lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1cn([C@@H]2O[C@H](CSCC[C@H](N)C(=O)O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: XLTWYAYAFLGUEQ-OPYVMVOTSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of N-terminal 6His-tagged SARS-CoV nsp14 extracted from Escherichia coli
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 408.44, ALogP -0.96, HBA 11, HBD 5, PSA 193.53, QED 0.35
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(CN3CCOCC3)cc1c2=O
InChIKey: QAUBWRHYUIABRL-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Uncompetitive inhibition of recombinant human IDO1 expressed in Escherichia coli BL21 cells assessed inhibition constant using varying concentration of L-tryptophan as substrate by Dixon plot analysis
Measurement: Ki = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 365.36, ALogP 1.9, HBA 6, HBD 0, PSA 64.43, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2L receptor expressed in CHOK1 cells assessed as suppression of dopamine-induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIELEUWQJRVBAG-IEBOQBBFSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor 10 (unknown origin) using Ac-QRSR-pNA as substrate after 30 mins relative to untreated control
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1575.88
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human carbonic anhydrase 7 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)CC5/C=C\CCCCC[C@H](NC(=O)OC5CCCC5)C(=O)N4C3)cc(-c3csc(NC(=O)C(C)C)n3)nc2c1C
InChIKey: YQCVJBZPFAJZFJ-DVUQJCTJSA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: GPCRScan assay: inhibition of Alpha2C
Measurement: Ki = 3235.94 nM (pChEMBL 5.489999771118164)
Descriptors: MW 816.98, ALogP 6.14, HBA 11, HBD 4, PSA 198.38, QED 0.18
Compound (SMILES): CCc1nc(N)nc(N)c1C#C[C@@H](C)c1cc(-c2ccncc2)ccc1OC
InChIKey: PPKWGSTVAQFAGZ-CQSZACIVSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Enzyme Inhibition: Enzyme activity and inhibition assays were performed by monitoring the NADPH-dependent reduction of dihydrofolate catalyzed by the DHFR enzyme. The rate of NADPH oxidation was measured spectrophotometrically at 340 nm in assay buffer containing 20 mM TES pH 7.0, 50 mM KCl, 10 mM 2-mercaptoethanol, 0.5 mM EDTA and 1 mg/mL bovine serum albumin. All measurements were performed at room temperature by adding pure enzyme (2 mg/mL), 100 μM NADPH and 100 μM DHF to the buffer. For inhibition assays, inhibitors, dissolved in 100% DMSO, were added to the mixture and incubated for 5 minutes before the addition of DHF. Average IC50 values and standard deviations were measured in triplicate.
Measurement: IC50 = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 373.46, ALogP 3.43, HBA 6, HBD 2, PSA 99.94, QED 0.68
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta6 in human HT-29 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): C[C@]1(C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC[C@H](C(=O)O)CC1
InChIKey: IFTFEJQRBOPQKV-ZKPUSUNFSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Activity at LXRbeta (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 667.62, ALogP 6.61, HBA 4, HBD 1, PSA 91.75, QED 0.29
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: GMCVFRQQOHKQTK-HPMMOBRVSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 3 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 958.09, ALogP -0.52, HBA 10, HBD 8, PSA 286.99, QED 0.1
Compound (SMILES): CCN1CCN(CCCOc2cc3nccc(Oc4c(F)cc(NC(=O)NN5C(=O)CSC5c5c(F)cccc5F)cc4F)c3cc2OC)CC1
InChIKey: GZVQZLVAKXRTHU-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF-1R (unknown origin) using FAM-labelled peptide and ATP incubated for 10 mins by mobility shift assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 728.77, ALogP 6.31, HBA 9, HBD 2, PSA 108.5, QED 0.13
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: VILBOPLLOHPBBF-AUEPDCJTSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 448.93, ALogP 2.11, HBA 5, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1ccc2c(c1)SC(=S)N1CCN=C21
InChIKey: GMZLHKSEGJIFAH-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 234.35, ALogP 2.45, HBA 3, HBD 0, PSA 15.6, QED 0.64
Compound (SMILES): N#CC(C(=O)NCC(=O)NC1CC1)c1nc2ccc(-c3ccccc3)cc2s1
InChIKey: SHNOGRNWVUNUKY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 390.47, ALogP 2.97, HBA 5, HBD 2, PSA 94.88, QED 0.68
Compound (SMILES): Cc1cnc([C@]2(CNC(=O)c3cc4cc(Cl)ccc4o3)NC(=O)NC2=O)n1C
