLMIIAINKTTAU-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT116 cells pre-incubated for 2 hrs before [1,2-14C] sodium acetate addition and measured after 3 hrs by [14C]-Acetate uptake assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 451.53, ALogP 4.62, HBA 5, HBD 3, PSA 95.83, QED 0.35
Compound (SMILES): Cc1c(C(F)CN2CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)CC2)ccc2c1COC2=O
InChIKey: VCTPBYIMYGVTND-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of ROMK (unknown origin) after 30 mins by 86Rb+ efflux assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 464.5, ALogP 2.04, HBA 8, HBD 0, PSA 93.45, QED 0.52
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(F)c2)n1)[C@@H](CC)N(O)C=O.N.N
InChIKey: CTMLNRVMRGLLNE-DWBSNKBKSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 617.63, ALogP 2.17, HBA 8, HBD 6, PSA 215.33, QED 0.05
Compound (SMILES): O=C1NC(c2ccccc2)(c2ccccc2)CC(O)=C1Sc1ccccc1Cl
InChIKey: ZRHCATRUHGMJSD-UHFFFAOYSA-N
Target: L-lactate dehydrogenase B chain (SINGLE PROTEIN), Homo sapiens
UniProt: P07195
Assay: Inhibition of human recombinant carboxy-terminal His-tagged LDHB by UV endpoint assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 407.92, ALogP 5.67, HBA 3, HBD 2, PSA 49.33, QED 0.59
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)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)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=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
InChIKey: FBRUYWYHBQGAGM-BTYOLASZSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of [125I]-labeled rat amylin from human amylin receptor expressed in BHK tkts13 whole cells co-expressing RAMP3 incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.352 nM (pChEMBL 9.449999809265137)
Descriptors: MW 3768.33
Compound (SMILES): Cc1c(C(=O)N2CCC(C(F)(F)F)CC2)cnn1-c1nc2sccc2c(=O)[nH]1
InChIKey: WYNYNSKOVXUIRV-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 411.41, ALogP 2.89, HBA 6, HBD 1, PSA 83.88, QED 0.7
Compound (SMILES): O=C1Nc2ccc(-c3cccs3)cc2C1=O
InChIKey: YOFGZEWPLABWQJ-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK cells assessed as reduction in [3H]GABA uptake by measuring remaining [3H]GABA uptake levels preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting analysis
Measurement: IC50 = 24547.09 nM (pChEMBL 4.610000133514404)
Descriptors: MW 229.26, ALogP 2.55, HBA 3, HBD 1, PSA 46.17, QED 0.76
Compound (SMILES): Nc1nc(-c2ccccc2)nc2sc(-c3ccccc3)nc12
InChIKey: CCWIRVKMRZKCHH-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cells after 3 hrs by scintillation counting method
Measurement: Ki = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 304.38, ALogP 4, HBA 5, HBD 1, PSA 64.69, QED 0.61
Compound (SMILES): O=C1CCc2cc(N3CC[C@](O)(C(=O)NCc4c(F)cccc4F)C3=O)ccc2N1
InChIKey: MRAITFMPEIETKJ-NRFANRHFSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of MetAP2 in HUVEC assessed as reduction in viability incubated for 3 days by CyQUANT Direct Cell proliferation assay
Measurement: IC50 = 809 nM (pChEMBL 6.090000152587891)
Descriptors: MW 415.4, ALogP 1.63, HBA 4, HBD 3, PSA 98.74, QED 0.66
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OP(=O)(N[C@@H](C)C(=O)OC)Oc1ccccc1.N.N.N
InChIKey: IGDMQCBIBDJECC-CWSARAQLSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 903.83, ALogP 3.57, HBA 14, HBD 7, PSA 315.74, QED 0.01
Compound (SMILES): CNc1nccc(N2CC[C@H](NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)C2)n1
InChIKey: AUXBXQOZTPVFRD-NSHDSACASA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 in IFN-gamma-induced human HCT116 cells assessed as suppression of STAT1 phosphorylation at serine727 residue incubated for 24 hrs by infrared scanning analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.82, ALogP 3.59, HBA 5, HBD 3, PSA 82.18, QED 0.71
