lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCC[C@@H](NC(=O)[C@H]2O[C@@H](n3cc(-c4ccn(C)n4)c4c(N)ncnc43)[C@H](O)[C@@H]2O)C1
InChIKey: HMABXZUBNVAHQP-NPZWOMMPSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 456.51, ALogP -0.76, HBA 11, HBD 4, PSA 156.58, QED 0.4
Compound (SMILES): CC(C)(C)c1cnc(CSc2cnc(CC(=O)C3CCNCC3)s2)o1
InChIKey: YKCGAMRTHVAZHZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/Cyclin H (unknown origin)
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 379.55, ALogP 3.83, HBA 7, HBD 1, PSA 68.02, QED 0.77
Compound (SMILES): COc1nc(OCc2cccc(-c3ccccc3)c2C)ccc1CNCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O
InChIKey: SZVXUVSGDAOXRG-YMLRRHDESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD-1/PD-L1 interaction overexpressed in human HEK293T cells by flow cytometry analysis
Measurement: IC50 = 49.42 nM (pChEMBL 7.309999942779541)
Descriptors: MW 581.67, ALogP 1.69, HBA 10, HBD 5, PSA 151.63, QED 0.19
Compound (SMILES): CC(=O)N[C@H]1C[C@H](Nc2cc(C(C)C)nc3ccnn23)C1
InChIKey: WDOIPKCSUUDRMZ-HAQNSBGRSA-N
Target: CDK1/Cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of human CDK1/Cyclin A preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 4275 nM (pChEMBL 5.369999885559082)
Descriptors: MW 287.37, ALogP 1.93, HBA 5, HBD 2, PSA 71.32, QED 0.9
Compound (SMILES): CC[C@H](CO)NC1=N/C(=C\c2ccc3ncsc3c2)C(=O)N1
InChIKey: MFLKPCAUPXBTPC-CGYDICSFSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 316.39, ALogP 1.48, HBA 6, HBD 3, PSA 86.61, QED 0.75
Compound (SMILES): FC(F)Oc1cc(-n2cc(CNc3ccccn3)nn2)ccc1Cl
InChIKey: QVFZWKFTJHULNK-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Negative allosteric modulation of human GluN1A/GluN2B receptor expressed in T-REX-CHO cells preincubated for 5 mins followed by glutamate and glycine addition and measured after 5 mins by FLIPR assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 351.74, ALogP 3.53, HBA 6, HBD 1, PSA 64.86, QED 0.74
Compound (SMILES): Nc1ccc(Nc2nc(Nc3ccc(S(=O)(=O)N4CCCC4)cc3)c3scc(C4=CCCCC4)c3n2)cn1
InChIKey: YJLZNRXIUFCVFH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin E (unknown origin) expressed in Sf9 insect cells using histone H1 and ATP as substrate in presence of [gamma-33P]ATP as substrate by radiometric assay
Measurement: IC50 = 17204 nM (pChEMBL 4.760000228881836)
Descriptors: MW 547.71, ALogP 5.9, HBA 9, HBD 3, PSA 126.13, QED 0.26
Compound (SMILES): Cl.N[C@H]1CCN(c2c3c(nc4ccc(-c5cc(NC(=O)C6CC6)ncn5)cc24)CCCCC3)C1
InChIKey: WHHHELMURHCMDD-FERBBOLQSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/CyclinT1 (unknown origin) by ADP-Glo kinase assay
Measurement: IC50 = 5.75 nM (pChEMBL 8.239999771118164)
Descriptors: MW 442.57, ALogP 3.85, HBA 6, HBD 2, PSA 97.03, QED 0.6
Compound (SMILES): O=S(=O)(c1ccc(Nc2nc(C3=CCCCC3)nc3c(C4=CCCCC4)csc23)cc1)N1CCCC1
InChIKey: JGWGKJURXOIDPO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin E (unknown origin) expressed in Sf9 insect cells using histone H1 and ATP as substrate in presence of [gamma-33P]ATP as substrate by radiometric assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.72, ALogP 7.13, HBA 6, HBD 1, PSA 75.19, QED 0.37
Compound (SMILES): COC[C@@H](CC(C)C)NC1=N/C(=C\c2ccc3ncsc3c2)C(=O)N1
InChIKey: CHQYAWLKOUOTQO-QVYJARAXSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.47, ALogP 2.77, HBA 6, HBD 2, PSA 75.61, QED 0.78
Compound (SMILES): O=C(O)c1ccccc1OCCc1cn(-c2ccc(-c3c(Cl)cccc3Cl)cc2)c2ccc(-c3ccc(F)cc3)cc12
InChIKey: ITDFMPUKGDSVPP-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3/METTL14 in human MOLM-13 cells assessed as reduction in m6A/A ratio
