lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)NC[C@H]4CC[C@@H](O)CC4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: MHYITYGETZOBDO-WEJIIORJSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 471.52, ALogP -0.3, HBA 11, HBD 5, PSA 173.57, QED 0.33
Compound (SMILES): Cc1c(N[C@@H]2CCCC[C@H]2O)nnc(-c2ccc(C(F)(F)F)cc2O)c1C
InChIKey: ZZWSXJAUWNSSBZ-HUUCEWRRSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Qpatch assay
Measurement: IC50 = 34500 nM (pChEMBL 4.460000038146973)
Descriptors: MW 381.4, ALogP 4.2, HBA 5, HBD 3, PSA 78.27, QED 0.74
Compound (SMILES): O=C(c1nn(-c2ccccc2Cl)c(-c2ccc(Cl)cc2)c1Cc1nn[nH]n1)N1CCC(Oc2ccc(C(F)(F)F)cc2)CC1
InChIKey: SCXVKMCZTPGTKX-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Inverse agonist activity at human CB1 receptor expressed in African green monkey COS7 cells co-expressing G-protein in presence of CP55940 by IP3 assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 642.47, ALogP 6.65, HBA 7, HBD 1, PSA 101.82, QED 0.21
Compound (SMILES): COC(=O)N1CCC(CC(=O)N2CCCN(Cc3ccc(NC(=O)N[C@@]45C[C@@H]6C[C@@](C)(C[C@@](C)(C6)C4)C5)c(F)c3)CC2)CC1
InChIKey: UULYLBFRAZWZHN-FQHNBINKSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 611.8, ALogP 5.6, HBA 5, HBD 2, PSA 94.22, QED 0.44
Compound (SMILES): O=C1CC(c2nc(-c3ccc(F)cc3Cl)no2)CCCN1c1ccc(F)cc1
InChIKey: VNQBOKCOVOUAOU-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation measured after 30 mins by Glosensor assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 403.82, ALogP 4.97, HBA 4, HBD 0, PSA 59.23, QED 0.62
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCN1CC(N3CCC(c4ccc5c(c4)CN(C4CCC(=O)NC4=O)C5=O)CC3)C1)c1nnc(C)n1-2
InChIKey: LHUVKOFLIPGEIS-CDRRMRQFSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to Nano-Luc fused CRBN (unknown origin) expressed in digitonin-permeabilized HEK293 cells incubated for 10 mins by NanoBRET target engagement assay
Measurement: IC50 = 10.1 nM (pChEMBL 8)
Descriptors: MW 808.41, ALogP 4.63, HBA 11, HBD 2, PSA 145.13, QED 0.23
Compound (SMILES): CN1CCN(c2ccc(C(=O)N3CCC4(CC3)CCN(c3ccc(C#N)c(Cl)c3)C4)cc2)CC1
InChIKey: PSNAJRMTQXQQTK-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding affinity to GST-tagged androgen receptor LBD (unknown origin) incubated for 4 hrs by fluorescence polarization assay
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 478.04, ALogP 4.1, HBA 5, HBD 0, PSA 53.82, QED 0.67
Compound (SMILES): Cn1ncc2c(NC34CC(F)(C3)C4)nc(NCC(N)c3ccccc3)nc21
InChIKey: GSLQXSOSEVGGFC-UHFFFAOYSA-N
Target: RNA 5'-monophosphate methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z5W3
Assay: Binding affinity towards N-terminal ePL-tagged BCDIN3D (unknown origin) transfected in human A549 cells preincubated for 1 hr and measured by InCellPulse thermal stability assay
Measurement: IC50 = 616 nM (pChEMBL 6.210000038146973)
Descriptors: MW 367.43, ALogP 2.53, HBA 7, HBD 3, PSA 93.68, QED 0.62
Compound (SMILES): O=C1CN(C(=O)c2cc(Cn3c(=O)[nH]c(=O)c4ccccc43)ccc2F)CCN1CC1CCCCC1
InChIKey: XMLOXTGVMSYKHN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 492.55, ALogP 2.74, HBA 5, HBD 1, PSA 95.48, QED 0.59
Compound (SMILES): COc1ccc2nccc(OC[C@@H]3CC[C@@H](NC(=O)c4ccc(I)c(F)c4)CO3)c2n1
InChIKey: QUDWUIDMIRCCRB-CABCVRRESA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling incubated for 30 mins in presence of ATP
Measurement: IC50 = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 537.33, ALogP 3.74, HBA 6, HBD 1, PSA 82.57, QED 0.48
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(N3CCSc4ccccc43)cc2)[C@H]1NC(C)=O
InChIKey: QKQJUYKNXGRHQU-DKRHUIDYSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Memphis/1/1971(H3N2))
UniProt: P03471
Assay: Inhibition of Influenza A virus A/Babo1/36/2005 (H3N2) neuraminidase using 2(4-methylurnbellifery1)-a-u-acetyl neuraminic acid sodium salt hydrate (4-MUNANA) as Fluorogenic substrate preincubated for 10 mins followed by substrate addition by fluorescence based microplate reader analysis
Measurement: IC50 = 4840 nM (pChEMBL 5.320000171661377)
Descriptors: MW 523.7, ALogP 4.88, HBA 6, HBD 3, PSA 90.9, QED 0.41
Compound (SMILES): Cl.NCCCCN1N=C(CCc2ccc(O)cc2)c2ccc(C(=O)NCCCc3ccccc3)cc2N(Cc2ccc(-c3ccccc3)cc2)C1=O
InChIKey: BPJZBJSKRCTGHO-UHFFFAOYSA-N
Target: Guanine nucleotide-binding protein G(q) subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P50148
Assay: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)
Measurement: EC50 = 5.888 nM (pChEMBL 8.229999542236328)
Descriptors: MW 679.87, ALogP 7.94, HBA 5, HBD 3, PSA 111.26, QED 0.1
Compound (SMILES): O=C(NS(=O)(=O)c1sccc1Cc1ccccc1)c1cc2cc(Oc3ccc(Cl)c(Cl)c3)ccc2[nH]1
InChIKey: LBVNKYABASNBOL-UHFFFAOYSA-N
Target: Galectin-8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00214
Assay: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay
Measurement: Kd = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 557.48, ALogP 7.04, HBA 5, HBD 2, PSA 88.26, QED 0.22
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCN)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: BZXDRURNUJWBEW-FKWFRFQNSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity against mouse MC3R expressed in HEK293 cells assessed as increase in cAMP level incubated for 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 785.69, ALogP 0.29, HBA 7, HBD 9, PSA 247.41, QED 0.04
