lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1CN(c2cc(F)c(-c3ncc(C(=O)N(C)C4CCCCC4)s3)cc2NC(=O)c2c[nH]c(=O)cc2C(F)(F)F)C[C@H](C)N1C
InChIKey: LYYCISKTVJXSEH-HDICACEKSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Surface Plasmon Resonance (SPR) Assay: Exemplary compounds of the application were dissolved in 100% DMSO at 10 mM, assayed fresh, and then stored at −20° C. for repeat studies and other experiments. Full length WDR5 with an N-terminal His tag and C-terminal AviTag (Avidity Inc.) was expressed in E. coli with coexpression of BirA to biotin labelled protein in vivo. Purification of the protein was performed using Ni-NTA. The purified WDR5 protein has a molecular weight of 41976 Da.SPR studies were performed using a Biacore T200 instrument (GE Health Sciences Inc.). Biotinylated WDR5 protein (approximately 3000 RU) was stably captured to streptavidin coupled SA chips according to the manufacture's protocol (GE Health Sciences Inc.). The running buffer used was HBS-EP (20 mM Hepes pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.05% P-20) plus 5% DMSO with a flow rate of 40 μl/min. For SPR analysis, 5 different concentrations of each exemplary compound of the application were sprayed into 96 or 384 well plates using an HP D300 digital dispenser. The concentration ranged from about 195 nM to about 12 nM in a two-fold series. Concentration ranges were adjusted higher or lower for weaker or more potent compounds respectively when necessary. For the KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 or 600 seconds. Curve fitting and KD calculations were performed with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 648.73, ALogP 5.84, HBA 7, HBD 2, PSA 101.64, QED 0.33
Compound (SMILES): C[C@@H]1CN(c2cc(F)c(-c3ncc(C(=O)N4CCOCC4)s3)cc2NC(=O)c2c[nH]c(=O)cc2C(F)(F)F)C[C@H](C)N1C
InChIKey: LTNYVUGUYWIGTP-IYBDPMFKSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Surface Plasmon Resonance (SPR) Assay: Exemplary compounds of the application were dissolved in 100% DMSO at 10 mM, assayed fresh, and then stored at −20° C. for repeat studies and other experiments. Full length WDR5 with an N-terminal His tag and C-terminal AviTag (Avidity Inc.) was expressed in E. coli with coexpression of BirA to biotin labelled protein in vivo. Purification of the protein was performed using Ni-NTA. The purified WDR5 protein has a molecular weight of 41976 Da.SPR studies were performed using a Biacore T200 instrument (GE Health Sciences Inc.). Biotinylated WDR5 protein (approximately 3000 RU) was stably captured to streptavidin coupled SA chips according to the manufacture's protocol (GE Health Sciences Inc.). The running buffer used was HBS-EP (20 mM Hepes pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.05% P-20) plus 5% DMSO with a flow rate of 40 μl/min. For SPR analysis, 5 different concentrations of each exemplary compound of the application were sprayed into 96 or 384 well plates using an HP D300 digital dispenser. The concentration ranged from about 195 nM to about 12 nM in a two-fold series. Concentration ranges were adjusted higher or lower for weaker or more potent compounds respectively when necessary. For the KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 or 600 seconds. Curve fitting and KD calculations were performed with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 1.85 nM (pChEMBL 8.729999542236328)
Descriptors: MW 622.64, ALogP 3.91, HBA 8, HBD 2, PSA 110.87, QED 0.42
Compound (SMILES): COC[C@@](OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)(C(=O)O)P(=O)(O)O
InChIKey: IMWXADAFBCLROW-HFBDYMDKSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Biochemical Assay: Assay Reaction ConditionsAssay Volume: 70 μlReaction Volume: 50 μlCD73: 0.3208 nMAMP: 15 μMAssay Buffer: 25 mM Tris-HCL, pH 7.4, 0.01% Brij-35, 0.01% BSA, 5 mM MgCl2Assay Procedure:Used 384 clear plate.Made dose titration of testing compounds in assay buffer, 10 points ½ log titrations in duplicates starting at 100 μM.Added 25 μl of CD73 to each well for a final concentration of 320 pM.Incubated at RT for 15 min.Added 25 μl of AMP to each well for a final concentration of 15 μM.Incubated at RT for 10 min.Added 10 μl of Malachite Green Reagent A, incubate at RT for 10 min.Added 10 of Malachite Green Reagent B, incubate at RT for 45 min.Read the Absorbance on Envision plate reader using excitation filter: Cy5 620 nM.The ability of the compounds disclosed herein to inhibit CD73 activity was quantified and the respective IC50 values were determined.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 551.88, ALogP 0.07, HBA 12, HBD 6, PSA 218.61, QED 0.17
Compound (SMILES): COC[C@](OC[C@H]1O[C@@H](n2ncc3c(NC4CCCC4)nc(Cl)nc32)[C@H](O)[C@@H]1O)(C(=O)O)P(=O)(O)O
