lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Nc1nc(F)c(CN2CC[C@H](OCc3noc(C)n3)C[C@@H]2C)s1
InChIKey: FRVXHWNHGWUTQO-CABZTGNLSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of full length N-terminal his-tagged human OGA expressed in baculovirus expression system preincubated for for 30 mins followed by substrate addition and measured after 60 mins by fluorescence based analysis
Measurement: IC50 = 2.36 nM (pChEMBL 8.630000114440918)
Descriptors: MW 383.45, ALogP 2.5, HBA 8, HBD 1, PSA 93.38, QED 0.82
Compound (SMILES): Cc1c(Nc2c(F)ccc(NS(=O)(=O)CCCF)c2Cl)ccc2ncn(C)c(=O)c12
InChIKey: VVLVISDSGRHLMB-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 = 49700 nM (pChEMBL 4.300000190734863)
Descriptors: MW 456.9, ALogP 3.88, HBA 6, HBD 2, PSA 93.09, QED 0.56
Compound (SMILES): COCCN(CCCCC1=CC=C2CCCN=C2N1)CC[C@H](Nc1ncnc2ccccc12)C(=O)O
InChIKey: CWOFQJBATWQSHL-DEOSSOPVSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of recombinant human alphavbeta6 integrin incubated for 2 hrs by microplate reader assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 492.62, ALogP 3.61, HBA 8, HBD 3, PSA 111.97, QED 0.34
Compound (SMILES): Cc1ccc(-c2noc(C)c2COc2ccc(C(=O)NC3CCOCC3)nn2)cn1
InChIKey: ACZCJTHHWMBFKC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Electrophysiology: Electrophysiological experiments were performed on days 3 to 5 after the micro-injection of mRNA. During the experiment the oocytes were constantly superfused by a solution containing (in mM) NaCl 90, KCl 1, HEPES 5, MgCl2 1, CaCl2 1 (pH 7.4). Oocytes were impaled by two glass microelectrodes (resistance: 0.4 MΩ) which were filled with a solution containing KCl 1M+K-acetate 1.5 M and voltage-clamped to −80 mV. The recordings were performed at room temperature using the Roboocyte two-electrode voltage clamp system (Multichannelsystem). After an initial equilibration period of 1.5 min GABA was added for 1.5 min at a concentration evoking approximately 20% of a maximal current response (EC20). After another rest interval of 2.5 min GABA was again added evoking a response of similar amplitude and shape. 0.5 min after the onset of this second GABA application the test compound, at a concentration corresponding to approximatively 30 fold its Ki, was added while GABA was still present. Current traces were recorded at a digitization rate of 10 Hz during and shortly before and after the GABA application.
Measurement: Ki = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 409.45, ALogP 2.63, HBA 8, HBD 1, PSA 112.26, QED 0.66
Compound (SMILES): C[C@@H]1COCCN1c1cc([C@]2(O)C[C@H]3CC[C@@H](C2)O3)c2cnn(-c3cc[nH]n3)c2n1
InChIKey: YIHHYCIYAIVQKX-MBIULKOWSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of human recombinant ATR incubated for 40 mins by fluorescence based analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 410.48, ALogP 1.9, HBA 8, HBD 2, PSA 101.32, QED 0.68
Compound (SMILES): Cc1cc(N2CCc3cc(F)ccc3C2)cc(C)c1NC(=O)CC(C)(C)C
InChIKey: FJNPZKZPWVVSON-UHFFFAOYSA-N
Target: Potassium voltage-gated channel subfamily KQT member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43526
Assay: FluxOR potassium ion channel assay: Cell preparation: CHO-KCNQ2 cells were cultured in a 175 cm2 culture flask, and when the cells was grown to a density of 60-80%, the culture medium was removed, washed with 7 mL PBS (Phosphate Buffered Saline) once, then 3 mL 0.25% Trypsin was added to digest. After the digestion was completed, 7 mL culture medium (90% DMEM/F12+10% FBS+500 μg/mL G418) was added to neutralize, centrifugated for 3 minutes at 800 rpm. The supernatant was aspirated, then 5 mL culture medium was added to resuspend, and then the cells were counted.Cell plating: The density to 3×104/well was adjusted according to the results of cell counting. After standing at room temperature for 30 minutes, the cells were placed in a 37° C. CO2 incubator and incubated overnight for 16-18 hours. The cell density reached about 80%.Fluorescent dye incubation: The cell culture medium was discarded, 80 μL/well loading buffer was added, and the cells were incubated in dark at room temperature for 60 minutes.Compound incubation: the loading buffer was discarded, 80 μL/well prepared compound solution was added, incubated at room temperature and in dark for 20 minutes.Fluorescence data collection: FDSS/μCELL instrument for real-time fluorescence is used for signal recording, wherein excitation wavelength was 480 nm, emission wavelength was 540 nm, and signals were recorded 1 times per second, after baseline was recorded for 10 seconds, the addition of 20 μL/well stimulation buffer was started, and then the signal was continuously record until the end of 180 seconds.
