lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCC(Cn2nc(-c3ccc4cc(OCC5CC5)ccc4c3)c3c(N)ncnc32)CC1
InChIKey: OMIGQQMOKATBDK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 442.57, ALogP 4.36, HBA 7, HBD 1, PSA 82.09, QED 0.48
Compound (SMILES): COc1nc(N[C@H]2CC[C@H](NS(=O)(=O)CCC(C)C)CC2)nc2[nH]nc(N3CCOC[C@H]3C)c12
InChIKey: VZBBAPFIHSZTRP-BRWVUGGUSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 495.65, ALogP 2.28, HBA 9, HBD 3, PSA 134.36, QED 0.48
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1Cc2ccccc2C[C@@H]1C(N)=O
InChIKey: QHGVNDDQKJSMFK-GWMMUDDPSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene assessed as inhibition of NDP-MSH-induced cAMP accumulation up to 10 uM after 6 hrs by beta-galactosidase reporter gene assay
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 712.26, ALogP -0.68, HBA 7, HBD 10, PSA 274.5, QED 0.06
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)CCNC3=O)cc(C)c1Cl
InChIKey: SKZRLKLCHRPYDV-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 525.48, ALogP 6.34, HBA 5, HBD 1, PSA 61.08, QED 0.3
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccccc2)o1)[C@@H](CC)N(C=O)OC(=O)OC(C)(C)C
InChIKey: KQFFYSQAPWYUKD-FGZHOGPDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 529.63, ALogP 5.05, HBA 7, HBD 2, PSA 127.18, QED 0.12
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)/C(Cc2ccc(O)c(Br)c2)=N/OC2CCCCO2)cc1
InChIKey: WXBYLMYSRZIUAD-JJIBRWJFSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 expressed in Escherichia coli GOLD BL21 (DE3) by stopped-flow CO2 hydration assay
Measurement: Ki = 35.9 nM (pChEMBL 7.449999809265137)
Descriptors: MW 512.38, ALogP 2.88, HBA 7, HBD 3, PSA 140.31, QED 0.39
Compound (SMILES): CC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N[C@@H](CC1CCCCC1)C(N)=O
InChIKey: CPVMFOXNQUPDOW-NFGXINMFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene assessed as inhibition of NDP-MSH-induced cAMP accumulation up to 10 uM after 6 hrs by beta-galactosidase reporter gene assay
Measurement: Kd = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 687.25, ALogP 0.53, HBA 7, HBD 9, PSA 250.07, QED 0.06
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN3Cc2ccc(Cl)cc2)n(C)c1=O
InChIKey: VRRLACXMIMNFLB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB603 from recombinant human adenosine A2b receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 345.79, ALogP 1.11, HBA 7, HBD 0, PSA 65.06, QED 0.7
Compound (SMILES): Cn1c(N)nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](O)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c1=O
InChIKey: PCGZLBNJZQNWTE-XPWFQUROSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype R71H/G230A/R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 688.44, ALogP -2.33, HBA 21, HBD 6, PSA 318.79, QED 0.12
Compound (SMILES): CCOc1ccccc1-n1nnnc1SCC(=O)Nc1cc(C(C)(C)C)nn1-c1ccccc1
InChIKey: BGUYPHQCUACHCL-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of recombinant full length human TrkB transfected in CHO cells assessed as inhibition of NGF-stimulated calcium influx by FLIPR assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 477.59, ALogP 4.28, HBA 9, HBD 1, PSA 99.75, QED 0.38
Compound (SMILES): O=C(O)c1cc2c3c(c1)C1C=CCC1C(c1ccccc1Cl)N3CC1CC=CC21
InChIKey: RKRFFBBVYHOUSA-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to N-terminal 6x-His-tagged recombinant human SOS1 catalytic domain (residues 564 to 1049 residues) expressed in Escherichia coli BL21 (DE3) by label-free microscale thermophoresis analysis
Measurement: Kd = 13677.29 nM (pChEMBL 4.860000133514404)
Descriptors: MW 403.91, ALogP 5.93, HBA 2, HBD 1, PSA 40.54, QED 0.63
Compound (SMILES): CCc1cc(Cc2ccc(CC(N)=O)cc2)nc(-c2cccc(Cl)c2)n1
