lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=Cc1c(O)ccc2cc(-c3ccc(C(=O)N4CCOCC4)cc3)ccc12
InChIKey: NBHZRTPTDVODBZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 361.4, ALogP 3.5, HBA 4, HBD 1, PSA 66.84, QED 0.73
Compound (SMILES): CN1CCN(C(=O)c2cccc(-c3ccc4c(C=O)c(O)ccc4c3)n2)CC1
InChIKey: GEAJABVEYURERR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: In Vitro Enzyme Assays: IRE-1 alpha, T1 RNase, and RNase A assays carried out in vitro with several o-vanillin derivatives to demonstrate selectivity of the derivatives for IRE-1 alpha. T1 RNase was assayed as follows. Five ul of a reaction mixture comprising 1x reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water were added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution were added to test wells. Three ul of a 1/48,000 dilution of an approximately 200,000 U/ml RNase T1 (Worthington) preparation were added to each test well and to positive control wells (final concentration 49.5 pg/well). Negative control wells contained only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 ul of the mini-XBP-1 mRNA stem-loop substrate described in Example 1 were added to each well of a control plate.
Measurement: IC50 = 389 nM (pChEMBL 6.409999847412109)
Descriptors: MW 375.43, ALogP 2.81, HBA 5, HBD 1, PSA 73.74, QED 0.71
Compound (SMILES): O=Cc1c(O)ccc2ncccc12
InChIKey: TUVJXIJXRIXXMI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: In Vitro Enzyme Assays: IRE-1 alpha, T1 RNase, and RNase A assays carried out in vitro with several o-vanillin derivatives to demonstrate selectivity of the derivatives for IRE-1 alpha. T1 RNase was assayed as follows. Five ul of a reaction mixture comprising 1x reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water were added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution were added to test wells. Three ul of a 1/48,000 dilution of an approximately 200,000 U/ml RNase T1 (Worthington) preparation were added to each test well and to positive control wells (final concentration 49.5 pg/well). Negative control wells contained only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 ul of the mini-XBP-1 mRNA stem-loop substrate described in Example 1 were added to each well of a control plate.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 173.17, ALogP 1.75, HBA 3, HBD 1, PSA 50.19, QED 0.67
Compound (SMILES): O=Cc1c(O)ccc2cccnc12
InChIKey: USROEJBTXWQSKM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 173.17, ALogP 1.75, HBA 3, HBD 1, PSA 50.19, QED 0.67
Compound (SMILES): Cc1cc(O)nc2ccc(O)c(C=O)c12
InChIKey: NMIXKRAZLHFFDG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 203.2, ALogP 1.77, HBA 4, HBD 2, PSA 70.42, QED 0.69
Compound (SMILES): COc1cc(Br)cc(C2NCC(C(=O)O)S2)c1O
InChIKey: PAZDIYSQBDEGKJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 334.19, ALogP 1.95, HBA 5, HBD 3, PSA 78.79, QED 0.78
Compound (SMILES): CCOC(=O)C1CNC(c2cc(Br)cc(OC)c2O)S1
InChIKey: CMEGUYPXYPDAGH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 362.25, ALogP 2.43, HBA 6, HBD 2, PSA 67.79, QED 0.8
Compound (SMILES): COc1cc(Br)cc(C2NCCS2)c1O
InChIKey: GTTMAAKFNJFEQG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 290.18, ALogP 2.5, HBA 4, HBD 2, PSA 41.49, QED 0.88
Compound (SMILES): O=C(O)c1ccc(Br)c(C2NCCS2)c1O
InChIKey: HYLCMVHTEPFTQQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 304.17, ALogP 2.19, HBA 4, HBD 3, PSA 69.56, QED 0.78
