lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCC(=O)CCCN1CCN(C(=O)Cc2c[nH]c3ccccc23)C(c2ncc(-c3ccc4ccccc4c3)[nH]2)C1
InChIKey: STCYKOADSAEWEK-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 533.68, ALogP 5.9, HBA 4, HBD 2, PSA 85.09, QED 0.25
Compound (SMILES): N/C(=N\O)c1cccc(/C=C/c2ccnc(-c3cc(F)ccc3O)c2)c1
InChIKey: AJXYGYQSEVLLRJ-SNAWJCMRSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 349.37, ALogP 3.86, HBA 4, HBD 3, PSA 91.73, QED 0.29
Compound (SMILES): O=c1c2cc(NS(=O)(=O)c3ccc([N+](=O)[O-])cc3)ccc2nc2n1CCc1c-2[nH]c2ccccc12
InChIKey: YDAQUJGTXJONTG-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butyrylthiocholine iodide as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 30 mins by Ellman's method
Measurement: IC50 = 16510 nM (pChEMBL 4.78000020980835)
Descriptors: MW 487.5, ALogP 3.81, HBA 7, HBD 2, PSA 139.99, QED 0.29
Compound (SMILES): COc1ncc(-c2cc3c(c(OC[C@H]4CN(C5COC5)CCO4)c2)COC3)cc1NS(C)(=O)=O
InChIKey: SSSURQNVDUYQTK-LJQANCHMSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110alpha/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 491.57, ALogP 1.64, HBA 9, HBD 1, PSA 108.45, QED 0.59
Compound (SMILES): NC(=O)c1cc(-c2ccccc2)cc2c(C3CCN(S(=O)(=O)CCCN4CCCC4)CC3)c[nH]c12
InChIKey: ROHVMXPLAXOWHS-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKKbeta in human CD14-positive monocytes assessed as reduction in LPS-stimulated TNFalpha secretion preincubated for 30 mins followed by LPS stimulation and measured after 24 hrs by Alpha screen assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 494.66, ALogP 3.93, HBA 4, HBD 2, PSA 99.5, QED 0.5
Compound (SMILES): CN1CCC2=C(C1)N(Cc1ccc(C(=O)NO)cc1)c1ccccc1S2
InChIKey: LUEVVNYYGUOJAL-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant N-terminal GST-tagged human HDAC6 expressed in baculovirus expression system using fluorogenic ZMAL as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 367.47, ALogP 3.47, HBA 5, HBD 2, PSA 55.81, QED 0.64
Compound (SMILES): CC(=O)/C=C/[C@H](CCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1cc(F)cc(F)c1
InChIKey: GEULOUADNQVKSL-SNVPWJSWSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human Cathepsin L assessed as inhibition constant using Cbz-Phe-Arg-AMC as substrate by fluorescence assay
Measurement: Ki = 14.8 nM (pChEMBL 7.829999923706055)
Descriptors: MW 490.55, ALogP 4.57, HBA 3, HBD 2, PSA 75.27, QED 0.39
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)NCCOCC(=O)N[C@H](CCCCN)C(N)=O)[C@@H](C)O)C(C)(C)S
InChIKey: NTUKUWPURDQSMB-LPNUFCQFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 1932.32
Compound (SMILES): CC(Cl)C(=O)Nc1c(C#N)cnn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: RLCSMEASWTXBRD-UHFFFAOYSA-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 = 108.3 nM (pChEMBL 6.960000038146973)
Descriptors: MW 353.79, ALogP 0.96, HBA 6, HBD 2, PSA 130.87, QED 0.79
Compound (SMILES): C[C@@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)C(=O)NC1CCOC1
InChIKey: PXAODIKTYVKVME-NFJWQWPMSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of recombinant human PDE9A2 catalytic domain (181 to 506 residues) expressed in Escherichia coli BL21 using 3H-cGMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 360.42, ALogP 0.94, HBA 7, HBD 3, PSA 113.93, QED 0.73
Compound (SMILES): COc1ncc(-c2ccc3ccncc3c2)cc1NS(C)(=O)=O
InChIKey: GHSMJMXULNPLLA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin)
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 329.38, ALogP 2.68, HBA 5, HBD 1, PSA 81.18, QED 0.8
Compound (SMILES): O=C(Nc1nccs1)C1CCN(Cc2ccccc2)CC1
InChIKey: IGLSOIZXSPXUHP-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AChE using acetylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 51100 nM (pChEMBL 4.289999961853027)
Descriptors: MW 301.42, ALogP 2.99, HBA 4, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): N#Cc1ccccc1/C=N/Nc1nc(N)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1