Compound (SMILES): O=C(NC[C@@H](O)CNCC1CCCCC1)C(c1ccccc1)c1ccccc1
InChIKey: FUOOCCYGXAKPCY-QFIPXVFZSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human recombinant BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 380.53, ALogP 3.47, HBA 3, HBD 3, PSA 61.36, QED 0.62
Compound (SMILES): C[C@]12C[C@@H]3C[C@](C)(C1)C[C@@](NC(=O)Nc1ccc(C(=O)NC4CCC(C(=O)NC(CO)CO)CC4)cc1F)(C3)C2
InChIKey: VGHQROODSKDUDO-PKQRLPCPSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human soluble epoxide hydrolase using PHOME as substrate assessed as 6-methoxynaphthaldehyde product formation preincubated with compound for 10 mins followed by substrate addition and measured by fluorescence based analysis
Measurement: IC50 = 0.91 nM (pChEMBL 9.039999961853027)
Descriptors: MW 558.7, ALogP 3.45, HBA 5, HBD 6, PSA 139.79, QED 0.29
Compound (SMILES): Cc1cc(N2CCc3c(c(C)nn3CC34CCC(N5CCCC5)(CC3)CC4)C2)c2cnn(C)c2n1
InChIKey: WRMAEJQLGNASMS-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human PBMC cells expressed in Drosophila S2 expression system assessed as reduction in IL-6 level measured after 20 hrs by AlphaLISA assay
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 473.67, ALogP 4.53, HBA 7, HBD 0, PSA 55.01, QED 0.56
Compound (SMILES): C[C@H](NC(=O)Cn1ncc2cccn2c1=O)c1ccc(Br)cc1
InChIKey: QHRSGWKGRDMXOV-NSHDSACASA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 transfected in CHO-K1 cells assessed as increase in calcium mobilization by FLIPR analysis
Measurement: EC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 375.23, ALogP 2.14, HBA 5, HBD 1, PSA 68.4, QED 0.76
Compound (SMILES): Cc1csc2c(N3CCC[C@H]3CN3CCN(S(=O)(=O)c4ccc(Cl)c(Cl)c4)CC3)ncnc12
InChIKey: OVGGVUYXPYFHLH-INIZCTEOSA-N
Target: Lysophosphatidic acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92633
Assay: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 526.52, ALogP 4.28, HBA 7, HBD 0, PSA 69.64, QED 0.49
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCN)C(N)=O
InChIKey: YEMGKUJZEBAMPK-ZXYZSCNASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity against mouse MC3R expressed in HEK293 cells assessed as increase in cAMP level incubated for 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 799.72, ALogP 0.68, HBA 7, HBD 9, PSA 247.41, QED 0.04
Compound (SMILES): CCn1c(=O)[nH]c(=O)c2c1nc(Cc1cn3ccccc3n1)n2Cc1ccc(C(=O)OC)cc1
InChIKey: YITCJRJDTZUJTI-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: In Vitro Enzyme Activity Assay: The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, Mass., USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 458.48, ALogP 1.98, HBA 9, HBD 1, PSA 116.28, QED 0.39
Compound (SMILES): COC(=O)NCCc1c(C(O)c2ccccc2)[nH]c2ccc(OC)cc12
InChIKey: XUEPCOYZPABNSW-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[125I]iodomelatonin from human melatonin MT2 receptor stably expressed in human HEK293 cell membrane assessed as inhibition constant incubated for 120 mins by rapid filtration based competition binding assay
Measurement: Ki = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 354.41, ALogP 3.16, HBA 4, HBD 3, PSA 83.58, QED 0.63
Compound (SMILES): CC[C@@H](Nc1c(Nc2cccc(C(=O)N(C)CCNC(=O)OC(C)(C)C)c2O)c(=O)c1=O)c1ccc(C)o1
InChIKey: IEPJACCAWDWJHM-QGZVFWFLSA-N
Target: C-X-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25025
Assay: Binding affinity to NanoLuc fused Snap CXCR2 (unknown origin) expressed in HEK293 cell membrane assessed as inhibition constant using furimazine as substrate incubated with substrate for 5 mins and measured every 15 secs for 60 mins by luminescence based NanoBRET fluorescent binding assay
Measurement: Ki = 1.349 nM (pChEMBL 8.869999885559082)
Descriptors: MW 526.59, ALogP 3.79, HBA 9, HBD 4, PSA 150.21, QED 0.23
Compound (SMILES): N[C@@H](CO)Cn1nnc(-c2ccc(Oc3ncc(Cl)cc3F)cc2)n1
InChIKey: VPYZGXYQYYTKOV-LLVKDONJSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of LTA4H in human whole blood assessed as ionophore-stimulated LTB4 release preincubated for 15 mins by competitive immunoassay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 364.77, ALogP 1.64, HBA 8, HBD 2, PSA 111.97, QED 0.68
Compound (SMILES): CN(C)/C(N)=N/C(=N/S(=O)(=O)c1ccc(Cl)cc1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: GFPSOIHVITYMOK-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: P47746
Assay: Radioligand Displacement Assay: Measuring its tissue levels 1 hour after administration of 10 mg/kg to mice, plasma levels were comparable after oral or i.p. administration (indicating good oral bioavailability), and brain tissue level was <2% of plasma level, indicating low brain penetrance/peripheral selectivity. 1 h after oral administration of compound 2 at 10 mg/kg dose in mice, the metabolite generation in plasma was monitored by LC-MS/MS. As expected, this compound underwent in vivo metabolism to liberate the amidine moiety and a metabolite (structure 41V in the FIG. 1). Besides CB1R antagonism, both intact compound and its metabolically cleaved amidine moiety were able to inhibit iNOS activity about 48% and 37% at 1 μM concentration in lung homogenates from LPS-treated mouse (FIG. 4). Mice with diet-induced obesity (DIO) mice were orally treated for 14 days with the compound 2 (10 mg/kg/day).
