lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2ccccc2C(=O)OC)o1
InChIKey: QZNUPBNMSWWTAF-MRXNPFEDSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 459.5, ALogP 2.58, HBA 7, HBD 3, PSA 138.18, QED 0.1
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1ccc(OP(=O)(O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: JVCLXDNXAUQCLR-ASNOGBRRSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay
Measurement: IC50 = 1.862 nM (pChEMBL 8.729999542236328)
Descriptors: MW 1823.01
Compound (SMILES): CCc1ccc(C(=O)Nc2cccc(C(F)(F)F)c2F)cc1-c1cc(C)cc(-c2cnc3cnccn23)c1
InChIKey: LQBSFUBGTMSCSY-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of recombinant human GST-tagged DDR2 cytoplasmic domain (427 to 855 residues) expressed in baculovirus expression system using Fluorescein-poly GAT as substrate incubated for 1 hr in presence of ATP by LanthaScreen Eu kinase assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 518.51, ALogP 7.34, HBA 4, HBD 1, PSA 59.29, QED 0.25
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCCCC(=O)CN(C)C
InChIKey: VDTSETQUTFVUDZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin)
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 530.4, ALogP 4.69, HBA 7, HBD 2, PSA 96.45, QED 0.27
Compound (SMILES): S=C1Sc2ccccc2C2=NCCN12
InChIKey: RBWKPQSLRCNQCK-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC2 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 220.32, ALogP 2.14, HBA 3, HBD 0, PSA 15.6, QED 0.62
Compound (SMILES): CN1CC/C=C/[C@H](OCCOCC(F)F)[C@@H]2CC[C@H]2CN2C[C@@]3(CCCc4cc(Cl)ccc43)COc3ccc(cc32)[C@@](O)(C(=O)NS(=O)(=O)N(C)C)CC1=O
InChIKey: PWAAOENXQJXVEE-RMOOEYGHSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of recombinant C-terminal His6x-tagged human Mcl-1 (171 to 327 residues) interaction with biotinylated human Bim (51 to 76 residues) incubated for 60 mins in presence of 5 nM biotin-Bim by HTRF assay
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 809.37, ALogP 4.42, HBA 9, HBD 2, PSA 137.95, QED 0.28
Compound (SMILES): NC1=N[C@H](CC(=O)O)CS1
InChIKey: ANCWBXJZUCHVHL-GSVOUGTGSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18507
Assay: Agonist activity at recombinant human GABA-A alpha5beta2gamma2S receptor transiently expressed in human tsA201 cells incubated for 30 mins and measured up to 90 secs by FMP dye based FLIPR membrane potential blue assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 160.2, ALogP -0.11, HBA 4, HBD 2, PSA 75.68, QED 0.59
Compound (SMILES): O=C(O)c1ccc2c(c1)CCCC(c1ccc(OC(F)(F)F)cc1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: KVZDTTJONYGOOD-MHZLTWQESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 241 nM (pChEMBL 6.619999885559082)
Descriptors: MW 569.6, ALogP 7.39, HBA 4, HBD 1, PSA 59, QED 0.27
Compound (SMILES): CCCCCc1[nH]c2nc(N)nn2c(=O)c1Cc1cccc(Cl)c1
InChIKey: WFQUTDBZBQIOGC-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method
Measurement: Ki = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 345.83, ALogP 2.98, HBA 5, HBD 2, PSA 89.07, QED 0.67
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4cccc(NC5CCCCC5)c4n3)nnc21
InChIKey: UVGKRGCBYGNVGI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of His tagged human recombinant PIM2 using PIM tide (ARKRRRHPSGPPTA) as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 3330 nM (pChEMBL 5.480000019073486)
Descriptors: MW 415.5, ALogP 3.91, HBA 8, HBD 1, PSA 80.47, QED 0.54
Compound (SMILES): CC(=O)S[C@H]1CC[C@H](c2cc(=O)c3ccc4ccccc4c3o2)CC1
InChIKey: FUWOOYFXEWDHNG-WKILWMFISA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of human recombinant CYP1A1 using 7-ethoxyresorufin as substrate after 15 mins in presence of NADPH by EROD assay
Measurement: IC50 = 15.9 nM (pChEMBL 7.800000190734863)