InChIKey: IMWXADAFBCLROW-MKHSKWLFSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Biochemical Assay: Assay Reaction ConditionsAssay Volume: 70 μlReaction Volume: 50 μlCD73: 0.3208 nMAMP: 15 μMAssay Buffer: 25 mM Tris-HCL, pH 7.4, 0.01% Brij-35, 0.01% BSA, 5 mM MgCl2Assay Procedure:Used 384 clear plate.Made dose titration of testing compounds in assay buffer, 10 points ½ log titrations in duplicates starting at 100 μM.Added 25 μl of CD73 to each well for a final concentration of 320 pM.Incubated at RT for 15 min.Added 25 μl of AMP to each well for a final concentration of 15 μM.Incubated at RT for 10 min.Added 10 μl of Malachite Green Reagent A, incubate at RT for 10 min.Added 10 of Malachite Green Reagent B, incubate at RT for 45 min.Read the Absorbance on Envision plate reader using excitation filter: Cy5 620 nM.The ability of the compounds disclosed herein to inhibit CD73 activity was quantified and the respective IC50 values were determined.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 551.88, ALogP 0.07, HBA 12, HBD 6, PSA 218.61, QED 0.17
Compound (SMILES): C[C@H]1[C@@H](C(=O)Nc2cc(F)c(F)c(Br)c2)CCN1C(=O)C(=O)NC1(c2c[nH]nn2)CC(F)(F)C1
InChIKey: NNERUVSFXNYPKR-ONGXEEELSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Anti-HBV Activity: The anti HBV activity was measured using the HepG2.117 cell line, a stable, inducible HBV producing cell line, which replicates HBV in the absence of doxicycline (Tet-off system). The HepG2 cell line is available from ATCC®) under number HB-8065. Transfection of the HepG2 cell line can be as described in Sun and Nassal 2006 Journal of Hepatology 45 (2006) 636-645 Stable HepG2- and Huh7-based human hepatoma cell lines for efficient regulated expression of infectious hepatitis B virus.For the antiviral assay, HBV replication was induced, followed by a treatment with serially diluted compound in 96-well plates. After 3 days of treatment, the antiviral activity was determined by quantification of intracellular HBV DNA using real-time PCR and an HBV specific primer set and probe.Cytotoxicity of the compounds was tested using HepG2 or HepG2.117 cells, incubated for 3 days in the presence of compounds. The viability of the cells was assessed using the Perkin Elmer ATPlite Luminescence Assay System.
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 547.31, ALogP 2.46, HBA 5, HBD 3, PSA 120.08, QED 0.31
Compound (SMILES): CCn1c(-c2cccnc2[C@H](C)OC)c2c3cc(ccc31)-c1cc(O)cc(c1)C[C@H](NC(=O)[C@H](C(C)C)N(C)C(=O)c1nc(NC(=O)/C=C/CN(C)C)cs1)C(=O)N1CCC[C@H](N1)C(=O)OCC(C)(C)C2
InChIKey: CELWXOSQLDUBSO-VZXMIGGVSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Biochemical Assay: A variety of Ras proteins may be inhibited by compounds of the present invention (e.g., K-Ras, N-Ras, H-Ras, and mutants thereof at positions 12, 13 and 61, such as G12C, G12D, G12V, G12S, G13C, G13D, and Q61L, and others described herein). The purpose of this biochemical assay is to measure the ability of test compounds to covalently label nucleotide-loaded K-Ras isoforms. In assay buffer containing 12.5 mM HEPES pH 7.4, 75 mM NaCl, 1 mM MgCl2, 1 mM BME, 5 uM Cyclophilin A and 2 uM test compound, a 5 uM stock of GMP-PNP-loaded K-Ras (1-169) G12C is diluted 10-fold to yield a final concentration of 0.5 uM; with final sample volume being 100 uL. The sample is incubated at 25�� C. for a time period of up to 24 hours prior to quenching by the addition of 10 uL of 5% Formic Acid. Quenched samples are centrifuged at 15000 rpm for 15 minutes in a benchtop centrifuge before injecting a 10 uL aliquot onto a reverse phase C4 column and eluting into the mass spectrometer with an increasing acetonitrile gradient in the mobile phase. Analysis of raw data may be carried out using Waters MassLynx MS software, with % bound calculated from the deconvoluted protein peaks for labeled and unlabeled K-Ras.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 990.24, ALogP 6.76, HBA 14, HBD 4, PSA 200.56, QED 0.07
Compound (SMILES): CC1(CNC(=O)OCCSSCCOC(=O)NCC2(C)CCN(c3cnc4c(N5CCCc6ncccc65)n[nH]c4n3)CC2)CCN(c2cnc3c(N4CCCc5ncccc54)n[nH]c3n2)CC1
InChIKey: WTOVMKYGZGTWPM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition Assay: SHP2 is allosterically activated through binding of bis-tyrosyl-phorphorylated peptides to its Src Homology 2 (SH2) domains. The latter activation step leads to the release of the auto-inhibitory interface of SHP2, which in turn renders the SHP2 protein tyrosine phosphatase (PTP) active and available for substrate recognition and reaction catalysis. The catalytic activity of SHP2 was monitored using the surrogate substrate DiFMUP in a prompt fluorescence assay format.The inhibition of SHP2 by compounds of the disclosure (concentrations varying from 0.003-100 μM) was monitored using an assay in which 0.25 nM of SHP2 was incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222 (sequence: H2N-LN(pY)IDLDLV(dPEG8)LST(pY)ASINFQK-amide) After 30-60 minutes incubation at 25° C., the surrogate substrate DiFMUP (Invitrogen, cat #D6567, 100 μM final) was added to the reaction and the conversion of DiFMUP to 6,8-difluoro-7-hydroxyl-4-methyl coumarin (DiFMU) was monitored continuously for 10 minutes with excitation at 355 nm and emission at 460 nm using a microplate reader (PolarStar, BMG).