Measurement: Ki = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 543.48, ALogP 4.42, HBA 3, HBD 1, PSA 103.72, QED 0.39
Compound (SMILES): Cc1csc2c(N[C@@H](C)CN3CCN(S(=O)(=O)C(=O)c4ccc(Cl)c(Cl)c4)CC3)ncnc12
InChIKey: KAIFUYNQVLCGRL-AWEZNQCLSA-N
Target: Lysophosphatidic acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92633
Assay: Antagonist activity at human LPA1 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis
Measurement: IC50 = 20417.38 nM (pChEMBL 4.690000057220459)
Descriptors: MW 528.49, ALogP 3.89, HBA 8, HBD 1, PSA 95.5, QED 0.52
Compound (SMILES): O=S(=O)(Oc1ccc(Br)cc1)C1CC2OC1C(c1ccc(-n3cncn3)cc1)=C2c1ccc(O)cc1
InChIKey: PKIIMWVWMVSBBB-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to ERbeta (unknown origin) assessed as inhibition constant
Measurement: Ki = 5240 nM (pChEMBL 5.28000020980835)
Descriptors: MW 566.43, ALogP 4.59, HBA 8, HBD 1, PSA 103.54, QED 0.34
Compound (SMILES): Cl.N[C@H]1CCN(c2c3c(nc4ccc(-c5ccnc(NC(=O)C6CCC6)c5)cc24)CCC3)C1
InChIKey: RHXZAHXCRFJYGK-FYZYNONXSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/CyclinT1 (unknown origin) by ADP-Glo kinase assay
Measurement: IC50 = 6.39 nM (pChEMBL 8.1899995803833)
Descriptors: MW 427.55, ALogP 4.06, HBA 5, HBD 2, PSA 84.14, QED 0.66
Compound (SMILES): O[C@@H]1C[C@@H]2C[C@]2(Cn2cnc3c(NCc4cccc(Br)c4)nc(Cl)nc32)[C@@H]1O
InChIKey: DFHKWQUOWHFEGC-FKQYMORYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Binding affinity to PPARdelta (unknown origin) assessed as inhibition constant by TR-FRET based LanthaScreen competitive binding assay
Measurement: Ki = 938 nM (pChEMBL 6.03000020980835)
Descriptors: MW 464.75, ALogP 2.99, HBA 7, HBD 3, PSA 96.09, QED 0.5
Compound (SMILES): COc1cc(-c2cnc3[nH]ccc3c2)cc(OC)c1OC
InChIKey: QGRWEFHVAHCGQH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD2 (E352-M457) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells by 5-FAM-labeled (+)-JQJ based FP competition assay
Measurement: Ki = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 284.31, ALogP 3.26, HBA 4, HBD 1, PSA 56.37, QED 0.8
Compound (SMILES): C[C@@H]1CC[C@@H]2[C@H](C1)OCO[C@@]2(C)CN1CCC(Cc2ccccc2)CC1
InChIKey: VGSOWHKANVNNDG-QQUTXWOLSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]di-o-tolylguanidine from rat liver membrane sigma 2 receptor assessed as inhibition constant measured after 120 mins by scintillation counting method
Measurement: Ki = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 357.54, ALogP 4.51, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): Cn1nc(NCc2cccc(C(=O)N3CCN(C(=O)c4ccc(Cl)cc4Cl)CC3)c2)c2ccccc21
InChIKey: KXRBLQPDZJZWBX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin) using ULight-4E-BP1 peptide as substrate incubated for 90 mins in presence of ATP by Lance ultra assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 522.44, ALogP 5.09, HBA 5, HBD 1, PSA 70.47, QED 0.4
Compound (SMILES): CCCCOc1ccc(C(=O)NC2CCC(=O)NC2=O)c(F)c1
InChIKey: VWKWRZUXWYSGOU-UHFFFAOYSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to human CRBN TBD assessed as inhibition constant using BODIPY-uracil as substrate by MST assay
Measurement: Ki = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 322.34, ALogP 1.54, HBA 4, HBD 2, PSA 84.5, QED 0.61
Compound (SMILES): CN1CCN(c2cc3nc(-c4nccc(NCc5cccnc5N(C)S(C)(=O)=O)n4)[nH]c3cc2F)CC1
InChIKey: MTOYMUXELJMTQW-UHFFFAOYSA-N
Target: SRSF protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P78362
Assay: Inhibition of human SRPK2 using GRSRSRSRSR as substrate in presence of [gamma-33p]-ATP by radiometric hotspot kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.61, ALogP 2.31, HBA 9, HBD 2, PSA 123.24, QED 0.37
Compound (SMILES): CC(C)(C)NC(=O)OC12CC3CC(CC(NC4=N/C(=C\c5ccc6ncsc6c5)C(=O)N4)(C3)C1)C2
InChIKey: YAXGFAAKCUOWNM-GXHLCREISA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.63, ALogP 4.33, HBA 7, HBD 3, PSA 104.71, QED 0.55
Compound (SMILES): CCCN(C)C(=O)Oc1ccc(Cc2nc3cc(C(=O)N(CC)CC)ccc3n2CCC(C)C)cc1
InChIKey: CMTWRVDDBPJIFL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Pseudo-irreversible inhibition of human BChE using butyrylthiocholine iodide as substrate incubated for 20 mins followed by substrate addition by Ellman's method based UV analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 492.66, ALogP 6, HBA 5, HBD 0, PSA 67.67, QED 0.33
Compound (SMILES): Cl.NCCCCN1N=C(/C=C/c2ccc(O)cc2)c2ccc(C(=O)NCC(c3ccccc3)c3ccccc3)cc2N(Cc2ccc(-c3ccccc3)cc2)C1=O
InChIKey: JFNFZTVEWIJGIE-KKNNLOHISA-N