Compound (SMILES): O=C(O)c1ccc(Br)c(C2NC(C(=O)O)CS2)c1O
InChIKey: GTYPLLUJKXJPPT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 348.17, ALogP 1.64, HBA 5, HBD 4, PSA 106.86, QED 0.66
Compound (SMILES): CCOC(=O)C1CSC(c2c(O)c(OCC)cc(Br)c2Br)N1
InChIKey: MCDVEBMIILVHIK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 455.17, ALogP 3.58, HBA 6, HBD 2, PSA 67.79, QED 0.66
Compound (SMILES): COc1cc(-c2cccs2)cc(C2NCCS2)c1O
InChIKey: SPLWICNVGMBXDY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 293.41, ALogP 3.46, HBA 5, HBD 2, PSA 41.49, QED 0.91
Compound (SMILES): COc1cc(-c2cccs2)cc(C2NC(C(=O)O)CS2)c1O
InChIKey: AXRSCCUEBKBDSD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 337.42, ALogP 2.92, HBA 6, HBD 3, PSA 78.79, QED 0.8
Compound (SMILES): CCOc1cc(Br)c(Br)c(C2NC(C(=O)O)CS2)c1O
InChIKey: DHIWIOZWSSQJPE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 427.11, ALogP 3.1, HBA 5, HBD 3, PSA 78.79, QED 0.69
Compound (SMILES): COc1cc(Br)cc(/C=N/CCSSCC/N=C/c2cc(Br)cc(OC)c2O)c1O
InChIKey: HPQUXXASEDJCLW-ASIDMNOUSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 578.35, ALogP 5.56, HBA 8, HBD 2, PSA 83.64, QED 0.21
Compound (SMILES): COc1ccc(C/N=C/c2cc(Br)cc(OC)c2O)cc1
InChIKey: DNBYBUFULJDRSF-VCHYOVAHSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 350.21, ALogP 3.79, HBA 4, HBD 1, PSA 51.05, QED 0.84
Compound (SMILES): COc1cc(Br)cc(/C=N/C2CC2)c1O
InChIKey: ZPFBYRHROPKYTD-AWNIVKPZSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 270.13, ALogP 2.74, HBA 3, HBD 1, PSA 41.82, QED 0.86
Compound (SMILES): COc1cc(-c2cccs2)cc(/C=N/C2CC2)c1O
InChIKey: GOEZJVUXLULBEN-CXUHLZMHSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 273.36, ALogP 3.71, HBA 4, HBD 1, PSA 41.82, QED 0.86
Compound (SMILES): COc1ccc(C/N=C/c2cc(-c3cccs3)cc(OC)c2O)cc1
InChIKey: OBYPICOTTJUVPF-FYJGNVAPSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 353.44, ALogP 4.76, HBA 5, HBD 1, PSA 51.05, QED 0.65
Compound (SMILES): COc1cc(-c2cccs2)cc(/C=N\CCO)c1O
InChIKey: DEFNFYIIOJJXCW-DHDCSXOGSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 277.35, ALogP 2.54, HBA 5, HBD 2, PSA 62.05, QED 0.83
Compound (SMILES): COc1cc(Br)cc(/C=N/CCO)c1O
InChIKey: OPZVGOXKSBKGRR-WUXMJOGZSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 274.11, ALogP 1.57, HBA 4, HBD 2, PSA 62.05, QED 0.82
Compound (SMILES): COc1cc(Br)cc(/C=N/c2nccs2)c1O
InChIKey: PGWBOUAOTSSDPT-MKMNVTDBSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 313.18, ALogP 3.37, HBA 5, HBD 1, PSA 54.71, QED 0.88
Compound (SMILES): COc1cc(-c2cccs2)cc(/C=N/c2ccccn2)c1O
InChIKey: UXDFHQKTKVMODK-YBFXNURJSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: In Vitro Enzyme Assays: IRE-1 alpha, T1 RNase, and RNase A assays carried out in vitro with several o-vanillin derivatives to demonstrate selectivity of the derivatives for IRE-1 alpha. T1 RNase was assayed as follows. Five ul of a reaction mixture comprising 1x reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water were added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution were added to test wells. Three ul of a 1/48,000 dilution of an approximately 200,000 U/ml RNase T1 (Worthington) preparation were added to each test well and to positive control wells (final concentration 49.5 pg/well). Negative control wells contained only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 ul of the mini-XBP-1 mRNA stem-loop substrate described in Example 1 were added to each well of a control plate.