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 963.21, ALogP 6.72, HBA 18, HBD 4, PSA 224.32, QED 0.06
Compound (SMILES): [2H]C([2H])([2H])n1cc(-c2ccnc(Nc3cc(NC(=O)C=C)c(N(C)CCN(C)C)cc3OC)n2)c2ccccc21
InChIKey: DUYJMQONPNNFPI-VPYROQPTSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (unknown origin) using Glu/Tyr as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 499.62, ALogP 4.51, HBA 8, HBD 2, PSA 87.55, QED 0.31
Compound (SMILES): C[C@@H](CO)NC(=O)c1cc(-c2ccc(Cl)cc2)nn(-c2cnn(C)c2)c1=O
InChIKey: YAGSZKAJPHGVOV-NSHDSACASA-N
Target: Aryl hydrocarbon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35869
Assay: Antagonist activity at AHR receptor (unknown origin)
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 387.83, ALogP 1.4, HBA 7, HBD 2, PSA 102.04, QED 0.69
Compound (SMILES): CCc1cc(N2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(NCCCN2CCOCCC2=O)n1
InChIKey: CNBTYICEJGEABG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Inhibition of ULK1 (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 535.62, ALogP 3.6, HBA 8, HBD 2, PSA 85.86, QED 0.47
Compound (SMILES): COc1ccc(C)cc1[C@@]1(C(=O)NS(=O)(=O)c2cccc3nc(C)ccc23)C[C@H](c2ccccc2)CO1
InChIKey: ILQPLXMPYBURHT-PZGXJGMVSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Activation of CFTR F508del mutant (unknown origin)
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 516.62, ALogP 4.76, HBA 6, HBD 1, PSA 94.59, QED 0.4
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C(F)(F)F)nc(C2=C(F)[C@H](O)C(F)(F)CC2)n1)C(F)(F)F
InChIKey: CECMHVJGNAFHKN-KCRUCZTKSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin) using alpha-ketoglutarate as substrate preincubated with compound for 16 hrs followed by substrate addition and measured after 1 hr in presence of NADPH by fluorescence based analysis
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 453.31, ALogP 4.07, HBA 6, HBD 3, PSA 82.96, QED 0.58
Compound (SMILES): Cc1cn(C)nc1[C@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)C1(C)CCCC1
InChIKey: WZBSYWCLIMRAHO-QFIPXVFZSA-N
Target: C-C chemokine receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P32248
Assay: Displacement of Mz437 from CCR7 (unknown origin) extracted from HEK293T cell membrane harbouring CCR7_GSSG_Nluc assessed as inhibition constant using furimazine as substrate incubated for 90 mins by NanoBRET based competitive binding assay
Measurement: Ki = 81.2 nM (pChEMBL 7.090000152587891)
Descriptors: MW 466.54, ALogP 2.6, HBA 9, HBD 3, PSA 129.45, QED 0.45
Compound (SMILES): COC1CCN(C2CCN(c3cc(C(=O)NS(=O)(=O)N(C)C)nc4c3c(C3CCC3)nn4-c3ccc(F)cc3)CC2)CC1
InChIKey: JPIAJLPRTOWAEC-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Activation of CFTR F508del mutant (unknown origin)
Measurement: EC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 613.76, ALogP 3.44, HBA 9, HBD 1, PSA 112.9, QED 0.41
Compound (SMILES): CCc1c(N2CCN(C(=O)c3ncnc(C)c3O)CC2)c(=O)n2nc(C3=CCOCC3)nc2n1CC(=O)Nc1ccc(C(F)(F)F)cc1Cl
InChIKey: XKYVECRUZPCRQR-UHFFFAOYSA-N
Target: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (SINGLE PROTEIN), Homo sapiens
UniProt: Q14191
Assay: Inhibition of N-terminal GST-tagged WRN (500 to 946 residues) (unknown origin) expressed in Escherichia coli BL21 cells preincubated with compound for 15 mins followed by DNA and ATP addition for 3 hrs and measured after 40 mins by ADP-GLO kinase assay
Measurement: IC50 = 30.8 nM (pChEMBL 7.510000228881836)
Descriptors: MW 702.09, ALogP 3.33, HBA 12, HBD 2, PSA 160.08, QED 0.29
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(Oc4ccn5ncnc5c4)c(C)c3)c2cc1NC(=O)/C(F)=C/[C@H]1CCCN1C
InChIKey: HTAMCULFUCGZAM-FKYOTISTSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 3.51 nM (pChEMBL 8.460000038146973)
Descriptors: MW 582.64, ALogP 5.8, HBA 10, HBD 2, PSA 118.8, QED 0.21
Compound (SMILES): Fc1ccc([C@@H]2C[C@H]2NCc2cn(-c3ccc4[nH]ncc4c3)nn2)cc1F
InChIKey: BVNIBOGSMAIXSI-HNAYVOBHSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant LSD1 (852 residues) incubated for 1 hr by HTRF method
Measurement: IC50 = 8.33 nM (pChEMBL 8.079999923706055)
Descriptors: MW 366.38, ALogP 3.07, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): [2H]C([2H])([2H])n1cc(-c2ccnc(Nc3cc(NC(=O)C=C)c(N(C)CCN(C)C)cc3OC)n2)c2ccccc21
InChIKey: DUYJMQONPNNFPI-VPYROQPTSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) using Glu/Tyr as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 499.62, ALogP 4.51, HBA 8, HBD 2, PSA 87.55, QED 0.31