InChIKey: FUJWOWGJBPZCTE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYPC19 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 365.86, ALogP 3.98, HBA 3, HBD 1, PSA 68.87, QED 0.72
Compound (SMILES): NS(=O)(=O)c1ccc(N2C(=O)C[C@H](C(=O)NCCC(=O)O)[C@H]2c2ccc(Cl)cc2)cc1
InChIKey: ZXWOFYXXMIUWJC-QFBILLFUSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 465.92, ALogP 1.67, HBA 5, HBD 3, PSA 146.87, QED 0.57
Compound (SMILES): COc1ccc(C(C/C=C\CN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2)c2ccc(OC)cc2)cc1
InChIKey: YZTTZGKNHRIXLQ-PLNGDYQASA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 85113.8 nM (pChEMBL 4.070000171661377)
Descriptors: MW 515.65, ALogP 5.79, HBA 5, HBD 1, PSA 68.23, QED 0.26
Compound (SMILES): COc1cc(N2CCN(CC(N)=O)C2=O)ccc1Nc1ncc(Cl)c(Nc2ccccc2S(=O)(=O)C(C)C)n1
InChIKey: SXTUUDANYSHGTB-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of N-terminal GST-tagged human ROS1 cytoplasmic domain (1883 to 2347 residues) expressed in Baculovirus expression system using IRS1 as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 574.06, ALogP 3.54, HBA 9, HBD 3, PSA 159.85, QED 0.33
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O)[C@@H](C)O)[C@@H](C)CC)C(C)C
InChIKey: QWXITWPMQUYSSB-BDDBCRLQSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay
Measurement: EC50 = 5888.44 nM (pChEMBL 5.230000019073486)
Descriptors: MW 2125.43
Compound (SMILES): Cn1ccnc1CN1C[C@H](CCCB(O)O)[C@](N)(C(=O)O)C1
InChIKey: QYTBWEJMHPQCLS-GWCFXTLKSA-N
Target: Arginase-2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P78540
Assay: Inhibition Assay of Arginase: Inhibition of arginase I (ARG I) and arginase II (ARG II) by Formula I or Formula II compounds is followed spectrophotometrically at 530 nm. The compound to be tested was dissolved in DMSO at an initial concentration 50-fold greater than its final concentration in the cuvette. 10 μl of the stock solution was diluted in 90 μl of the assay buffer that comprises 0.1M sodium phosphate buffer containing 130 mM NaCl, pH 7.4, to which is added ovalbumin (OVA) at a concentration of 1 mg/ml. Solutions of arginase I and II were prepared in 100 mM sodium phosphate buffer, pH 7.4 containing 1 mg/ml of OVA to give an arginase stock solution at a final concentration of 100 ng/ml. To each well of a 96-well microtiter plate was added 40 μl of enzyme, 10 μl of an inventive compound and 10 μl of enzyme substrate (L-arginine+manganese sulfate). For wells that were used as positive controls, only the enzyme and its substrate were added, while wells used as negative controls contained only manganese sulfate. After incubating the microtiter plate at 37° C. for 60 minutes, 150 μl of a urea reagent obtained by combining equal proportions (1:1) of reagents A and B is added to each well of the microtiter plate to stop the reaction. The urea reagent is made just before use by combining Reagent A (10 mM o-phthaldialdehyde, and 0.4% polyoxyethylene (23) lauryl ether (w/v) in 1.8 M sulfuric acid) with Reagent B (1.3 mM primaquine diphosphate, 0.4% polyoxyethylene (23) lauryl ether (w/v), 130 mM boric acid in 3.6 mM sulfuric acid). After quenching the reaction mixture, the microtiter plate is allowed to stand for an additional 10 minutes at room temperature to allow the color to develop. The inhibition of arginase was computed by measuring the optical density (OD) of the reaction mixture at 530 nm and normalizing the OD value to percent inhibition observed in the control. The normalized OD is then used to generate a dose-response curve by plotting the normalized OD values against log [concentration] and using regression analysis to compute the IC50 values.