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 310.38, ALogP 4.27, HBA 5, HBD 1, PSA 54.71, QED 0.73
Compound (SMILES): O=Cc1cc2ccccc2c(CN2CCCCC2)c1O
InChIKey: XQZATKUVVVKTRP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 269.34, ALogP 3.34, HBA 3, HBD 1, PSA 40.54, QED 0.87
Compound (SMILES): COc1cc(-c2ccccn2)cc(C=O)c1O
InChIKey: USRFMONMCQGCIP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 229.24, ALogP 2.28, HBA 4, HBD 1, PSA 59.42, QED 0.82
Compound (SMILES): O=Cc1cc(-c2ccc(C(=O)N3CCOCC3)cc2)cc(F)c1O
InChIKey: HSHBSCLGZZKDRH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: In Vitro Enzyme Assays: IRE-1 alpha, T1 RNase, and RNase A assays carried out in vitro with several o-vanillin derivatives to demonstrate selectivity of the derivatives for IRE-1 alpha. T1 RNase was assayed as follows. Five ul of a reaction mixture comprising 1x reaction buffer (5x reaction buffer is 100 mM Hepes pH 7.5, 250 mM KOAc, 2.5 mM MgCl2), 3 mM DTT, and 0.4% polyethylene glycol water were added to each well of 384 well plates. Twenty-five nanoliters of a 1 mM test compound solution were added to test wells. Three ul of a 1/48,000 dilution of an approximately 200,000 U/ml RNase T1 (Worthington) preparation were added to each test well and to positive control wells (final concentration 49.5 pg/well). Negative control wells contained only reaction mixture and test compound. After spinning the plates at 1200 rpm for 30 seconds, 3 ul of the mini-XBP-1 mRNA stem-loop substrate described in Example 1 were added to each well of a control plate.
Measurement: IC50 = 221 nM (pChEMBL 6.659999847412109)
Descriptors: MW 329.33, ALogP 2.48, HBA 4, HBD 1, PSA 66.84, QED 0.88
Compound (SMILES): COc1ncc(-c2cc(C=O)c(O)c(OC)c2)s1
InChIKey: BNBRGNGOBBDZQO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 265.29, ALogP 2.35, HBA 6, HBD 1, PSA 68.65, QED 0.86
Compound (SMILES): O=Cc1c(O)ccc2cc(Br)ccc12
InChIKey: GSZLSWQEDNSDKG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 251.08, ALogP 3.12, HBA 2, HBD 1, PSA 37.3, QED 0.79
Compound (SMILES): Cc1nc2ccccc2c(C=O)c1O
InChIKey: NINIEBVPQSTZAO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 187.2, ALogP 2.06, HBA 3, HBD 1, PSA 50.19, QED 0.69
Compound (SMILES): COc1cc(C#Cc2cccnc2)cc(C=O)c1O
InChIKey: WRQZMBDWLKIEHY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Cell-Based Assay: Initial cell-based XBP-1 mRNA splicing assays confirmed IRE-1α inhibition with several potent 5-bromo and 6 bromo o-vanillins. HEK293 cells were incubated with compound either overnight or for 2 hours prior to IRE-1α activation with the UPR inducing reagent thapsigargin. IRE-1α mediated XBP-1 splicing was measured by RT-PCR using XBP-1 specific primers flanking the 26 bp intron excised by IRE-1α. The results are shown in FIG. 1. It can be observed that at the higher concentrations, there is relatively more of the unspliced XBP-1 (upper band: substrate) compared to the spliced form (lower band: product).