InChIKey: ORLWPRGZVCSJEU-LKCJKRFLSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]CGS21680 from human cloned adenosine receptor A2A expressed in HEK-293 cell membrane incubated for 60 mins by microbeta counting method
Measurement: Ki = 1306 nM (pChEMBL 5.880000114440918)
Descriptors: MW 410.39, ALogP -0.66, HBA 12, HBD 5, PSA 187.72, QED 0.27
Compound (SMILES): CCN1CCN(c2cnn(-c3ccc(S(N)(=O)=O)cc3)c(=O)c2)CC1
InChIKey: VEEDWNISCIZQOY-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 = 41.3 nM (pChEMBL 7.380000114440918)
Descriptors: MW 363.44, ALogP 0.02, HBA 7, HBD 1, PSA 101.53, QED 0.82
Compound (SMILES): N#CN1CCC(NS(=O)(=O)N2CCN(c3ccccc3)CC2)C1
InChIKey: QPXSOTQDCAFXPX-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 to 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 hr incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 335.43, ALogP 0.2, HBA 5, HBD 1, PSA 79.68, QED 0.8
Compound (SMILES): CCN(Cc1cccc(NC(C)=O)c1)C(=O)Cn1c2ccccc2c2ccccc21
InChIKey: CYGUEHBZWVZYPO-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Displacement of [3H]PK11195 from human TSPO A147T mutant expressed in HEK293 cell membranes after 90 mins by scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 399.49, ALogP 4.8, HBA 3, HBD 1, PSA 54.34, QED 0.51
Compound (SMILES): CCCN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2cc(Cl)ccc21
InChIKey: NFHPILICJCHGBZ-PGMHBOJBSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 48.9 nM (pChEMBL 7.309999942779541)
Descriptors: MW 392.87, ALogP 2.56, HBA 5, HBD 2, PSA 104.86, QED 0.76
Compound (SMILES): Cc1c(N2CCN(Cc3cccc([N+](=O)[O-])c3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: NAGZEMJCNODDCR-NDEPHWFRSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity against human GnRH receptor expressed in HEK293 cells co-transfected with pGL4-NFAT promoter AP1-luc assessed as inhibition of 20 nM GnRH-induced NFAT activation pre-incubated for 1 hr before GnRH stimulation and measured after 6 hrs by luciferase reporter gene assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 640.64, ALogP 4.46, HBA 9, HBD 1, PSA 119.64, QED 0.16
Compound (SMILES): NS(=O)(=O)c1ccc(C[Te]c2ccccc2)cc1
InChIKey: IADBBIVGFJVNCF-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 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 374.92
Compound (SMILES): CC(=O)N[C@@H](C)C(=O)N[C@@H](CO)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](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](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)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: HFKRRUJCHMMMDK-XZOLBATGSA-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 = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 3717.28
Compound (SMILES): O=C1NC(=S)N/C1=C/c1ccc(-c2ccc(Cl)c(Cl)c2)o1
InChIKey: FYXULBBAJZXNDR-IZZDOVSWSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human GSK-3beta H350L mutant (2 to end residues) at 10 uM using phospho GS2 peptide as substrate after 40 mins by [gamma-33ATP] radiometric assay
Measurement: IC50 = 678 nM (pChEMBL 6.170000076293945)
Descriptors: MW 339.2, ALogP 3.6, HBA 3, HBD 2, PSA 54.27, QED 0.65
Compound (SMILES): O=[N+]([O-])c1cccc(C2C=C(c3cccc4ccccc34)Nc3nncn32)c1
InChIKey: UYUDNALWNUOOCC-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by Ellman method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 369.38, ALogP 4.4, HBA 6, HBD 1, PSA 85.88, QED 0.43
Compound (SMILES): CC(C)(COCCO)Nc1nc(-c2ccncc2)nc2cnccc12
InChIKey: JVCDXTHYVYGMQC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase LATS2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRM7
Assay: Inhibition of human LATS2 kinase domain (553 to 1088 amino acids) incubated for 3 hrs in presence of FAM-KKLRRTLSVA-COOH by fluorescence detection based biochemical caliper assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 339.4, ALogP 2.29, HBA 7, HBD 2, PSA 93.05, QED 0.64
Compound (SMILES): CCCCCNC(=S)NCCCC[C@H](NC(=O)OCc1ccccc1)C(=O)Nc1cccc(O)c1
