lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccccc2OC)CC1
InChIKey: DPFPGZSWZKCTBK-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 416.49, ALogP 3.16, HBA 8, HBD 0, PSA 68.54, QED 0.49
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccccc2C)CC1
InChIKey: WCYMZGBRFVGEJB-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 400.49, ALogP 3.46, HBA 7, HBD 0, PSA 59.31, QED 0.52
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cccc(F)c2)CC1
InChIKey: OBLZUEWTOIEOKI-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 404.45, ALogP 3.29, HBA 7, HBD 0, PSA 59.31, QED 0.52
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cccc(C#N)c2)CC1
InChIKey: SLJHJMKUVDGUKD-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 411.47, ALogP 3.02, HBA 8, HBD 0, PSA 83.1, QED 0.51
Compound (SMILES): COc1cccc(-n2ncc3c(N4CCN(c5ccccc5OC)CC4)ncnc32)c1
InChIKey: NRSNOIKPAFOCRX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 416.49, ALogP 3.16, HBA 8, HBD 0, PSA 68.54, QED 0.49
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cccc(C)c2)CC1
InChIKey: SWQOBZQTIKRHNX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 400.49, ALogP 3.46, HBA 7, HBD 0, PSA 59.31, QED 0.52
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccc(F)cc2)CC1
InChIKey: DBMPNCBTGSGUJB-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 404.45, ALogP 3.29, HBA 7, HBD 0, PSA 59.31, QED 0.52
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccc(C#N)cc2)CC1
InChIKey: ONEQVTDJEHHOEX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 411.47, ALogP 3.02, HBA 8, HBD 0, PSA 83.1, QED 0.51
Compound (SMILES): COc1ccc(-n2ncc3c(N4CCN(c5ccccc5OC)CC4)ncnc32)cc1
InChIKey: HXRCCVXGXJOFHE-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 416.49, ALogP 3.16, HBA 8, HBD 0, PSA 68.54, QED 0.49
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cc(F)cc(F)c2)CC1
InChIKey: OKRVHKNCIFLKMU-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 422.44, ALogP 3.43, HBA 7, HBD 0, PSA 59.31, QED 0.5
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cc(F)ccc2OC)CC1
InChIKey: SPRLNKQKOJIGIN-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 434.48, ALogP 3.3, HBA 8, HBD 0, PSA 68.54, QED 0.48
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3C(C)c2ccccc2)CC1
InChIKey: YXCLYEYNTSZAEF-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 414.51, ALogP 3.77, HBA 7, HBD 0, PSA 59.31, QED 0.5
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccccn2)CC1
InChIKey: GYBUADPJPWFDQT-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 387.45, ALogP 2.55, HBA 8, HBD 0, PSA 72.2, QED 0.53
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2cccnc2)CC1
InChIKey: NJRPVPREOSVFPG-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 387.45, ALogP 2.55, HBA 8, HBD 0, PSA 72.2, QED 0.53
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ccncc2)CC1
InChIKey: ZNYRBISOQWRKBE-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 387.45, ALogP 2.55, HBA 8, HBD 0, PSA 72.2, QED 0.53
Compound (SMILES): NC1=N[C@H](c2ccc(Br)cc2)CO1
InChIKey: CWSFSFQMKPGYPP-QMMMGPOBSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 241.09, ALogP 1.84, HBA 3, HBD 1, PSA 47.61, QED 0.81
Compound (SMILES): NC1=N[C@@H](c2ccc(-c3ccccc3)cc2)CO1
InChIKey: VXPAHLKILGDCAD-CQSZACIVSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 2670 nM (pChEMBL 5.570000171661377)
Descriptors: MW 238.29, ALogP 2.74, HBA 3, HBD 1, PSA 47.61, QED 0.87
Compound (SMILES): NC1=NC(c2cccc(Oc3ccccc3)c2)CO1