InChIKey: SPAODDWHKVLWKW-SFHVURJKSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of human TACE using Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH as substrate measured after 2 to 4 hrs by fluorescence analysis
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 401.81, ALogP 1.59, HBA 6, HBD 3, PSA 118.26, QED 0.57
Compound (SMILES): Cc1ccc(C2CCN(CC(=O)Nc3cccc(C)c3)CC2)nc1
InChIKey: MGIQZTZYUIHPIO-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as suppression of dopamine-induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 453 nM (pChEMBL 6.340000152587891)
Descriptors: MW 323.44, ALogP 3.52, HBA 3, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): Cn1cc(-c2ccc3c(c2)CC[C@]32NC(=O)N(CC(=O)N3Cc4cc(F)ccc4OC[C@H]3C(F)(F)F)C2=O)cn1
InChIKey: VDEZYUOBIXKTHI-NVQXNPDNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 557.5, ALogP 3.27, HBA 6, HBD 1, PSA 96.77, QED 0.39
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(NCCCC(=O)NO)c2c(=O)n1-c1ccccc1
InChIKey: WKYDWGAPOSGMLN-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 513.56, ALogP 3.31, HBA 10, HBD 5, PSA 162.74, QED 0.11
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C)CC5)c4)c3c2)cc1OC
InChIKey: IPRGWYNVQSWAJM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Mus musculus
UniProt: O35904
Assay: Inhibition of PI3Kdelta in Balb/c mouse B cells assessed as reduction in anti-IgM induced CD86 expression preincubated for 1 hr followed by anti-IgM stimulation for 24 hrs by flow cytometry
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 468.56, ALogP 4.37, HBA 6, HBD 0, PSA 67.79, QED 0.43
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)NCc3ccc(F)cc3)nc3cnc4[nH]ccc4c32)CC1
InChIKey: MMAFBZVPAFVVFX-RUCARUNLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 444.51, ALogP 4.56, HBA 5, HBD 2, PSA 99.39, QED 0.46
Compound (SMILES): S=C1Sc2ccc(Br)cc2C2=NCCCN12
InChIKey: OIPZIHODGKWSSX-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 313.25, ALogP 3.29, HBA 3, HBD 0, PSA 15.6, QED 0.68
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: RNAWZJCKLNMMPX-MRXNPFEDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: ERG Channel Binding Assay: Fluorescence polarization assay based on the principle of fluorescence polarization where a red-shifted fluorescent tracer is displaced from the hERG channel by compounds that bind to the channel was used to establish the binding of the compounds to hERG channel. Briefly, the compounds in serial dilutions were incubated with a membrane fraction containing hERG channel protein and a high-affinity red fluorescent hERG channel ligand in black 384-well plate. The reaction was incubated for 4 h at room temperature followed by the measurement of the fluorescence polarization using Tecan Spark multimode plate reader at excitation wavelength of 535 nm and emission wavelength 590 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 360.89, ALogP 2.72, HBA 5, HBD 2, PSA 74.07, QED 0.88
Compound (SMILES): O=C(NC1CC(F)(F)C1)c1nsc2cc(Nc3n[nH]c4cccnc34)ccc12
InChIKey: NWYHEWQGANWLFU-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Metabotropic Glutamate Receptor Activity: In the first mode, a range of concentrations of the disclosed compounds are added to cells, followed by a single fixed concentration of agonist. If the compound acts as a potentiatior, an EC50 value for potentiation and a maximum extent of potentiation by the compound at this concentration of agonist is determined by non-linear curve fitting. If the compound acts as a noncompetitive antagonist, an IC50 value is determined by non-linear curve fitting. In the second mode, several fixed concentrations of the disclosed compounds are added to various wells on a plate, followed by a range in concentrations of agonist for each concentration of disclosed compound. The EC50 values for the agonist at each concentration of compound are determined by non-linear curve fitting. A decrease in the EC50 value of the agonist with increasing concentrations of the sample compound (a leftward shift of the agonist concentration-response curve) is an indication of the degree of mGluR4 potentiation at a given concentration of the sample compound. A decrease in the maximal response of the agonist with increasing concentrations of the sample compounds, with or without a rightward shift in agonist potency, is an indication of the degree of noncompetitive antagonism at mGluR4. The second mode also indicates whether the sample compounds also affect the maximum response to mGluR4 to agonists.