Compound (SMILES): CC1(C)[C@@H](O)CC[C@]2(C)[C@H]3CC=C4[C@@H]5C[C@@](C)(CO)CC[C@]5(C)CC[C@@]4(C)[C@]3(C)CC[C@@H]12
InChIKey: OYONPFUYHNGECE-UBWAPJCPSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 expressed in baculovirus infected sf21 cells assessed as decrease in PGE2 formation using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition measured after 45 mins by LC-MS analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 442.73, ALogP 7.14, HBA 2, HBD 2, PSA 40.46, QED 0.42
Compound (SMILES): N#Cc1cccc(Cn2cc(CNC3=C(Cl)C(=O)c4cccnc4C3=O)nn2)c1
InChIKey: UEAAADYZDNBGJA-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of recombinant human Cdc25B using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 404.82, ALogP 2.21, HBA 8, HBD 1, PSA 113.56, QED 0.69
Compound (SMILES): CNC(=O)Nc1cc(Oc2cnccc2C)c(-c2ccc(OCCO)nc2)cn1
InChIKey: XJJQINAUBRDFIN-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of human recombinant glucokinase using 5 mM glucose monitored over 5 mins in presence of NAD+ by glucose 6-phosphate dehydrogenase coupled assay
Measurement: EC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 395.42, ALogP 2.76, HBA 7, HBD 3, PSA 118.49, QED 0.56
Compound (SMILES): O=C1C(O)=C(Nc2ccc(F)cc2)C(=O)c2ccccc21
InChIKey: AVGHWZUEYVXFON-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH using DHO as substrate measured at 4 secs interval for 60 secs by DCIP reduction based indirect assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 283.26, ALogP 3.09, HBA 4, HBD 2, PSA 66.4, QED 0.89
Compound (SMILES): COc1ccc2nc3c(c(NCCCCCCCCNC(=S)NC45CC6CC(CC(C6)C4)C5)c2c1)CCCC3
InChIKey: XKQZQFKGCCBLCH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 548.84, ALogP 7.31, HBA 4, HBD 3, PSA 58.21, QED 0.19
Compound (SMILES): Nc1nc(N2CCC(N3CCOCC3)CC2)c2ccn(CCN3CCOCC3)c2n1
InChIKey: MSZHWMGTHFTEJS-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]histamine from human histamine H4 receptor expressed in Sf9 cell membranes by radioligand displacement assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 415.54, ALogP 0.65, HBA 9, HBD 1, PSA 84.91, QED 0.76
Compound (SMILES): CCN1CCN(c2cccc3c2CCN3S(=O)(=O)c2ccccc2)CC1
InChIKey: XEMCNPZNSNBIMI-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]raclopride from human recombinant dopamine D3 receptor expressed in CHO-K1 cells incubated for 120 mins by liquid scintillation counting analysis
Measurement: Ki = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 371.51, ALogP 2.58, HBA 4, HBD 0, PSA 43.86, QED 0.83
Compound (SMILES): COc1cc(NCc2cc3cc(C)ccc3[nH]c2=O)ccc1-n1cnnn1
InChIKey: GGLPMVYVIFIYHC-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 362.39, ALogP 2.43, HBA 7, HBD 2, PSA 97.72, QED 0.57
Compound (SMILES): COc1cc(-c2cc3cccc(C)c3oc2=O)cc(OC)c1OC
InChIKey: GJHMFSWAQGAFON-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine receptor A2A expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 32900 nM (pChEMBL 4.480000019073486)
Descriptors: MW 326.35, ALogP 3.79, HBA 5, HBD 0, PSA 57.9, QED 0.68
Compound (SMILES): O=C(Nc1cc(Oc2ccc(Nc3nccc4[nH]cc(-c5ccc(F)cc5)c(=O)c34)cc2F)ccn1)C1CCC1
InChIKey: VYMTUJBEYOVPCB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of purified recombinant MET kinase domain (unknown origin) using biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 to 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 539.54, ALogP 6.54, HBA 6, HBD 3, PSA 109, QED 0.22
Compound (SMILES): Cn1ccc2ccc(-c3ccc4ccn(Cc5cc(F)cc(C(=O)O)c5)c4c3)cc21
InChIKey: LOABWWGPCQVABV-UHFFFAOYSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: Inhibition of HIV1 gp41-induced cell-cell fusion between viral protein expressing human HL2/3 cells and TZM-bl target cells preincubated overnight with TZM-bl cells followed by co-incubation with HL2/3 cells for 6 hrs by luciferase reporter gene assay
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 398.44, ALogP 5.69, HBA 3, HBD 1, PSA 47.16, QED 0.42