Measurement: IC50 = 4920 nM (pChEMBL 5.309999942779541)
Descriptors: MW 596.49, ALogP 9.73, HBA 3, HBD 1, PSA 51.46, QED 0.19
Compound (SMILES): COCCCN(C)C(=O)[C@H]1O[C@@H](n2cc(-c3ccn(C)n3)c3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: DGQGNNBZYHBMBH-KSVNGYGVSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 445.48, ALogP -0.47, HBA 11, HBD 3, PSA 153.78, QED 0.41
Compound (SMILES): CN1CCC2(CC1)CC(NC1=N/C(=C\c3ccc4ncsc4c3)C(=O)N1)C2
InChIKey: VDJFUWZMISVQGO-PXNMLYILSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.51, ALogP 2.59, HBA 6, HBD 2, PSA 69.62, QED 0.78
Compound (SMILES): CC(C)C[C@H](CF)NC1=N/C(=C\c2ccc3ncsc3c2)C(=O)N1
InChIKey: FIVWKNZKXNNFCW-KXQKXUNCSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 346.43, ALogP 3.1, HBA 5, HBD 2, PSA 66.38, QED 0.82
Compound (SMILES): CN(C)C(=O)[C@@H](NC(=O)c1nnccc1-c1ccc(C(F)(F)F)cc1)c1cccc(C(F)(F)F)c1
InChIKey: GQZVJOGZLKPYTR-SFHVURJKSA-N
Target: NKGD2-ULBP6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 496.41, ALogP 4.74, HBA 4, HBD 1, PSA 75.19, QED 0.52
Compound (SMILES): CN1CCN(c2cnc(NC3=N/C(=C\c4ccc5ncsc5c4)C(=O)N3)cn2)CC1
InChIKey: UBUJLBVNZCRWPX-NVNXTCNLSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 420.5, ALogP 1.78, HBA 9, HBD 2, PSA 98.64, QED 0.62
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)N(CC[C@H](N)C(=O)O)C4CCNCC4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: XZMINAYRJJTQSC-IQIZDACOSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 543.59, ALogP -1.58, HBA 13, HBD 6, PSA 219.9, QED 0.19
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)NCC4CCOCC4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: KCBNBEMHWTZFDP-GRXQJBFDSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5/MEP50 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates incubated for 60 mins and measured by TopCount scintillation counter method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 457.49, ALogP -0.42, HBA 11, HBD 4, PSA 162.57, QED 0.4
Compound (SMILES): O=C1NC(Nc2cccnc2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: QVLJVHWQAKYGQI-MLPAPPSSSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 321.37, ALogP 2.63, HBA 6, HBD 2, PSA 79.27, QED 0.71
Compound (SMILES): O=C1NC(NC2CCC(F)(F)C2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: SJYQOVMGZOATNK-XGICHPGQSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00535
Assay: Inhibition of N-terminal GST/His6-fused human full length CDK5 (1 to 292 residues)/N-terminal His6-fused human p25 (104 to 307 residues) coexpressed in Sf9 cells using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 = 5498 nM (pChEMBL 5.260000228881836)
Descriptors: MW 348.38, ALogP 2.9, HBA 5, HBD 2, PSA 66.38, QED 0.82
Compound (SMILES): CC(=O)N[C@H]1C[C@H](Nc2cc(C(C)C)nc3ccnn23)C1
InChIKey: WDOIPKCSUUDRMZ-HAQNSBGRSA-N
Target: CDK2/Cyclin A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human CDK2/Cyclin A preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 5645 nM (pChEMBL 5.25)
Descriptors: MW 287.37, ALogP 1.93, HBA 5, HBD 2, PSA 71.32, QED 0.9
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: OHQOGIWNBYQPBT-GRRBOJRFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P20782
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 3426.92
Compound (SMILES): COc1ccc(-c2cnc3c(Nc4ccc(S(=O)(=O)N5CCCC5)cc4)cc(N[C@H]4CC[C@H](N)CC4)nn23)cc1OC