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 400.41, ALogP 3.84, HBA 6, HBD 3, PSA 95.59, QED 0.48
Compound (SMILES): COc1cccc(Cc2cc(C)nn(C(C)C(=O)Nc3ccc(Cl)cc3)c2=O)c1
InChIKey: JQMCPEBDJPMQGI-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Biased agonist activity at human FPR2 expressed in FlpIn-CHO cells assessed as intracellular calcium mobilization by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.89, ALogP 4, HBA 5, HBD 1, PSA 73.22, QED 0.66
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(=O)O)CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](Cc4c[nH]c5ccccc45)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](Cc4ccccc4)NC1=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC2=O
InChIKey: DFBDAHMZXJYZJG-AALCJKKVSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y9
Assay: Inhibition of human Nav1.8 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 4271.96
Compound (SMILES): COC[C@H]1C[C@@H](c2ncc(-c3cc4c5c(c3)OCc3cc(-c6cnc([C@@H]7CC[C@H](C)N7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)cc(c3-5)OC4)[nH]2)N(C(=O)[C@H](NC(=O)OC)c2ccccc2)C1
InChIKey: MKXHOXQZCNYTGQ-HATOFZBRSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 6a HK6 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.022 nM (pChEMBL 10.65999984741211)
Descriptors: MW 887.01, ALogP 6.98, HBA 11, HBD 4, PSA 202.33, QED 0.1
Compound (SMILES): N#Cc1cn([C@@H]2O[C@H](CSCC[C@H](N)C(=O)O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: XLTWYAYAFLGUEQ-OPYVMVOTSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Binding affinity to SARS-CoV-2 nsp14 assessed as dissociation constant
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 408.44, ALogP -0.96, HBA 11, HBD 5, PSA 193.53, QED 0.35
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(CN3CCOCC3)cc1c2=O
InChIKey: QAUBWRHYUIABRL-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Uncompetitive inhibition of C-terminal His6-tagged human IDO2 (14 to 420 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant using varying concentration of L-tryptophan as substrate by Dixon plot analysis
Measurement: Ki = 17540 nM (pChEMBL 4.760000228881836)
Descriptors: MW 365.36, ALogP 1.9, HBA 6, HBD 0, PSA 64.43, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at human D4 receptor expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 568 nM (pChEMBL 6.25)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIELEUWQJRVBAG-IEBOQBBFSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of activated beta-factor 12 (unknown origin) using Ac-QRFR-pNA as substrate after 30 mins relative to untreated control
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1575.88
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human carbonic anhydrase 9 expressed in mammalian cell expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)CC5/C=C\CCCCC[C@H](NC(=O)OC5CCCC5)C(=O)N4C3)cc(-c3csc(NC(=O)C(C)C)n3)nc2c1C
InChIKey: YQCVJBZPFAJZFJ-DVUQJCTJSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: GPCRScan assay: inhibition of Beta3
Measurement: Ki = 3620.76 nM (pChEMBL 5.440000057220459)
Descriptors: MW 816.98, ALogP 6.14, HBA 11, HBD 4, PSA 198.38, QED 0.18
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha5beta1 in human K562 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): C[C@]1(C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC[C@H](C(=O)O)CC1
InChIKey: IFTFEJQRBOPQKV-ZKPUSUNFSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: General RORgamma SPA binding assay : The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA). The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM, for 10 min at rt in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% glycerol (Sigma Cat#G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce [3H] 25-hydroxycholesterol specific binding by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 667.62, ALogP 6.61, HBA 4, HBD 1, PSA 91.75, QED 0.29
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: GMCVFRQQOHKQTK-HPMMOBRVSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 4 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 958.09, ALogP -0.52, HBA 10, HBD 8, PSA 286.99, QED 0.1
Compound (SMILES): CCN1CCN(CCCOc2cc3nccc(Oc4c(F)cc(NC(=O)NN5C(=O)CSC5c5c(F)cccc5F)cc4F)c3cc2OC)CC1
InChIKey: GZVQZLVAKXRTHU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using FAM-labelled peptide and ATP incubated for 10 mins by mobility shift assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 728.77, ALogP 6.31, HBA 9, HBD 2, PSA 108.5, QED 0.13