Measurement: IC50 = 625 nM (pChEMBL 6.199999809265137)
Descriptors: MW 310.16
Compound (SMILES): COc1ccc(NC(=O)c2ccc3c(c2)C(=O)N(Cc2ccccc2)C3=O)c(C(=O)O)c1
InChIKey: QQKKYAYCZMPFCU-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 41900 nM (pChEMBL 4.380000114440918)
Descriptors: MW 430.42, ALogP 3.44, HBA 5, HBD 2, PSA 113.01, QED 0.58
Compound (SMILES): C=CC(=O)Nc1cccc(CNc2cc(Nc3ccc(N4CCOCC4)cc3)ncn2)c1
InChIKey: BFVJWOMAZHKZRD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 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 = 1286 nM (pChEMBL 5.889999866485596)
Descriptors: MW 430.51, ALogP 3.79, HBA 7, HBD 3, PSA 91.41, QED 0.47
Compound (SMILES): CCOc1cccc2cc(-c3ccc(Br)cc3)c(=O)oc12
InChIKey: PHMNRGKWKPYDEL-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine receptor A3 expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 345.19, ALogP 4.62, HBA 3, HBD 0, PSA 39.44, QED 0.65
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](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(N)=O
InChIKey: OBJYUNZPDRRJGE-YXRHCLBHSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 925.11, ALogP -2.51, HBA 12, HBD 13, PSA 360.84, QED 0.03
Compound (SMILES): COc1ccc(CCOC(=O)N(c2ccccc2)C2CN3CCC2CC3)cc1OC
InChIKey: JEUYGMLCHUFKRY-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 3490 nM (pChEMBL 5.460000038146973)
Descriptors: MW 410.51, ALogP 3.98, HBA 5, HBD 0, PSA 51.24, QED 0.69
Compound (SMILES): C=CC(=O)N1CC(NC(=O)Cn2c(C)c(C(=O)N3CCc4c(cccc4OC)C3)c3cc(Cl)ccc32)C1
InChIKey: QGKUIZBLZNWAAC-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Coupled Nucleotide Exchange Assay (20 hours): Purified GDP-bound KRAS protein (aa 1-169), containing both G12C and C118A amino acid substitutions and an N-terminal His-tag, was pre-incubated in assay buffer (25 mM HEPES pH 7.4, 10 mM MgCl2, and 0.01% Triton X-100) with a compound dose-response titration for 20 hours. Following compound pre-incubation, purified SOS protein (aa 564-1049) and GTP (Roche 10106399001) were added to the assay wells and incubated for an additional 30 min (for 5 min compound pre-incubation) or 1 hour (for 2 hour compound pre-incubation). To determine the extent of inhibition of SOS-mediated nucleotide exchange, purified GST-tagged cRAF (aa 1-149), nickel chelate AlphaLISA acceptor beads (PerkinElmer AL108R), and AlphaScreen glutathione donor beads (PerkinElmer 6765302) were added to the assay wells and incubated for 10 minutes. The assay plates were then read on a PerkinElmer EnVision Multilabel Reader, using AlphaScreen® technology, and data were analyzed using a 4-parameter logistic model to calculate IC50 values.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 521.02, ALogP 3.32, HBA 5, HBD 1, PSA 83.88, QED 0.51
Compound (SMILES): Cc1nn(C)c2c1Cc1cnc(N)c(c1)O[C@H](C)c1cc(F)ccc1C(=O)N(C)C2
InChIKey: UEPIXSNYZDRAQN-CYBMUJFWSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M (unknown origin)
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 409.47, ALogP 3.16, HBA 6, HBD 1, PSA 86.27, QED 0.62
Compound (SMILES): N#CN1CCC(NC(=O)c2ccc(N3CCC(Oc4ccccc4)CC3)nc2)C1
InChIKey: QDOUYTYLACIKAP-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity 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 0.001 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; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 391.48, ALogP 2.41, HBA 6, HBD 1, PSA 81.49, QED 0.79
Compound (SMILES): CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1c1ccc(OCCCCCN2CCCCC2)cc1
InChIKey: LEFLUEYSKFGASD-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Antagonist activity at human H4 receptor expressed in CHO-K1 cells co-expressing G protein alpha16 assessed as inhibition of histamine-induced calcium mobilization incubated for 16 hrs by aequorin-based functional assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 498.66, ALogP 5.08, HBA 7, HBD 1, PSA 77.1, QED 0.32