InChIKey: JZQCLAZEGFXKME-UHFFFAOYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 254.29, ALogP 2.86, HBA 4, HBD 1, PSA 56.84, QED 0.92
Compound (SMILES): Cc1ccccc1[C@H]1COC(N)=N1
InChIKey: BWXAYUSVBSUOTI-SECBINFHSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 176.22, ALogP 1.38, HBA 3, HBD 1, PSA 47.61, QED 0.7
Compound (SMILES): Cc1cc(Cl)ccc1[C@H]1COC(N)=N1
InChIKey: VICOLHFTEAKJRI-SECBINFHSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 210.66, ALogP 2.03, HBA 3, HBD 1, PSA 47.61, QED 0.77
Compound (SMILES): Cc1c(F)cccc1[C@H]1COC(N)=N1
InChIKey: IOHOUWIYOVWGHV-SECBINFHSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RJ0
Assay: Agonist activity at human TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 194.21, ALogP 1.52, HBA 3, HBD 1, PSA 47.61, QED 0.74
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc(Br)cc2)c2ccccc2c1O
InChIKey: RDWKYGQFJBSFGL-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 51400 nM (pChEMBL 4.289999961853027)
Descriptors: MW 422.26, ALogP 3.81, HBA 4, HBD 3, PSA 103.7, QED 0.59
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)NCc2ccccc2)c2ccccc2c1O
InChIKey: KFYCLGDNWSQMFJ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 56300 nM (pChEMBL 4.25)
Descriptors: MW 357.39, ALogP 2.72, HBA 4, HBD 3, PSA 103.7, QED 0.65
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)NCc2ccccc2Cl)c2ccccc2c1O
InChIKey: SRCMPGMYNOFYLZ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 50300 nM (pChEMBL 4.300000190734863)
Descriptors: MW 391.83, ALogP 3.38, HBA 4, HBD 3, PSA 103.7, QED 0.62
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)NCc2cccc(Cl)c2)c2ccccc2c1O
InChIKey: CDPRUQXLZPEQSD-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 5030 nM (pChEMBL 5.300000190734863)
Descriptors: MW 391.83, ALogP 3.38, HBA 4, HBD 3, PSA 103.7, QED 0.62
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)NCc2ccc(Cl)cc2)c2ccccc2c1O
InChIKey: KRLITVFCQFXSTJ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 391.83, ALogP 3.38, HBA 4, HBD 3, PSA 103.7, QED 0.62
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)NCC2CCCCC2)c2ccccc2c1O
InChIKey: HOPDZELMPICECF-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 77600 nM (pChEMBL 4.110000133514404)
Descriptors: MW 363.44, ALogP 3.1, HBA 4, HBD 3, PSA 103.7, QED 0.76
Compound (SMILES): CN(C)S(=O)(=O)c1cc(C(=O)O)c(O)c2ccccc12
InChIKey: ZFPJQLBFNKCFRE-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 25700 nM (pChEMBL 4.590000152587891)
Descriptors: MW 295.32, ALogP 1.49, HBA 4, HBD 2, PSA 94.91, QED 0.89
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)N2CCCCC2)c2ccccc2c1O
InChIKey: OGTOVDMYTARVKS-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 2950 nM (pChEMBL 5.53000020980835)
Descriptors: MW 335.38, ALogP 2.42, HBA 4, HBD 2, PSA 94.91, QED 0.9
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)N2CCN(c3ccccc3)CC2)c2ccccc2c1O
InChIKey: ORKWHMREWDJSCF-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 4540 nM (pChEMBL 5.340000152587891)
Descriptors: MW 412.47, ALogP 2.75, HBA 5, HBD 2, PSA 98.15, QED 0.68
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)N2CCN(Cc3ccccc3)CC2)c2ccccc2c1O
InChIKey: UZSDKWNQNYWAPK-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 3410 nM (pChEMBL 5.46999979019165)
Descriptors: MW 426.49, ALogP 2.75, HBA 5, HBD 2, PSA 98.15, QED 0.65
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccccc2Br)c2ccccc2c1O
InChIKey: ZGOONDIGLCVNFD-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 6840 nM (pChEMBL 5.170000076293945)
