lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase LATS2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRM7
Assay: Inhibition of LATS2 at compound concentration of 10.0 uM using the ScanMax (DiscoverX)
Measurement: Kd = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000305b IKBKE
Measurement: IC50 = 1725 nM (pChEMBL 5.760000228881836)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of ROCK1 at compound concentration of 10.0 uM using the ScanMax (DiscoverX)
Measurement: Kd = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 10950 nM (pChEMBL 4.960000038146973)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Affinity Biochemical interaction (TR-FRET-based kinase activity inhibition assay (1 µM ATP)) EUB0000305b TBK1
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 at compound concentration of 10.0 uM using the ScanMax (DiscoverX)
Measurement: Kd = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 4550 nM (pChEMBL 5.340000152587891)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Affinity Biochemical interaction (TR-FRET-based kinase activity inhibition assay (1 µM ATP)) EUB0000305b IKBKE
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: TGF-beta receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37173
Assay: Inhibition of TGFBR2 at compound concentration of 10.0 uM using the ScanMax (DiscoverX)
Measurement: Kd = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Selectivity interaction (Enzymatic assay) EUB0000305b STK17A
Measurement: IC50 = 311 nM (pChEMBL 6.510000228881836)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Inhibition of ULK1 at compound concentration of 10.0 uM using the ScanMax (DiscoverX)
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 4065 nM (pChEMBL 5.389999866485596)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Selectivity interaction (Enzymatic assay) EUB0000305b FLT3
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Affinity Phenotypic Cellular interaction (Anti-proliferation assay (A375SM cells)) EUB0000298b MAPK1
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 3340 nM (pChEMBL 5.480000019073486)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000305b FLT3
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Affinity Phenotypic Cellular interaction (Anti-proliferation assay (A375SM cells)) EUB0000298b MAPK3
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 3460 nM (pChEMBL 5.460000038146973)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000305b HTR2B
Measurement: Ki = 1305.2 nM (pChEMBL 5.880000114440918)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000298b MAPK1
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13163
Assay: Selectivity interaction (Enzymatic assay) EUB0000305b MAP2K5
Measurement: IC50 = 847 nM (pChEMBL 6.070000171661377)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000298b MAPK3
Measurement: IC50 = 6690 nM (pChEMBL 5.170000076293945)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 746 nM (pChEMBL 6.130000114440918)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13163
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000305b MAP2K5
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Affinity Biochemical interaction (KdELECT (DiscoverX)) EUB0000298b MAPK1
Measurement: Kd = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)cc1
InChIKey: MNAYBFFSFQRSIT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 2.91 nM (pChEMBL 8.539999961853027)
Descriptors: MW 316.79, ALogP 3.41, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase kinase kinase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: Q56UN5
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000305b MAP3K19
Measurement: Kd = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Affinity Biochemical interaction (KdELECT (DiscoverX)) EUB0000298b MAPK3
Measurement: Kd = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Mitogen-activated protein kinase kinase kinase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: Q56UN5
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000305b MAP3K19
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b CLK4
Measurement: Kd = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Ribosomal protein S6 kinase alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK32
Assay: Selectivity interaction (Enzymatic assay) EUB0000305b RPS6KA6
Measurement: IC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b ADRBK1
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000305b STK17A