Compound (SMILES): C[C@@H](CO)NC(=O)c1cc(-c2ccc(Cl)cc2)nn(-c2cnn(C)c2)c1=O
InChIKey: YAGSZKAJPHGVOV-NSHDSACASA-N
Target: Aryl hydrocarbon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35869
Assay: Antagonist activity at AHR receptor in human Huh-7 cells transfected with CYP1A1 regulated luciferase reporter gene assessed as inhibition of TCDD-induced receptor activation incubated for 20 hrs by dual luciferase assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 387.83, ALogP 1.4, HBA 7, HBD 2, PSA 102.04, QED 0.69
Compound (SMILES): CCc1cc(N2CCN(C)CC2)ccc1Nc1ncc(C(F)(F)F)c(NCCCN2CCOCCC2=O)n1
InChIKey: CNBTYICEJGEABG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ULK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IYT8
Assay: Inhibition of ULK2 (unknown origin)
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 535.62, ALogP 3.6, HBA 8, HBD 2, PSA 85.86, QED 0.47
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C(F)(F)F)nc(C2=C(F)[C@H](O)C(F)(F)CC2)n1)C(F)(F)F
InChIKey: CECMHVJGNAFHKN-KCRUCZTKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by manual patch-clamp assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 453.31, ALogP 4.07, HBA 6, HBD 3, PSA 82.96, QED 0.58
Compound (SMILES): Cc1cn(C)nc1[C@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)C1(C)CCCC1
InChIKey: WZBSYWCLIMRAHO-QFIPXVFZSA-N
Target: C-C chemokine receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P32248
Assay: Displacement of Mz437 from CCR7 (unknown origin) extracted from HEK293T cell membrane harbouring CCR7_GSSG_Nluc assessed as inhibition constant using furimazine as substrate incubated for 90 mins by NanoBRET based competitive binding assay
Measurement: Ki = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 466.54, ALogP 2.6, HBA 9, HBD 3, PSA 129.45, QED 0.45
Compound (SMILES): CCc1c(N2CCN(C(=O)c3ncnc(C)c3O)CC2)c(=O)n2nc(C3=CCOCC3)nc2n1CC(=O)Nc1ccc(C(F)(F)F)cc1Cl
InChIKey: XKYVECRUZPCRQR-UHFFFAOYSA-N
Target: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (SINGLE PROTEIN), Homo sapiens
UniProt: Q14191
Assay: Inhibition of N-terminal GST-tagged WRN (500 to 946 residues) (unknown origin) expressed in Escherichia coli BL21 cells preincubated with compound for 15 mins followed by DNA and ATP addition by fluorometric helicase assay
Measurement: IC50 = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 702.09, ALogP 3.33, HBA 12, HBD 2, PSA 160.08, QED 0.29
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(Oc4ccn5ncnc5c4)c(C)c3)c2cc1NC(=O)/C(F)=C/[C@H]1CCCN1C
InChIKey: HTAMCULFUCGZAM-FKYOTISTSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 8.13 nM (pChEMBL 8.09000015258789)
Descriptors: MW 582.64, ALogP 5.8, HBA 10, HBD 2, PSA 118.8, QED 0.21
Compound (SMILES): Fc1ccc([C@@H]2C[C@H]2NCc2cn(-c3ccc4[nH]ncc4c3)nn2)cc1F
InChIKey: BVNIBOGSMAIXSI-HNAYVOBHSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human N-terminal Flag-tagged MAOA extracted baculovirus infected in Sf9 cells measured after 0.5 hrs by MAO-Glo Assay
Measurement: IC50 = 242.97 nM (pChEMBL 6.610000133514404)
Descriptors: MW 366.38, ALogP 3.07, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C(F)(F)F)nc(C2=C(F)[C@H](O)C(F)(F)CC2)n1)C(F)(F)F
InChIKey: CECMHVJGNAFHKN-KCRUCZTKSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Inhibition of adenosine A3 receptor (unknown origin)
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 453.31, ALogP 4.07, HBA 6, HBD 3, PSA 82.96, QED 0.58
Compound (SMILES): Cc1cn(C)nc1[C@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)C1(C)CCCC1
InChIKey: WZBSYWCLIMRAHO-QFIPXVFZSA-N
Target: C-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P51684
Assay: Binding affinity to CCR6 (unknown origin) extracted from HEK293T cell membrane harbouring CCR6_Nluc assessed as inhibition constant incubated for 90 mins by NanoBERT competition assay
Measurement: Ki = 3.09 nM (pChEMBL 8.510000228881836)
Descriptors: MW 466.54, ALogP 2.6, HBA 9, HBD 3, PSA 129.45, QED 0.45
Compound (SMILES): CCc1c(N2CCN(C(=O)c3ncnc(C)c3O)CC2)c(=O)n2nc(C3=CCOCC3)nc2n1CC(=O)Nc1ccc(C(F)(F)F)cc1Cl
InChIKey: XKYVECRUZPCRQR-UHFFFAOYSA-N
Target: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (SINGLE PROTEIN), Homo sapiens
UniProt: Q14191
Assay: Inhibition of N-terminal Hexa-histidine-tagged human recombinant WRN helicase domain (517 to 945 residues) extracted from Baculovirus infected Sf9 cells by fluorescence based analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 702.09, ALogP 3.33, HBA 12, HBD 2, PSA 160.08, QED 0.29