Descriptors: MW 352.46, ALogP 5.25, HBA 4, HBD 0, PSA 47.28, QED 0.59
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(C2CCN(S(=O)(=O)CCN(C)C)CC2)nc(N2CCOCC2)n1
InChIKey: VXJVZZVXASVKQD-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human N-terminal p110delta/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 580.66, ALogP 2.06, HBA 11, HBD 0, PSA 118.81, QED 0.37
Compound (SMILES): CCNC(=O)c1cc2c(-c3cc(S(=O)(=O)CC)ccc3Oc3c(C)cccc3C(F)(F)F)cn(C)c(=O)c2[nH]1
InChIKey: RNNIEDANKZEVPX-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 561.58, ALogP 5.2, HBA 6, HBD 2, PSA 110.26, QED 0.32
Compound (SMILES): COc1cc2c(cc1OC)CN(Cc1ccc(-c3ccc(OCCCOc4nonc4[S+]([O-])c4ccccc4)cc3)cc1)CC2
InChIKey: NQYXUEQNOKDVCE-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of MDR1 (unknown origin) expressed in MDCK cells assessed as decrease in calcein-AM transport after 30 mins by fluorescence assay
Measurement: EC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 625.75, ALogP 6.33, HBA 9, HBD 0, PSA 102.14, QED 0.11
Compound (SMILES): CNCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)O)C(C)C
InChIKey: NOJLLMGJALVLSM-NVKOMBKQSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1R expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 950.07, ALogP -2.99, HBA 13, HBD 14, PSA 383.73, QED 0.02
Compound (SMILES): Cc1cc(-c2ccc(NC(=O)N3CC[C@@H]4CN(C#N)C[C@@H]43)c(F)c2)ccn1
InChIKey: ORRROJOQVQBSPY-APWZRJJASA-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 365.41, ALogP 3.22, HBA 4, HBD 1, PSA 72.26, QED 0.83
Compound (SMILES): N#CC1=C(N)OC(c2ccc(Cl)cc2)=CC1c1cn(-c2ccccc2)nc1-c1ccc(OCc2ccccc2)cc1
InChIKey: NPOAKDNVUFRFCB-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX1 assessed as decrease in prostaglandin production using arachidonic acid as substrate pretreated for 15 mins followed by substrate addition and measured after 2 mins by enzyme immunoassay
Measurement: IC50 = 9680 nM (pChEMBL 5.010000228881836)
Descriptors: MW 557.05, ALogP 7.62, HBA 6, HBD 1, PSA 86.09, QED 0.22
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)c2sc(CN3CCCC3)cc2n1
InChIKey: QKSTXCOSRYSBHV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31421
Assay: Negative allosteric modulation of rat mGlu2R expressed in HEK293 cells co-expressing Galpha15 assessed as decrease in glutamate-induced calcium mobilization preincubated for 2.3 mins followed by glutamate addition and measured after 1.7 mins by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 6606.93 nM (pChEMBL 5.179999828338623)
Descriptors: MW 355.44, ALogP 3.8, HBA 4, HBD 1, PSA 59.22, QED 0.77
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2ccc(/N=C3\C(=O)N(Cc4cccc(F)c4)c4ccc(Cl)cc43)cc2)cc1
InChIKey: YIAGJBQUZMZVAD-FSRJSHLRSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 by stopped flow CO2 hydration assay
Measurement: Ki = 5095.8 nM (pChEMBL 5.289999961853027)
Descriptors: MW 578.03, ALogP 5.44, HBA 5, HBD 3, PSA 133.96, QED 0.28
Compound (SMILES): CN(C)c1ccc(C(=O)NCCNC(=O)c2ccc(-c3ccc4c(N)n[nH]c4c3)cc2)cc1
InChIKey: MRCMFAWPPPUHNS-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of BCR/ABL T315I mutant (unknown origin) measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 442.52, ALogP 3.04, HBA 5, HBD 4, PSA 116.14, QED 0.33
Compound (SMILES): O=C1CCc2cc(N3CC[C@](O)(C(=O)NCc4cccc(Cl)c4F)C3=O)ccc2N1
InChIKey: XCZMADNFSHXZKG-NRFANRHFSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of MetAP2 in HUVEC assessed as reduction in viability incubated for 3 days by CyQUANT Direct Cell proliferation assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 431.85, ALogP 2.15, HBA 4, HBD 3, PSA 98.74, QED 0.65
Compound (SMILES): c1cc(-c2nc(NC3CCCC3)c3ccncc3n2)ccn1