Compound (SMILES): Cc1c(C(=O)N2CCN(c3cnccn3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: VRGQBGQABQRGKL-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 405.42, ALogP 0.27, HBA 9, HBD 1, PSA 117.31, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: LFNQMWJMSBXZBR-OBXLUMITSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 0.3548 nM (pChEMBL 9.449999809265137)
Descriptors: MW 873.11, ALogP 2.34, HBA 10, HBD 6, PSA 218.62, QED 0.1
Compound (SMILES): COc1ccc2[nH]cc(C3CC(=O)N(CCN4CCC(c5c[nH]c6ccccc56)CC4)C3=O)c2c1
InChIKey: BSTUCRCQYKCWRT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO-K1 cell membranes incubated for 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 48.7 nM (pChEMBL 7.309999942779541)
Descriptors: MW 470.57, ALogP 4.38, HBA 4, HBD 2, PSA 81.43, QED 0.41
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1ccc(Cl)cc1Cl
InChIKey: NGYGCHRHGPTEAF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 428.3, ALogP 3.27, HBA 5, HBD 1, PSA 102.06, QED 0.81
Compound (SMILES): C=CC(=O)N1CC(Oc2c(N)ncnc2-c2cc(F)cc(NC(=O)c3ccc(C4CC4)cc3F)c2C)C1
InChIKey: OSLWRSOLKHYZCC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in vitamin D3 differentiated human THP1 cells assessed as inhibition of FCgammaR-induced IL8 production measured after 24 hrs by HTRF assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 505.53, ALogP 4.22, HBA 6, HBD 2, PSA 110.44, QED 0.47
Compound (SMILES): CCC(CC)CNc1c(C(N)=O)cnc2ccc(-c3ccc(C)nc3)cc12
InChIKey: GISUXDZKZZWMHN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in Chk1 phosphorylation at Ser-345 residue after 60 mins in presence of 4-nitroquinoline-1-oxide by Hoechst 33258 staining based plate reader analysis
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 362.48, ALogP 4.55, HBA 4, HBD 2, PSA 80.9, QED 0.65
Compound (SMILES): Cc1c(C(=O)N2CCC(n3cccc3S(=O)(=O)C(F)(F)F)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: QMVLXJBUUOJBGD-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 523.5, ALogP 2.09, HBA 9, HBD 1, PSA 127.36, QED 0.44
Compound (SMILES): Cc1cc(N2CCCNCC2)c2ccccc2n1
InChIKey: JQCNKRUGSCMMQA-UHFFFAOYSA-N
Target: Neutrophil cytosol factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14598
Assay: Binding affinity to immobilized recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR assay
Measurement: Kd = 296000 nM (pChEMBL 3.5299999713897705)
Descriptors: MW 241.34, ALogP 2.34, HBA 3, HBD 1, PSA 28.16, QED 0.83
Compound (SMILES): CCN(CC)C(=O)/C(C#N)=C(\N)c1cc(O)c(O)c([N+](=O)[O-])c1
InChIKey: LZMDLBYNPFDWBC-XFXZXTDPSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21964
Assay: Inhibition of COMT (unknown origin) in presence of AdoMet and Esculetin by reaction kinetic model based assay relative to control
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 320.31, ALogP 1.07, HBA 7, HBD 3, PSA 153.72, QED 0.24
Compound (SMILES): COc1ccc(-c2cc(C(=O)N[C@@H]3CCN(C#N)C3)on2)cc1OC
InChIKey: GLXWRJDUQUUWQA-GFCCVEGCSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Kinetic Assay/Biochemical Fluorescence Intensity Assay: USP30 Biochemical Fluorescence Intensity Kinetic Assay.Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. USP30 CD (Boston Biochem E-582 or 57-517, #64-0057-050 Ubiquigent) was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0, 0.0005, 0.001, 0.005, and 0.01 μl/well. Buffer was optimised for optimal temperature, pH, reducing agent, salts, time of incubation, and detergent. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555, Boston Biochem) at a final concentration of 100 nM. Reactions were incubated at room temperature and read every 2 min for 120 min. Readings were performed on a Pherastar Plus (BMG Labtech). Excitation 487 nm; λ Emission 535 nm.USP30 Biochemical Fluorescence Intensity IC50 AssayDilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; 2 Emission 535 nm.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 342.36, ALogP 1.64, HBA 7, HBD 1, PSA 100.62, QED 0.82