Descriptors: MW 422.26, ALogP 3.81, HBA 4, HBD 3, PSA 103.7, QED 0.59
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2cccc(Br)c2)c2ccccc2c1O
InChIKey: IMEDQDQJCFEBNZ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 5640 nM (pChEMBL 5.25)
Descriptors: MW 422.26, ALogP 3.81, HBA 4, HBD 3, PSA 103.7, QED 0.59
Compound (SMILES): O=C1c2ccccc2C(=O)N1CNc1ccc(F)cc1
InChIKey: ABKVYGLHDZFOJO-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 8740 nM (pChEMBL 5.059999942779541)
Descriptors: MW 270.26, ALogP 2.49, HBA 3, HBD 1, PSA 49.41, QED 0.87
Compound (SMILES): Cc1ccc(NCN2C(=O)c3ccccc3C2=O)cc1
InChIKey: PJRYJXNGQASRBP-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 266.3, ALogP 2.66, HBA 3, HBD 1, PSA 49.41, QED 0.87
Compound (SMILES): CCc1ccc(NCN2C(=O)c3ccccc3C2=O)cc1
InChIKey: WROOCEJCXHMKCY-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 4310 nM (pChEMBL 5.369999885559082)
Descriptors: MW 280.33, ALogP 2.91, HBA 3, HBD 1, PSA 49.41, QED 0.88
Compound (SMILES): COc1ccc(NCN2C(=O)c3ccccc3C2=O)cc1
InChIKey: NBPCFJQUQFKOHN-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 282.3, ALogP 2.36, HBA 4, HBD 1, PSA 58.64, QED 0.87
Compound (SMILES): O=C1c2ccccc2C(=O)N1CNc1ccc(O)cc1
InChIKey: BJICDFLREVNSMS-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 268.27, ALogP 2.06, HBA 4, HBD 2, PSA 69.64, QED 0.66
Compound (SMILES): CCOc1ccc(NCN2C(=O)c3ccccc3C2=O)cc1
InChIKey: UFTIHDWDIDPBGV-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 296.33, ALogP 2.75, HBA 4, HBD 1, PSA 58.64, QED 0.86
Compound (SMILES): CCN(CC)c1ccc(NCN2C(=O)c3ccccc3C2=O)c(C)c1
InChIKey: GFZMGVOOUHJBBS-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 337.42, ALogP 3.51, HBA 4, HBD 1, PSA 52.65, QED 0.82
Compound (SMILES): COc1ccc(N(C)CN2C(=O)c3ccccc3C2=O)cc1
InChIKey: PZFWFOSUKMFYDJ-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 296.33, ALogP 2.39, HBA 4, HBD 0, PSA 49.85, QED 0.81
Compound (SMILES): CCOc1ccc(NCN2C(=O)c3ccc([N+](=O)[O-])cc3C2=O)cc1
InChIKey: PGMXSOHKNBQNGZ-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 2830 nM (pChEMBL 5.550000190734863)
Descriptors: MW 341.32, ALogP 2.66, HBA 6, HBD 1, PSA 101.78, QED 0.49
Compound (SMILES): COc1ccc(NCN2C(=O)c3cccc(N)c3C2=O)cc1
InChIKey: KBRRWLPSQBYCTR-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 3530 nM (pChEMBL 5.449999809265137)
Descriptors: MW 297.31, ALogP 1.94, HBA 5, HBD 2, PSA 84.66, QED 0.67
Compound (SMILES): COc1ccc(NCN2C(=O)c3ccc(N)cc3C2=O)cc1
InChIKey: SXPBRGINZHOHQK-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 297.31, ALogP 1.94, HBA 5, HBD 2, PSA 84.66, QED 0.67
Compound (SMILES): COc1ccc(NCN2C(=O)c3cccc(NC(=O)c4ccccc4)c3C2=O)cc1
InChIKey: BKRWSEAAVXWARD-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15349
Assay: Inhibition of N-terminal His6 tagged full-length human recombinant active RSK2 using S6 peptide after 20 mins by fluorescence assay
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 401.42, ALogP 3.61, HBA 5, HBD 2, PSA 87.74, QED 0.62
Compound (SMILES): Cl.N[C@@H]1C[C@H]1c1ccc(NC(=O)c2ccc(NC(=O)OCc3ccccc3)c(N3CCOCC3)c2)cc1
InChIKey: HVQAVRGTDVWKEI-KZDWWKKTSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 486.57, ALogP 4.34, HBA 6, HBD 3, PSA 105.92, QED 0.46
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3ccc([C@@H]4C[C@H]4N)cc3)cc2NC(=O)OCc2ccccc2)CC1.Cl.Cl
InChIKey: PXIGWLFKDTVIQC-PEAFHPNTSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 499.62, ALogP 4.25, HBA 6, HBD 3, PSA 99.93, QED 0.45