InChIKey: SEWKTWJOFMCKCB-AFARHQOCSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin E (unknown origin) expressed in Sf9 insect cells using histone H1 and ATP as substrate in presence of [gamma-33P]ATP as substrate by radiometric assay
Measurement: IC50 = 1435 nM (pChEMBL 5.840000152587891)
Descriptors: MW 591.74, ALogP 4.62, HBA 10, HBD 3, PSA 136.11, QED 0.25
Compound (SMILES): CC[C@H](C)[C@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: DPUJGORMIRYLGB-QLUCNORFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P20782
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 1940 nM (pChEMBL 5.710000038146973)
Descriptors: MW 3367.85
Compound (SMILES): Nc1ccc(Nc2cc(Nc3ccc(S(=O)(=O)N4CCCC4)cc3)c3ncn(C4CCCCC4)c3n2)nc1
InChIKey: PYPZDIPJTZEVBD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/Cyclin E (unknown origin) expressed in Sf9 insect cells using histone H1 and ATP as substrate in presence of [gamma-33P]ATP as substrate by radiometric assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 532.67, ALogP 5.19, HBA 9, HBD 3, PSA 131.06, QED 0.3
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: UCADOYBDKMCAKG-KXXJSBBQSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P20782
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 2930 nM (pChEMBL 5.53000020980835)
Descriptors: MW 3367.85
Compound (SMILES): CC(=O)N[C@H]1C[C@H](Nc2cc(C(C)C)nc3ccnn23)C1
InChIKey: WDOIPKCSUUDRMZ-HAQNSBGRSA-N
Target: CDK3/Cyclin E (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00526
Assay: Inhibition of human CDK3/Cyclin E preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 8930 nM (pChEMBL 5.050000190734863)
Descriptors: MW 287.37, ALogP 1.93, HBA 5, HBD 2, PSA 71.32, QED 0.9
Compound (SMILES): CC(=O)N[C@H]1C[C@H](Nc2cc(C(C)C)nc3ccnn23)C1
InChIKey: WDOIPKCSUUDRMZ-HAQNSBGRSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of human CDK4/Cyclin D1 preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 2840 nM (pChEMBL 5.550000190734863)
Descriptors: MW 287.37, ALogP 1.93, HBA 5, HBD 2, PSA 71.32, QED 0.9
Compound (SMILES): CCn1cc(-c2ccc3c(c2)ncn3-c2cc(OC)c(CO)c(OC)c2)cn1
InChIKey: UNBNKYSPLOMIOY-UHFFFAOYSA-N
Target: AMPK alpha1/beta2/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43741
Assay: Inhibition of AMPK alpha1/beta2/gamma1 (unknown origin) using SAMStide as substrate incubated for 45 to 60 mins in presence of 5'AMP and ATP by [33P]-gammaATP based Topcount scintillation counting analysis
Measurement: IC50 = 2127 nM (pChEMBL 5.670000076293945)
Descriptors: MW 378.43, ALogP 3.42, HBA 7, HBD 1, PSA 74.33, QED 0.56
Compound (SMILES): C[C@@]12COCCN1c1nc(-c3cccc4[nH]ccc34)ncc1N(C1CCOCC1)C2=O
InChIKey: ZTBJFQZREBPBTH-QHCPKHFHSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 419.49, ALogP 2.75, HBA 6, HBD 1, PSA 83.58, QED 0.69
Compound (SMILES): CO[C@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@H]([C@H](C)C[C@@H]2CC[C@@H](OCCOCc3cn(CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCn4nc(-c5cc6cc(O)ccc6[nH]5)c5c(N)ncnc54)nn3)[C@H](OC)C2)CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C/1C
InChIKey: GQCPOWLHVMDLGD-YOWUXWTGSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in P70S6K phosphorylation at Thr389 by AlphaLISA assay
Measurement: IC50 = 0.47 nM (pChEMBL 9.329999923706055)
Descriptors: MW 1783.18
Compound (SMILES): COc1cc(-c2scnc2C)c(F)cc1[C@H](C)NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)C1(F)CC1)C(C)(C)C
InChIKey: PWPAOVSRKMPDRI-SKSOZTCFSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P40337
Assay: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay
Measurement: Kd = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 578.68, ALogP 3.44, HBA 7, HBD 3, PSA 120.86, QED 0.44