Measurement: EC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 368.5, ALogP 5.38, HBA 2, HBD 1, PSA 32.34, QED 0.79
Compound (SMILES): O=C(O)CCC[C@H]1CC[C@@H]2[C@@H](/C=C/[C@@H](O)COc3cc(F)ccc3F)[C@H](O)C[C@@H]2OC1
InChIKey: PRIYCPZIGUYJAL-PRDSGWKNSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Agonist activity at EP3 (unknown origin)
Measurement: EC50 = 28.6 nM (pChEMBL 7.539999961853027)
Descriptors: MW 440.48, ALogP 3.31, HBA 5, HBD 3, PSA 96.22, QED 0.51
Compound (SMILES): COc1nsc(NC(=O)N2C[C@H]3C[C@H](N(C)c4ncnc5[nH]ccc45)C[C@H]3C2)n1
InChIKey: DNBCBAXDWNDRNO-GDNZZTSVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: JAK1 Kinase Assay: TBDIn vitro kinase assays described below can be used to determine the activity of a test compound for inhibiting the activity of JAK1 kinase. The test compounds were dissolved in dimethyl sulfoxide and diluted with water to a serial concentration gradient as required in the experiment. JAK1 substrates (Cell Signaling Technology, Catalog Number: 1305s) and ATP (2 mM) solution were diluted with water to obtain a final concentration of 20 μM ATP and 1.2 μM substrate solution. The appropriate amount of JAK1 kinase (Invitrogen, Catalog Number: pv4774) was mixed with 4× buffer (prepared by user, and comprising 50 mM HEPES, pH 7.3, 125 mM NaCl, 24 mM MgCl2, 1.25 mM DTT) to a final concentration of 8 ng/μL. To each well of a microplate [DELFIA® Streptavidin-coated clear plate (Perkin Elmer, Catalog Number: AAAND-0005)]17.5 μL of ATP/substrate mixture, 5 μL of an aqueous solution of a test compound (5 μL of pure water only were added to the control and blank), and 7.5 μL of the kinase solution prepared above (4× buffer only was added to the control) were added. Each well was mixed sufficiently, then incubated at room temperature (27° C.) for 50 minutes, washed with wash buffer, and dried three times, then HRP conjugated antibody was added [Phospho-Tyrosine Mouse mAb (P-Tyr-100) (HRP Conjugate, Cell Signaling Technology, Catalog Number: 5465)], and incubated for 1 hour. The microplate was washed with wash buffer and dried three times, and then TMB (Sigma, Catalog Number: T4444) was added, and incubated for 5 to 15 minutes to allow for color change. Stop solution (1 N sulfuric acid solution) was added to stop the reaction.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 414.5, ALogP 2.2, HBA 8, HBD 2, PSA 112.16, QED 0.67
Compound (SMILES): CCN1CCC(S(=O)(=O)NC(=O)Nc2c3c(cc4c2CCC4)CCC3)CC1
InChIKey: OHIFQOUPTWBQLE-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production pre incubated for 3 hrs followed by nigericin addition measured after 1 hrs by resazurin staining based assay
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 391.54, ALogP 2.6, HBA 4, HBD 2, PSA 78.51, QED 0.83
Compound (SMILES): COc1cc2cc(-c3ccc(CC(=O)Nc4cc(C(C)(C)C(F)(F)F)no4)cn3)cnc2cc1OC