InChIKey: OCRGFIAWWYJUTP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase LATS1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95835
Assay: Inhibition of human LATS1 kinase domain (589 to 1130 amino acids) incubated for 3 hrs in presence of FAM-KKLRRTLSVA-COOH by fluorescence detection based biochemical caliper assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 291.36, ALogP 3.44, HBA 5, HBD 1, PSA 63.59, QED 0.8
Compound (SMILES): COc1cc(/C=C/c2nc3ccccc3n(CC(=O)NS(=O)(=O)C(F)(F)F)c2=O)ccc1O
InChIKey: SITSNQLXXVHJOV-SOFGYWHQSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of Wistar rat lens ALR2 using L-glyceraldehyde as substrate preincubated for 10 mins followed by substrate addition and measured for 4 mins by spectrophotometric method
Measurement: IC50 = 3274 nM (pChEMBL 5.489999771118164)
Descriptors: MW 483.42, ALogP 2.25, HBA 8, HBD 2, PSA 127.59, QED 0.55
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3ccc(CCCN4CCN(C)CC4)cc3)cc1C(Nc1ccc(Cl)cc1)CC2
InChIKey: AWRROGKYSWVYPQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human recombinant BRD4 BD2 (333 to 460 residues) by fluorescence polarization assay
Measurement: Ki = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 541.14, ALogP 6.18, HBA 6, HBD 1, PSA 49.22, QED 0.3
Compound (SMILES): COc1ccc2c(c1)C(Cc1ccc(C(=N)N)c(OCc3cccnc3)c1)OB2O.Cl
InChIKey: CZCQHLKWYANBTR-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of human recombinant N-terminal His-tagged and enterokinase cleavage site-fused KLK1 (19 to 262 residues) expressed in baculovirus infected Sf9 insect cells using R110 labelled GSK3162232A as substrate measured at 30 secs interval for 5 mins by FLINT assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 403.25
Compound (SMILES): CC(C)Sc1ncccc1CNc1ncc(C#N)c(NCC23CC4CC(C2)C(NC[C@H]2CC[C@H](O)CC2)C(C4)C3)n1
InChIKey: WUXGYBADOQHIAC-RJQVWWFHSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKCtheta in human Jurkat cells assessed as reduction in IL2 production after 14 hrs by luciferase reporter gene assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 575.83, ALogP 5.6, HBA 9, HBD 4, PSA 118.78, QED 0.25
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2cc1NC(=O)CCCCC1CCSS1
InChIKey: JHALKKQEOZXQLC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of probe binding to wild type EGFR (unknown origin) using rabbit reticulate lysate system after 1 hr by luminescence assay
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 651.23, ALogP 9.27, HBA 8, HBD 2, PSA 96.27, QED 0.11
Compound (SMILES): CCOc1ccc(-c2ccc(CCCc3nn(-c4ccc(SC)cc4)c(=O)n3-c3ccccc3F)cc2)cc1CC(=O)O
InChIKey: SWXIVACFIFNMSA-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Antagonist activity at recombinant human PPARalpha assessed as inhibition of GW7647-induced receptor activation after overnight incubation by cell-based luciferase reporter gene assay
Measurement: IC50 = 1240 nM (pChEMBL 5.909999847412109)
Descriptors: MW 597.71, ALogP 6.75, HBA 7, HBD 1, PSA 86.35, QED 0.16
Compound (SMILES): CCn1cccc(NCc2cc3cc(Cl)ccc3[nH]c2=O)c1=O
InChIKey: GWBZTYSDSZBEJE-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Cell Based Assays: The cellular potency of Compound 1 in suppressing intracellular 2-HG levels was determined in cell lines expressing five different mutated IDH-1 proteins found in human cancers (R132H, R132C, R132G, R132L, R132S). The human fibrosarcoma cell line HT-1080 harbors a naturally occurring heterozygous IDH-1 R132C mutation. The human colorectal carcinoma cell line HCT 116 is wild type for IDH-1, but heterozygous mutations coding for IDH-1 R132H or R132C were introduced by knock-in into the endogenous IDH-1 gene locus. Finally, the human astrocytoma cell line U-87 MG is