Compound (SMILES): CCN1CCN(c2cnn(-c3ccc(S(N)(=O)=O)cc3)c(=O)c2Cl)CC1
InChIKey: MIZOVKCXRDKVOZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of membrane bound human CA 9 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 397.89, ALogP 0.68, HBA 7, HBD 1, PSA 101.53, QED 0.81
Compound (SMILES): CC(C)(C)C(=O)N(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)CC1CCCCC1
InChIKey: YRCFFDCYNJRTGN-QEIWAGNOSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-DPN from recombinant human delta opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 453.67, ALogP 4.95, HBA 3, HBD 1, PSA 66.64, QED 0.64
Compound (SMILES): Cc1c(C(=O)N2CCc3nc(-c4ccccn4)sc3C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: PWDROTSWNCAYNB-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 458.51, ALogP 2.23, HBA 9, HBD 1, PSA 114.07, QED 0.44
Compound (SMILES): COc1nc(N(CC(C)C)c2cc(C(F)(F)F)ccc2F)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: DHFTZUKKLBRROT-STQMWFEESA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of LTC4S in zymosan-stimulated human PBMC assessed as inhibition of LTC4 production preincubated for 45 mins followed by zymosan stimulation and measured after 20 mins by LC-MS/MS analysis
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 455.41, ALogP 4.34, HBA 6, HBD 1, PSA 92.62, QED 0.47
Compound (SMILES): Cc1cc(=O)[nH]c(-n2ccc(C(=O)N3c4ccccc4CC3C)n2)n1
InChIKey: ZTHQGONJXBLVPJ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 335.37, ALogP 1.86, HBA 5, HBD 1, PSA 83.88, QED 0.77
Compound (SMILES): CCOCCOc1cc(N)nc2ccccc12
InChIKey: WXXDQKIIJFFHFV-UHFFFAOYSA-N
Target: Neutrophil cytosol factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14598
Assay: Binding affinity to immobilized recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR assay
Measurement: Kd = 153000 nM (pChEMBL 3.809999942779541)
Descriptors: MW 232.28, ALogP 2.23, HBA 4, HBD 1, PSA 57.37, QED 0.8
Compound (SMILES): CN(C)c1ccc(CNC(=O)[C@@H]2CNC[C@H]2c2ccc(C(F)(F)F)c(Cl)c2)cc1
InChIKey: ZOCBKLKCLNCENK-DLBZAZTESA-N
Target: Plasmepsin II (SINGLE PROTEIN), Plasmodium falciparum
UniProt: P46925
Assay: Inhibition of Plasmodium falciparum plasmepsin 2 using EDANS-CO-CH2-CH2-CO-ALERMFLSFP-Dap(DABCYL)OH as substrate measured after 60 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.88, ALogP 4.04, HBA 3, HBD 2, PSA 44.37, QED 0.76
Compound (SMILES): CN1c2ccc(OC(=O)NCCCCCCCCCCN3CCOCC3)cc2CN2CCc3ccccc3C21
InChIKey: FGIRYRPHYPRPJZ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human plasma BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 2.5 mins by DTNB reagent based spectrometric method
Measurement: IC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 534.75, ALogP 5.73, HBA 6, HBD 1, PSA 57.28, QED 0.35
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(=O)O
InChIKey: XWASFAWNEBGWJU-IDBRVYLJSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1R expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 917.12, ALogP -1.75, HBA 12, HBD 13, PSA 352.39, QED 0.03
Compound (SMILES): Cc1ccc(-c2cc(-c3cccc(NC(=O)c4cc(-n5cnc(C)c5)cc(C(F)(F)F)c4)c3)[nH]n2)cc1
InChIKey: FJTHHJHRDPNCHM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant (unknown origin)
Measurement: IC50 = 3250 nM (pChEMBL 5.489999771118164)
Descriptors: MW 501.51, ALogP 6.82, HBA 4, HBD 2, PSA 75.6, QED 0.28
Compound (SMILES): O=C(O)CNC(=O)c1c(O)c2c(n(Cc3cnc(C(F)(F)F)cn3)c1=O)COC2
InChIKey: JDLGXHQNBSGCLL-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of recombinant human HIF-PHD2 expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL and 2-oxoglutarate as substrates preincubated for 30 mins followed by substrates addition and measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 414.3, ALogP 0.26, HBA 8, HBD 3, PSA 143.64, QED 0.63