InChIKey: KOLQINCWMXQEOF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Kinase Inhibiting Activity: A reaction buffer (100 mM HEPES (pH 7.4), 10 mM MgCl2, 0.003% Brij-35, 0.004% Tween-20, and 1 mM DTT) was mixed with a RET recombinant protein (RETwild type; Invitrogen # PV3819, final concentration: 80 pg/ul, or a RETGatekeeper mutation (V804L); Invitrogen # PV4397, final concentration: 80 pg/ul) to prepare a RET kinase solution. The test compound was prepared to have a final concentration of 4000 nm with DMSO, and further, test compound samples at 12 different concentrations were prepared with a dilution magnification of √10. 19 uL of the RET kinase solution was added to each of lines A to P of a 384-well plate, and thereafter, the test compound at each concentration was added to lines C to N, and further, 1 uL of dimethyl sulfoxide (hereinafter referred to as DMSO) was added to each of lines A, B, O and P. Thereafter, the obtained mixtures were each preincubated at room temperature for 20 minutes. Furthermore, a substrate solution A containing ATP (final concentration: 1 mM) and a substrate solution B containing no ATP, both in addition to a reaction buffer and FL-Peptide 22 (PerkinElmer, #760366, final concentration: 1.5 uM) were produced. The substrate solution A was added in an amount of 5 uL to lines B to 0, whereas the substrate solution B was added in an amount of 5 uL to lines A and P. The obtained mixtures were each incubated at 28° C. for 45 minutes. A reaction termination solution (100 mM HEPES (pH 7.4), 0.015% Briji-35, 40 mM EDTA, and 0.1% Coating Reagent 3) was added in an amount of 40 ul to the reaction mixture, so as to terminate the reaction.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 500.48, ALogP 5.32, HBA 7, HBD 1, PSA 99.37, QED 0.37
Compound (SMILES): Cc1nnn(C)c1-c1cc2c(cc1Cl)c1ncc(C(C)(C)O)cc1n2[C@H](c1ccccc1)C1CCOCC1
InChIKey: JVPYSHCVNWGQBI-GDLZYMKVSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: All assay components were dissolved in buffer composition 20 mM Hepes pH 7.5, 150 mM NaCl, 5 mM DTT, 0.005% Tween 20, and 100 ug/ml BSA for BRD4 (1-477 and 44-460). The final concentrations of the bromodomain proteins are 1.6 nM BRD4(44-168), 1 nM BRD4(333-460), and 1 nM BRD4(1-477 or 44-460), and the fluorescent probe molecule is 100 nM, 50 nM, and 7.5 nM respectively. All proteins were biotinylated. A streptavidin labeled with terbium cryptate (Cisbio SA-Tb) was used as detection, and pre-mixed with the bromodomain protein at a final concentration of 0.2 nM. In some instances for BRD4 (44-460), anti-His terbium cryptate was used as a detection. 7.5 nl of dose-responsed test compound or dmso vehicle (0.0375%) was pre-spotted in a black Corning 384 well plate and 10 ul each of bromodomain/detection reagent and fluorescent small molecule solution were added to the plate, and the reaction incubated for 60 min at room temperature. Plates were then read on EnVision plate reader, (λex=340 nm, acceptor λEm=520 nm, and donor λEm=615 nm, LANCE D400 mirror). Time resolved fluorescence intensity measurements were made at both emissions, and the ratio of acceptor/donor was calculated and used for data analysis.