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: VILBOPLLOHPBBF-AUEPDCJTSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 448.93, ALogP 2.11, HBA 5, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1ccc(C2CCN(CC(=O)Nc3cccc(C)c3)CC2)nc1
InChIKey: MGIQZTZYUIHPIO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2L receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 323.44, ALogP 3.52, HBA 3, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C)CC5)c4)c3c2)cc1OC
InChIKey: IPRGWYNVQSWAJM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG transfected in HEK293 cell membranes after 60 mins by scintillation counting
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 468.56, ALogP 4.37, HBA 6, HBD 0, PSA 67.79, QED 0.43
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)NCc3ccc(F)cc3)nc3cnc4[nH]ccc4c32)CC1
InChIKey: MMAFBZVPAFVVFX-RUCARUNLSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 444.51, ALogP 4.56, HBA 5, HBD 2, PSA 99.39, QED 0.46
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(=O)O)CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](Cc4c[nH]c5ccccc45)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](Cc4ccccc4)NC1=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC2=O
InChIKey: DFBDAHMZXJYZJG-AALCJKKVSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Mus musculus
UniProt: Q62205
Assay: Inhibition of mouse Nav1.7 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 4271.96
Compound (SMILES): COC[C@H]1C[C@@H](c2ncc(-c3cc4c5c(c3)OCc3cc(-c6cnc([C@@H]7CC[C@H](C)N7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)cc(c3-5)OC4)[nH]2)N(C(=O)[C@H](NC(=O)OC)c2ccccc2)C1
InChIKey: MKXHOXQZCNYTGQ-HATOFZBRSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 3a S52 infected in human HuH7 transient chimeric replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 887.01, ALogP 6.98, HBA 11, HBD 4, PSA 202.33, QED 0.1
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(CN3CCOCC3)cc1c2=O
InChIKey: QAUBWRHYUIABRL-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Uncompetitive inhibition of recombinant human TDO expressed in Escherichia coli BL21 (DE3) assessed as assessed as inhibition constant using varying concentration of L-tryptophan as substrate by Dixon plot analysis
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 365.36, ALogP 1.9, HBA 6, HBD 0, PSA 64.43, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as suppression of dopamine-induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 2120 nM (pChEMBL 5.670000076293945)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIELEUWQJRVBAG-IEBOQBBFSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using Ac-ATPR-pNA as substrate after 30 mins relative to untreated control
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1575.88
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)CC5/C=C\CCCCC[C@H](NC(=O)OC5CCCC5)C(=O)N4C3)cc(-c3csc(NC(=O)C(C)C)n3)nc2c1C
InChIKey: YQCVJBZPFAJZFJ-DVUQJCTJSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: GPCRScan assay: inhibition of Beta3
Measurement: Ki = 3630.78 nM (pChEMBL 5.440000057220459)
Descriptors: MW 816.98, ALogP 6.14, HBA 11, HBD 4, PSA 198.38, QED 0.18
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Antagonist activity at alpha5beta1 in human K562 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): C[C@]1(C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC[C@H](C(=O)O)CC1
InChIKey: IFTFEJQRBOPQKV-ZKPUSUNFSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding Assay : The binding of potential ligands to RORγ is measured by competition with [3H]25-hydroxycholesterol (Perkin Elmer NET674250UC) using a scintillation proximity assay (SPA). The ligand binding domain of human RORγ (A262-S507) with an N-terminal His tag is expressed in E. coli and purified using nickel affinity chromatography. 15 μg/well RORγ (A262-S507) is incubated with test compound at varying concentrations in 3-fold serial dilution, with final concentrations ranging from 16.6 μM to 0.28 nM, for 10 min at rt in PBS buffer (Invitrogen #14190-144) containing 0.5% fatty acid free BSA (Gemini Bio-Products, Cat. #700-107P) and 0.1% glycerol (Sigma Cat # G5516). 10 nM of [3H] 25-hydroxycholesterol is then added, and the reaction is incubated for 10 min. 10 mg/mL of Copper-His Tag-PVT beads (Perkin Elmer cat # RPNQ0095) are added, and the mixture is incubated for 60 min. The reaction is read on a TopCount Microplate scintillation plate reader (Perkin Elmer). The competition data of the test compound over a range of concentrations was plotted as percentage inhibition of radioligand specifically bound in the absence of test compound (percent of total signal). After correcting for non-specific binding, IC50 values were determined.