Compound (SMILES): CSc1ncc(-c2c(CO)n(Cc3ccc(F)cc3F)c3ccc(OC(F)(F)F)cc23)cn1
InChIKey: MPMANRVGSPMYBN-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity against PAR4 activating peptide domain in human platelets assessed as inhibition of alpha2bbeta3 activation level by PAC1 binding assay
Measurement: IC50 = 1348.96 nM (pChEMBL 5.869999885559082)
Descriptors: MW 481.45, ALogP 5.54, HBA 6, HBD 1, PSA 60.17, QED 0.22
Compound (SMILES): COc1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: SVHOPJCSYNTLAH-RPKMEZRRSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 376.35, ALogP -2.74, HBA 12, HBD 4, PSA 197.93, QED 0.42
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N(CCCN2CCOCC2)C2CCN(S(C)(=O)=O)CC2)n1
InChIKey: FCMUYRXLBHFCQT-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human N-terminal p110delta/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 665.77, ALogP 1.95, HBA 13, HBD 0, PSA 131.28, QED 0.3
Compound (SMILES): Cc1nn(-c2nc3ccc(Cl)c(Cl)c3[nH]2)c(O)c1C1OC(=O)c2ccccc21
InChIKey: VIQXILLOJLATEF-UHFFFAOYSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of human cGAS expressed in THP1-Dual cells transfected with HT-DNA assessed as suppression of lipofectamine 2000:ds-DNA complex induced activation of cGAS incubated for 1 hr by Quanti-luc reagent based assay
Measurement: IC50 = 32900 nM (pChEMBL 4.480000019073486)
Descriptors: MW 415.24, ALogP 4.33, HBA 6, HBD 2, PSA 93.03, QED 0.48
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@@H](C)c3cc(F)c(N4CCNCC4)cc3F)sc2n1
InChIKey: DIMLWPCIAHNRFA-GFCCVEGCSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) 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 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before 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 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 445.54, ALogP 3.41, HBA 6, HBD 3, PSA 83.28, QED 0.56
Compound (SMILES): Cc1c(N2CCN(Cc3cccnc3Cl)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: LQMHGCMQLZFNCZ-SANMLTNESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Displacement of [125I]D-Trp6-LHRH from human GnRH receptor expressed in CHO-K1 cell membranes incubated for 1 hr by competitive binding assay
Measurement: IC50 = 2.57 nM (pChEMBL 8.59000015258789)
Descriptors: MW 631.07, ALogP 4.6, HBA 8, HBD 1, PSA 89.39, QED 0.23
Compound (SMILES): COP(C)(=O)NCCCCCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: AQQVTVTWLDGYNJ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant N-terminal His-tagged human IDO1 expressed in Escherichia coli assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 493.27, ALogP 3.86, HBA 8, HBD 4, PSA 133.9, QED 0.09
Compound (SMILES): CCN1CCN(c2ccc(C(=O)Nc3n[nH]c4nc(-c5c(Cl)c(OC)cc(OC)c5Cl)ccc34)cc2)CC1
InChIKey: YMOVCVRDNUJTLA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzyme Kinase Activity Assay: The enzyme reaction substrate Poly(Glu,Tyr) 4:1 was diluted with PBS without potassium ion (10 mM sodium phosphate buffer, 150 mM NaCl, pH7.2-7.4) to 20 μg/mL, 125 μL/well to coat the enzyme plate, and reacted at 37° C. for 12-16 hours. After the liquid was removed from the wells, the plate was washed three times with 200 μL/well of T-PBS (PBS containing 0.1% Tween-20) for 5 minutes each. The enzyme plate was dried in a 37° C. oven for 1-2 hours.50 μL of the ATP solution diluted with the reaction buffer (50 mM HEPES pH 7.4, 50 mM MgCl2, 0.5 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT) was added into each well at a 5 μM final concentration. The compounds were diluted to the appropriate concentration in DMSO, 1 μL/well or containing the corresponding concentrations of DMSO (negative control wells). The reaction was initiated by addition of each kinase domain recombinant protein diluted with 49 μL of reaction buffer. Two control wells without ATP were set in each experiment. The reaction mixtures were placed on a shaker (100 rpm) to react at 37° C. for 1 hour. The plates were washed with T-PBS for three times. 