Measurement: IC50 < 1500 nM (pChEMBL 5.823999881744385)
Descriptors: MW 530.07, ALogP 6.19, HBA 7, HBD 1, PSA 77.99, QED 0.29
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2cccc(Cl)c2)NC(=O)c2ccc(CN)c(Cl)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: KJIZCHCIGKMOHD-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 681.54, ALogP 4.93, HBA 6, HBD 4, PSA 139.62, QED 0.2
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](CCCCN)NC(=O)c2cccc(Cl)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: BYDMMHNQDBFVLP-VABKMULXSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 599.05, ALogP 3.71, HBA 6, HBD 4, PSA 139.62, QED 0.24
Compound (SMILES): CC(C)C[C@H](NC(=O)OCC1CCC(F)(F)CC1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(O)S(=O)(=O)O
InChIKey: BHZBRFONZANPNK-ZYHFAYPJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS CoV-2 Main protease by FRET assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 527.59, ALogP 1.17, HBA 7, HBD 5, PSA 171.13, QED 0.25
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C(c2ccc(Cl)cc2)C2CCC2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: RMPSTYWLAAJPFH-IPDPXPSLSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 16.4 nM (pChEMBL 7.789999961853027)
Descriptors: MW 715.21, ALogP 5.55, HBA 6, HBD 4, PSA 139.62, QED 0.16
Compound (SMILES): CCCCCCCCCCCCCCCCSCCCOP(=O)(O)CO[C@H](C)Cn1cnc2c(N)ncnc21
InChIKey: SOKBJKWMFMTFHS-RUZDIDTESA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 585.8, ALogP 7.58, HBA 9, HBD 2, PSA 125.38, QED 0.09
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C(F)(F)c2cccc(Cl)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: WKTXXGMWCJUNLV-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 697.1, ALogP 4.76, HBA 6, HBD 4, PSA 139.62, QED 0.18
Compound (SMILES): Cc1nnn(C)c1-c1cc2c(cn1)c1ncc(C(C)(C)O)cc1n2[C@H](c1ccccc1)C1CCOCC1
InChIKey: GUESIHAGQSIQQN-MUUNZHRXSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The binding of compounds to bromodomain BRD4 (44-168), BRD4 (333-460), and BRD4 (1-477 or 44-460) was assessed using a time resolved fluorescent resonance energy transfer binding assay (1), that measures the binding of a fluorescently labeled probe molecule to the bromodomain protein. The bromodomain protein, fluorescent probe molecule (either a biotinylated histone peptide or a fluorescently labeled small molecule), and dose-responded test compound are incubated together to reach thermodynamic equilibrium. In the absence of a test compound, the bromodomain and small molecule are bound, resulting in a high fluorescent signal. In the presence of a sufficient concentration of inhibitor, this intercation is disrupted resulting in a lost of fluorescent resonance energy transfer.All assay components were dissolved in buffer composition 20 mM Hepes pH 7.5, 150 mM NaCl, 5 mM DTT, 0.005% Tween 20, and 100 ug/ml BSA for BRD4 (1-477 and 44-460). The final concentrations of the bromodomain proteins are 1.6 nM BRD4(44-168), 1 nM BRD4(333-460), and 1 nM BRD4(1-477 or 44-460), and the fluorescent probe molecule is 100 nM, 50 nM, and 7.5 nM respectively. All proteins were biotinylated. A streptavidin labeled with terbium cryptate (Cisbio SA-Tb) was used as detection, and pre-mixed with the bromodomain protein at a final concentration of 0.2 nM. In some instances for BRD4 (44-460), anti-His terbium cryptate was used as a detection. 7.5 nl of dose-responded test compound or dmso vehicle (0.0375%) was pre-spotted in a black Corning 384 well plate and 10 ul each of bromodomain/detection reagent and fluorescent small molecule solution were added to the plate, and the reaction incubated for 60 min at room temperature. Plates were then read on EnVision plate reader, (λex=340 nm, acceptor λEm=520 nm, and donor λEm=615 nm, LANCE D400 mirror). Time resolved fluorescnce intensity measurements were made at both emissions, and the ratio of acceptor/donor was calculated and used for data analysis.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 496.62, ALogP 4.93, HBA 8, HBD 1, PSA 90.88, QED 0.37
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C2(C(F)(F)F)CCCC2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: RUZZRYVQWZTESR-SDHOMARFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 672.67, ALogP 4.43, HBA 6, HBD 4, PSA 139.62, QED 0.23
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C(F)(F)c2ccccc2C(F)(F)F)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: XYIFKBDKRHIXJN-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 730.65, ALogP 5.12, HBA 6, HBD 4, PSA 139.62, QED 0.17
Compound (SMILES): COc1cc(CN2CCc3c(-c4ccc(F)cc4F)cc(C(N)=O)nc3C2)ccn1
InChIKey: URBPVDLWYBJTSG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Biological Assays: The utility of the compounds of the invention as antagonists of metabotropic glutamate receptor activity, in particular mGluR2 activity, may be demonstrated by methodology known in the art. Antagonist constants are determined as follows. The compounds of the invention were tested in a fluorescence laser imaging plate reader based assay. This assay is a common functional assay to monitor Ca2+ mobilization in whole cells expressing recombinant receptor coupled with a promiscuous G-protein. CHO dhfr-cells stably expressing recombinant human mGluR2 and Gα16 loaded with Fluo-4 AM (Invitrogen, Carlsbad Calif.) were treated with various concentrations of antagonists of compounds and the Ca2+ response was monitored on a FLIPR384 (Molecular Devices, Sunnydale Calif.) for agonist activity. Then 2,500 nM glutamate was added and the antagonist response was monitored. The maximum calcium response at each concentration of compound for agonist or antagonist were plotted as dose responses and the curves were fitted with a four parameter logistic equation giving IC50 and Hill coefficient using the iterative non linear curve fitting software ADA (Merck & Co).