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 667.62, ALogP 6.61, HBA 4, HBD 1, PSA 91.75, QED 0.29
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: GMCVFRQQOHKQTK-HPMMOBRVSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 5 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 958.09, ALogP -0.52, HBA 10, HBD 8, PSA 286.99, QED 0.1
Compound (SMILES): CCN1CCN(CCCOc2cc3nccc(Oc4c(F)cc(NC(=O)NN5C(=O)CSC5c5c(F)cccc5F)cc4F)c3cc2OC)CC1
InChIKey: GZVQZLVAKXRTHU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) using FAM-labelled peptide and ATP incubated for 10 mins by mobility shift assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 728.77, ALogP 6.31, HBA 9, HBD 2, PSA 108.5, QED 0.13
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: VILBOPLLOHPBBF-AUEPDCJTSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant full length N-terminal His6x-tagged human CA5B expressed in Escherichia coli Rosetta 2 (DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.055 nM (pChEMBL 10.260000228881836)
Descriptors: MW 448.93, ALogP 2.11, HBA 5, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1ccc(C2CCN(CC(=O)Nc3cccc(C)c3)CC2)nc1
InChIKey: MGIQZTZYUIHPIO-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 = 394 nM (pChEMBL 6.409999847412109)
Descriptors: MW 323.44, ALogP 3.52, HBA 3, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(=O)O)CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](Cc4c[nH]c5ccccc45)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)N[C@@H](Cc4ccccc4)C(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](Cc4ccccc4)NC1=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC2=O
InChIKey: DFBDAHMZXJYZJG-AALCJKKVSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08562
Assay: Inhibition of rat Nav1.7 expressed in HEK293 cells by electrophysiology assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 4271.96
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2L receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 = 11847 nM (pChEMBL 4.929999828338623)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIELEUWQJRVBAG-IEBOQBBFSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of tPA (unknown origin) using Z-Pyr-Gly-Arg-MCA as substrate after 30 mins relative to untreated control
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1575.88
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human carbonic anhydrase 13 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as increase in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: GMCVFRQQOHKQTK-HPMMOBRVSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-MSH from human melanocortin receptor 4 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 958.09, ALogP -0.52, HBA 10, HBD 8, PSA 286.99, QED 0.1
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: VILBOPLLOHPBBF-AUEPDCJTSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human CA6 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 448.93, ALogP 2.11, HBA 5, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human D3 receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: LIELEUWQJRVBAG-IEBOQBBFSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of uPA (unknown origin) using Z-Pyr-Gly-Arg-MCA as substrate after 30 mins relative to untreated control
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1575.88
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant human carbonic anhydrase 14 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Agonist activity at alpha2bbeta3 in human HEL cells assessed as increase in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc(Cl)cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: VILBOPLLOHPBBF-AUEPDCJTSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 448.93, ALogP 2.11, HBA 5, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): Cc1cccc(NC(=O)CCN2CCN(c3ncccn3)CC2)c1
InChIKey: LPWRTRRXYPVJKD-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 325.42, ALogP 1.94, HBA 5, HBD 1, PSA 61.36, QED 0.91
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 18 nM (pChEMBL 7.75)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Antagonist activity at alpha2bbeta3 in human HEL cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P05107
Assay: Agonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as increase in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P05107
Assay: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUBRGAXHAIBSRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 448.99, ALogP 3.1, HBA 6, HBD 2, PSA 115.56, QED 0.47
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)O
InChIKey: NMHXECODTXNHIV-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of fibronectin binding to human recombinant alphaVbeta3 expressed in HEK293 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 262.26, ALogP 1.6, HBA 3, HBD 2, PSA 86.71, QED 0.81