Compound (SMILES): CCOC(=O)Sc1cnc(NC(C)=O)s1
InChIKey: HKTJWTUXBUULTK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin)
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 246.31, ALogP 2.35, HBA 6, HBD 1, PSA 68.29, QED 0.65
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4cccc(NC(=O)C5CCNCC5)c4n3)nnc21
InChIKey: XUBFCYANDUSCNL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of N-terminal 6-His tagged human recombinant PIM3 using PIM tide (ARKRRRHPSGPPTA) as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 444.5, ALogP 2.11, HBA 9, HBD 2, PSA 109.57, QED 0.49
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)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](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)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](CO)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)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: RPQTZMUTFWXPIR-YGWUALCTSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.143 nM (pChEMBL 9.850000381469727)
Descriptors: MW 3824.26
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cnc(NCCO)nc3)c(O)c(F)c2Br)C1=O
InChIKey: CTENAOIBPBRRMN-XGICHPGQSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with mock Sendai virus and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 499.32, ALogP 2.73, HBA 9, HBD 3, PSA 124.88, QED 0.49
Compound (SMILES): Cc1ccc(-c2cccc(S(=O)(=O)c3cnc(CN)s3)c2)cc1.Cl
InChIKey: NQDDCXVLKJMNKC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in baculovirus infected BTI insect cells incubated for 1 hr by luminescence based assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 344.46, ALogP 3.41, HBA 5, HBD 1, PSA 73.05, QED 0.79
Compound (SMILES): CC1(c2cccc(Cl)c2)CCN(CCc2cnn(-c3nccc4c(=O)[nH]cnc34)c2)CC1
InChIKey: BPCMQRINPLMHHT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 448.96, ALogP 3.75, HBA 6, HBD 1, PSA 79.7, QED 0.5
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Cl)s4)ccc3o2)cc1
InChIKey: NOEOUVNROHOIIO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 95000 nM (pChEMBL 4.019999980926514)
Descriptors: MW 483.98, ALogP 4.38, HBA 7, HBD 2, PSA 118.37, QED 0.42
Compound (SMILES): Cc1cccnc1CNC(=O)c1csc(CCNCc2nc3ccccc3[nH]2)n1.Cl.Cl.Cl
InChIKey: CSNNZPQJMKBCMD-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 406.52, ALogP 2.99, HBA 6, HBD 3, PSA 95.59, QED 0.39
Compound (SMILES): O=C(CCCN1CCN(c2ccc(Cl)cn2)CC1)c1ccc(F)cc1
InChIKey: MXKZBMGRCYCKSV-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement [3H]-Pentazocine from sigma 1 receptor (unknown origin) expressed in HEK cell membranes
Measurement: Ki = 24.55 nM (pChEMBL 7.610000133514404)
Descriptors: MW 361.85, ALogP 3.66, HBA 4, HBD 0, PSA 36.44, QED 0.74
Compound (SMILES): Nc1ncc(N2CCN(c3cccc(-c4cncnc4)c3)CC2)c(N)n1
InChIKey: JYHQPYJPVMGKIX-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: TBD: TBD
Measurement: IC50 = 3090 nM (pChEMBL 5.510000228881836)
Descriptors: MW 348.41, ALogP 1.42, HBA 8, HBD 2, PSA 110.08, QED 0.73
Compound (SMILES): Cc1c(C(F)CN2CCN(CC(F)c3ccc4c(c3C)COC4=O)CC2)ccc2c1COC2=O
InChIKey: VYYGLESFPYPITB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [35S]MK-499 from human ERG
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 470.52, ALogP 3.98, HBA 6, HBD 0, PSA 59.08, QED 0.6
Compound (SMILES): CC(=O)N1CCN(c2ccc(CN3[C@@H](C)COC[C@H](c4ccccc4)S3(=O)=O)c(F)c2)CC1
InChIKey: LUFNTVBOMKDTDQ-MHECFPHRSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Inverse agonist activity at GAL4-fused human RORa expressed in HEK293 cells assessed as activation of basal transcriptional activity by dual-glo luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.59, ALogP 2.79, HBA 5, HBD 0, PSA 70.16, QED 0.68