InChIKey: ONMGRNMRIWBDSB-QHCPKHFHSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant human N-terminal His6-tagged/SUMO-fused SIRT2 (38 to 356 residues) expressed in Escherichia coli BL21 assessed as reduction in deacetylase activity using acetylated H3K9 as substrate preincubated for 15 mins followed by substrate addition and measured after 6 mins by UV-HPLC analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 500.67, ALogP 4.45, HBA 5, HBD 5, PSA 111.72, QED 0.19
Compound (SMILES): COc1ccc(N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)CN2C(=O)Nc3ccccc3S2(=O)=O)cc1
InChIKey: QSPPXZFUUNLFGI-QFIPXVFZSA-N
Target: Structural capsid protein (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q76129
Assay: Binding affinity to HIV1 NL4-3 capsid protein hexamer by SPR analysis
Measurement: Kd = 1190 nM (pChEMBL 5.920000076293945)
Descriptors: MW 522.58, ALogP 2.62, HBA 6, HBD 2, PSA 125.12, QED 0.47
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)/C=C\c2ccccc2)CC1
InChIKey: OTFVYUFJLHHPBE-QXMHVHEDSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 306.41, ALogP 3.36, HBA 2, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): Cc1cc(CN2C(=O)c3ccc(Cl)cc3NC(=O)[C@H]2Cc2ccccn2)ccc1C(=O)Nc1ccc(F)cn1
InChIKey: VJYORFBDISGWGH-RUZDIDTESA-N
Target: Toxin A (SINGLE PROTEIN), Clostridioides difficile
UniProt: P16154
Assay: Inhibition of Clostridium difficile toxin A transfected in CHO cells assessed as reduction in caspase 3/7 activation pre-incubated for 1 hr before TcdA addition by luminescence based assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 543.99, ALogP 5.04, HBA 5, HBD 2, PSA 104.29, QED 0.35
Compound (SMILES): O=C(Nc1cccnc1)c1cc(C(=O)c2c(F)cccc2Br)c[nH]1
InChIKey: ATKCERYALDNMPL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of HA-tagged ERK5 (unknown origin) coexpressed with mutationally activated EGFP-MEK5D and Gal4-MEF2D in HEK293 cells assessed as reduction in MEF2 transcription by measuring luciferase signal after 20 hrs by luciferase reporter gene assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 388.2, ALogP 3.79, HBA 3, HBD 2, PSA 74.85, QED 0.67
Compound (SMILES): CC(C)(C)C(=O)N1N=CCC1c1ccc(S(C)(=O)=O)cc1
InChIKey: BNEBONHNRMQHEE-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 308.4, ALogP 2.4, HBA 4, HBD 0, PSA 66.81, QED 0.84
Compound (SMILES): Cn1cc(NC(=O)c2cccc(-c3ccc(C4CC4)nc3)n2)c(C(N)=O)n1
InChIKey: CGIKUWBEYOYGOY-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant N-terminal GST-tagged full-length IRAK4 in human THP1-XBlue cells assessed as decrease in NF-kappaB level preincubated for 1 hr followed by stimulation with LPS for 4 to 5 hrs measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 307 nM (pChEMBL 6.510000228881836)
Descriptors: MW 362.39, ALogP 2.11, HBA 6, HBD 2, PSA 115.79, QED 0.72
Compound (SMILES): CCCn1nc(C(=O)N(C)C)c2c1CCC(OCc1ccc(F)cc1)C2
InChIKey: HYBOJXGBVWSNGV-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-DTG from sigma2 receptor (unknown origin) after 120 mins in presence of sigma1 antagonist (+)-SKF10047 by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 359.45, ALogP 3.21, HBA 4, HBD 0, PSA 47.36, QED 0.8
Compound (SMILES): CCSC[C@H]1O[C@@H](n2cnc3c(NC(C4CCC4)C4CCC4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: AGGLMBTXRADTOW-HAXDFEGKSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Mus musculus
UniProt: Q60612
Assay: Displacement of [3H]N6-R-phenylisopropyladenosine from mouse A1A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 3.58 nM (pChEMBL 8.449999809265137)
Descriptors: MW 433.58, ALogP 2.58, HBA 9, HBD 3, PSA 105.32, QED 0.58
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC4CCCC4)cc3CCO)nc2N1C1CCCC1
InChIKey: CAVRDKDHKZOOIF-HSZRJFAPSA-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 = 36.04 nM (pChEMBL 7.440000057220459)
Descriptors: MW 506.65, ALogP 3.93, HBA 7, HBD 3, PSA 110.69, QED 0.5