Compound (SMILES): CC(=O)N1CCC(N2C(=O)[C@]3(C)COCCN3c3nc(-c4cccc5[nH]ccc45)ncc32)CC1
InChIKey: DMJNPFVKLJNTLB-VWLOTQADSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 460.54, ALogP 2.58, HBA 6, HBD 1, PSA 94.66, QED 0.63
Compound (SMILES): COc1cc(-c2scnc2C)cc(OC)c1CNC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)C1(C#N)CC1)C(C)(C)C
InChIKey: CALGVIRTTPEDRQ-LJFZDNNRSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P40337
Assay: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay
Measurement: Kd = 6240 nM (pChEMBL 5.210000038146973)
Descriptors: MW 583.71, ALogP 2.55, HBA 9, HBD 3, PSA 153.88, QED 0.41
Compound (SMILES): CO[C@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@H]([C@H](C)C[C@@H]2CC[C@@H](OCCOCc3cn(CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCn4nc(-c5cc6cc(O)ccc6[nH]5)c5c(N)ncnc54)nn3)[C@H](OC)C2)CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C/1C
InChIKey: GQCPOWLHVMDLGD-YOWUXWTGSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction in 4EBP1 phosphorylation at Thr37/46 by AlphaLISA assay
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 1783.18
Compound (SMILES): COc1cc(-c2scnc2C)c(F)cc1[C@H](C)NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)C1(F)CC1)C(C)(C)C
InChIKey: PWPAOVSRKMPDRI-SKSOZTCFSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P40337
Assay: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis
Measurement: Kd = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 578.68, ALogP 3.44, HBA 7, HBD 3, PSA 120.86, QED 0.44
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: OHQOGIWNBYQPBT-GRRBOJRFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P09690
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 3426.92
Compound (SMILES): CC[C@H](C)[C@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: DPUJGORMIRYLGB-QLUCNORFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P09690
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 1940 nM (pChEMBL 5.710000038146973)
Descriptors: MW 3367.85
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: UCADOYBDKMCAKG-KXXJSBBQSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P09690
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 2930 nM (pChEMBL 5.53000020980835)
Descriptors: MW 3367.85
Compound (SMILES): CCn1cc(-c2ccc3c(c2)ncn3-c2cc(OC)c(CO)c(OC)c2)cn1
InChIKey: UNBNKYSPLOMIOY-UHFFFAOYSA-N
Target: AMPK alpha1/beta2/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13131
Assay: Inhibition of AMPK alpha1/beta2/gamma1 (unknown origin) using SAMStide as substrate incubated for 45 to 60 mins in presence of 5'AMP and ATP by [33P]-gammaATP based Topcount scintillation counting analysis
Measurement: IC50 = 2127 nM (pChEMBL 5.670000076293945)
Descriptors: MW 378.43, ALogP 3.42, HBA 7, HBD 1, PSA 74.33, QED 0.56
Compound (SMILES): C[C@@]12COCCN1c1nc(-c3cccc4[nH]ccc34)ncc1N(C1CCOCC1)C2=O
InChIKey: ZTBJFQZREBPBTH-QHCPKHFHSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 419.49, ALogP 2.75, HBA 6, HBD 1, PSA 83.58, QED 0.69
Compound (SMILES): CC(=O)N1CCC(N2C(=O)[C@]3(C)COCCN3c3nc(-c4cccc5[nH]ccc45)ncc32)CC1
InChIKey: DMJNPFVKLJNTLB-VWLOTQADSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 460.54, ALogP 2.58, HBA 6, HBD 1, PSA 94.66, QED 0.63
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: OHQOGIWNBYQPBT-GRRBOJRFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P04756
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 3426.92