Measurement: EC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 253.26, ALogP 2.01, HBA 4, HBD 1, PSA 59.42, QED 0.66
Compound (SMILES): CC(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: VMYNMIVIUVJIHY-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.02511 nM (pChEMBL 10.600000381469727)
Descriptors: MW 322.37, ALogP 2.05, HBA 5, HBD 2, PSA 86.8, QED 0.77
Compound (SMILES): COC(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: YEMGRNZLFUZGTR-LLVKDONJSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.1723 nM (pChEMBL 9.760000228881836)
Descriptors: MW 338.37, ALogP 2.27, HBA 6, HBD 2, PSA 96.03, QED 0.76
Compound (SMILES): CS(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: NONQHXZJSJTQSM-LLVKDONJSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.01047 nM (pChEMBL 10.979999542236328)
Descriptors: MW 358.43, ALogP 1.47, HBA 6, HBD 2, PSA 103.87, QED 0.73
Compound (SMILES): CC(=O)N1CCC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: SBOGQLBMEWOYIL-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.01281 nM (pChEMBL 10.890000343322754)
Descriptors: MW 336.4, ALogP 2.44, HBA 5, HBD 2, PSA 86.8, QED 0.77
Compound (SMILES): COC(=O)N1CCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)CC1
InChIKey: SQPIIYGBMFSLFR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.1604 nM (pChEMBL 9.789999961853027)
Descriptors: MW 352.4, ALogP 2.66, HBA 6, HBD 2, PSA 96.03, QED 0.75
Compound (SMILES): CC(=O)N1CCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)CC1
InChIKey: YKBQLVVJJHUKDV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.6049 nM (pChEMBL 9.220000267028809)
Descriptors: MW 336.4, ALogP 2.44, HBA 5, HBD 2, PSA 86.8, QED 0.77
Compound (SMILES): CC(=O)N1CC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: VMYNMIVIUVJIHY-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.06345 nM (pChEMBL 10.199999809265137)
Descriptors: MW 322.37, ALogP 2.05, HBA 5, HBD 2, PSA 86.8, QED 0.77
Compound (SMILES): COC(=O)N1CC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: YEMGRNZLFUZGTR-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.2198 nM (pChEMBL 9.65999984741211)
Descriptors: MW 338.37, ALogP 2.27, HBA 6, HBD 2, PSA 96.03, QED 0.76
Compound (SMILES): CS(=O)(=O)N1CC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: NONQHXZJSJTQSM-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.01794 nM (pChEMBL 10.75)
Descriptors: MW 358.43, ALogP 1.47, HBA 6, HBD 2, PSA 103.87, QED 0.73
Compound (SMILES): CC(=O)N1CCCCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: RUGKMJBVTQEPHN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.0191 nM (pChEMBL 10.720000267028809)
Descriptors: MW 350.43, ALogP 2.83, HBA 5, HBD 2, PSA 86.8, QED 0.76
Compound (SMILES): COC(=O)N1CCCCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: CYEYGIKHGQVFKY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.02529 nM (pChEMBL 10.600000381469727)
Descriptors: MW 366.43, ALogP 3.05, HBA 6, HBD 2, PSA 96.03, QED 0.74
Compound (SMILES): CS(=O)(=O)N1CCCCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: XNDQNBFQNOZWQD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.0209 nM (pChEMBL 10.680000305175781)
Descriptors: MW 386.48, ALogP 2.25, HBA 6, HBD 2, PSA 103.87, QED 0.71
Compound (SMILES): CC(C)S(=O)(=O)N1CCC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: HHXSVVCZOVUGCW-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.7792 nM (pChEMBL 9.109999656677246)