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(Oc4ccn5ncnc5c4)c(C)c3)c2cc1NC(=O)/C(F)=C/[C@H]1CCCN1C
InChIKey: HTAMCULFUCGZAM-FKYOTISTSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 D769H mutant (unknown origin)
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 582.64, ALogP 5.8, HBA 10, HBD 2, PSA 118.8, QED 0.21
Compound (SMILES): Fc1ccc([C@@H]2C[C@H]2NCc2cn(-c3ccc4[nH]ncc4c3)nn2)cc1F
InChIKey: BVNIBOGSMAIXSI-HNAYVOBHSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human N-terminal Flag-tagged MAOB extracted baculovirus infected in Sf9 cells measured after 0.5 hrs by MAO-Glo Assay
Measurement: IC50 = 8049.67 nM (pChEMBL 5.090000152587891)
Descriptors: MW 366.38, ALogP 3.07, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): Cc1cn(C)nc1[C@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)C1(C)CCCC1
InChIKey: WZBSYWCLIMRAHO-QFIPXVFZSA-N
Target: C-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P51684
Assay: Binding affinity to CCR6 (unknown origin) extracted from HEK293T cell membrane harbouring CCR6_Nluc assessed as inhibition constant incubated for 90 mins by NanoBERT competition assay
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 466.54, ALogP 2.6, HBA 9, HBD 3, PSA 129.45, QED 0.45
Compound (SMILES): CCc1c(N2CCN(C(=O)c3ncnc(C)c3O)CC2)c(=O)n2nc(C3=CCOCC3)nc2n1CC(=O)Nc1ccc(C(F)(F)F)cc1Cl
InChIKey: XKYVECRUZPCRQR-UHFFFAOYSA-N
Target: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (SINGLE PROTEIN), Homo sapiens
UniProt: Q14191
Assay: Inhibition of N-terminal FLAG-tagged human full length WRN expressed in baculovirus-infected Sf9 cells assessed as inhibition of ATPase activity using M13ssDNA and ATP as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by ADP-Glo kinase assay based luminescence analysis
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 702.09, ALogP 3.33, HBA 12, HBD 2, PSA 160.08, QED 0.29
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc(Oc4ccn5ncnc5c4)c(C)c3)c2cc1NC(=O)/C(F)=C/[C@H]1CCCN1C
InChIKey: HTAMCULFUCGZAM-FKYOTISTSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 D769Y mutant (unknown origin)
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 582.64, ALogP 5.8, HBA 10, HBD 2, PSA 118.8, QED 0.21
Compound (SMILES): Fc1ccc([C@@H]2C[C@H]2NCc2cn(-c3ccc4[nH]ncc4c3)nn2)cc1F
InChIKey: BVNIBOGSMAIXSI-HNAYVOBHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by whole cell patch clamp assay
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 366.38, ALogP 3.07, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): CCn1c(-c2cccnc2[C@H](C)OC)c2c3cc(ccc31)-c1cc(O)cc(c1)C[C@H](NC(=O)[C@H](C(C)C)N(C)C(=O)c1nc(NC(=O)/C=C/CN(C)C)cs1)C(=O)N1CCC[C@H](N1)C(=O)OCC(C)(C)C2
InChIKey: CELWXOSQLDUBSO-VZXMIGGVSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Biochemical Assay: A variety of Ras proteins may be inhibited by compounds of the present invention (e.g., K-Ras, N-Ras, H-Ras, and mutants thereof at positions 12, 13 and 61, such as G12C, G12D, G12V, G12S, G13C, G13D, and Q61L, and others described herein). The purpose of this biochemical assay is to measure the ability of test compounds to covalently label nucleotide-loaded K-Ras isoforms. In assay buffer containing 12.5 mM HEPES pH 7.4, 75 mM NaCl, 1 mM MgCl2, 1 mM BME, 5 uM Cyclophilin A and 2 uM test compound, a 5 uM stock of GMP-PNP-loaded K-Ras (1-169) G12C is diluted 10-fold to yield a final concentration of 0.5 uM; with final sample volume being 100 uL. The sample is incubated at 25�� C. for a time period of up to 24 hours prior to quenching by the addition of 10 uL of 5% Formic Acid. Quenched samples are centrifuged at 15000 rpm for 15 minutes in a benchtop centrifuge before injecting a 10 uL aliquot onto a reverse phase C4 column and eluting into the mass spectrometer with an increasing acetonitrile gradient in the mobile phase. Analysis of raw data may be carried out using Waters MassLynx MS software, with % bound calculated from the deconvoluted protein peaks for labeled and unlabeled K-Ras.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 990.24, ALogP 6.76, HBA 14, HBD 4, PSA 200.56, QED 0.07
Compound (SMILES): Cc1cn(C)nc1[C@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)C1(C)CCCC1
InChIKey: WZBSYWCLIMRAHO-QFIPXVFZSA-N
Target: C-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P51684
Assay: Antagonist activity at human CCR6 expressed in CHO-K1 cells incubated for 4 hrs