Target: Guanine nucleotide-binding protein G(q) subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P50148
Assay: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)
Measurement: EC50 = 6.918 nM (pChEMBL 8.15999984741211)
Descriptors: MW 739.92, ALogP 9.22, HBA 5, HBD 3, PSA 111.26, QED 0.1
Compound (SMILES): CC(C)(C)OC(=O)NC12CC3CC(CC(NCC(=O)N4Cc5ccc(F)cc5C4)(C3)C1)C2
InChIKey: KUTDPSLQKVFTBP-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of N-terminal human recombinant DPP8 expressed in Sf9 insect cells using Ala-Pro-paranitroanilide as substrate incubated for 15 mins by fluorescence based analysis
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 443.56, ALogP 3.87, HBA 4, HBD 2, PSA 70.67, QED 0.74
Compound (SMILES): COc1cc2c3c(c1OC)-c1ccccc1CC3N(C(=O)c1cc[n+](Cc3cccc(F)c3F)cc1)CC2.[Br-]
InChIKey: SZYCXKSRERWKGH-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured every 20 secs for 3 mins by Ellman's method
Measurement: IC50 = 1540 nM (pChEMBL 5.809999942779541)
Descriptors: MW 513.56, ALogP 5.28, HBA 3, HBD 0, PSA 42.65, QED 0.34
Compound (SMILES): CCCC[C@](C)(O)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: HJAPNLHSOAFOSO-PRQSBNOCSA-N
Target: Oxysterol-binding protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969R2
Assay: Displacement of [3H]-25-OHC from human ORP4 overexpressed in HEK293T cell lysate assessed as inhibition constant by competitive binding assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 374.61, ALogP 5.87, HBA 2, HBD 2, PSA 40.46, QED 0.6
Compound (SMILES): CCOc1ccccc1-c1ccc(N2CCN(C(=O)c3ccc(C(F)(F)F)cc3Cl)C[C@H]2CC)c(C(=O)NCCN)c1
InChIKey: LKHAJNVVGWDYGV-JOCHJYFZSA-N
Target: Adrenocorticotropic hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01718
Assay: Displacement of [[125I]-Tyr23]-ACTH (1-39) from human MC2R incubated for 1.5 hrs by Topcount scintillation counting method
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 603.09, ALogP 5.85, HBA 5, HBD 2, PSA 87.9, QED 0.32
Compound (SMILES): O=C(NS(=O)(=O)c1cc(Cl)c(Cl)s1)c1cc2cc(Oc3ccc(Br)c(Cl)c3)ccc2[nH]1
InChIKey: MKJXLKUONBXDOG-UHFFFAOYSA-N
Target: Galectin-8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00214
Assay: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay
Measurement: Kd = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 580.7, ALogP 6.86, HBA 5, HBD 2, PSA 88.26, QED 0.27
Compound (SMILES): COc1ccc(CNC2CCN(CCCOc3cc(=O)oc4cc(-c5cccnc5)ccc34)CC2)cc1
InChIKey: JUUSFJDTWBMGRX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butylthiocholine iodine as substrate preincubated for 20 mins followed by substrate addition and measured after 20 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 11350 nM (pChEMBL 4.949999809265137)
Descriptors: MW 499.61, ALogP 4.89, HBA 7, HBD 1, PSA 76.83, QED 0.25
Compound (SMILES): COC(=O)/C(C#N)=C/c1cn(CC(=O)Nc2ccccc2OC)c2ccccc12
InChIKey: SJBZNEJHGBRUMZ-RVDMUPIBSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 in human A2780 ADR cells incubated for 30 mins by calcein AM dye based fluorescence microplate reader analysis
Measurement: IC50 = 24300 nM (pChEMBL 4.610000133514404)
Descriptors: MW 389.41, ALogP 3.37, HBA 6, HBD 1, PSA 93.35, QED 0.4
Compound (SMILES): Cn1ncc2cc(-c3ncc4c(ccn4C[C@@H]4CCCNC4)c3-c3ccc(C#N)c(F)c3)ccc21
InChIKey: LFASOUSJBANSHU-GOSISDBHSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: LSD1 Activity: Human recombinant LSD1 protein expressed in E. coli cells was purchased from Active Motif (Carlsbad, Calif.). Biotin-labeled Histone H3K4Me peptide (residues 1-21 with Lys 4 monomethylated) substrate was purchased from Anaspec (Fremont, Calif.). Enzymatic activity was assessed using the AlphaLISA technology from Perkin Elmer Life Sciences (Waltham, Mass.). 2.5 μL of compound solution and 5 μL of LSD1 solutions in the assay buffer (50 mM Tris, pH 9.0, 50 mM NaCl with 0.01% Tween20 and 1 mM DTT added right before the assay) were added into a white low volume 384 well microtiter plate. This mixture solution was incubated for 15 minutes with gentle shaking at room temperature. Demethylation reaction was initiated by adding 2.5 μL of Biotin-H3K4Me peptide substrate solution in the assay buffer. Final concentrations of LSD1, Biotin-H3K4Me peptide substrate, and DMSO were 4 nM, 80 nM, and 1%, respectively. The reaction was allowed to proceed for 60 minutes in dark with gentle shaking at room temperature, after which 5 μL of Anti-H3K4 AlphaLISA acceptor beads in detection buffer from the manufacturer was added into the reaction mixture followed by incubation for 60 minutes. 10 μL of Streptavidin labeled AlphaLISA donor beads in detection buffer was added into the mixture followed by 30-minute incubation. Final acceptor and donor beads concentrations were both at 10 μg/mL. Plates were read on a BMG CLARIOStar multimode plate reader from BMG Labtech (Ortenberg, Germany) with an excitation wavelength of 680 nm and emission wavelength of 615 nm. IC50 values of inhibitors were obtained by fitting the fluorescence intensity vs inhibitor concentrations in a sigmoidal dose-response curve (variable slope) with a non-linear regression using Prism 7 (La Jolla, Calif.).