100 μL/well of the primary antibody PY99 dilution was added, and reacted on a shaker (100 rpm) at 37° C. for 0.5 hour. The plates were washed with T-PBS for three times. 100 μL/well of the secondary anti-horseradish peroxidase-labeled goat anti-mouse IgG dilution was added, and reacted on a shaker at 37° C. for 0.5 hour. The plates were washed with T-PBS for three times. 100 μL/well of 2 mg/mL OPD developing solution (diluted with 0.1M citric acid-sodium citrate buffer containing 0.03% H2O2 (pH=5.4)), and reacted in dark for 1-10 minutes at 25° C. (Ultrasound is needed in OPD dissolution, and the developing solution should be prepared on the site). The reaction was quenched with 50 μL/well of 2M H2SO4, and read out at 490 nm using a tunable microplate microplate reader SPECTRA MAX 190.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 555.47, ALogP 5.34, HBA 7, HBD 2, PSA 95.61, QED 0.32
Compound (SMILES): CC(=O)CC(=O)c1c(O)c2c(=O)oc3ccccc3c2oc1=O
InChIKey: NUIYQQLCPIINTN-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of LEDGF/p75-dependent full length HIV-1 integrase expressed in Escherichia coli BL21(DE3) cells preincubated for 1 hr further incubated for 90 mins with biotin-labeled donor DNA and target DNA by HTRF assay
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 314.25, ALogP 1.77, HBA 7, HBD 1, PSA 114.79, QED 0.34
Compound (SMILES): COc1ccccc1NC(=O)C1=C(C)NC2=C(C(=O)CCC2)C1c1ccco1
InChIKey: DOHGSZRKARZSJP-UHFFFAOYSA-N
Target: Free fatty acid receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14843
Assay: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay
Measurement: EC50 = 371.54 nM (pChEMBL 6.429999828338623)
Descriptors: MW 378.43, ALogP 3.89, HBA 5, HBD 2, PSA 80.57, QED 0.84
Compound (SMILES): N#Cc1cnn(-c2ccc(S(N)(=O)=O)cc2)c1/N=C/c1ccc(Br)cc1
InChIKey: FJVLAYQCSAEMHG-UFFVCSGVSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2 assessed as reduction in PGF2alpha formation using arachidonic acid as substrate preincubated with enzyme for 10 mins followed by substrate addition for 30 secs and measured after 1 hr by microplate reader based enzyme immunoassay
Measurement: IC50 = 64.9 nM (pChEMBL 7.190000057220459)
Descriptors: MW 430.29, ALogP 2.9, HBA 6, HBD 1, PSA 114.13, QED 0.64
Compound (SMILES): Cn1nccc1Nc1nccc(-c2ccc3c(c2)C(=O)N(C(CO)c2cccc(Cl)c2)C3)n1
InChIKey: SCFLWNGBEZTNIR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin) using lipid as substrate after 40 mins by ADP-Glo luminescence assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 460.93, ALogP 3.96, HBA 7, HBD 2, PSA 96.17, QED 0.45
Compound (SMILES): CC(=O)Nc1ccc(Cl)c(S(=O)(=O)N2CCCC2)c1
InChIKey: IMQJAVZVMWRWMW-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of Alexa Fluor 647-labeled GSK tracer from FLAG-6His-Tev-fused CECR2 (424 to 543 residue) (unknown origin) measured after 15 mins by TR-FRET assay
Measurement: IC50 = 79432.82 nM (pChEMBL 4.099999904632568)
Descriptors: MW 302.78, ALogP 2.08, HBA 3, HBD 1, PSA 66.48, QED 0.93
Compound (SMILES): Cc1c(C(=O)N2CCN(C3CCC3(F)F)CC2)nnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: VNQJBXYOXVKLTJ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 418.41, ALogP 0.47, HBA 8, HBD 1, PSA 104.42, QED 0.66
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(C(=O)NCP(=O)(O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: UPGVKKCQHRSRKC-FGZHOGPDSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 610.6, ALogP 2.84, HBA 8, HBD 6, PSA 207.74, QED 0.04
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1cccc(Cl)c1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1cccc(Cl)c1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(C)=O)C(C)C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: FUULMMJUSQXRLZ-NBIMRMOJSA-N