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 466.54, ALogP 2.6, HBA 9, HBD 3, PSA 129.45, QED 0.45
Compound (SMILES): O=C1c2cccc3cccc(c23)C(=O)N1O
InChIKey: KTWCUGUUDHJVIH-UHFFFAOYSA-N
Target: DNA excision repair protein ERCC-1/DNA repair endonuclease XPF (PROTEIN COMPLEX), Homo sapiens
UniProt: P07992
Assay: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 213.19, ALogP 1.82, HBA 3, HBD 1, PSA 57.61, QED 0.54
Compound (SMILES): Nc1ccc(Nc2cc(S(=O)(=O)O)c(N)c3c2C(=O)c2ccccc2C3=O)cc1
InChIKey: ZCQMYMXRGJWSHH-UHFFFAOYSA-N
Target: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P59768
Assay: Inhibition of biotinylated Gbeta1gamma2 (unknown origin)-mediated PLCbeta2 activation incubated for 16 hrs
Measurement: IC50 = 75000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 409.42, ALogP 2.62, HBA 7, HBD 4, PSA 152.58, QED 0.3
Compound (SMILES): Nc1ccc(Nc2cc(S(=O)(=O)O)c(N)c3c2C(=O)c2ccccc2C3=O)cc1
InChIKey: ZCQMYMXRGJWSHH-UHFFFAOYSA-N
Target: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P59768
Assay: Inhibition of SIGKAFKILGYPDYD binding to biotinylated Gbeta1gamma2 (unknown origin) incubated for 1 hr by phage ELISA
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 409.42, ALogP 2.62, HBA 7, HBD 4, PSA 152.58, QED 0.3
Compound (SMILES): Nc1ccc(Nc2cc(S(=O)(=O)O)c(N)c3c2C(=O)c2ccccc2C3=O)cc1
InChIKey: ZCQMYMXRGJWSHH-UHFFFAOYSA-N
Target: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P59768
Assay: Inhibition of biotinylated Gbeta1gamma2 (unknown origin)-mediated PLCbeta3 activation incubated for 16 hrs
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 409.42, ALogP 2.62, HBA 7, HBD 4, PSA 152.58, QED 0.3
Compound (SMILES): Nc1ccc(Nc2cc(S(=O)(=O)O)c(N)c3c2C(=O)c2ccccc2C3=O)cc1
InChIKey: ZCQMYMXRGJWSHH-UHFFFAOYSA-N
Target: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P59768
Assay: Inhibition of biotinylated Gbeta1gamma2 (unknown origin)-mediated PI3Kgamma activation incubated for 16 hrs
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 409.42, ALogP 2.62, HBA 7, HBD 4, PSA 152.58, QED 0.3
Compound (SMILES): CC[C@@](C)(Nc1ccnc(-c2c[nH]c3ncccc23)n1)C(=O)NCC(F)(F)F
InChIKey: ASUGUQWIHMTFJL-QGZVFWFLSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as inhibition of IFN-alpha-induced STAT-3 phosphorylation preincubated for 45 mins followed by IFN-alpha addition measured after 15 mins by FACS analysis
Measurement: IC50 = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 392.39, ALogP 3.28, HBA 5, HBD 3, PSA 95.59, QED 0.6
Compound (SMILES): CC[C@@](C)(Nc1ccnc(-c2c[nH]c3ncccc23)n1)C(=O)NCC(F)(F)F
InChIKey: ASUGUQWIHMTFJL-QGZVFWFLSA-N
Target: JAK1/JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK1/JAK2/TYK2 in human whole blood assessed as inhibition of IL-6-induced STAT-1 phosphorylation preincubated for 45 mins followed by IL-6 addition measured after 15 mins by FACS analysis
Measurement: IC50 = 1870 nM (pChEMBL 5.730000019073486)
Descriptors: MW 392.39, ALogP 3.28, HBA 5, HBD 3, PSA 95.59, QED 0.6
Compound (SMILES): CC[C@@](C)(Nc1ccnc(-c2c[nH]c3ncccc23)n1)C(=O)NCC(F)(F)F
InChIKey: ASUGUQWIHMTFJL-QGZVFWFLSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2/TYK2 in human whole blood assessed as inhibition of IL-23-induced STAT-3 phosphorylation preincubated for 45 mins followed by IL-23 addition measured after 15 mins by FACS analysis
Measurement: IC50 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 392.39, ALogP 3.28, HBA 5, HBD 3, PSA 95.59, QED 0.6
Compound (SMILES): CC[C@@](C)(Nc1ccnc(-c2c[nH]c3ncccc23)n1)C(=O)NCC(F)(F)F
InChIKey: ASUGUQWIHMTFJL-QGZVFWFLSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2/TYK2 in human whole blood assessed as inhibition of IL-12-induced STAT-4 phosphorylation preincubated for 45 mins followed by IL-12 addition measured after 15 mins by FACS analysis
Measurement: IC50 = 16400 nM (pChEMBL 4.789999961853027)
Descriptors: MW 392.39, ALogP 3.28, HBA 5, HBD 3, PSA 95.59, QED 0.6
Compound (SMILES): O=C(NO)c1ccc(CNc2cccc3cccnc23)cc1
InChIKey: BPDQUKCPNSRTTR-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in insect cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 7750 nM (pChEMBL 5.110000133514404)
Descriptors: MW 293.33, ALogP 2.97, HBA 4, HBD 3, PSA 74.25, QED 0.51
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](OC(=O)c2cccc3ccccc23)[C@H]1OC(=O)c1cccc2ccccc12
InChIKey: PSBROSWEMLTASJ-BQOYKFDPSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Antagonist activity at human P2X2R/P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: IC50 = 11481.54 nM (pChEMBL 4.940000057220459)