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 410.42, ALogP 3.09, HBA 5, HBD 1, PSA 81.34, QED 0.7
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)c2cccc(Cl)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: RMOHQVGMRDKLDA-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 647.09, ALogP 4.28, HBA 6, HBD 4, PSA 139.62, QED 0.22
Compound (SMILES): CC1(C)Cn2nc(-c3ccc(F)cn3)c(-c3ccnc4[nH]ncc34)c2CO1
InChIKey: WZMIWVZGYMKUDV-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Displacement of kinase tracer 8 from NanoLuc-tagged CK1 delta (unknown origin) transfected in CHO cells by BRET assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 364.38, ALogP 3.33, HBA 6, HBD 1, PSA 81.51, QED 0.59
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C(c2cccc(C(F)(F)F)c2)C(F)(F)F)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: DAJQEOBDONZPDT-ZXTYARETSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 762.67, ALogP 5.68, HBA 6, HBD 4, PSA 139.62, QED 0.16
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)[C@@H](c2ccc(Cl)cc2)C(C)C)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: UWQMSEUKOSQYLM-JVVMDBNWSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 703.2, ALogP 5.4, HBA 6, HBD 4, PSA 139.62, QED 0.17
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2cccc(Cl)c2)NC(=O)c2ccc(CN)cc2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: GTUPFRAWJQTUPU-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 647.09, ALogP 4.28, HBA 6, HBD 4, PSA 139.62, QED 0.22
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)C2(c3ccc(Cl)cc3)CCCC2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: VUYYGNOOBBWBAU-CHQNGUEUSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 715.21, ALogP 5.48, HBA 6, HBD 4, PSA 139.62, QED 0.17
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2cccc(Cl)c2)NC(=O)Cc2ccc(CN)cc2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: SCWYJQCFTORHRR-ZXRKZBAXSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 661.12, ALogP 4.21, HBA 6, HBD 4, PSA 139.62, QED 0.2
Compound (SMILES): COc1ccc2nc3ccc(OC)cc3c(SCCCN)c2c1
InChIKey: ZFOMCSNUEHMROO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of human DYRK2
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 328.44, ALogP 3.85, HBA 5, HBD 1, PSA 57.37, QED 0.42
Compound (SMILES): CCCCCCCCCCCCCCCCCCCCOP(=O)(O)CO[C@H](C)Cn1cnc2c(N)ncnc21
InChIKey: OVZZUHCTLJGKGA-AREMUKBSSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 567.76, ALogP 8.01, HBA 8, HBD 2, PSA 125.38, QED 0.09
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](C)NC(=O)c2ccc(CN)cc2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: SVIMEEXLVAYGAH-JHVJFLLYSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 536.55, ALogP 2.4, HBA 6, HBD 4, PSA 139.62, QED 0.35
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)[C@H](c2ccc(Cl)cc2)C(C)C)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: UWQMSEUKOSQYLM-ORYMTKCHSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 703.2, ALogP 5.4, HBA 6, HBD 4, PSA 139.62, QED 0.17
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](CCCCN)NC(=O)C(F)(F)c2cccc(Cl)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: ZJCHODKGGSIAKG-VABKMULXSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 649.06, ALogP 4.18, HBA 6, HBD 4, PSA 139.62, QED 0.17
Compound (SMILES): COc1nc(C(=O)NCC(C)(O)C(F)(F)F)c(N)cc1C(F)(F)F
InChIKey: USHQRIKZLHNPQR-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Potentiator Assay: Fischer Rat Thyroid (FRT) epithelial cells, stably expressing human ΔF508-CFTR were used as monolayer cultures on permeable supports. Cl− current was measured using the short circuit current technique, under an imposed basolateral to apical Cl− gradient in Ussing chambers. To measure stable Cl− currents, FRT cells were cultured for 48 h at 27° C. to facilitate the insertion of ΔF508 CFTR into the plasma membrane. Ussing chamber studies were likewise conducted at 27° C. Under these conditions, the effects of cumulative additions of test compounds on ΔF508 CFTR currents could be quantitated with both potency and efficacy endpoints. Compounds were added to both the apical and basloalteral sides subsequent to addition of 10 μM forskolin. Efficacy of compounds was compared to a known potentiator such as gensitein.