also wild type for IDH-1, but expression of five different mutated IDH-1 proteins was achieved by stable transfection.The parental HCT 116 line (colon) line does not produce high levels of 2-HG, but the variants used herein (X-MAN HCT-116 lines obtained from Horizon Discovery Ltd.) are engineered to knock-in a heterozygous mutation of either IDH-1 R132H or IDH-1 R132C. This recapitulates the cellular context in mIDH-1 cancer cells where there are both wild type and mutant IDH-1 subunits that together form a heterodimer that is responsible for the production of elevated levels of 2-HG. These modified lines can be used as models of IDH-1 mutant disease.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.79, ALogP 2.98, HBA 4, HBD 2, PSA 66.89, QED 0.77
Compound (SMILES): O=C(O)c1ccc(C(=O)N2CCc3nc4n(c(=O)c3C2)CCCC4)cc1
InChIKey: JLUHGDBGYVYCNZ-UHFFFAOYSA-N
Target: C-1-tetrahydrofolate synthase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: P11586
Assay: Inhibition of recombinant MTHFD1 (unknown origin) assessed as reduction in methenyl-THF formation using tetrahydrofolate, NADP and formaldehyde incubated for 30 mins by NADP-dependent dehydrogenase assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 353.38, ALogP 1.48, HBA 5, HBD 1, PSA 92.5, QED 0.88
Compound (SMILES): Cc1cc(-c2ccccc2)c(O)c2c1C[C@@H](C)OC2=O
InChIKey: PDFVUCVNCYAJLJ-LLVKDONJSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB using kynuramine as substrate incubated for 10 mins by UPLC-ESI-MS/MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 268.31, ALogP 3.47, HBA 3, HBD 1, PSA 46.53, QED 0.81
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(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(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](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: BYEIOOLUVDZFJP-VFZHCUGZSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of TFPI in human plasma with induced factor-8 deficiency assessed as increase in thrombin generation by measuring FEIBA using thrombin-specific fluorogenic substrate Z-Gly-Gly-Arg-AMC by calibrated automated thrombography
Measurement: EC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 2871.51
Compound (SMILES): COc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1OC
InChIKey: PCZWTWBBTBZKBM-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from human adenosine A1 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 363.38, ALogP 2.15, HBA 8, HBD 1, PSA 96.67, QED 0.6
Compound (SMILES): CSC(=S)NCc1c[nH]c2ccc(Br)cc12
InChIKey: CSBVYUFFKAVSAH-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 expressed in COS1 cells assessed as reduction in N-formyl-kynurenine level incubated for 16 hrs
Measurement: EC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 315.26, ALogP 3.67, HBA 2, HBD 2, PSA 27.82, QED 0.83
Compound (SMILES): COc1ccc(NC(=O)c2ccc3c(c2)C(=O)N(Cc2ccc(S(N)(=O)=O)cc2)C3=O)c(C(=O)O)c1
InChIKey: XCFBYGHTZLADMA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 509.5, ALogP 2.09, HBA 7, HBD 3, PSA 173.17, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2nc(Nc3ccc(S(N)(=O)=O)cc3)nc(N3CCCCC3)n2)cc1
InChIKey: BHDYGFBXVITGOY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 28.4 nM (pChEMBL 7.550000190734863)
Descriptors: MW 547.62, ALogP 1.54, HBA 10, HBD 5, PSA 215.39, QED 0.29
Compound (SMILES): COc1ccc(NC(=O)c2ccc3c(c2)C(=O)N(CCc2ccccc2)C3=O)c(C(=O)O)c1
InChIKey: QOEMLNKQEKLJQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 444.44, ALogP 3.48, HBA 5, HBD 2, PSA 113.01, QED 0.54
Compound (SMILES): N#Cc1ccc(S(=O)(=O)N2C[C@H](S(=O)(=O)c3ccc(Cl)cn3)[C@](O)(CN)C2)c(Cl)c1