Descriptors: MW 815.52, ALogP 4.41, HBA 16, HBD 5, PSA 291.27, QED 0.08
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: GABA A receptor alpha-3/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha3beta2gamma2 GABAA receptor expressed in HEKcells by FMP assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: GABA A receptor alpha-3/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha3beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK cells by FMP assay
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: Ki = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK cells by FMP assay
Measurement: IC50 = 51.29 nM (pChEMBL 7.289999961853027)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P47870
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: IC50 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): Cc1ccccc1NC(=O)Nc1ccc(C[C@H]2NC(=O)C[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC2=O)cc1
InChIKey: FXYDXLJEJBXFBD-JAUZHHQJSA-N
Target: Integrin alpha1/beta2 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P56199
Assay: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay
Measurement: IC50 = 652 nM (pChEMBL 6.190000057220459)
Descriptors: MW 737.81, ALogP 1.27, HBA 8, HBD 9, PSA 261.23, QED 0.17
Compound (SMILES): Cc1ccccc1NC(=O)Nc1ccc(C[C@H]2NC(=O)C[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC2=O)cc1
InChIKey: FXYDXLJEJBXFBD-JAUZHHQJSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Binding affinity to alpha5beta1 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in fibronectin coated wells by fluorescence based assay
Measurement: IC50 = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 737.81, ALogP 1.27, HBA 8, HBD 9, PSA 261.23, QED 0.17
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@H]3CC[C@@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-RDJZCZTQSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK3 in human PBMC assessed as inhibition of IL2-stimulated phosphorylation of STAT5
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@H]3CC[C@@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-RDJZCZTQSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK3 in CD3+ human PBMC assessed as inhibition of IL4-stimulated phosphorylation of STAT6
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@H]3CC[C@@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-RDJZCZTQSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK1/JAK2 in CD3+ human PBMC assessed as inhibition of IL6-stimulated phosphorylation of STAT3
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@H]3CC[C@@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-RDJZCZTQSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK1/JAK2 in CD3+ human HT-29 cells assessed as inhibition of IL22-stimulated phosphorylation of STAT3
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@H]3CC[C@@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-RDJZCZTQSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK1/JAK2 in IFNgamma-induced human HEK-dual cells by SEAP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): CC[C@@](C)(Nc1ccnc(-c2c[nH]c3ncccc23)n1)C(=O)NCC(F)(F)F
InChIKey: ASUGUQWIHMTFJL-QGZVFWFLSA-N
Target: JAK1/JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK2/TYK2 in human whole blood assessed as inhibition of IL-6-induced STAT-1 phosphorylation preincubated for 45 mins followed by IL-6 addition measured after 15 mins by FACS analysis
Measurement: IC50 = 1870 nM (pChEMBL 5.730000019073486)
Descriptors: MW 392.39, ALogP 3.28, HBA 5, HBD 3, PSA 95.59, QED 0.6
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: GABA A receptor alpha-3/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18507
Assay: Antagonist activity at human alpha3beta2gamma2 GABAA receptor expressed in HEKcells by FMP assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: GABA A receptor alpha-3/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18507
Assay: Antagonist activity at human alpha3beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK cells by FMP assay
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: Ki = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): O=C(Nc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1)c1cccs1
InChIKey: PQGDUNWRHHLMNT-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK cells by FMP assay
Measurement: IC50 = 51.29 nM (pChEMBL 7.289999961853027)