Compound (SMILES): Cl.N[C@@H]1C[C@H]1c1ccc(NC(=O)c2ccc(N3CCCCC3)c(NC(=O)OCc3ccccc3)c2)cc1
InChIKey: FYQMFGITROVBSR-CLSOAGJSSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis
Measurement: IC50 = 307.5 nM (pChEMBL 6.510000228881836)
Descriptors: MW 484.6, ALogP 5.49, HBA 5, HBD 3, PSA 96.69, QED 0.41
Compound (SMILES): N[C@H]1CC[C@H](N[C@@H]2C[C@H]2c2ccccc2)CC1
InChIKey: ALHBJBCQLJZYON-ZQDZILKHSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Fluorescence-Based (Inhibitor)-Screening Assay: In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescence-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropanamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAO-A and MAO-B activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in duplicate within the same experiment.Briefly, a fixed amount of MAO (0.25 ug for MAO-A and 0.5 ug for MAO-B) was incubated on ice for 15 minutes in the reaction buffer, in the absence and/or in the presence of at least eight 3-fold serial dilutions each. Clorgyline and Deprenyl (Sigma Aldrich) was used as a control for specific inhibition of MAO-A and MAO-B respectively. After leaving the enzyme(s) interacting with the inhibitor, KM of kynuramine was added to each reaction for MAO-B and MAO-A assay respectively, and the reaction was left for 1 hour at 37° C. in the dark. The oxidative deamination of the substrate was stopped by adding 50 uL of NaOH 2N. The conversion of kynuramine to 4-hydroxyquinoline, was monitored by fluorescence (excitation at 320 nm, emission at 360 nm) using a microplate reader (Infinite 200, Tecan). Arbitrary units were used to measure levels of fluorescence produced in the absence and/or in the presence of inhibitor. The maximum of oxidative deamination activity was obtained by measuring the amount of 4-hydroxyquinoline formed from kynuramine deamination in the absence of inhibitor and corrected for background fluorescence in the absence of MAO enzymes. The IC50 values of each inhibitor were calculated with GraphPad Prism Software.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 230.35, ALogP 2.4, HBA 2, HBD 2, PSA 38.05, QED 0.84
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3ccc([C@H]4C[C@@H]4N)cc3)cc2)CC1.Cl.Cl
InChIKey: HFSFENIQYFFMGC-AAYDIPMQSA-N
Target: LSD1/CoREST complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UKL0
Assay: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 350.47, ALogP 2.51, HBA 4, HBD 2, PSA 61.6, QED 0.89
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCCNC(=O)CCCCCCC(=O)NCCCC[C@H](NC(C)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCNC(C)=S)C(=O)N1)C(N)=O
InChIKey: ANBJLSODZNSLHK-LJADHVKFSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+
Measurement: IC50 = 37.1 nM (pChEMBL 7.429999828338623)
Descriptors: MW 899.24, ALogP 0.83, HBA 11, HBD 10, PSA 284.84, QED 0.08
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCNC(=O)C(F)(F)F)NC1=O
InChIKey: GVDVRWSREIPDDL-MPWRRKJZSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of SIRT3 (unknown origin)
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 1859.97
Compound (SMILES): O=C1N=C(Nc2ccc(O)cc2)S/C1=C1\C(=O)Nc2ccccc21
InChIKey: MHLJDVDSEAUVCD-YPKPFQOOSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 subtype B protease
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 337.36, ALogP 2.8, HBA 5, HBD 3, PSA 90.79, QED 0.55
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3-c2ncccc2F)CC1
InChIKey: QEUPQTFBXOQKEA-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 405.44, ALogP 2.68, HBA 8, HBD 0, PSA 72.2, QED 0.52