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 464.55, ALogP 5.27, HBA 6, HBD 1, PSA 71.46, QED 0.39
Compound (SMILES): O=C(Cn1c(=S)[nH]c2ccccc21)NCc1ccccc1
InChIKey: VDYUDHWMLSEUBC-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of human MPO peroxidase activity incubated in presence of H2O2 by amplex red assay
Measurement: IC50 = 97290 nM (pChEMBL 4.010000228881836)
Descriptors: MW 297.38, ALogP 3.02, HBA 3, HBD 2, PSA 49.82, QED 0.73
Compound (SMILES): CCOC(=O)c1cnc(Nc2ccc(Br)cc2C)nc1NCCCNC(=S)NCCC(=O)O
InChIKey: SYKQHPWIDDWEPX-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+
Measurement: IC50 = 2697.74 nM (pChEMBL 5.570000171661377)
Descriptors: MW 539.46, ALogP 3.21, HBA 8, HBD 5, PSA 137.5, QED 0.15
Compound (SMILES): CN(C)[C@H](CNC(=O)N[C@H](c1ccccc1)C(C)(C)C)Cc1ccc(O)cc1
InChIKey: KLQSGTIKZYWTPK-PZJWPPBQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Antagonist activity at human mu opioid receptor stably transfected in CHO cells assessed as decrease in DAMGO induced receptor activation by cAMP assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 383.54, ALogP 3.95, HBA 3, HBD 3, PSA 64.6, QED 0.68
Compound (SMILES): Cc1ccc(Cl)cc1-c1cc(N[C@H]2CC[C@H](N)C2)n2nccc2n1
InChIKey: WLIJQAGXRURARW-KBPBESRZSA-N
Target: CDK1/Cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human CDK1/Cyclin A preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 2330 nM (pChEMBL 5.630000114440918)
Descriptors: MW 341.85, ALogP 3.65, HBA 5, HBD 2, PSA 68.24, QED 0.76
Compound (SMILES): COCCn1cc(C(=O)NCc2nc3ccccc3s2)c2c(Cl)cccc21
InChIKey: WZVIIQQULFCCKA-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Pore Permeation Assay: Agonist-induced pore formation was determined by measuring cellular uptake of YO PRO fluorescence dye in HEK293 transfected with human P2X7 receptor. A HEK293 cell over expressing human P2X7 was harvested using HQTase reagent to detach the cells from T75 cm flask. The harvested cells are centrifuged @ 1200 rpm for 5 min at room temperature. The viability of cells was determined by Trypan blue dye and the cells are plated @ 10,000 cell/well in 50 ul volume in a 384W BD Poly lysine coated plate and incubated overnight at 37 C. After overnight incubation, the culture medium was replaced with 35 ul/well assay buffer (5 mM KCl, 0.1 mM CaCl2, 5 mM Glucose, 10 mM HEPES buffer pH7.4 containing 125 mM NaCl. The serial dilution of compounds was performed using Bravo liquid handling instrument and the compounds were added using Bravo to the cell assay plate starting at 2.5 uM with three dilutions for 10 points. The positive control inhibitor compound was added to column 23. The plate was shaken slowly on a plate shaker for 10 seconds. The cells were incubated with the compound for 20 minutes at room temperature. After the incubation period, YO PRO dye (1 uM) along with BzATP (10 uM) were added to cells at 10 ul/well. The plate was centrifuged at 1000 rpm for 5 seconds and incubated at room temperature for 30 minutes. The uptake of YO PRO dye into the cells was measured using Envision Fluorescence plate reader instrument (Perkin Elmer).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 399.9, ALogP 4.48, HBA 5, HBD 1, PSA 56.15, QED 0.52
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC[C@H](NC(=O)Nc3ccc([N+](=O)[O-])cc3)C2)nc1
InChIKey: HGLYTFYXKZEQKR-LBPRGKRZSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 406.42, ALogP 1.04, HBA 7, HBD 3, PSA 160.56, QED 0.49
Compound (SMILES): COCCNc1ccnc(NC(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)c1
InChIKey: CPJMLOLDZRVYHI-QPXQOZNCSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 509.53, ALogP 0.13, HBA 13, HBD 5, PSA 187.49, QED 0.2
Compound (SMILES): c1cncc(-c2noc(-c3nnon3)n2)c1