Compound (SMILES): CC[C@H](C)[C@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: DPUJGORMIRYLGB-QLUCNORFSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P04756
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 1940 nM (pChEMBL 5.710000038146973)
Descriptors: MW 3367.85
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: UCADOYBDKMCAKG-KXXJSBBQSA-N
Target: Nicotinic acetylcholine receptor alpha1/beta1/epsilon/delta (PROTEIN COMPLEX), Mus musculus
UniProt: P04756
Assay: Antagonist activity at mouse alpha1beta1deltaepsilon nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 2930 nM (pChEMBL 5.53000020980835)
Descriptors: MW 3367.85
Compound (SMILES): CC(=O)NC(C(=O)NC(C(=O)NC(=N)c1ccccc1)c1cccc(Cl)c1)c1ccccc1
InChIKey: JMINPJQOVGUNLG-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: TBD: TBD
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 462.94, ALogP 3.52, HBA 4, HBD 4, PSA 111.15, QED 0.32
Compound (SMILES): O=C(O)c1ccc2nc(C3(O)CCc4cc(-c5cc(Cl)ccc5-n5cnnn5)c[n+](O)c43)[nH]c2c1
InChIKey: WXLYAAFLDZEADN-UHFFFAOYSA-O
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Factor XIa Assay: Factor XIa determinations were made in 50 mM HEPES buffer at pH 7.4 containing 150 mM NaCl, 5 mM CaCl2, and 0.1% PEG 8000 (polyethylene glycol; JT Baker or Fisher Scientific). Determinations were made using purified human Factor XIa at a final concentration of 40 pM (Sekisui Diagnostics) and the synthetic substrate, Z-Gly-Pro-Arg-AFC, TFA salt (Sigma #C0980) at a concentration of 10004.Activity assays were performed by diluting a stock solution of substrate at least tenfold to a final concentration ≤0.1 Km into a solution containing enzyme or enzyme equilibrated with inhibitor. Times required to achieve equilibration between enzyme and inhibitor were determined in control experiments. Initial velocities of product formation in the absence (Vo) or presence of inhibitor (Vi) were measured. Assuming competitive inhibition, and that unity is negligible compared Km/[S], [I]/e, and [I]/e (where [S], [I], and e respectively represent the total concentrations, of substrate, inhibitor and enzyme), the equilibrium constant (Ki) for dissociation of the inhibitor from the enzyme can be obtained from the dependence of Vo/Vi on [I] shown in the following equation.V o /V i=1+[I]/Ki.
Measurement: IC50 = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 490.89, ALogP 2.26, HBA 8, HBD 4, PSA 153.92, QED 0.22
Compound (SMILES): CCOC(=O)/C=C/c1c(N)ncnc1N1CCCC(c2cccc(NC(=O)Nc3ccccc3)c2)C1
InChIKey: QNJCBOAUKWTGAS-BUHFOSPRSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: In Vitro BTK Kinase Assay: The purpose of the BTK in vitro assay is to determine compound potency against BTK through the measurement of IC50. Compound inhibition is measured after monitoring the amount of phosphorylation of a fluorescein-labeled polyGAT peptide (Invitrogen PV3611) in the presence of active BTK enzyme (Upstate 14-552), ATP, and inhibitor. The BTK kinase reaction was done in a black 96 well plate (costar 3694). For a typical assay, a 24 μL aliquot of a ATP/peptide master mix (final concentration; ATP 10 μM, polyGAT 100 nM) in kinase buffer (10 mM Tris-HCl pH 7.5, 10 mM MgCl2, 200 μM Na3PO4, 5 mM DTT, 0.01% Triton X-100, and 0.2 mg/ml casein) is added to each well. Next, 1 μL of a 4-fold, 40× compound titration in 100% DMSO solvent is added, followed by adding 15 uL of BTK enzyme mix in 1× kinase buffer (with a final concentration of 0.25 nM). The assay is incubated for 30 minutes before being stopped with 28 μL of a 50 mM EDTA solution. Aliquots (5 μL) of the