InChIKey: WLVZWRUVPREQAW-RDJZCZTQSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Reversible inhibition of CYP3A4 (unknown origin) in presence of NADPH by vivid red substrate-based assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 491.38, ALogP 0.8, HBA 8, HBD 2, PSA 154.45, QED 0.62
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Cl)s4)ccc3o2)cc1)c1ccc(F)c(C(F)(F)F)c1
InChIKey: HJOPZBCZBRUBTD-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTPN1 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 632.04, ALogP 6.97, HBA 7, HBD 2, PSA 118.37, QED 0.19
Compound (SMILES): c1cc(CNc2ccn3ncc(-c4ccc5c(c4)OCO5)c3n2)ccn1
InChIKey: DJMJVMXMRFYVLC-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET V804M mutant (unknown origin)expressed in human BaF3 cells assessed as reduction in cell viability incubated for 48 hrs by celltiter glo luminescence cell viability assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 345.36, ALogP 3.13, HBA 7, HBD 1, PSA 73.57, QED 0.61
Compound (SMILES): Cc1c(C(=O)N2CCC(C(F)(F)F)CC2)cnn1-c1nc2c(c(=O)[nH]1)CC2
InChIKey: FVTQRPXFLXGOIJ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 381.36, ALogP 1.78, HBA 5, HBD 1, PSA 83.88, QED 0.86
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O)C(C)C
InChIKey: FTKVMQSYQHWAOE-XUJYPJAKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 746.65, ALogP 0.67, HBA 6, HBD 7, PSA 212.6, QED 0.06
Compound (SMILES): O=[N+]([O-])c1ccc(Nn2cnnc2)cc1Br
InChIKey: NKVMADUKKQVLFZ-UHFFFAOYSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of recombinant human aromatase using 7-methoxy-trifluoromethylcoumarin as substrate incubated for 30 mins by fluorescence microplate reader analysis
Measurement: IC50 = 90.78 nM (pChEMBL 7.039999961853027)
Descriptors: MW 284.07, ALogP 1.82, HBA 6, HBD 1, PSA 85.88, QED 0.69
Compound (SMILES): Cc1ccc(-c2cc(-c3cccc(NC(=O)c4ccc5ccccc5n4)c3)[nH]n2)cc1
InChIKey: YLAXDJIMXGQCDI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant (unknown origin)
Measurement: IC50 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 404.47, ALogP 5.85, HBA 3, HBD 2, PSA 70.67, QED 0.39
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3ccc(F)c(C(F)F)c3)cc21
InChIKey: DNBUFJYOCPLTQY-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Negative allosteric modulation of recombinant human GluN1a/GluN2B expressed in CHO-T-REx cells assessed as inhibition of glutamate/glycine-induced response preincubated for 5 mins followed by glutamate/glycine addition and measured after 5 mins by calcium 5 dye based FLIPR TETRA analysis
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 347.34, ALogP 3.87, HBA 3, HBD 0, PSA 38.13, QED 0.72
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@@H](C)c3cc(F)c(N4CC5CCC(C4)N5)cc3F)sc2n1
InChIKey: KISMBELUPLJYMH-LRVUVFPRSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 471.58, ALogP 3.94, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): CC/C=N/c1c(C#N)c2n(c1C(=O)Nc1ccccc1)CCCC2
InChIKey: WFUZFBZSOJKKFQ-SRZZPIQSSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 2 mins by ELISA method
Measurement: IC50 = 7140 nM (pChEMBL 5.150000095367432)
Descriptors: MW 320.4, ALogP 4.06, HBA 4, HBD 1, PSA 70.18, QED 0.86
Compound (SMILES): CN(Cc1ccc2c(c1)OCCO2)c1nc(-c2cccnc2)nc2ccccc12
InChIKey: QONSZJAECYJUQF-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 = 3980 nM (pChEMBL 5.400000095367432)
Descriptors: MW 384.44, ALogP 4.1, HBA 6, HBD 0, PSA 60.37, QED 0.53
Compound (SMILES): COc1ccc(CCc2nc(CCC(=O)NO)cs2)cc1
InChIKey: PQAMMSYSGJYGIP-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using fluorogenic HDAC substrate 3 pre-incubated for 30 mins followed by HDAC developer addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 83.71 nM (pChEMBL 7.079999923706055)
Descriptors: MW 306.39, ALogP 2.37, HBA 5, HBD 2, PSA 71.45, QED 0.61