Descriptors: MW 400.51, ALogP 2.63, HBA 6, HBD 2, PSA 103.87, QED 0.68
Compound (SMILES): CCS(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: XGRFWJQVCIPXOC-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1919 nM (pChEMBL 9.720000267028809)
Descriptors: MW 372.45, ALogP 1.86, HBA 6, HBD 2, PSA 103.87, QED 0.71
Compound (SMILES): CCCS(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: VVAGTJJOXKEOOR-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.542 nM (pChEMBL 9.270000457763672)
Descriptors: MW 386.48, ALogP 2.25, HBA 6, HBD 2, PSA 103.87, QED 0.67
Compound (SMILES): CC(C)S(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: NXHURUHKYZXIRH-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.8052 nM (pChEMBL 9.09000015258789)
Descriptors: MW 386.48, ALogP 2.24, HBA 6, HBD 2, PSA 103.87, QED 0.7
Compound (SMILES): CC(C)CS(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: UBVVFSWHJMHBPY-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.662 nM (pChEMBL 9.180000305175781)
Descriptors: MW 400.51, ALogP 2.49, HBA 6, HBD 2, PSA 103.87, QED 0.66
Compound (SMILES): CCC(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: NKIGZOJXNGMDHT-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1948 nM (pChEMBL 9.710000038146973)
Descriptors: MW 336.4, ALogP 2.44, HBA 5, HBD 2, PSA 86.8, QED 0.76
Compound (SMILES): CCCC(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: QWFFOELVGDLHSA-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.7003 nM (pChEMBL 9.149999618530273)
Descriptors: MW 350.43, ALogP 2.83, HBA 5, HBD 2, PSA 86.8, QED 0.74
Compound (SMILES): CC(C)C(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: GJFCCGNALMSJGQ-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1684 nM (pChEMBL 9.770000457763672)
Descriptors: MW 350.43, ALogP 2.69, HBA 5, HBD 2, PSA 86.8, QED 0.76
Compound (SMILES): CC(C)CC(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: XEGGRPXMVKBQIS-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 364.45, ALogP 3.08, HBA 5, HBD 2, PSA 86.8, QED 0.73
Compound (SMILES): C[C@H]1C[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)CN(S(C)(=O)=O)C1
InChIKey: BSFUWLNZPOVRBF-STQMWFEESA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.03714 nM (pChEMBL 10.430000305175781)
Descriptors: MW 386.48, ALogP 2.1, HBA 6, HBD 2, PSA 103.87, QED 0.71
Compound (SMILES): CC(C)CCS(=O)(=O)N1CC[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: AEDGJZHEZKVHKW-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.5467 nM (pChEMBL 9.260000228881836)
Descriptors: MW 414.54, ALogP 2.88, HBA 6, HBD 2, PSA 103.87, QED 0.62
Compound (SMILES): CC(C)S(=O)(=O)N1C[C@@H](C)C[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: SCNCLWXRXWWBQJ-GJZGRUSLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.01517 nM (pChEMBL 10.819999694824219)
Descriptors: MW 414.54, ALogP 2.88, HBA 6, HBD 2, PSA 103.87, QED 0.67
Compound (SMILES): CC(=O)N1CCCC(Nc2nc(C)ccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: KYGMSHBHSDBHRQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.06075 nM (pChEMBL 10.220000267028809)
Descriptors: MW 350.43, ALogP 2.75, HBA 5, HBD 2, PSA 86.8, QED 0.76
Compound (SMILES): Cc1ccc(-c2cnc3[nH]ccc3n2)c(NC2CCCN(S(C)(=O)=O)C2)n1
InChIKey: UXPYEJLTPMRCCL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.0464 nM (pChEMBL 10.329999923706055)
Descriptors: MW 386.48, ALogP 2.16, HBA 6, HBD 2, PSA 103.87, QED 0.71