kinase reaction are transferred to a low volume white 384 well plate (Corning 3674), and 5 μL of a 2× detection buffer (Invitrogen PV3574, with 4 nM Tb-PY20 antibody, Invitrogen PV3552) is added. The plate is covered and incubated for 45 minutes at room temperature. Time resolved fluorescence (TRF) on Molecular Devices M5 (332 nm excitation; 488 nm emission; 518 nm fluorescein emission) is measured. IC50 values are calculated using a four parameter fit with 100% enzyme activity determined from the DMSO control and 0% activity from the EDTA control.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.58, ALogP 4.66, HBA 7, HBD 3, PSA 122.47, QED 0.33
Compound (SMILES): COc1cc2c(cc1CC(=O)O)nc(Nc1ccc(C(C)C)cc1)n2C1CC(C)CC(C)(C)C1
InChIKey: OLGPLGPOVKGOOE-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Biochemical Assay: mIDH1 catalyzes the NADPH-dependent reduction of alpha-ketoglutarate (α-KG) to (2R)-2-hydroxyglutarate (2-HG). NADPH consumption was measured by luminescent readout.The biochemical reactions were performed at 32° C. in 384-well plates using a reaction volume of 41 μL and the following assay buffer conditions: 50 mM Tris pH 7.5, 100 mM NaCl, 20 mM MgCl2, 0.05% BSA, 0.01% Brij, 1 μM NADPH, and 250 μM α-KG. The IDH1 R132H enzyme was used in a final concentration of 1.5 nM. Test compounds were used in a concentration range between 0.002 and 10 μM. The final DMSO concentration was 2.4%.The reaction was incubated for 30 minutes, then 40 μL of detection mix (0.75 μg/ml Luciferase, 0.02 U/ml Oxidoreductase, 4 μg/mL FMN, 2 μL/ml decanal/ethanol, 50 mM Tris pH 7.5, 0.5% Glycerin, 0.01% Tween-20, 0.05% BSA) was added. Luminescence was measured on a luminescent reader (10 seconds measuring time, 1 second integration period, 30% sensitivity). The decrease in luminescence is proportional to mIDH1 activity. IC50 values are determined by interpolation from plots of relative luminescence versus inhibitor concentration.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 463.62, ALogP 6.93, HBA 5, HBD 2, PSA 76.38, QED 0.4
Compound (SMILES): Cc1nc(C2CCN(c3ncnc4[nH]c(-c5cnn(C(F)F)c5)cc34)CC2)[nH]c1-c1ccccc1
InChIKey: RDMPWRMMTKATPY-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Biochemical Assay: The c-kit mutant D816V (or kinase domain thereof) is an active kinase in AlphaScreen. IC50 values are determined with respect to inhibition of c-Kit mutant D816V kinase activity, where inhibition of phosphorylation of a peptide substrate is measured as a function of compound concentration. Compounds to be tested were dissolved in DMSO to a concentration of 30 mM. These were diluted 30 ml into 130 ml of DMSO (4 mM) and 1 μl was added to an assay plate. These were then serially diluted 1:3 (50 μl to 100 ml DMSO) for a total of 8 points. Plates were prepared such that each kinase reaction is 30 ml in 1× kinase buffer (25 mM HEPES, pH 7.2, 8 mM MgCl2, 2 mM MnCl2, 50 mM NaCl, 0.01% Brij, 1 mM DTT, 0.01% BSA), 5% DMSO and 10 μM ATP. Substrate was 30 nM biotin-(E4Y)10 (EMD Millipore, Cat#12-440). C-kit mutant D816V kinase was at 0.75 ng per sample. After incubation of the kinase reaction for 30 minutes at room temperature, 5 μl of donor beads (Streptavidin coated beads (Perkin Elmer Life Science) final concentration 7.5 μg/ml) in stop buffer (25 mM Hepes pH 7.5, 100 mM EDTA, 0.01% BSA) was added, the sample was mixed and incubated for 30 minutes at room temperature before adding 5 ml of acceptor beads (PY30 coated beads (Perkin Elmer Life Science) final concentration 7.5 μg/ml) in stop buffer.