Measurement: Kd = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: G protein-coupled receptor kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35626
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b ADRBK2
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Selectivity interaction (Enzymatic assay (Eurofins)) EUB0000305b STK17A
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b GSG2
Measurement: Kd = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Selectivity interaction (NanoBRET assay (HEK293T cells)) EUB0000305b STK17A
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase LATS2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRM7
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b LATS2
Measurement: Kd = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000305b TMEM97
Measurement: Ki = 1155.57 nM (pChEMBL 5.940000057220459)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Mitogen-activated protein kinase 15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TD08
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b MAPK15
Measurement: Kd = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@H](c1ccnc(Nc2nc3ccc(-c4cc(N(C)C)ncn4)cc3[nH]2)c1)N1CCN(C(=O)CC(F)(F)F)CC1
InChIKey: HZRJHVDNTDBTOZ-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Selectivity interaction (Enzymatic assay) EUB0000305b ULK1
Measurement: IC50 = 7930 nM (pChEMBL 5.099999904632568)
Descriptors: MW 553.59, ALogP 4.38, HBA 8, HBD 2, PSA 106.17, QED 0.35
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b ROCK1
Measurement: Kd = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b ROCK2
Measurement: Kd = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: TGF-beta receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37173
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b TGFBR2
Measurement: Kd = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase ULK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75385
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b ULK1
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): C[C@@H](NC(=O)Nc1cc2[nH]ncc2c(CO)n1)c1ccccc1
InChIKey: RAXZSEGXMBWYQK-SNVBAGLBSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Selectivity interaction (ScanMAX (DiscoverX)) EUB0000298b CDK7
Measurement: Kd = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 311.35, ALogP 2.33, HBA 4, HBD 4, PSA 102.93, QED 0.59
Compound (SMILES): COc1ncc(-c2ccc3ncc(-c4cn(CCCN5CCOCC5)nn4)n3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: VUZIKMDBCRTJST-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by kinase-glo assay
Measurement: IC50 = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 610.65, ALogP 3.46, HBA 11, HBD 1, PSA 128.77, QED 0.25
Compound (SMILES): O=C(CCN1CCc2ccccc2C1)Nc1nccc(C(F)(F)F)n1
InChIKey: VDHPHCRRVHLPGH-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues) /human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells pretreated for 15 mins followed by substrate and [3H]-SAM addition measured after 60 mins by scintillation proximity assay
Measurement: IC50 = 69870 nM (pChEMBL 4.159999847412109)
Descriptors: MW 350.34, ALogP 2.88, HBA 4, HBD 1, PSA 58.12, QED 0.92
Compound (SMILES): Cc1cc(NC(=O)Cn2nnc(-c3cccc(C#N)c3)n2)n(C2CCCCC2)n1
InChIKey: MQRZGOHLKSFXAK-UHFFFAOYSA-N
Target: Kir3.1/Kir3.2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48549
Assay: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assay
Measurement: EC50 = 183 nM (pChEMBL 6.739999771118164)
Descriptors: MW 390.45, ALogP 2.86, HBA 8, HBD 1, PSA 114.31, QED 0.72
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: CFZDPWGUGKBVRZ-PLAJYJEJSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.481 nM (pChEMBL 9.319999694824219)
Descriptors: MW 3731.22
Compound (SMILES): C/C=C/C(=O)Nc1cccc(S(=O)(=O)N2CC[C@@H](NC(=O)c3n[nH]cc3NC(=O)c3c(Cl)cccc3Cl)C2)c1.O=C(O)C(F)(F)F
InChIKey: SJYVNEQKHYLYSN-WOQRJVAFSA-N
Target: Cyclin-dependent kinase 14/Cyclin-Y (PROTEIN COMPLEX), Homo sapiens
UniProt: O94921
Assay: Inhibition of recombinant GST-tagged human full length CDK14/cyclin Y (2 to end residues) preincubated for 30 mins by Lantha screen eu binding assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 591.48, ALogP 3.68, HBA 6, HBD 4, PSA 153.36, QED 0.29
Compound (SMILES): CC(C)c1c(-c2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2F)cnn1C
InChIKey: UKSFDLFTRMYZGG-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 410.5, ALogP 3.03, HBA 8, HBD 1, PSA 75, QED 0.69
Compound (SMILES): CCC(C)n1nc(C)cc1NC(=O)Cn1nnc(-c2ccccc2)n1
InChIKey: HGWDQYPRYXCANJ-UHFFFAOYSA-N
Target: Kir3.1/Kir3.2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48549