Compound (SMILES): Cc1cc(-n2cc(C(=O)N3CCO[C@H](C)C3)c3ccc(O[C@H](C)c4ccc(F)cn4)nc32)[nH]n1
InChIKey: UTDAGOYVDYQGFI-HZPDHXFCSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human ALK expressed in HEK293 cells assessed as reduction in ALK autophosphorylation at Tyr1604 residue incubated for 60 mins by sandwich ELISA
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 464.5, ALogP 3.59, HBA 7, HBD 1, PSA 98.16, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2ccc(/N=C3\C(=O)N(Cc4ccccc4)c4ccc(Br)cc43)cc2)cc1
InChIKey: HCMURDGFGIQIRT-ZXPTYKNPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped flow CO2 hydration assay
Measurement: Ki = 41.2 nM (pChEMBL 7.380000114440918)
Descriptors: MW 604.49, ALogP 5.41, HBA 5, HBD 3, PSA 133.96, QED 0.27
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN3Cc2ccccc2Br)n(C)c1=O
InChIKey: PABAXIXJXJGVMS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB603 from recombinant human adenosine A2b receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 390.24, ALogP 1.22, HBA 7, HBD 0, PSA 65.06, QED 0.66
Compound (SMILES): Cc1cccc(-c2ccc3c(c2)CCNC3=O)c1
InChIKey: VWRQKYYMULSAJC-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 237.3, ALogP 2.95, HBA 1, HBD 1, PSA 29.1, QED 0.81
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@H]1CCC(=O)NC[C@@H](C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)CC)CCC(=O)NC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(N)=O)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: MHVNLICAQPKHCJ-CACADROISA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of (sCy5)-[Lys2 Arg4]-BVD15 from GFP-tagged Y4R in human HEK293T cells assessed as inhibitory constant incubated for 5 mins followed by (sCy5)-[Lys2 Arg4]-BVD15 addition and measured after 30 mins by fluorescence based assay
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 2260.69
Compound (SMILES): CCOC(=O)c1ccc(Nc2ccnc(SCC(=O)c3ccc(C#N)cc3)n2)cc1
InChIKey: DLNAZINCLYSSMT-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of PDGFR beta (unknown origin)
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 418.48, ALogP 4.24, HBA 8, HBD 1, PSA 104.97, QED 0.25
Compound (SMILES): Cc1c(C(=O)N2CCC(C(O)(C(F)(F)F)C(F)(F)F)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: QRXQHWCLMSCGIN-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 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 492.38, ALogP 2.22, HBA 7, HBD 2, PSA 108.52, QED 0.55
Compound (SMILES): CCCN(CCC/C=C/c1ccc(O)c(OC)c1)[C@H]1CCc2nc(N)sc2C1
InChIKey: DCTJWNXQZKKVMP-UABRLCRWSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human D2 dopamine receptor expressed in CHO cells by [35S]GTPgammaS binding assay
Measurement: EC50 = 37.7 nM (pChEMBL 7.420000076293945)
Descriptors: MW 401.58, ALogP 4.5, HBA 6, HBD 2, PSA 71.61, QED 0.61
Compound (SMILES): CNC(=O)C[C@H]1COc2cc(Br)ccc2N1C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: POJKNBHEJAUGMR-ZDUSSCGKSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Binding affinity to recombinant human GR LBD by fluormone GS red-fluorescence polarization assay
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 460.28, ALogP 2.32, HBA 5, HBD 2, PSA 96.97, QED 0.73
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)NCP(=O)(O)O)cc2)n1)[C@@H](CC)N(O)C=O
InChIKey: MSVVUMAOMLTMTH-NFBKMPQASA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 577.58, ALogP 2.24, HBA 7, HBD 6, PSA 198.26, QED 0.04
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc(CN5CCN(C(=O)C6CCC6)CC5)ccn4)[nH]c3c2)n1
InChIKey: LSYVMTFICMPMTL-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 433 nM (pChEMBL 6.360000133514404)
Descriptors: MW 472.55, ALogP 3.5, HBA 8, HBD 2, PSA 116.07, QED 0.44
Compound (SMILES): O=C1N(c2ccc(-c3ccccc3)cc2)C(=O)C2(CCN(Cc3cccs3)CC2)N1c1ncccn1