Descriptors: MW 383.52, ALogP 3.61, HBA 4, HBD 2, PSA 61.44, QED 0.85
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5/beta-2/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Antagonist activity at human alpha5beta2gamma2 GABAA receptor expressed in HEK293 cells by FMP assay
Measurement: IC50 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3c2cc(F)cc(Cl)c2)ccc1-n1cnc(C)c1
InChIKey: ZOEPMNJUXPITLU-HDOHGRBBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 466.94, ALogP 5.55, HBA 6, HBD 0, PSA 51.88, QED 0.51
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3c2cc(F)c(OC)c(F)c2)ccc1-n1cnc(C)c1
InChIKey: YXJHASQNMKYCLV-VULPMGHGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 480.52, ALogP 5.04, HBA 7, HBD 0, PSA 61.11, QED 0.51
Compound (SMILES): COc1cc(/C=C2\O[C@@H](C)CN3C2=NOC[C@@H]3c2cc(F)cc(F)c2)ccc1-n1cnc(C)c1
InChIKey: ODEIUBHPOCSQNG-TXWZOQMOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 466.49, ALogP 4.61, HBA 7, HBD 0, PSA 61.11, QED 0.56
Compound (SMILES): COc1cc(/C=C2\O[C@H](C)CN3C2=NOC[C@@H]3c2cc(F)cc(F)c2)ccc1-n1cnc(C)c1
InChIKey: ODEIUBHPOCSQNG-HCLFYLLCSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 466.49, ALogP 4.61, HBA 7, HBD 0, PSA 61.11, QED 0.56
Compound (SMILES): COc1cc(/C=C2\O[C@@H](C)CN3C2=NOC[C@@H]3c2cc(F)c(F)c(F)c2)ccc1-n1cnc(C)c1
InChIKey: DHCFQUMNNPDWHH-VUPRUQKZSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 484.48, ALogP 4.75, HBA 7, HBD 0, PSA 61.11, QED 0.5
Compound (SMILES): COc1cc(/C=C2\O[C@H](C)CN3C2=NOC[C@@H]3c2cc(F)c(F)c(F)c2)ccc1-n1cnc(C)c1
InChIKey: DHCFQUMNNPDWHH-NILGRDHESA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 484.48, ALogP 4.75, HBA 7, HBD 0, PSA 61.11, QED 0.5
Compound (SMILES): COc1cc(/C=C2\CCCN3C(=O)C(c4cc(F)cc(F)c4)ON=C23)ccc1-n1cnc(C)c1
InChIKey: ZVQADJZRUKIVDU-CAOOACKPSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 464.47, ALogP 4.56, HBA 6, HBD 0, PSA 68.95, QED 0.57
Compound (SMILES): COc1cc(/C=C2\CCCN3CCON=C23)ccc1-n1cnc(C)c1
InChIKey: PXKJCAGNTGYOSL-MHWRWJLKSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 338.41, ALogP 3.01, HBA 6, HBD 0, PSA 51.88, QED 0.86
Compound (SMILES): COc1cc(/C=C2\CCCN3C(=O)CON=C23)ccc1-n1cnc(C)c1
InChIKey: OUGPFPUBTIPZKQ-OVCLIPMQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 352.39, ALogP 2.54, HBA 6, HBD 0, PSA 68.95, QED 0.85
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3C(C)C)ccc1-n1cnc(C)c1
InChIKey: RZJFAXNLNLKCSK-ACEGTKJHSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 380.49, ALogP 4.04, HBA 6, HBD 0, PSA 51.88, QED 0.8
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3CC(C)C)ccc1-n1cnc(C)c1
InChIKey: SEMGDCNPEKJXOY-FHTAPLDASA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 394.52, ALogP 4.43, HBA 6, HBD 0, PSA 51.88, QED 0.75
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3C(C)(C)C)ccc1-n1cnc(C)c1
InChIKey: NZIUOHIPZKVYDE-LAINMTBBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 394.52, ALogP 4.43, HBA 6, HBD 0, PSA 51.88, QED 0.77
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3C2CCOCC2)ccc1-n1cnc(C)c1
InChIKey: SIOAZNRGFZWGSW-FNUHDPNESA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 422.53, ALogP 3.81, HBA 7, HBD 0, PSA 61.11, QED 0.75
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3CO)ccc1-n1cnc(C)c1
InChIKey: VEMJBOHGJBKGOD-BDBSJLECSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 368.44, ALogP 2.37, HBA 7, HBD 1, PSA 72.11, QED 0.9
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3COCc2ccccc2)ccc1-n1cnc(C)c1
InChIKey: HDEVFDLQJIGYKU-NXAROGRYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 458.56, ALogP 4.6, HBA 7, HBD 0, PSA 61.11, QED 0.52
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOCC3C(O)c2ccc(Cl)cc2)ccc1-n1cnc(C)c1
InChIKey: NKUHIYVIEOLYJK-UDWIEESQSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 478.98, ALogP 4.77, HBA 7, HBD 1, PSA 72.11, QED 0.57
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NOC[C@@H]3Cc2ccccc2)ccc1-n1cnc(C)c1
InChIKey: GEAXGUUWFUZNAF-YQZDYSOMSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 428.54, ALogP 4.62, HBA 6, HBD 0, PSA 51.88, QED 0.59
Compound (SMILES): CCc1csc(C[C@H]2CON=C3/C(=C/c4ccc(-n5cnc(C)c5)c(OC)c4)CCCN32)n1
InChIKey: YSQHNBXDPUPJFX-KEBMYNNESA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase expressed in HEK293 cells co-expressing APPsw-lon assessed as reduction of amyloid-beta-42 level by sandwich immunoassay
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 463.61, ALogP 4.64, HBA 8, HBD 0, PSA 64.77, QED 0.53