Assay: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 339.4, ALogP 2.45, HBA 7, HBD 1, PSA 90.52, QED 0.74
Compound (SMILES): COc1c(C#N)ccc2[nH]c(-c3nc4n(n3)CCCC4c3ccc(F)cc3C)cc12
InChIKey: FOPPSCNSHAZUGU-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of gamma secretase in human SKNBE2 cells expressing human APP695 assessed as increase in Abeta38 levels incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 401.45, ALogP 4.68, HBA 5, HBD 1, PSA 79.52, QED 0.54
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(CNC(=O)c2n[nH]cc2NC(=O)c2c(Cl)cccc2Cl)cc1.O=C(O)C(F)(F)F
InChIKey: IMZFJUZJDHJADS-KQGICBIGSA-N
Target: Cyclin-dependent kinase 14/Cyclin-Y (PROTEIN COMPLEX), Homo sapiens
UniProt: O94921
Assay: Inhibition of recombinant GST-tagged human full length CDK14/cyclin Y (2 to end residues) preincubated for 30 mins by Lantha screen eu binding assay
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 515.4, ALogP 3.96, HBA 5, HBD 4, PSA 119.22, QED 0.32
Compound (SMILES): O=C(Nc1cccc(-c2cn(CCNc3c4c(nc5ccccc35)CCCC4)nn2)n1)Nc1cccc2c1C1CCCCN1C2=O
InChIKey: JRYNVBKKSAGWOO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of human recombinant CDK5/p25 using histone H1 as substrate in presence of [gamma-33P]ATP incubated for 30 mins by liquid scintillation counting assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 613.73, ALogP 6.2, HBA 8, HBD 3, PSA 129.96, QED 0.2
Compound (SMILES): COc1cc2[nH]c(-c3cn4c(n3)C(c3ccccc3Cl)OCC4)cc2cc1C#N
InChIKey: JPZWHWHOBQTYGJ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma-secretase in human SK-N-BE(2) cells expressing human APP695 assessed as reduction in amyloid beta 42 production incubated overnight by sandwich immunoassay
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 404.86, ALogP 4.68, HBA 5, HBD 1, PSA 75.86, QED 0.54
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1cnc(Nc2ccccc2)cn1
InChIKey: RXFXVQNNZNLCHJ-UHFFFAOYSA-N
Target: Histone deacetylase 3/NCoR1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3/GST-tagged NCOR1 DAD (397 to 503 residues) expressed in baculovirus expression system using Fluor de Lys as substrate measured after 15 mins by fluorescence assay
Measurement: IC50 = 71500 nM (pChEMBL 4.150000095367432)
Descriptors: MW 323.33, ALogP 3.19, HBA 5, HBD 3, PSA 92.93, QED 0.64
Compound (SMILES): Cn1cc(COCc2ccnc(NC(=O)Nc3cccc4c3C3CCCCN3C4=O)c2)nn1
InChIKey: CXLWAPHHTVIISB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of human recombinant CDK5/p25 using histone H1 as substrate in presence of [gamma-33P]ATP incubated for 30 mins by liquid scintillation counting assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 447.5, ALogP 3.25, HBA 7, HBD 2, PSA 114.27, QED 0.6
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cn(Cc3cccc(F)c3)c3ccccc23)[C@H](O)[C@@H]1O
InChIKey: SADMDVJVSZEYAB-AVSDHJAHSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBT2
Assay: Inhibition of SAE (unknown origin) using recombinant His-tagged human SUMO1 measured after 2 hrs by HTRF assay
Measurement: IC50 = 1650 nM (pChEMBL 5.78000020980835)
Descriptors: MW 555.59, ALogP 1.59, HBA 10, HBD 4, PSA 169.66, QED 0.22
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(O[C@H]3CCNC3)c(-c3ccc(F)cc3)c2)ccc1O[C@H]1CCNC1.Cl.Cl
InChIKey: SQEQIANZQSQRJA-WLKYSPGFSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P35222
Assay: Inhibition of C-terminal 6x-histidine tagged beta-catenin (138 to 686 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 /human BCL9 (350 to 375 residues) protein-protein interactions incubated for 1 hr by Alpha-screen assay
Measurement: Ki = 8450 nM (pChEMBL 5.070000171661377)
Descriptors: MW 475.56, ALogP 4.53, HBA 5, HBD 3, PSA 71.62, QED 0.47
Compound (SMILES): CNC(=O)c1cnc(Nc2cc(C)c(F)cn2)cc1Nc1cccc(C(N)=O)c1OC
InChIKey: OBYYHWSHMRWLSE-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/TYK2 in human Kit225 T cells assessed as inhibition of STAT phosphorylation by luciferase reporter assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 424.44, ALogP 2.88, HBA 7, HBD 4, PSA 131.26, QED 0.46
Compound (SMILES): [N-]=[N+]=NCCCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)NCCCC[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC1=O)C(=O)NCCCC[C@@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC1=O
InChIKey: MEEOVIQDSQIXOU-PQZQEJJQSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Binding affinity to alphaVbeta3 integrin in human SKOV3 cells assessed as inhibition of cell adhesion to fibrinogen measured after 2 hrs by MTT assay
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 1957.11