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2cc3c4c(c2)OCc2cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]5)cc(c2-4)OC3)[nH]1)C(C)C
InChIKey: CZJLHTLISCSKPK-ACZARZSMSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.022 nM (pChEMBL 10.65999984741211)
Descriptors: MW 794.91, ALogP 6.01, HBA 10, HBD 4, PSA 193.1, QED 0.15
Compound (SMILES): O=C(OC1C[N+]2(CCCc3cccc(F)c3)CCC1CC2)C(O)(c1ccccc1)c1ccccc1.[Br-]
InChIKey: GSJPLQNLECTWHL-UHFFFAOYSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human M2R expressed in CHOK1 cell membranes incubated for 2 hrs by microbeta scintillation counting method
Measurement: Ki = 0.69 nM (pChEMBL 9.15999984741211)
Descriptors: MW 474.6, ALogP 4.85, HBA 3, HBD 1, PSA 46.53, QED 0.38
Compound (SMILES): Cc1ccccc1N1CCN(S(=O)(=O)CSCc2c(C)noc2C)CC1
InChIKey: FMUHNCJGLSRVDD-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 395.55, ALogP 2.94, HBA 6, HBD 0, PSA 66.65, QED 0.75
Compound (SMILES): CNCc1ccccc1-c1ccc(C(C)Nc2nc(C)nc3cnc(OCC4CCNC(=O)C4)cc23)s1
InChIKey: DKERQUUVPREQSA-UHFFFAOYSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: P01116
Assay: Inhibition of human N-terminal GST-tagged K-RasG12C mutant/human N-terminal His-tagged SOS1 preincubated for 2 mis followed by SOS1 addition and measured after 20 mins in presence of GDP-Dy647P1 by HTRF assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 516.67, ALogP 4.86, HBA 8, HBD 3, PSA 101.06, QED 0.29
Compound (SMILES): COc1cc2sc(C(=O)C[C@H](C)C(=O)O)cc2c(F)c1OC
InChIKey: TVIOSAYLLOAJIU-ZETCQYMHSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: STING Biochemical [3H]cGAMP Competition Assay: The individual compounds described in the Examples herein are defined as STING agonists by (i) binding to the STING protein as evidenced by a reduction in binding of tritiated cGAMP ligand to the STING protein by at least 20% at 20 uM (concentration of compound being tested) in a STING Biochemical 13H1-cGAMP Competition Assay and (ii) demonstrating interferon production with a 6% or greater induction of IFN-β secretion at 30 uM in the THP1 cell assay (where induction caused by cGAMP at 30 uM was set at 100%).The ability of compounds to bind STING is quantified by the ability to compete with tritiated cGAMP ligand for human STING receptor membrane using a radioactive filter-binding assay. The binding assay employs STING receptor obtained from Hi-Five cell membranes overexpressing full-length HAQ STING prepared in-house and tritiated cGAMP ligand also purified in-house.
Measurement: EC50 = 2081 nM (pChEMBL 5.679999828338623)
Descriptors: MW 326.35, ALogP 3.35, HBA 5, HBD 1, PSA 72.83, QED 0.82
Compound (SMILES): O=C(OC1C[N+]2(CCCCCc3ccccc3)CCC1CC2)C(O)(c1ccccc1)c1ccccc1.[Br-]
InChIKey: AFFIUYZBOODVTQ-UHFFFAOYSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human M2R expressed in CHOK1 cell membranes incubated for 2 hrs by microbeta scintillation counting method
Measurement: Ki = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 484.66, ALogP 5.49, HBA 3, HBD 1, PSA 46.53, QED 0.24
Compound (SMILES): Cc1nc(-c2ccccc2)sc1COc1ccc(OCC(=O)O)c(F)c1
InChIKey: JSCZYYKEOGVEBB-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in CHO cells by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 = 374 nM (pChEMBL 6.429999828338623)
Descriptors: MW 373.41, ALogP 4.3, HBA 5, HBD 1, PSA 68.65, QED 0.67
Compound (SMILES): O=C(Nc1ccc(Nc2ncnc3sc4c(c23)CCOC4)cc1)Nc1ccc(Cl)c(C(F)(F)F)c1
InChIKey: DVCZKXCJLLSBEI-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using poly(Glu-Tyr) at 4:1 ratio as substrate in presence of ATP incubated for 60 mins by ELISA
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 519.94, ALogP 6.82, HBA 6, HBD 3, PSA 88.17, QED 0.28
Compound (SMILES): C=CC(=O)Nc1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1C(=O)Nc1c(C)cc(Cl)cc1Cl