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCC(O)(c3ccccc3)CC2)cc1
InChIKey: XEMCUUOBNNOBLG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant full length human carbonic anhydrase-2 assessed as reduction in CO2 hydration after 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 360.44, ALogP 1.46, HBA 4, HBD 2, PSA 100.7, QED 0.87
Compound (SMILES): CC(C)Cc1noc(-c2ccc3nc(Nc4cc(CN5CCN(C(=O)CC(F)(F)F)CC5)ccn4)[nH]c3c2)n1
InChIKey: UDQFLASTRAMKLW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of recombinant full length human N-terminal His-tagged TBK1 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 1 mM of ATP by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 542.57, ALogP 4.55, HBA 8, HBD 2, PSA 116.07, QED 0.33
Compound (SMILES): Cc1cc(-c2nc3ccccc3n2CCC2CCOCC2)cn(C)c1=O
InChIKey: GJFMDYJSPKGTHH-UHFFFAOYSA-N
Target: Bromodomain adjacent to zinc finger domain protein 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIF9
Assay: Inhibition of BAZ2A (unknown origin) by TR-FRET assay
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 351.45, ALogP 3.53, HBA 5, HBD 0, PSA 49.05, QED 0.72
Compound (SMILES): COc1ccc2c(c1)C[C@@H](C(=O)Nc1ccc(-c3ccncc3)cc1OCCN(C)C)CO2
InChIKey: MGSFSBWPBXVAEQ-OAQYLSRUSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin) using STK2 as substrate measured after 4 hrs by HTRF assay
Measurement: IC50 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 447.54, ALogP 3.89, HBA 6, HBD 1, PSA 72.92, QED 0.56
Compound (SMILES): Cc1c(C(=O)N2CC(c3ccc(F)cn3)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: AAWFOYRQYWEGEC-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 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 393.38, ALogP 1.29, HBA 7, HBD 1, PSA 101.18, QED 0.57
Compound (SMILES): Cc1cc(C)cc(Cn2cc(-c3ccc(C)c(C(=O)NCCN4CCOCC4)c3)nn2)c1
InChIKey: WEDFGVTXHPXYPZ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE preincubated for 6 mins followed by addition of S-butyrylthiocholine iodide by Ellman's method
Measurement: IC50 = 56230 nM (pChEMBL 4.25)
Descriptors: MW 433.56, ALogP 2.98, HBA 6, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3ccc(S(=O)(=O)N4CCN(c5ccc(Cl)cc5)CC4)cc3)nc2n(CC)c1=O
InChIKey: XLLICFZBPTYQNU-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX-2 from recombinant human A2A adenosine receptor expressed in CHO cell membranes measured after 30 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 322 nM (pChEMBL 6.489999771118164)
Descriptors: MW 557.08, ALogP 3.15, HBA 8, HBD 1, PSA 113.3, QED 0.37
Compound (SMILES): Cc1c(C(=O)N2CCN(C3CC(F)(F)C3)CC2)nnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: OTAKMBRMGDXZPK-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 418.41, ALogP 0.47, HBA 8, HBD 1, PSA 104.42, QED 0.66
Compound (SMILES): N#CN1CC[C@@H](NC(=O)N2CCN(c3ccccc3)CC2)C1
InChIKey: CHHJEBCRMKCLNQ-CQSZACIVSA-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 299.38, ALogP 1.07, HBA 4, HBD 1, PSA 62.61, QED 0.83
Compound (SMILES): COC(=O)c1ccc(CSc2nc(N)c(C#N)c(-c3ccco3)c2C#N)o1
InChIKey: IYHVFAWVQMTRPT-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human A2B expressed in CHO cells assessed as stimulation of cAMP production by alphascreen assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 380.39, ALogP 3.34, HBA 9, HBD 1, PSA 139.07, QED 0.52
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCc2cn(CCc3ccc(Br)cc3)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: FWJCUXNYXSSZSU-RBZQAINGSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Memphis/1/1971(H3N2))
UniProt: P03471
Assay: Inhibition of Influenza A virus (A/Chicken/Hebei/LZF/2014(H5N2)) Neuraminidase N2 preincubated for 10 mins followed by MUNANA substrate addition and measured after 40 mins by fluorescence method