InChIKey: HIKMWIUIHNDVGF-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at GAL4-tagged PPARalpha in human A498 cells assessed as transcriptional activation incubated for 72 hrs under hypoxic condition by luciferase assay
Measurement: EC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 216.16, ALogP 0.58, HBA 8, HBD 0, PSA 103.62, QED 0.61
Compound (SMILES): O=C1NC(=O)C(c2cn(CCCn3ccnc3)c3ccc(Br)cc23)=C1c1ccccc1[N+](=O)[O-]
InChIKey: KEHOXFWYRBEKDH-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of human glutaminyl cyclase activity assessed as fluorescence using H-Gln-AMC substrate
Measurement: IC50 = 4280 nM (pChEMBL 5.369999885559082)
Descriptors: MW 520.34, ALogP 4.17, HBA 7, HBD 1, PSA 112.06, QED 0.22
Compound (SMILES): COc1cc(-c2cnc(Nc3cc(N4CCOCC4)nc(C)n3)s2)cc2c1C(=O)N(CC(F)(F)F)CC2
InChIKey: XOZORSAAPNHXFP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase SIK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P57059
Assay: Inhibition of SIK1 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 534.56, ALogP 4.06, HBA 9, HBD 1, PSA 92.71, QED 0.51
Compound (SMILES): N#Cc1ccc(-c2ccc(F)nc2)cc1Cl
InChIKey: MTBSOWDPLMMANU-UHFFFAOYSA-N
Target: Cytochrome P450 11B2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P19099
Assay: Inhibition of human CYP11B2 stably transfected in mouse Y-1 cells using deoxycortisol or deoxycorticosterone as substrate incubated for 48 hrs by radioimmuno assay
Measurement: IC50 = 712 nM (pChEMBL 6.150000095367432)
Descriptors: MW 232.65, ALogP 3.41, HBA 2, HBD 0, PSA 36.68, QED 0.71
Compound (SMILES): CC#CC(=O)N1CC[C@H](n2ncc3c(O[C@@H](C)[C@@H]4CCCN4C)nc4c(F)c(-c5nccc6cccc(C#N)c56)c(Cl)cc4c32)C[C@H]1CC#N
InChIKey: CYKDGDVBWWLZAX-QXQHHZKDSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant (unknown origin) incubated for 2 hrs
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 689.19, ALogP 6.79, HBA 9, HBD 0, PSA 123.96, QED 0.18
Compound (SMILES): CCOc1cccc2cc(CNCCCCOc3ccc4c(c3)OCO4)oc12
InChIKey: JOGGRIOZZIZJAJ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from Dopamine D2 receptor (unknown origin) expressed in HEK293T cell membrane incubated for 2 hrs by radioligand competitive binding based MicroBeta TriLux reader method
Measurement: Ki = 446.68 nM (pChEMBL 6.349999904632568)
Descriptors: MW 383.44, ALogP 4.51, HBA 6, HBD 1, PSA 62.09, QED 0.52
Compound (SMILES): CC(C)C[C@@H](N)[C@H](O)C(=O)N1CCCC1
InChIKey: YSQMRWIBDJSWPH-ZJUUUORDSA-N
Target: Xaa-Pro aminopeptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQW7
Assay: Inhibition of 6-His tagged XPNPEP1 (unknown origin) expressed in Escherichia coli Rosetta DE3 cells using H-Lys(abz)-Pro-Pro-pNA as substrate incubated for 60 mins by fluorescence based analysis
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 214.31, ALogP 0.34, HBA 3, HBD 2, PSA 66.56, QED 0.71
Compound (SMILES): O=C1CC(c2nc(-c3ccncc3)no2)CCCN1c1ccc(F)cc1
InChIKey: OYGFGOFIFGYLGP-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation measured after 30 mins by Glosensor assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.37, ALogP 3.57, HBA 5, HBD 0, PSA 72.12, QED 0.72
Compound (SMILES): CNC(=O)N[C@@H]1CC[C@@H](Nc2cc(C(C)C)nc3ccnn23)C1
InChIKey: GXMWDMBAXOODGQ-VXGBXAGGSA-N
Target: CDK1/Cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human CDK1/Cyclin A preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 2470 nM (pChEMBL 5.610000133514404)
Descriptors: MW 316.41, ALogP 2.11, HBA 5, HBD 3, PSA 83.35, QED 0.81
Compound (SMILES): CCN(CC)CCCC(C)Nc1cnc(C(=O)Nc2cc(C(F)(F)F)cc3cccnc23)cn1
InChIKey: WKPMEBZKUOLVJC-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-ditolylguanidine from human sigma 2 receptor transfected in human HEK293T cells assessed as inhibition constant by radioligand competition binding assay
Measurement: Ki = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 474.53, ALogP 5.22, HBA 6, HBD 2, PSA 83.04, QED 0.42
Compound (SMILES): COc1cc(-c2cnc3cc(N4CCN(C)CC4)ccn23)cc(OC)c1C(=O)NCC(F)(F)F
InChIKey: PJFVPKCPIJSWQT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase SIK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0K1
Assay: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 35.5 nM (pChEMBL 7.449999809265137)
Descriptors: MW 477.49, ALogP 3.06, HBA 7, HBD 1, PSA 71.34, QED 0.59
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2cc(F)c(C3=CCCC3)cc2F)[C@H]1NC(C)=O
InChIKey: JVXBFFCKQLVHFR-ISJGIBHGSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus (A/Memphis/1/1971(H3N2))
UniProt: P03471