InChIKey: XCVYIHQGKOQMHU-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of recombinant human His-tagged full length SRC expressed in baculovirus expression system using tyrosine-2 peptide as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 631.57, ALogP 6.71, HBA 8, HBD 4, PSA 114.52, QED 0.15
Compound (SMILES): COc1ccc2nc(C)cc(N/N=C/c3ccc(O)cc3)c2c1
InChIKey: GVUUGFHWRRHAIW-YBFXNURJSA-N
Target: Ribosyldihydronicotinamide dehydrogenase [quinone] (SINGLE PROTEIN), Homo sapiens
UniProt: P16083
Assay: Inhibition of NQO2 in human SKOV3 cells assessed as reduction in cell viability in presence of 1 uM CB1954 and EPR incubated for 24 hrs measured after 72 hrs by MTT assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 307.35, ALogP 3.7, HBA 5, HBD 2, PSA 66.74, QED 0.57
Compound (SMILES): CSCC[C@@H]1NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CO)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: QYNISPUOKWBXTH-CKZLGHILSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 3421.1
Compound (SMILES): C[C@](O)(CN1CCc2ccc(F)cc21)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: HIABOGSWUZDUMS-IBGZPJMESA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Displacement of [3H]-mibolerone from recombinant wild-type GST-tagged androgen receptor LBD (unknown origin) after 16 hrs by scintillation counting analysis
Measurement: Ki = 273 nM (pChEMBL 6.559999942779541)
Descriptors: MW 407.37, ALogP 3.47, HBA 4, HBD 2, PSA 76.36, QED 0.76
Compound (SMILES): Nc1ncnc2c1c(SCc1ccnnc1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@@H]1F
InChIKey: VJULSRNDKGJSPC-AFCLKFOHSA-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
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 472.48, ALogP -0.69, HBA 13, HBD 3, PSA 194.25, QED 0.37
Compound (SMILES): O=C(NCc1ncccc1Cl)c1csc(C2CN(CCc3nc4ccccc4[nH]3)C2)n1
InChIKey: YYVHMSDPPLTAKT-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 = 3550 nM (pChEMBL 5.449999809265137)
Descriptors: MW 452.97, ALogP 3.64, HBA 6, HBD 2, PSA 86.8, QED 0.45
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c3c(cc(NCCN4CCN(C)CC4)nc13)C(=O)N2C
InChIKey: BZTKFLVEEALJFD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from recombinant human N-terminal His-tagged BRD4 BD2 (349 to 460 residues) expressed in Escherichia coli incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 1520 nM (pChEMBL 5.820000171661377)
Descriptors: MW 510.62, ALogP 2.29, HBA 8, HBD 2, PSA 107.11, QED 0.48
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)Cc1ccc(CNC(=N)N)cc1)C(N)=O
InChIKey: YJQOHQUKLHIWET-FKBYEOEOSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Inhibition of Zika virus unlinked NS2B-NS3 protease preincubated for 5 mins followed by benzoyl-nKRR-AMC addition and measured every 60 secs for 12 mins by fluorescence method
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 618.79, ALogP -2.33, HBA 8, HBD 12, PSA 306.23, QED 0.04
Compound (SMILES): Nc1ccc(-c2nc(N3CCOCC3)nc(N3CCN(C(=O)c4cc(Cc5n[nH]c(=O)c6ccccc56)ccc4F)CC3)n2)c(F)c1
InChIKey: AVOBSJNOVKNJNP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 1 hr by ADP-glo plus luminescence assay
Measurement: IC50 = 707.95 nM (pChEMBL 6.150000095367432)
Descriptors: MW 639.67, ALogP 3.03, HBA 10, HBD 2, PSA 146.46, QED 0.27
Compound (SMILES): O=S(=O)(c1ccc(CCCCC2CCCC2)cc1)C1C2CCC(N2)C1NCc1ccc2ccccc2c1
InChIKey: JRBAERUWXKCAOZ-UHFFFAOYSA-N
Target: Plasmepsin 4 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q17SB2
Assay: Inhibition of Plasmodium falciparum plasmepsin 4 using fluorescently labeled peptide substrate by fluorescence method
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 516.75, ALogP 6.18, HBA 4, HBD 2, PSA 58.2, QED 0.32
Compound (SMILES): O=[N+]([O-])c1ccc(CNc2ccc(-c3nc4ccccc4o3)cc2)cc1
InChIKey: ZGZVXBDBBVOAMQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate after 10 mins measured for every mins by Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 345.36, ALogP 5.02, HBA 5, HBD 1, PSA 81.2, QED 0.41
Compound (SMILES): Cc1cccc(CSc2nn([C@@H]3O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]3O)c3ncnc(N)c23)c1