Measurement: IC50 = 4540 nM (pChEMBL 5.340000152587891)
Descriptors: MW 547.5, ALogP 2.64, HBA 7, HBD 3, PSA 124.16, QED 0.4
Compound (SMILES): Nc1c(C(O)c2ccncc2)sc2nc(OCc3ccncc3)c3c(c12)CCC3
InChIKey: ANNRDPJKNDKBJH-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 404.5, ALogP 3.82, HBA 7, HBD 2, PSA 94.15, QED 0.53
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)c2ccc(-c3ccncn3)cc2N2CC[C@H](CN)C2)c1
InChIKey: PKLARINHGWEPSR-QZTJIDSGSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of GST-fused human recombinant ROCK2 (11 to 552 residues) expressed in Spodoptera frugiperda insect cells using STK S2 peptide substrate and 33P-ATP after 60 mins by HTRF assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 431.54, ALogP 3.43, HBA 6, HBD 2, PSA 93.37, QED 0.6
Compound (SMILES): N=C(CCl)NCCCc1cn(-c2cccc(-c3ccccc3)c2)nn1
InChIKey: KKRHFNFLOSUOPU-UHFFFAOYSA-N
Target: Protein-arginine deiminase type-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM07
Assay: Inhibition of recombinant human GST-tagged PAD4 expressed in Escherichia coli BL21-DE3 pLysS assessed as reduction in reduction in residual activity preincubated for 15 mins followed by addition of N-benzoylated arginine ethyl ester hydrochloride measured after 15 mins by colder assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 353.86, ALogP 3.67, HBA 4, HBD 2, PSA 66.59, QED 0.29
Compound (SMILES): CC(=O)C1=C(O)C(=O)N(c2ccc(C)cc2)C1c1cccc(Cl)c1
InChIKey: QBFPLWKBLBQKTJ-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of [3H]-CCR2-RA-[R] from human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor after 120 mins by scintillation spectrometry
Measurement: Ki = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 341.79, ALogP 4.14, HBA 3, HBD 1, PSA 57.61, QED 0.91
Compound (SMILES): Cc1cccc(/C=C/C2=NN(c3ccc(F)cc3)C(=O)CC2)c1
InChIKey: AEOWNQLDGCXORX-VMPITWQZSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 assessed as reduction in PGF2alpha production using arachidonic acid as substrate preincubated with enzyme for 10 mins followed by substrate addition by ELISA
Measurement: IC50 = 52.34 nM (pChEMBL 7.28000020980835)
Descriptors: MW 308.36, ALogP 4.33, HBA 2, HBD 0, PSA 32.67, QED 0.83
Compound (SMILES): CC(=O)OC[C@@H]1NC(=N)N2CCC(O)(O)[C@@]23NC(=N)N[C@@H]13
InChIKey: FYMGGEYPNDYSSU-HFJPGXAFSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 298.3, ALogP -2.96, HBA 6, HBD 7, PSA 153.79, QED 0.21
Compound (SMILES): Cc1ccccc1N1CCC(OC(=O)NCSCc2c(C)noc2C)CC1
InChIKey: OJXNVQDAMPVJSW-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 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 389.52, ALogP 4.19, HBA 6, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): Cc1cc(N)nc(CCc2cc(CC[C@H]3COCCN3C)cc(F)c2F)c1
InChIKey: WLROZYRNCCIRPN-SFHVURJKSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of rat neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay
Measurement: Ki = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 375.46, ALogP 3.3, HBA 4, HBD 1, PSA 51.38, QED 0.84
Compound (SMILES): COc1ccc(-c2cc3c(N[C@H](CO)[C@@H](C)O)c(C(N)=O)cnn3c2)cn1
InChIKey: SQANAFANUDMBOB-QMTHXVAHSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-tagged JAK1 (unknown origin) using fluoresceinated peptide as substrate measured after 3 hrs by electrophoresis method
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 371.4, ALogP 0.66, HBA 8, HBD 4, PSA 135, QED 0.48
Compound (SMILES): COc1cc(NCc2cc3ccc(C)cc3[nH]c2=O)ccc1-n1cnnn1
InChIKey: BPKREDZWJFPBSA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 362.39, ALogP 2.43, HBA 7, HBD 2, PSA 97.72, QED 0.57
Compound (SMILES): CCOC(=O)c1cn(-c2nn3cccc3c(=O)[nH]2)nn1