Measurement: EC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 361.24, ALogP 1.73, HBA 5, HBD 3, PSA 97.47, QED 0.71
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](C)NC(=O)Cc2ccc(CN)cc2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: BZJPOELBRJYOBD-GMWOSMDTSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 550.58, ALogP 2.33, HBA 6, HBD 4, PSA 139.62, QED 0.32
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)c2cccc(C(F)(F)F)c2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: VLOYTACYFJHDRZ-QKDODKLFSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 680.65, ALogP 4.64, HBA 6, HBD 4, PSA 139.62, QED 0.19
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccc(CN)cc2)NC(=O)c2ccc(Cl)s2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: WNIUMFAWZBLJAD-TUSQITKMSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 653.12, ALogP 4.34, HBA 7, HBD 4, PSA 139.62, QED 0.22
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)c2cc(-c3cccc(Cl)c3)nc3ccccc23)cc1
InChIKey: CGEUZPONROHUFH-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human recombinant carbonic anhydrase 1 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 838.2 nM (pChEMBL 6.079999923706055)
Descriptors: MW 437.91, ALogP 4.45, HBA 4, HBD 2, PSA 102.15, QED 0.49
Compound (SMILES): O=C(Sc1ncccn1)c1cc2ccccc2[nH]1
InChIKey: JNFJWTCLKULUSB-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant his tagged SARS CoV-2 main protease expressed in Escherichia coli BL21 using Boc-Abu-Tle-Leu-Gln-AMC37 as fluorogenic substrate pre-incubated for 5 mins followed by substrate addition measured after 60 mins by FRET based assay
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 255.3, ALogP 2.89, HBA 4, HBD 1, PSA 58.64, QED 0.56
Compound (SMILES): CC(C)Cn1cc(C#N)c2ccc(NC(=O)c3cc(=O)[nH]cn3)cc21
InChIKey: SRGHTGISLBEDFE-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition of xanthine oxidase (unknown origin) using xanthine as substrate incubated for 15 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.37, ALogP 2.5, HBA 5, HBD 2, PSA 103.57, QED 0.76
Compound (SMILES): C=CC(=O)Nc1cc(C(=O)NCc2cn([C@@H]3CCCC[C@H]3OC)nn2)cc(-c2n[nH]c3ccccc23)c1
InChIKey: MFUGWMODLTYDTQ-DNQXCXABSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O14733
Assay: Inhibition of N-terminal 6XHis-tagged recombinant MKK7 (117 to 423 residues) (unknown origin) expressed in Escherichia coli BL21-DE3 preincubated for 2 hrs in presence of ATP measured after 17 hrs
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 499.58, ALogP 4.01, HBA 7, HBD 3, PSA 126.82, QED 0.31
Compound (SMILES): CC1(N)CCN(c2cnc(Sc3cccc4ccccc34)c(N)n2)CC1
InChIKey: VVXNNCUCIGNYBG-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of wild-type human SHP2 (1 to 535 residues) using DiFMUP and 2p-IRS1 peptide as substrates preincubated for 1 hr and followed by substrate addition and measured by microplate reader method
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 365.51, ALogP 3.68, HBA 6, HBD 2, PSA 81.06, QED 0.74
Compound (SMILES): C=CCn1ccc2cc(Nc3ncnc4ccc(N)cc34)ccc21
InChIKey: HDEJJZVYOHWFLK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (14 to 721 residues) (unknown origin) by western blot analysis
Measurement: IC50 = 351.9 nM (pChEMBL 6.449999809265137)
Descriptors: MW 315.38, ALogP 4.1, HBA 5, HBD 2, PSA 68.76, QED 0.44
Compound (SMILES): CCCSc1nc(NCCN)c2nnn(Cc3ccc(Cl)cc3)c2n1
InChIKey: CJSFNVZMUYLMDJ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Inhibition of USP28 (unknown origin)