Compound (SMILES): COc1ccc(-n2ncc3c(N4CCN(c5ccccc5OC)CC4)ncnc32)cn1
InChIKey: ULIFJDPCRNCCTC-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 417.47, ALogP 2.55, HBA 9, HBD 0, PSA 81.43, QED 0.49
Compound (SMILES): COc1ccccc1N1CCN(c2ncnc3c2cnn3C2CCCC2)CC1
InChIKey: WEDVUYSNJHNVQD-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Inhibition of human GLUT1 expressed in DLD1 cells assessed as ATP production co-incubated with 100 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 378.48, ALogP 3.28, HBA 7, HBD 0, PSA 59.31, QED 0.69
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CCC[C@]2(C)NC(N)=O)[C@H]1CC[C@H](C)CCO
InChIKey: ZCRCXSHUPVSSAT-BEUFEYIVSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human recombinant PTP-1B using IR5 insulin receptor residues as substrate after 30 mins by malachite green assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 336.52, ALogP 3.98, HBA 2, HBD 3, PSA 75.35, QED 0.64
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CCC[C@]2(C)NC(N)=O)[C@H]1CC[C@H](C)CNC(N)=O
InChIKey: HIGGQZFLALXLKW-BWCMQUJESA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human recombinant PTP-1B using IR5 insulin receptor residues as substrate after 30 mins by malachite green assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 364.53, ALogP 3.27, HBA 2, HBD 4, PSA 110.24, QED 0.54
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CCC[C@]2(C)NC(N)=O)[C@H]1CC[C@H](C)C/C=N/OC(C)=O
InChIKey: XQYCITFIGSANGV-VZCFTISZSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human recombinant PTP-1B using IR5 insulin receptor residues as substrate after 30 mins by malachite green assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 391.56, ALogP 4.54, HBA 4, HBD 2, PSA 93.78, QED 0.29
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CCC[C@]2(C)NC(N)=O)[C@H]1CC[C@H](C)C/C=N/O
InChIKey: ZXMMICAFBQFJHZ-XFOKWMRESA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human recombinant PTP-1B using IR5 insulin receptor residues as substrate after 30 mins by malachite green assay
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 349.52, ALogP 4.45, HBA 3, HBD 3, PSA 87.71, QED 0.29
Compound (SMILES): O=C(O)CSc1nnc(NC(=S)Nc2ccccc2)s1
InChIKey: JXTXUEGMEHCULC-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 27700 nM (pChEMBL 4.559999942779541)
Descriptors: MW 326.43, ALogP 2.52, HBA 6, HBD 3, PSA 87.14, QED 0.57
Compound (SMILES): Cc1ccc(NC(=S)Nc2nnc(SCC(=O)O)s2)cc1
InChIKey: VPQXYFGQNWUWSW-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 54400 nM (pChEMBL 4.260000228881836)
Descriptors: MW 340.46, ALogP 2.83, HBA 6, HBD 3, PSA 87.14, QED 0.57
Compound (SMILES): O=C(O)CSc1nnc(NC(=S)Nc2ccc(F)cc2)s1
InChIKey: VJUFCWPOZUWCAD-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 20900 nM (pChEMBL 4.679999828338623)
Descriptors: MW 344.42, ALogP 2.66, HBA 6, HBD 3, PSA 87.14, QED 0.56
Compound (SMILES): O=C(O)CSc1nnc(NC(=S)Nc2ccc(Cl)cc2)s1
InChIKey: BFBCPWMMMDWBLA-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 26300 nM (pChEMBL 4.579999923706055)
Descriptors: MW 360.87, ALogP 3.18, HBA 6, HBD 3, PSA 87.14, QED 0.55
Compound (SMILES): COc1ccccc1NC(=S)Nc1nnc(SCC(=O)O)s1
InChIKey: KCWTZOWEGKJENR-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 27100 nM (pChEMBL 4.570000171661377)
Descriptors: MW 356.45, ALogP 2.53, HBA 7, HBD 3, PSA 96.37, QED 0.53
Compound (SMILES): O=C(O)CSc1nnc(NC(=S)Nc2cccc(F)c2)s1