Target: Frizzled-7 (SINGLE PROTEIN), Homo sapiens
UniProt: O75084
Assay: Binding affinity to recombinant human Frizzled-7 (Gln33 to Leu185 residues)/human IgG1 chimeric protein expressed in CHO cells by SPR assay
Measurement: Kd = 0.1 nM (pChEMBL 10)
Descriptors: MW 3238.44
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CC[C@@H](NC(C)C)C4)cc3)sc2n1
InChIKey: JAQANAMSDCJFSC-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 437.61, ALogP 3.74, HBA 6, HBD 3, PSA 83.28, QED 0.52
Compound (SMILES): Cc1cnc(CNC(=O)c2csc(CCNCCc3nc4ccccc4[nH]3)n2)nc1.Cl.Cl.Cl
InChIKey: CEINYMVFMALXDA-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as reduction in Fpn-mediated iron efflux incubated overnight by iron regulatory element -driven beta-lactamase reporter gene assay
Measurement: EC50 = 8170 nM (pChEMBL 5.090000152587891)
Descriptors: MW 421.53, ALogP 2.42, HBA 7, HBD 3, PSA 108.48, QED 0.36
Compound (SMILES): C[C@@H](Nc1ccnc2ccc(-c3cccnc3)cc12)c1ccc(Cl)cc1
InChIKey: LHVQEPIKUBGBJQ-OAHLLOKOSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in Chk1 phosphorylation at Ser-345 residue after 60 mins in presence of 4-nitroquinoline-1-oxide by Hoechst 33258 staining based plate reader analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 359.86, ALogP 6.12, HBA 3, HBD 1, PSA 37.81, QED 0.48
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(O)C(=O)NCc1ccccc1
InChIKey: WRDSLXQVNSZWEG-MMBKUXRPSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of 20S proteosome beta 2 purified from human HCT116 cells using Boc-LRR-AMC as substrate incubated for 30 to 120 mins by fluorimetry
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 498.58, ALogP 1.37, HBA 6, HBD 5, PSA 159.85, QED 0.28
Compound (SMILES): COc1cccc(-c2nnc(COc3ccc(Cl)cc3C)o2)c1
InChIKey: HWSMRVPKFALRIV-UHFFFAOYSA-N
Target: Anoctamin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQ90
Assay: Inhibition of YFP-fused ANO2 (unknown origin) expressed in FRT cells after 20 mins by fluorescence quenching method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 330.77, ALogP 4.29, HBA 5, HBD 0, PSA 57.38, QED 0.7
Compound (SMILES): CC(NC(=O)c1csc(CCNCc2nc3ccccc3[nH]2)n1)c1ccccn1
InChIKey: TZBXBPPGWROHQD-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 345 nM (pChEMBL 6.460000038146973)
Descriptors: MW 406.52, ALogP 3.24, HBA 6, HBD 3, PSA 95.59, QED 0.39
Compound (SMILES): Cc1noc(C)c1-c1ccc2nc(NC(=O)CC3CCN(C#N)C3)cn2c1
InChIKey: ACFBKIRZSKQCAR-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). A Excitation 540 nm; A Emission 590 nm.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 364.41, ALogP 2.74, HBA 7, HBD 1, PSA 99.46, QED 0.71
Compound (SMILES): [N-]=[N+]=Nc1nc2c(N)ncnc2n1[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O
InChIKey: PQISXOFEOCLOCT-UUOKFMHZSA-N
Target: P2X purinoceptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBL9
Assay: Agonist activity at human P2X2R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 548.2, ALogP -0.69, HBA 15, HBD 7, PSA 327.89, QED 0.09
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](CCC(N)=O)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](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)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](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: QBDRUEHIJBEDSE-OWJRSXPWSA-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 absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.027 nM (pChEMBL 10.569999694824219)
Descriptors: MW 3829.28
Compound (SMILES): N#CN1CCOC(C(=O)Nc2ncc(-c3ccc(F)cc3)s2)C1
InChIKey: RBEAVWVZUZTEQR-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: USP30 Biochemical IC50 Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 332.36, ALogP 2.07, HBA 6, HBD 1, PSA 78.25, QED 0.87