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 377.91, ALogP 2.8, HBA 8, HBD 2, PSA 94.54, QED 0.46
Compound (SMILES): Cc1cnc2c(n1)c(C(N)=O)c(N)n2-c1c(C)ccc(O)c1C
InChIKey: WHYJZCBTMCZRNS-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Inhibition of N-terminal recombinant PKMYT1 (76 to 362 residues) in CCNE1 amplified human FU-OV-1 cells assessed as phosphorylation of CDK1 at Thr14 incubated for 2 hrs by AlphaLisa assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 311.35, ALogP 1.73, HBA 6, HBD 3, PSA 120.05, QED 0.67
Compound (SMILES): Nc1nc(-c2ccco2)c2cnn(CCCCCCCC(=O)NO)c2n1
InChIKey: SECVDVLEPFNKCJ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]SCH5826 from human A2AAR incubated for 60 mins by scintillation counter analysis
Measurement: Ki = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 358.4, ALogP 2.51, HBA 8, HBD 3, PSA 132.09, QED 0.3
Compound (SMILES): CC(=O)Nc1ncc(CN2CCC(C(=O)Nc3ccc4ncccc4c3)CC2)s1
InChIKey: SBGCLXIHXJKXGT-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of human recombinant OGA pretreated for 20 mins followed by 4-Methylumbelliferyl N-acetyl-(3-D-glucosaminide substrate addition by fluorometer
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 409.52, ALogP 3.5, HBA 6, HBD 2, PSA 87.22, QED 0.67
Compound (SMILES): O=C(CCCCCCn1c(C(=O)NC2C3CC4CC(C3)CC2C4)cc2ccccc21)NO
InChIKey: FWISWOLPVMBVAL-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorescence plate reader assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 437.58, ALogP 4.65, HBA 4, HBD 3, PSA 83.36, QED 0.3
Compound (SMILES): Cc1cc(Nc2nc(NCc3ccc(F)cc3F)nc3c2cnn3C)n[nH]1
InChIKey: RXHAUQUQIMFCLS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00444
Assay: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay
Measurement: IC50 = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 370.37, ALogP 3.03, HBA 7, HBD 3, PSA 96.34, QED 0.5
Compound (SMILES): N#CCC(=O)OCCCCCCCCCCCCNC(=O)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: MZEJKCLZBXQZCV-HKTXSPCFSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15399
Assay: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 1044.31
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(N)=O)c2nc3cccc(-c4ccnn4C)c3nc21
InChIKey: YQIJZSUZISVPME-UHFFFAOYSA-N
Target: Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99640
Assay: Inhibition of N-terminal human recombinant PKMYT1 (76 to 362 residues) expressed in Escherichia coli (DE3) RIL preincubated with compound for 15 mins in presence of ATP followed by 1 hr incubation by ADP-glo luminescence assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 427.47, ALogP 2.98, HBA 8, HBD 3, PSA 137.87, QED 0.4
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOCCOc1cc(Cl)ccc1N3
InChIKey: ZWNHCTNZGMTQTA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 431.88, ALogP 3.84, HBA 8, HBD 1, PSA 83.96, QED 0.62
Compound (SMILES): COc1ccc(CC(=O)Nc2cccc(CO)c2)cc1
InChIKey: AJEFBTNVOWMPLN-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS/nigericin-stimulated PMA-differentiated human THP-1 macrophages assessed as reduction in pyroptosis pretreated with LPS followed by compound treatment for 30 mins then stimulation with nigericin and measured after 3 hrs by MTT assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 271.32, ALogP 2.37, HBA 3, HBD 2, PSA 58.56, QED 0.88
Compound (SMILES): CC(C)OC(=O)/C=C/c1cccc(N(Cc2ccc(-c3ccc(N(C)C)cc3)c(C#N)c2)C(=O)C2CCCCC2)c1F