InChIKey: KMLXXCKAOOPCFI-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 31300 nM (pChEMBL 4.5)
Descriptors: MW 344.42, ALogP 2.66, HBA 6, HBD 3, PSA 87.14, QED 0.56
Compound (SMILES): O=C(O)CSc1nnc(NC(=S)Nc2cccc(Cl)c2)s1
InChIKey: IJMFROKCQQYBGI-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of diphenolase activity of mushroom tyrosinase preincubated for 10 mins followed by addition of L-DOPA measured for 5 mins by spectrophotometry
Measurement: IC50 = 59700 nM (pChEMBL 4.21999979019165)
Descriptors: MW 360.87, ALogP 3.18, HBA 6, HBD 3, PSA 87.14, QED 0.55
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc(Br)cc2Br)c2ccccc2c1O
InChIKey: PNQLIFYZRPXTNT-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 2310 nM (pChEMBL 5.639999866485596)
Descriptors: MW 501.15, ALogP 4.57, HBA 4, HBD 3, PSA 103.7, QED 0.49
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2cccc3ccccc23)c2ccccc2c1O
InChIKey: YZODXDPPIXBQFA-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 393.42, ALogP 4.2, HBA 4, HBD 3, PSA 103.7, QED 0.48
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc3ccccc3c2)c2ccccc2c1O
InChIKey: JAMJDESZLZEKIH-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 68500 nM (pChEMBL 4.159999847412109)
Descriptors: MW 393.42, ALogP 4.2, HBA 4, HBD 3, PSA 103.7, QED 0.48
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccccc2-c2ccccc2)c2ccccc2c1O
InChIKey: AKARBYPGSQOLJR-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 419.46, ALogP 4.71, HBA 4, HBD 3, PSA 103.7, QED 0.43
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2cccc(-c3ccccc3)c2)c2ccccc2c1O
InChIKey: KZQOMSULEJYOHX-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 1880 nM (pChEMBL 5.730000019073486)
Descriptors: MW 419.46, ALogP 4.71, HBA 4, HBD 3, PSA 103.7, QED 0.43
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc(-c3ccccc3)cc2)c2ccccc2c1O
InChIKey: PTJQYBHWGDXXKK-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 1540 nM (pChEMBL 5.809999942779541)
Descriptors: MW 419.46, ALogP 4.71, HBA 4, HBD 3, PSA 103.7, QED 0.43
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccccc2C(F)(F)F)c2ccccc2c1O
InChIKey: GUIFYVYGJNYGTJ-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 19300 nM (pChEMBL 4.710000038146973)
Descriptors: MW 411.36, ALogP 4.06, HBA 4, HBD 3, PSA 103.7, QED 0.6
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc(Cl)cc2)c2ccccc2c1O
InChIKey: HTZLXGBKGMWQAM-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 1910 nM (pChEMBL 5.71999979019165)
Descriptors: MW 377.81, ALogP 3.7, HBA 4, HBD 3, PSA 103.7, QED 0.64
Compound (SMILES): O=C(O)c1cc(S(=O)(=O)Nc2ccc(C(F)(F)F)cc2)c2ccccc2c1O
InChIKey: OWKIKZUVFQBYSV-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 411.36, ALogP 4.06, HBA 4, HBD 3, PSA 103.7, QED 0.6
Compound (SMILES): Cc1ccc(NS(=O)(=O)c2cc(C(=O)O)c(O)c3ccccc23)cc1
InChIKey: ONHURQQWIIHOBL-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 34300 nM (pChEMBL 4.460000038146973)
Descriptors: MW 357.39, ALogP 3.35, HBA 4, HBD 3, PSA 103.7, QED 0.66
Compound (SMILES): CC(C)c1ccc(NS(=O)(=O)c2cc(C(=O)O)c(O)c3ccccc23)cc1
InChIKey: ARMZPDQJZRAVKH-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of His6-MBP tagged recombinant human Mcl-1 residues 172 to 327 expressed in Escherichia coli assessed as inhibition of interaction with Bak BH3 peptide (GQVGRQLAIIGDDINR) after 3 hrs by fluorescence polarization competition assay
Measurement: Ki = 3860 nM (pChEMBL 5.409999847412109)
Descriptors: MW 385.44, ALogP 4.17, HBA 4, HBD 3, PSA 103.7, QED 0.61