Compound (SMILES): FC(F)(F)CN1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: SNVFGNBQSYUPIG-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.1029 nM (pChEMBL 9.989999771118164)
Descriptors: MW 376.39, ALogP 3.46, HBA 5, HBD 2, PSA 69.73, QED 0.73
Compound (SMILES): CCS(=O)(=O)N1CCCC(Nc2nc(C)ccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: HLKWWAPBFBSHJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.05099 nM (pChEMBL 10.289999961853027)
Descriptors: MW 400.51, ALogP 2.55, HBA 6, HBD 2, PSA 103.87, QED 0.68
Compound (SMILES): Cc1ccc(-c2cnc3[nH]ccc3n2)c(NC2CCCN(S(=O)(=O)CC3CC3)C2)n1
InChIKey: UWIRTXHTCICCEB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.01988 nM (pChEMBL 10.699999809265137)
Descriptors: MW 426.55, ALogP 2.94, HBA 6, HBD 2, PSA 103.87, QED 0.63
Compound (SMILES): Cc1ccc(-c2cnc3[nH]ccc3n2)c(NC2CCCN(S(=O)(=O)CC(C)(C)C)C2)n1
InChIKey: QUTDVGIAVRPCRG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.01676 nM (pChEMBL 10.779999732971191)
Descriptors: MW 442.59, ALogP 3.58, HBA 6, HBD 2, PSA 103.87, QED 0.63
Compound (SMILES): CS(=O)(=O)N1CCCC(Nc2ncccc2-c2cnc3[nH]ccc3n2)CC1
InChIKey: AUWLNQDLZOSAFU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.03938 nM (pChEMBL 10.399999618530273)
Descriptors: MW 386.48, ALogP 2.25, HBA 6, HBD 2, PSA 103.87, QED 0.71
Compound (SMILES): CC(=O)N1CCCC(Nc2nc(C)ccc2-c2cnc3[nH]cc(Cl)c3n2)C1
InChIKey: JXUVCKRLKKIQLV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.06878 nM (pChEMBL 10.15999984741211)
Descriptors: MW 384.87, ALogP 3.4, HBA 5, HBD 2, PSA 86.8, QED 0.72
Compound (SMILES): Cc1ccc(-c2cnc3[nH]cc(Cl)c3n2)c(NC2CCCN(S(=O)(=O)CC3CC3)C2)n1
InChIKey: FZKHNSXOKWXUHM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.03508 nM (pChEMBL 10.449999809265137)
Descriptors: MW 460.99, ALogP 3.6, HBA 6, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): Cn1ccc2ncc(-c3cccnc3N[C@H]3CCCN(S(C)(=O)=O)C3)nc21
InChIKey: RLYDDKYLBSDJBO-ZDUSSCGKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 1.627 nM (pChEMBL 8.789999961853027)
Descriptors: MW 386.48, ALogP 1.87, HBA 7, HBD 1, PSA 93.01, QED 0.74
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3nc[nH]c3n2)C1
InChIKey: BOTKSPMLRQABAG-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 1.185 nM (pChEMBL 8.930000305175781)
Descriptors: MW 373.44, ALogP 1.25, HBA 7, HBD 2, PSA 116.76, QED 0.71
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ncc3n2)C1
InChIKey: XEMVVCSEZINFNJ-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.8586 nM (pChEMBL 9.069999694824219)
Descriptors: MW 373.44, ALogP 1.25, HBA 7, HBD 2, PSA 116.76, QED 0.71
Compound (SMILES): CCCS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ncc3n2)C1
InChIKey: ZVYNVRJNUSIWHA-ZDUSSCGKSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.8331 nM (pChEMBL 9.079999923706055)
Descriptors: MW 401.5, ALogP 2.03, HBA 7, HBD 2, PSA 116.76, QED 0.65
Compound (SMILES): CC(C)CS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ncc3n2)C1
InChIKey: PFPSPXFFLSAKPW-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.2906 nM (pChEMBL 9.539999961853027)
Descriptors: MW 415.52, ALogP 2.28, HBA 7, HBD 2, PSA 116.76, QED 0.63
Compound (SMILES): CCCS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3cc[nH]c3n2)C1
InChIKey: ROEWBSDPRROMGI-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.3102 nM (pChEMBL 9.510000228881836)
Descriptors: MW 400.51, ALogP 2.64, HBA 6, HBD 2, PSA 103.87, QED 0.66