InChIKey: PTNSQSVAPXXLEQ-XWXWGSFUSA-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
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 482.54, ALogP -0.15, HBA 12, HBD 4, PSA 188.7, QED 0.33
Compound (SMILES): N#CN1CC[C@@H](N2CCCN(c3cccc(N4CCOCC4)c3)S2(=O)=O)C1
InChIKey: KQVJIZOTYSEVMC-GOSISDBHSA-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 to 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 hr incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 391.5, ALogP 0.84, HBA 6, HBD 0, PSA 80.12, QED 0.71
Compound (SMILES): Cc1cc(Oc2nccc3occc23)ccc1-c1c(C)cnnc1C
InChIKey: WTTAMIBXPRNVCC-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay
Measurement: EC50 = 1.175 nM (pChEMBL 8.930000305175781)
Descriptors: MW 331.38, ALogP 5, HBA 5, HBD 0, PSA 61.04, QED 0.53
Compound (SMILES): CCCN(CC)[C@H](c1ccccn1)[C@@H](c1ccccn1)N(CC)CCC
InChIKey: QEOUREZPAIWERV-FGZHOGPDSA-N
Target: Potassium voltage-gated channel subfamily E member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15382
Assay: Inhibition of IKs (unknown origin)
Measurement: IC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 354.54, ALogP 4.72, HBA 4, HBD 0, PSA 32.26, QED 0.58
Compound (SMILES): O=C(Nc1cc(-c2[nH]c(SCc3ccccc3)nc2-c2ccc(F)cc2)ccn1)C1CCCC1
InChIKey: YRYHREVRGLXBSJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Competitive inhibition of human recombinant full length GSK3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate preincubated with enzyme for 10 mins followed by substrate and 25 uM ATP addition measured after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 663 nM (pChEMBL 6.179999828338623)
Descriptors: MW 472.59, ALogP 6.7, HBA 4, HBD 2, PSA 70.67, QED 0.29
Compound (SMILES): O=C(N1CCCC[C@@H]1Cc1ccccc1)n1cc(C(O)(c2ccc(F)cc2)c2ccc(F)cc2)nn1
InChIKey: QFWGNUHJRKVYAB-RUZDIDTESA-N
Target: Diacylglycerol lipase-alpha (SINGLE PROTEIN), Mus musculus
UniProt: Q6WQJ1
Assay: Inhibition of mouse DAGL-alpha expressed in HEK293T cell membranes assessed as inhibition constant pre-incubated for 20 mins before PNP-butyrate substrate addition and measured after 30 mins by surrogate substrate assay
Measurement: Ki = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 488.54, ALogP 4.91, HBA 5, HBD 1, PSA 71.25, QED 0.43
Compound (SMILES): CCn1nc(C)cc1C(=O)Nc1nc2cc(C(N)=O)ccc2n1CCCNC(=O)OCc1ccccc1
InChIKey: IJSHVJXGHLYOSD-UHFFFAOYSA-N
Target: Interferon regulatory factor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14653
Assay: Induction of IRF3 pathway in STING knockout human THP1 cells measured after 20 hrs by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 503.56, ALogP 3.23, HBA 8, HBD 3, PSA 146.16, QED 0.28
Compound (SMILES): Cc1nnc2ccc(C(=O)NC3CN(c4cc(Cl)ncc4Cl)C3)cc2c1C
InChIKey: XULUJYUVCVOHBY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31423
Assay: Positive allosteric modulation of rat M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization incubated with EC20 ACh for 140 secs and subsequent EC80 Ach addition further incubated for 120 secs by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 402.29, ALogP 3.57, HBA 5, HBD 1, PSA 71.01, QED 0.68
Compound (SMILES): CCOC(=O)/C=C/c1cc(O)c(O)c([N+](=O)[O-])c1
InChIKey: GDHIRLVANLHBTN-ONEGZZNKSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22734
Assay: Inhibition of S-COMT in Wistar rat liver assessed as metanephrine formation preincubated for 20 mins followed by addition of adrenaline as substrate and SAM measured after 5 mins by chromatographic analysis
Measurement: IC50 = 11.35 nM (pChEMBL 7.949999809265137)
Descriptors: MW 253.21, ALogP 1.58, HBA 6, HBD 2, PSA 109.9, QED 0.28
Compound (SMILES): CN1CCN(Cc2ccc3nc4n(c(=O)c3c2)-c2ccc(F)cc2C4=O)CC1
InChIKey: GJCZYPVNSMSOLT-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of C-terminal His6-tagged human IDO2 (14 to 420 residues) expressed in Escherichia coli BL21 (DE3) assessed as reduction in conversion of L-tryptophan to N-formyl kynurenine using L-tryptophan as substrate after 30 mins by methylene blue dye based microplate reader analysis