Assay: Inhibition of Influenza A virus A/Babo1/36/2005 (H3N2) neuraminidase using 2(4-methylurnbellifery1)-a-u-acetyl neuraminic acid sodium salt hydrate (4-MUNANA) as Fluorogenic substrate preincubated for 10 mins followed by substrate addition by fluorescence based microplate reader analysis
Measurement: IC50 = 1630 nM (pChEMBL 5.789999961853027)
Descriptors: MW 476.56, ALogP 4.48, HBA 4, HBD 3, PSA 87.66, QED 0.46
Compound (SMILES): C(=C/c1ccc2[nH]ncc2c1)\CN1CCC(Cc2ccccc2)CC1
InChIKey: OMPCMJFUWAFNPP-QPJJXVBHSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane assessed as inhibition constant measured after 120 mins by scintillation counting method
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 331.46, ALogP 4.53, HBA 2, HBD 1, PSA 31.92, QED 0.74
Compound (SMILES): CCOC(=O)c1cnc(Nc2ccc(C)cc2)nc1NCCCNC(=S)NCCC(=O)O
InChIKey: UHTNZBUIWXYODH-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+
Measurement: IC50 = 11641.26 nM (pChEMBL 4.929999828338623)
Descriptors: MW 460.56, ALogP 2.45, HBA 8, HBD 5, PSA 137.5, QED 0.18
Compound (SMILES): O=C(NC1CCCC1)c1cc(-c2cc(O)c3cccnc3c2)on1
InChIKey: NQEWZQIZAUEGOY-UHFFFAOYSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Inhibition of MLLT3 YD domain (unknown origin) assessed as disruption of histone peptide binding using histone peptide as substrate by HTRF assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 323.35, ALogP 3.27, HBA 5, HBD 2, PSA 88.25, QED 0.77
Compound (SMILES): NC(=O)CC[C@@H]1NC(=O)[C@H](Cc2ccc(/N=N\c3ccccc3)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: UENYJBNYNBUBSV-JFGZPOIZSA-N
Target: Vasopressin V1b receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47901
Assay: Agonist activity at human V1b receptor transfected in HEK293 cells incubated for 1 hr by IP-one HTRF assay
Measurement: EC50 = 20.2 nM (pChEMBL 7.699999809265137)
Descriptors: MW 1188.36
Compound (SMILES): CC(C)[C@H](NC(=O)c1cccs1)C(=O)Nc1ncco1
InChIKey: WOXQABQAUNWRLJ-JTQLQIEISA-N
Target: Heat shock-related 70 kDa protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P54652
Assay: Inhibition of HspA2 (unknown origin) by FP assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 293.35, ALogP 2.13, HBA 5, HBD 2, PSA 84.23, QED 0.88
Compound (SMILES): CCCN1CCN(c2ccc3c(c2)C(N(C)C(=O)/C=C/c2ccccc2)CCC3)CC1
InChIKey: MYSZLXOHEWPTDC-NTCAYCPXSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H](+)-pentazocine from human sigma 1 receptor transfected in HEK293 cells assessed as inhibition constant by competition binding assay
Measurement: Ki = 196 nM (pChEMBL 6.710000038146973)
Descriptors: MW 417.6, ALogP 4.77, HBA 3, HBD 0, PSA 26.79, QED 0.63
Compound (SMILES): COc1ccc(-c2onc(C(=O)Nc3c(C)n(C)n(-c4ccccc4F)c3=O)c2C)c(C)c1
InChIKey: PUEGOUZDMYDGCG-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase SMURF1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCE7
Assay: Stabilization of SMURF1 (unknown origin) assessed as decrease in auto-ubiquitination by measuring increase in protein level by cell-based assay
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 450.47, ALogP 4.16, HBA 7, HBD 1, PSA 91.29, QED 0.49
Compound (SMILES): O=C1NC(NC2COCCOC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: GHQYHWMWJLSKRP-ACAGNQJTSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.4, ALogP 1.13, HBA 7, HBD 2, PSA 84.84, QED 0.8
Compound (SMILES): CC(C)(C(=O)N1CCOCC1)c1ccc2c(-c3ccc(F)cc3)cc(C(N)=O)nc2c1
InChIKey: YWXCRRUERVFVAY-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at PXR (unknown origin)
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 421.47, ALogP 3.28, HBA 4, HBD 1, PSA 85.52, QED 0.7
Compound (SMILES): CCC(C(=O)Nc1ccc2nn(C)cc2c1)n1cc(OC)c(-c2cc(Cl)ccc2-n2cc(C(F)(F)F)nn2)cc1=O
InChIKey: YXQQDNTZJAXMNL-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: To determine the plasma kallikrein inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic plasma kallikrein substrate to determine the enzymatic activity of human plasma kallikrein. Here, plasma kallikrein cleaves from the peptic plasma kallikrein substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions is placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 585.97, ALogP 5.25, HBA 9, HBD 1, PSA 108.86, QED 0.28
Compound (SMILES): CN(c1ccc(Cl)cc1)c1ccnc(Nc2ccc(C(=O)Nc3nc4c(C(N)=O)cccc4[nH]3)cc2)n1
InChIKey: JKAXXNVLUPIPLQ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 (unknown origin)
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 512.96, ALogP 4.87, HBA 7, HBD 4, PSA 141.92, QED 0.24
Compound (SMILES): CCn1c(=O)[nH]c(=O)c2c1nc(Cc1cn3cc(C)sc3n1)n2CC1CCNCC1