InChIKey: OWGZODPWWIQKIS-CAPFRKAQSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR transfected in CHO-K1 cells coexpressed with beta-galactosidase incubated for 3 to 16 hrs by PathHunter chemiluminescence based assay
Measurement: EC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 567.71, ALogP 7.51, HBA 5, HBD 0, PSA 73.64, QED 0.2
Compound (SMILES): CC(C)c1cnc(N2CC(C#N)C2)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: AOHNZGASXYBKDI-NLFFAJNJSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST tagged recombinant wild type human EGFR expressed in baculovirus infected Sf9 insect cells expression system using 5-FAM-EEPLYINSFPAKKK-CONH peptide as substrate preincubated for 10 mins followed by peptide substrate addition in presence of ATP
Measurement: IC50 = 3401 nM (pChEMBL 5.46999979019165)
Descriptors: MW 476.56, ALogP 3.55, HBA 9, HBD 2, PSA 114.09, QED 0.57
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)N[C@H]1CC[C@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: VQJNNDGKPYTFNR-CZIWCDLHSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin)
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 397.88, ALogP 5.88, HBA 2, HBD 2, PSA 54.02, QED 0.58
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: WLJISDHXQJWDBI-YZXGFTLRSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 3074.59
Compound (SMILES): N#Cc1ccc(NC(=O)c2ccn(-c3ccc(C#N)c(C(F)(F)F)c3)n2)cc1
InChIKey: KVJHFSMFTAFWMX-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor (unknown origin) in human LNCap-ARR2PB-eGFP cells by measuring fluorescence intensity measured after 3 days by transcriptional assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 381.32, ALogP 3.89, HBA 5, HBD 1, PSA 94.5, QED 0.74
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(N)=O)C(C)C
InChIKey: WONMZRKDYXHZOT-UEOMBKFZSA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of human recombinant MMP-7 (Leu18 to Lys267 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 755.21, ALogP 1.13, HBA 8, HBD 6, PSA 234.17, QED 0.13
Compound (SMILES): CC(=O)Nc1ncc(CN2CCC(C(=O)Nc3ccc(Cl)cc3)CC2)s1
InChIKey: VHJAACZDWDHBFF-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Inhibition of human recombinant OGA pretreated for 20 mins followed by 4-Methylumbelliferyl N-acetyl-(3-D-glucosaminide substrate addition by fluorometer
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 392.91, ALogP 3.61, HBA 5, HBD 2, PSA 74.33, QED 0.81
Compound (SMILES): CS(=O)(=O)c1ccc(NC(=O)N/N=C\c2ccccc2)cc1
InChIKey: TYQCCECWXORCAL-WJDWOHSUSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human recombinant FAAH using arachidonoyl as substrate preincubated for 5 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 317.37, ALogP 2.25, HBA 4, HBD 2, PSA 87.63, QED 0.67
Compound (SMILES): CCN(CC)Cc1ccccc1CNC(=O)c1ccc(Br)c(NC(=O)c2ccc(F)cc2)c1
InChIKey: UMKPOYZZISVJJU-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 2.42 nM (pChEMBL 8.619999885559082)
Descriptors: MW 512.42, ALogP 5.61, HBA 3, HBD 2, PSA 61.44, QED 0.39
Compound (SMILES): CNS(=O)(=O)Cc1ccc(-n2nc(C(=O)O)cc2C)cc1
InChIKey: OTGFXQYWBGEGLL-UHFFFAOYSA-N
Target: RNA demethylase ALKBH5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P6C2
Assay: Inhibition of human recombinant ALKBH5 (66 to 292 residues) expressed in Escherichia coli BL21 (DE3) cells using FAM-labeled ssRNA (5'-CUCGAUACG(m^6A) UCCGGUCAAA-3') as substrate incubated for 60 mins by fluorescence polarization assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 309.35, ALogP 0.93, HBA 5, HBD 2, PSA 101.29, QED 0.86