InChIKey: CBTFGYCZFGWWPE-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of KDM4A (unknown origin) using H3 K9Me3 (1 to 15 residues) as substrate
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 495.61, ALogP 5.21, HBA 6, HBD 0, PSA 69.64, QED 0.36
Compound (SMILES): Cc1cc(C)n(-c2cccc([C@H](CC(=O)[O-])C[N@+]3(C)CC[C@@H](CCc4ccc5c(n4)NCCC5)C3)c2)n1
InChIKey: BXOSGYRJKCYDLH-UYMYSODTSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphavbeta3 (unknown origin) expressed in human K562 cells assessed as reduction in cell adhesion to GST-LAP1 (242 to 252 amino acids) incubated for 30 mins by fluorescent probe BCECF-AM based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 501.68, ALogP 3.57, HBA 6, HBD 1, PSA 82.87, QED 0.45
Compound (SMILES): N#CN1C[C@H]2CCN(C(=O)c3ccc(F)c(-c4ccncc4)c3)[C@H]2C1
InChIKey: OUGVBBDEQQIAEA-QAPCUYQASA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 336.37, ALogP 2.52, HBA 4, HBD 0, PSA 60.23, QED 0.79
Compound (SMILES): Cc1cc(C)c2c(N)c(C(=O)c3ccc(F)c(Cl)c3)sc2n1
InChIKey: VTNAPSAGJDJIOU-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 334.8, ALogP 4.52, HBA 4, HBD 1, PSA 55.98, QED 0.7
Compound (SMILES): CN(C)CCNc1nc(/C=C/c2ccc(S(C)(=O)=O)cc2)nc2ccc(Cl)cc12
InChIKey: FDFNIDALAFPZPM-IZZDOVSWSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 D835Y (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 430.96, ALogP 3.83, HBA 6, HBD 1, PSA 75.19, QED 0.61
Compound (SMILES): O=C(NC1CCc2cccnc21)c1csc(CCNCCc2nc3ccccc3[nH]2)n1
InChIKey: QJYQJKVPTOYDFZ-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 432.55, ALogP 3.21, HBA 6, HBD 3, PSA 95.59, QED 0.37
Compound (SMILES): COc1cccnc1CNC(=O)c1csc(CCNCc2nc3ccccc3[nH]2)n1
InChIKey: PXKVPDXVGUNFMG-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 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 422.51, ALogP 2.69, HBA 7, HBD 3, PSA 104.82, QED 0.36
Compound (SMILES): CO[C@@H](C(=O)Nc1nnc(N[C@@H]2CCN(c3cccnn3)C2)s1)c1ccccc1
InChIKey: KLQLQDLJJUAEGT-GDBMZVCRSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: GLS Enzyme Potency Assay: A Glutamate Oxidase/AmplexRed coupled assay was used to measure the ability of compounds to bind to and inhibit the activity of GLS1 in vitro. 6His tagged GLS protein (amino acids 63-669) expressed in E. Coli was purified and stored at −80° C. in aliquots. GLS1 was diluted to 2× working concentration and incubated at r.t. to allow the tetrameric/dimeric forms to reach steady state. Assay measurements were performed in buffer comprising 50 mM TRIS pH 7.8, 100 mM NaPO4, pH 7.8, 0.001% v/v Tween20. Purified recombinant GLS1 protein was diluted in assay buffer to 12 nM and pre-incubated at r.t. for 30 minutes. Test compounds were prepared by dilution in 100% DMSO to give the correct dose range for 12 point concentration response and an appropriate volume (2.5-60 nl) dispensed into 384 well micro assay plates (Greiner product code 784900) using a Labcyte Echo 555 acoustic dispenser. DMSO concentration was maintained at 2% by back filling with DMSO solution. 3 μL of diluted GLS1 protein (12 nM) was then dispensed into each well using a BioRaptr automated dispenser (Beckman-Coulter) and incubated for 15 minutes at r.t. 3 μL of 100 mM glutamine diluted in assay buffer was then added and the reaction incubated at r.t. for 60 minutes. The reaction was then stopped by addition of 45 μM 6-(2-bromoethynyl)-2,3-dimethyl-quinazolin-4-one, 75 μM Amplex Red, 0.375 units/mL Horseradish Peroxidase, 0.12 units/mL Glutamate Oxidase in 100 mM TRIS pH7.5. After 30 minutes at room temp in the dark, plates were read on a Perkin Elmer EnVision using 535/590 nm optic filters and raw data analysed using Genedata to generate IC50 values. An artefact version of the assay where the 6His tagged GLS protein and glutamine were replaced with assay buffer was also used to rule out non specific effects on the assay components.