InChIKey: DYLXPGWGAYSIJH-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 274.24, ALogP -0.22, HBA 8, HBD 1, PSA 107.17, QED 0.66
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccc(F)cc1C(C)C
InChIKey: DTJVAIISWATYCI-JMJMSVOMSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 796.85, ALogP 5.27, HBA 10, HBD 5, PSA 230.88, QED 0.04
Compound (SMILES): Cc1c(C(=O)N2CCC(c3nc(-c4ccccn4)cs3)CC2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: NDPAGVRGTFWXMX-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 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 487.59, ALogP 3.29, HBA 8, HBD 1, PSA 109.66, QED 0.47
Compound (SMILES): CCC(Oc1cc(/C=C2\SC(=O)N(C)C2=O)c(Br)c(F)c1O)c1cnc(N)nc1
InChIKey: CFRHBJJMDMGLOR-XGICHPGQSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 483.32, ALogP 3.86, HBA 8, HBD 2, PSA 118.64, QED 0.62
Compound (SMILES): Cc1nc2ccccc2n1CCC(=O)Nc1ccc(O)c2ncccc12
InChIKey: LKUPDFVBMOASDZ-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 using thiopeptide as substrate preincubated for 30 mins followed by substrate addition and measured every min for 20 mins by colorimetric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 346.39, ALogP 3.63, HBA 5, HBD 2, PSA 80.04, QED 0.55
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cc(OCC(=O)O)cc(C(=O)O)c2)n1)[C@@H](CC)N(O)C=O.O=C(O)C(F)(F)F
InChIKey: XVTGILJSRKUSHT-KFWGXXPESA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 558.59, ALogP 2.54, HBA 8, HBD 5, PSA 195.46, QED 0.06
Compound (SMILES): C#Cc1ccc2c(c1)C(c1ccccc1F)=N[C@@H](C)c1c(C(=O)OCC)ncn1-2
InChIKey: NGYKELBMVXBFSM-AWEZNQCLSA-N
Target: GABA-A receptor; alpha-3/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P28472
Assay: Displacement of [3H]-flunitrazepam from human GABAA alpha3beta3gamma2 expressed in HEK293T cells by liquid scintillation counting method
Measurement: Ki = 292 nM (pChEMBL 6.539999961853027)
Descriptors: MW 387.41, ALogP 4.08, HBA 5, HBD 0, PSA 56.48, QED 0.5
Compound (SMILES): Cc1ccc2[nH]c(CNc3ccc(C(=N)N)cc3)nc2c1.O=CO
InChIKey: WPRMECBDLOUPKB-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Inhibition of recombinant bovine enterokinase activated N-terminal His-tagged recombinant human KLK1 (19 to 262 residues) expressed in baculovirus infected Sf9 insect cells using 3',6'-bis(prolylphenylalanylarginylamino)3H-spiro(2-benzofuran-1,9'-xanthen)-3-one;TFA as substrate measured at 30 secs interval for 5 mins by fluorescence intensity assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 279.35, ALogP 2.77, HBA 3, HBD 4, PSA 90.58, QED 0.44
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N[C@@](C)(CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: GKMGAQOCFUAWCL-GDUQHNAJSA-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 1676.88
Compound (SMILES): Cc1c(C(=O)N2CC(O)(C3CC3)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: QERCDGJBZFLGBD-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 354.37, ALogP 0.11, HBA 7, HBD 2, PSA 108.52, QED 0.69
Compound (SMILES): COC[C@H]1C[C@@H](c2ncc(-c3ccc4c(c3)COc3cc5c(ccc6nc([C@@H]7C[C@@H]8C[C@H]8N7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c65)cc3-4)[nH]2)N(C(=O)[C@H](NC(=O)OC)c2ccccc2)C1
InChIKey: TYKRKURWQMJOHX-RIMOTITASA-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 = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 881, ALogP 7.34, HBA 10, HBD 4, PSA 193.1, QED 0.1
Compound (SMILES): Cc1cc(-c2nc3sc4c(c3c(=O)[nH]2)CCN(C)C4)cc(C)c1OCc1cccc(C(=O)Nc2ccccc2N)c1
InChIKey: HUTZGAHEIGKNPE-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using biotinylated histone H3 KAc peptide (1 to 21 residues) as substrate by HTRF assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 565.7, ALogP 5.67, HBA 7, HBD 3, PSA 113.34, QED 0.23