Measurement: IC50 = 18440 nM (pChEMBL 4.730000019073486)
Descriptors: MW 378.41, ALogP 1.82, HBA 6, HBD 0, PSA 58.44, QED 0.53
Compound (SMILES): Cn1cc(-c2ccc(C(=O)N[C@@H]3CCN(C#N)C3)cn2)cn1
InChIKey: QLKZFMMKSCFPSU-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 296.33, ALogP 0.77, HBA 6, HBD 1, PSA 86.84, QED 0.85
Compound (SMILES): CN(Cc1nc2ccccc2[nH]1)c1nc(-c2cccnc2)nc2ccccc12
InChIKey: YVYRTECTGBSHBB-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: High Throughput Screening (HTS) by Fluorescence Polarization (pH = 7.2): The enzyme in GCase enzyme activity buffer (25 μL/well) was added to a 384-well black plate. The fluorescent probe 3 (25 nL/well, 50 nM final concentration) was transferred to a 384-well black plate using a Labcyte Echo 550 Liquid Handler system. Compounds in DMSO stock solution (50 nL) were transferred to the plate. The plate was shaken at room temperature in dark for 20 min. The final concentration was 19.5 nM to 10 μM, 10 concentrations, 2 times dilution. The fluorescence polarization was measured in a Molecular Devices Analyst GT with Ex=535 nm and Em=580 nm, G Factor=1.05. To the recombinant wild type enzyme (22 μM, 95 μL, 1 equiv) in 0.1 M phosphate buffer (pH 7.2) was added 2,5-dioxopyrrolidin-1-yl 3-(2-(2-(4-(4-(2,4-dimethylpyrrolo [1,2-a]pyrimidine-8-carboxamido)phenyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)propanoate (4) in DMSO (0.89 mM, 5 μL, 2 equiv) in one portion, and was vortexed for 5 sec immediately. At indicated time points, the reaction solution (2 μL) was sampled and diluted (1:3125 dilution) into the assay buffer (50 mM citric acid, 176 mM K2HPO4, and 0.01% Tween-20 at pH 5.9). After 2 h the reaction solution was dialyzed three times with 0.1 M phosphate buffer (pH 7.2). The enzyme was adjusted to the same concentration and sampled for activity. The dilution solutions were assayed with three substrates, resorufin substrate, 4-MU substrate, and natural substrate using the methods described in the examples above without adding compounds.
Measurement: IC50 = 8910 nM (pChEMBL 5.050000190734863)
Descriptors: MW 366.43, ALogP 4.2, HBA 5, HBD 1, PSA 70.59, QED 0.52
Compound (SMILES): COc1cc(Cl)cc2cc(C(=O)N[C@H](C)c3ccc(C(=O)O)cc3)n(C)c12
InChIKey: PSODJMSNWQUOCO-LLVKDONJSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 250 uM NAD+ and PSAT1 by diaphorase based luminescence assay
Measurement: IC50 = 746 nM (pChEMBL 6.130000114440918)
Descriptors: MW 386.84, ALogP 4.03, HBA 4, HBD 2, PSA 80.56, QED 0.69
Compound (SMILES): COc1cc(OC)cc(-c2ccc3c(NC(=O)c4ccc(N5CCN(C)CC5)cc4)n[nH]c3n2)c1
InChIKey: CGYUQNOPKJQHHX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human VEGFR2 using poly (Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 548.4 nM (pChEMBL 6.260000228881836)
Descriptors: MW 472.55, ALogP 3.65, HBA 7, HBD 2, PSA 95.61, QED 0.44
Compound (SMILES): COc1ccc(C2(c3ccsc3)CC(O)=C(Sc3ccccc3Cl)C(=O)N2)cc1
InChIKey: MTLBGNNVWKKIGS-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 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 443.98, ALogP 5.74, HBA 5, HBD 2, PSA 58.56, QED 0.53
Compound (SMILES): Cc1cc(C)c(-c2cc(NC(=O)CSc3nnc4c(n3)[nH]c3ccccc34)n(-c3ccccc3)n2)cc1C
InChIKey: NOTFJSIATRPNAH-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp mediated multidrug resistance in human DU145-TxR cells overexpressing P-gp assessed as potentiation of paclitaxel-induced cytotoxicity by measuring paclitaxel IC50 at 5 uM after 48 hrs by MTT assay (Rvb = 2120 nM)
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 519.63, ALogP 6.01, HBA 7, HBD 2, PSA 101.38, QED 0.26
Compound (SMILES): CCC(C(=O)O)c1ccc2cc(OC)ccc2c1
InChIKey: LSDAHSHHKKHOKE-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52895