Measurement: IC50 = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 411.49, ALogP 2.35, HBA 9, HBD 2, PSA 105.16, QED 0.61
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC4CCOCC4)c4ncnc(N)c34)ccc2n1
InChIKey: DLTOWLQGMKBWAV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 404.47, ALogP 3.45, HBA 8, HBD 1, PSA 100.97, QED 0.54
Compound (SMILES): N#Cc1ccc(Cn2c3c(c(O)c(C(=O)NCC(=O)O)c2=O)COCC3)c(F)c1
InChIKey: YJVGISWUWWGULL-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition of recombinant human HIF-PHD1 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 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 401.35, ALogP 0.5, HBA 7, HBD 3, PSA 141.65, QED 0.66
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3cc(F)c(C(=O)NCCN4CCOCC4)cc3OCCO)nc2N1C1CCCC1
InChIKey: NCCZKHZUPCPIOT-HSZRJFAPSA-N
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 366.3 nM (pChEMBL 6.440000057220459)
Descriptors: MW 585.68, ALogP 2.3, HBA 10, HBD 3, PSA 132.39, QED 0.36
Compound (SMILES): Nc1ccc(-c2cn(-c3ccc(C(=O)O)cc3)nn2)cc1
InChIKey: GOWLCEQWOYBWGX-UHFFFAOYSA-N
Target: ORF 73 (SINGLE PROTEIN), Human herpesvirus 8
UniProt: O40947
Assay: Inhibition of fluorescent labelled LBS3 DNA binding to human herpesvirus 8 C-terminal His-tagged LANA oligomerization deficient mutant DBD (1008 to 1146 residues) expressed in Escherichia coli BL21 (DE3) preincubated for 60 mins followed by fluorescent labelled LBS2 addition and measured after 90 mins by fluorescence polarization assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 280.29, ALogP 2.21, HBA 5, HBD 2, PSA 94.03, QED 0.72
Compound (SMILES): CC(=O)Nc1nc(C)c(-c2c(C)n(S(=O)(=O)c3ccccc3)c3ccccc23)[nH]1
InChIKey: BEEWYYBUVYXWGQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 408.48, ALogP 3.84, HBA 5, HBD 2, PSA 96.85, QED 0.54
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(S)O[C@H]4[C@@H](O)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: JJWOITPMMIENLI-NIKBJLPMSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype G230A/R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 690.48, ALogP -1.4, HBA 20, HBD 7, PSA 309.42, QED 0.09
Compound (SMILES): CCn1cncc1-c1c[nH]c2cc(F)ccc12
InChIKey: CHAJDPQKGNVBRW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H] LSD from human recombinant 5-HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 5888 nM (pChEMBL 5.230000019073486)
Descriptors: MW 229.26, ALogP 3.19, HBA 2, HBD 1, PSA 33.61, QED 0.72
Compound (SMILES): CC1(C)C(N)=Nc2cc(OCCCN3Cc4ccc(OCc5cn(CCC(=O)N6CCC(CCN7CCCC7)CC6)nn5)cc4C3)c(OCC3CC3)cc21
InChIKey: FUNYEINMYOUMKK-UHFFFAOYSA-N
Target: Spindlin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y657
Assay: Binding affinity to recombinant human His-tagged SPIN1 (49 to 262 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry
Measurement: Kd = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 738.98, ALogP 5.83, HBA 11, HBD 1, PSA 123.57, QED 0.17
Compound (SMILES): COc1ccc(C)cc1NC(=O)Nc1nnc(SCc2cc(=O)n3cccc(C)c3n2)s1
InChIKey: LAJAAZMLLWPYKV-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human full length TRKB expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 358.6 nM (pChEMBL 6.449999809265137)
Descriptors: MW 468.56, ALogP 4.11, HBA 9, HBD 2, PSA 110.51, QED 0.32
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NC2CCCCC2)c(Sc2ccccc2)cc1Cl
InChIKey: IGLDOHLJJIKASI-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 56 nM (pChEMBL 7.25)
Descriptors: MW 424.98, ALogP 4.2, HBA 4, HBD 2, PSA 89.26, QED 0.75
Compound (SMILES): COc1ccc(S(=O)(=O)n2cc3c(=O)oc4ccccc4c3n2)cc1
InChIKey: RXOJHCKBULWXOV-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 diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 18240 nM (pChEMBL 4.739999771118164)
Descriptors: MW 356.36, ALogP 2.39, HBA 7, HBD 0, PSA 91.4, QED 0.52
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@H](CN(Cc1ccc(-c2ccccn2)cc1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)OC(=O)[C@@H](N)Cc1ccccc1)C(C)(C)C
InChIKey: SVEGMNKHZVDHDG-BMYMHALSSA-N
Target: UDP-glucuronosyltransferase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22309