InChIKey: OAGQPQPMAVXHST-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWU9
Assay: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.53, ALogP 1.51, HBA 9, HBD 2, PSA 102.01, QED 0.5
Compound (SMILES): CS(=O)(=O)c1cccc(-c2cnc3[nH]nc(-c4cc(F)cc(NC(=O)Nc5cncnc5)c4)c3c2)c1
InChIKey: OEHGEOWDIWFUCT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00444
Assay: Displacement of kinase tracer 236 from human recombinant PLK4 incubated for 60 mins by LanthScreen Eu kinase binding assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 503.52, ALogP 4.27, HBA 7, HBD 3, PSA 142.62, QED 0.33
Compound (SMILES): Cc1c(-c2ccc3cnc(Nc4ccc5c(c4)C(C)(C)OC5=O)nc3c2)cnc2c1NCCO2
InChIKey: AGUZOOLSSUKXNN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human Jurkat cells assessed as reduction in SLP76 phosphorylation at Ser376 residue preincubated for 60 mins followed by alphaCD3/alphaCD28 DynabeadsTM stimulation for 15 mins by AlphaLISA assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 453.5, ALogP 4.95, HBA 8, HBD 2, PSA 98.26, QED 0.42
Compound (SMILES): Nc1cc(NC(=O)c2cn(-c3ccccc3)nc2-c2ccccc2)cc(Oc2cccnc2)c1
InChIKey: ODZPKVAISZKCGI-UHFFFAOYSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to ERR-gamma LBD (unknown origin) assessed as dissociation constant by ITC analysis
Measurement: Kd = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 447.5, ALogP 5.56, HBA 6, HBD 2, PSA 95.06, QED 0.33
Compound (SMILES): CCCCc1nc2c(N)nc3ccsc3c2n1CCCCCN
InChIKey: VXMRUBSRPNRLRS-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at human TLR8 expressed in HEK-Blue hTLR8 cells by reporter gene assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 331.49, ALogP 3.7, HBA 6, HBD 2, PSA 82.75, QED 0.62
Compound (SMILES): COc1cccc(C2CC(Cc3cccs3)=NN2C(=O)CCl)c1OC
InChIKey: FVNLPFDDZZPEHX-UHFFFAOYSA-N
Target: YAP1-TEAD4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P46937
Assay: Inhibition of GST-tagged TEAD4 (217 to 434 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/FAM-labelled YAP1 (60 to 99 residues)(unknown origin) protein-protein interaction preincubated for 0.5 hrs at 4 degree C with TEAD4 followed by fluorescent labelled YAP1 addition by fluorescence polarization assay
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 378.88, ALogP 3.88, HBA 5, HBD 0, PSA 51.13, QED 0.72
Compound (SMILES): CC1=NN(c2ccc(C(=O)O)cc2)C(=O)/C1=C\c1cccn1C
InChIKey: OXIDWSAFNKKQPK-GDNBJRDFSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of recombinant human KAT3B (1287 to 1673 residues) using histone H3 peptide and [3H]-acetyl-coA as substrates incubated for 1 hrs by liquid scintillation counter analysis
Measurement: IC50 = 20800 nM (pChEMBL 4.679999828338623)
Descriptors: MW 309.33, ALogP 2.53, HBA 4, HBD 1, PSA 74.9, QED 0.89
Compound (SMILES): C[C@H]1CCCN(Cc2cc3c(c(C(F)(F)F)c2)CN(c2cccc([C@]4(c5nncn5C)C[C@@H](C)C4)c2)C3=O)C1
InChIKey: HUOLMBXGHHSYHC-QWQFASRJSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Displacement of FAM-labeled probe from recombinant biotinylated Cbl-b (unknown origin) expressed in Escherichia coli BL21(DE3) Tuner cells by TR-FRET assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 537.63, ALogP 5.94, HBA 5, HBD 0, PSA 54.26, QED 0.4
Compound (SMILES): CCn1nc(C)cc1C(=O)Nc1nc2cc(C(N)=O)cc(OC)c2n1CCCNc1ncc(-c2ccccc2C#N)o1
InChIKey: PZAJWVLKRPVRRW-UHFFFAOYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human 293-Dual hSTING-R232 cells assessed as INF-beta activation by measuring lucia luciferase activity by QUANTI-Blue assay
Measurement: EC50 = 609 nM (pChEMBL 6.210000038146973)
Descriptors: MW 567.61, ALogP 3.95, HBA 11, HBD 3, PSA 178.91, QED 0.2
Compound (SMILES): COc1cc2c(cc1O)CCn1c-2c(-c2ccc(O)c(O)c2)c2c3cc(O)c(OC)cc3oc(=O)c21
InChIKey: PCWYFKMEMPTOQC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of N-terminal full length human recombinant CDK5/p25 expressed in baculovirus-infected Sf21 cells incubated for 60 mins in presence of ATP by kinase-glo luminescent assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 487.46, ALogP 4.48, HBA 9, HBD 4, PSA 134.52, QED 0.22
Compound (SMILES): c1cncc(-c2noc(-c3nc[nH]n3)n2)c1
InChIKey: LAUQCCKKPQGMEY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at GAL4-tagged PPARalpha in human A498 cells assessed as transcriptional activation incubated for 72 hrs under hypoxic condition by luciferase assay
Measurement: EC50 = 7040 nM (pChEMBL 5.150000095367432)
Descriptors: MW 214.19, ALogP 0.92, HBA 6, HBD 1, PSA 93.38, QED 0.68