Assay: Inhibition of human recombinant AKR1C2 using S-tetralol as substrate assessed as reduction in NADP+-dependent S-tetralol oxidation preincubated for 10 mins followed by protein addition by fluorometric assay
Measurement: IC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 244.29, ALogP 3.43, HBA 2, HBD 1, PSA 46.53, QED 0.9
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@@H]2CSCC[C@H](NC(C)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc3c[nH]c4ccccc34)C(=O)N[C@@H](CCC(N)=O)C(=O)N2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N[C@@](C)(CCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)cc1
InChIKey: VHHZGQFQCJBRHX-XKGNXMRFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1591.77
Compound (SMILES): Cc1ccc(C(=O)Nc2nnc(-c3ccc4c(c3)CCCC4)o2)cc1
InChIKey: WADUBPFJLJLQRX-UHFFFAOYSA-N
Target: Adenylate cyclase type 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40145
Assay: Inhibition of human AC8 expressed in HEK293 cells assessed as decrease in A23187-stimulated cAMP accumulation preincubated for 30 mins followed by A23187 stimulation and measured after 1 hr by fluorescence assay
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 333.39, ALogP 4.18, HBA 4, HBD 1, PSA 68.02, QED 0.78
Compound (SMILES): CCCCCc1ccc(C#Cc2ccc(C(=O)N3C[C@H](O)C[C@H]3C(=O)NO)cc2)cc1
InChIKey: HMXFQXRHTFBPFX-PKTZIBPZSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence assay
Measurement: IC50 = 282 nM (pChEMBL 6.550000190734863)
Descriptors: MW 420.51, ALogP 2.9, HBA 4, HBD 3, PSA 89.87, QED 0.29
Compound (SMILES): CC(C)c1ccc(NC(=S)Nc2ccc(-c3nc4ccccc4o3)cc2)cc1
InChIKey: LEABSMDYTQSHFG-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electric eel AChE using acetylthiocholine iodide as substrate after 10 mins measured for every mins by Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 387.51, ALogP 6.43, HBA 3, HBD 2, PSA 50.09, QED 0.4
Compound (SMILES): CC(C)(CN)C(=O)N1N=CCC1c1ccccc1
InChIKey: GAJFODMYMGJOEB-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 245.33, ALogP 1.93, HBA 3, HBD 1, PSA 58.69, QED 0.88
Compound (SMILES): CO[C@H](C(=O)Nc1nnc(N[C@@H]2CCN(c3cccnn3)C2)s1)c1ccccc1
InChIKey: KLQLQDLJJUAEGT-ZBFHGGJFSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of GLS1 GAC isoform (unknown origin) using glutamine as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by amplex red staining-based horseradish peroxidase/glutamate oxidase coupled assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 411.49, ALogP 2.35, HBA 9, HBD 2, PSA 105.16, QED 0.61
Compound (SMILES): O=C(CN1CCOCC1)Nc1n[nH]c2ncccc12
InChIKey: RVWMNZMCXBRAGC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 261.29, ALogP 0.23, HBA 5, HBD 2, PSA 83.14, QED 0.83
Compound (SMILES): O=C(Oc1cccc(N2CCS(=O)(=O)CC2)c1)N1CCC(c2ccc(F)cc2)CC1
InChIKey: UKNIOGPEKIQXSP-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat recombinant His/GST-tagged FAAH expressed in Escherichia coli cells using AAMCA as substrate incubated for 15 mins followed by substrate addition and measured after every 20 mins for 4 hrs by fluorescence based assay
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 432.52, ALogP 3.44, HBA 5, HBD 0, PSA 66.92, QED 0.74
Compound (SMILES): CC(C)(C)n1nc(-c2ccc3scnc3c2)c(C(N)=O)c1N
InChIKey: PDZAPYOZOLWESW-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Inhibition of RIPK2 in MDP-stimulated human whole blood assessed as TNF-alpha level preincubated for 30 mins followed by MDP stimulation and measured after 6 hrs by immunoassay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 315.4, ALogP 2.6, HBA 6, HBD 2, PSA 99.82, QED 0.76
Compound (SMILES): CC(C)C(=O)C1=C(O)C(=O)N(c2ccc(-c3ccsc3)cc2)C1c1ccccc1OCC[S+](C)[O-]
InChIKey: WLLMHLXFTTYNGV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 509.65, ALogP 5.3, HBA 6, HBD 1, PSA 89.9, QED 0.4
Compound (SMILES): C[C@@](CCN1Cc2cc(C#CC#CC3CN(CCO)C3)cn2C1=O)(C(=O)NO)S(C)(=O)=O
InChIKey: PCBKVWPRZYCNFU-OAQYLSRUSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 462.53, ALogP -0.75, HBA 8, HBD 3, PSA 132.18, QED 0.28