Assay: Inhibition of UGT1A1 in human liver microsomes using beta-estradiol as substrate preincubated for 5 mins followed by substrate addition and measured after 40 mins by LC-MS/MS analysis
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 852.05, ALogP 5.33, HBA 11, HBD 5, PSA 203.31, QED 0.05
Compound (SMILES): CCC(=O)Nc1ccc(Cc2ccccc2)cc1CNC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C.O=C(O)C(F)(F)F
InChIKey: VOEYLXRKOHJIJY-UQIIZPHYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa-type opioid receptor expressed in CHO cell membranes incubated for 1 hr in shaker by liquid scintillation counting method
Measurement: Ki = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 459.59, ALogP 4.13, HBA 4, HBD 4, PSA 104.45, QED 0.39
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)c(Cl)c(C)c1S(N)(=O)=O
InChIKey: QNNLWBCXVKKVRW-PGGKNCGUSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 483.38, ALogP 2.76, HBA 5, HBD 2, PSA 121.93, QED 0.5
Compound (SMILES): COc1ccc(-c2c(Nc3ccccn3)[nH]c3c(C4=CCCCC4)c(-c4ccccc4)nn3c2=O)cc1
InChIKey: HSVRUECLQUGTDS-UHFFFAOYSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Inhibition of OATP1B1 (unknown origin)
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 489.58, ALogP 6.46, HBA 6, HBD 2, PSA 84.31, QED 0.29
Compound (SMILES): CCn1c(SCc2ccc(/C=C/C(=O)Nc3ccccc3N)cc2)nc2cc(OC)ccc2c1=O
InChIKey: MUTSCGGZWZWVHL-NTCAYCPXSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant His-tagged HDAC6 expressed in baculovirus infected insect cells using FLUOR DE LYS SIRT1 as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence method
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 486.6, ALogP 4.95, HBA 7, HBD 2, PSA 99.24, QED 0.16
Compound (SMILES): COc1ccccc1/C=C/C(=O)c1ccc(OCCCCN2CCc3ccccc3C2)cc1O
InChIKey: NQFHMBDPSBUHPJ-NTCAYCPXSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using kynuramine as substrate incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 30100 nM (pChEMBL 4.519999980926514)
Descriptors: MW 457.57, ALogP 5.51, HBA 5, HBD 1, PSA 59, QED 0.25
Compound (SMILES): Nc1ncnc2c1c(CCc1ccccc1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: WEYQHDMGURKOGT-SCFUHWHPSA-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 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 450.48, ALogP -0.97, HBA 11, HBD 4, PSA 188.7, QED 0.35
Compound (SMILES): CC(=O)Nc1cccc(CCN2CCC3(CC2)CN(c2ccccc2)C(=O)C(C)O3)c1
InChIKey: GFMRIFXLIUPAFX-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-(+)-pentazocine from human sigma-1 receptor expressed in HEK293 membranes incubated for 120 mins by liquid scintillation counting method
Measurement: Ki = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 421.54, ALogP 3.47, HBA 4, HBD 1, PSA 61.88, QED 0.8
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCc2ccccc2)c(S(=O)(=O)C2CCCCC2)cc1Cl
InChIKey: ICDSIUVYLWJHJY-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 471, ALogP 3.02, HBA 5, HBD 2, PSA 123.4, QED 0.67
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(CC(=O)O)cc2)n1)[C@@H](CC)N(O)C=O
InChIKey: HKZWVYVISBVNTQ-NFBKMPQASA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 498.58, ALogP 3, HBA 6, HBD 4, PSA 148.93, QED 0.1
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(C(F)(F)F)c2)nc1N[C@H]1CC[C@H](O)CC1.O=C(O)/C=C/C(=O)O
InChIKey: WBQQSFLHICZFOW-OKULZBKHSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged human FLT3 cytoplasmic domain (564 to 993 amino acids) expressed in baculovirus expression system pre-incubated before peptide substrate and ATP addition and measured after 30 mins
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 604.72, ALogP 3.83, HBA 9, HBD 4, PSA 122.88, QED 0.36
Compound (SMILES): CC(=O)Nc1nc(-c2ccccc2)nc2oc(-c3ccc(Cl)cc3)nc12
InChIKey: JJHXIFYTZYNKJR-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Inhibition of rat striatal adenosine A2A receptor using [3H]MXS-2 measured after 30 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 364.79, ALogP 4.56, HBA 5, HBD 1, PSA 80.91, QED 0.58