Measurement: Ki = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 474.52, ALogP 5.3, HBA 6, HBD 2, PSA 91.31, QED 0.36
Compound (SMILES): O=C(Cc1cc2ncccc2cc1F)Nc1scc(Br)c1-c1ncn[nH]1
InChIKey: WASYKACWTDBGKU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: HTRF Assay: (1) Assay buffer #1 with 0.0025% Tween and 1 mM DTT was prepared using JNK buffer stock solution.(2) Assay buffer #2 with 0.025% BSA was prepared using the assay buffer #1.(3) Test compound solution preparation: 5× compound solution was prepared using assay buffer #1 with 5% DMSO. The compound solution (10 μl/well) was added to a 384-well plate (Corning, Cat No. 3654).(4) aJNK1, 2 or 3 preparation: aJNK stock (100 μg/ml) at −80° C. was thawed on ice and an aJNK (1.6 ng/ml) solution was prepared using assay buffer #2. The aJNK solution (20 μl/well) was added to the plate and the plate was shaken. The enzyme was incubated with the compound at RT for 10 min.(5) ATP/substrate solution preparation: ATP and substrate stocks were thawed on ice. 2.5×ATP/substrate (e.g., 25 μM or 2.5 mM ATP/50 nM EPIW-1) was prepared using assay buffer #1. The ATP/substrate (20 μl/well) was added to the plate and the plate was shaken. The plate was incubated at RT for 15 min. Note: In an exemplary assay, the final ATP concentration was about 1 mM.(6) EDTA preparation: 30 mM EDTA was prepared using 0.5M EDTA stock and assay buffer #1. The EDTA (10 μl/well) was added to the plate to quench the enzyme reaction and the plate was shaken well.(7) Detection reagent preparation: Eu-63 and SA-XL stocks were thawed on ice. 4× Eu-63/SA-XL (2 nM Eu-63/9.4 nM SA-XL) was prepared using JNK detection buffer. The Eu-63/SA-XL solution (20 μl/well) was added to the plate and the plate was shaken. The plate was incubated at RT for 1 hr before reading the plate on LJL using ratiometric method named HTRF.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 432.28, ALogP 4.16, HBA 5, HBD 2, PSA 83.56, QED 0.51
Compound (SMILES): Nc1nc2c(ncn2[C@H]2O[C@@H]3COP(=O)(S)OCCn4c(nc5cnccc54)COP(=O)(S)O[C@@H]2[C@H]3F)c(=O)[nH]1
InChIKey: FRJKWYDLRRJHJT-HQSBPKDTSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Binding Assay: A human STING [3H] 2′,3′-cGAMP scintillation proximity competition binding assay was utilized to detect binding of compounds to STING protein. The competition binding assay was conducted with either a wild-type (WT, SEQ ID NO: 1) or an AQ variant (SEQ ID NO: 2) of truncated human STING protein that lacks the N-terminal four transmembrane domains and contains amino acids 155-379. The protein encoding plasmid contained a HIS tag, followed by an Avi tag and then a SUMO tag, which were followed by the STING coding sequence within the pET-28a (+) vector. The plasmid was transfected into a BL21 (DE3)/BirA E. coli co-expression strain. Protein was purified from the bacterial lysate using a cobalt-affinity column. The purified protein was dialyzed against PBS and then 20% glycerol was added prior to storage at −80° C.The assay was conducted in a 384-well plate containing final concentration of 25 nM biotin-STING protein and 17.5 nM [3H] 2′,3′-cGAMP in assay buffer (50 mM Tris pH 7.5, 100 mM NaCl, 0.1% Fatty Acid Free BSA). Test compounds (2.5 μL) were added to the plate first followed by a 25 μL mixture of STING protein, streptavidin PVT SPA beads (Perkin Elmer) and 10 μL [3H] 2′,3′-cGAMP. Plates were incubated at room temperature for 18 hrs and read on a Wallac MicroBeta TriLux (Perkin Elmer). 2′,2′-cGAMP was used as a reference compound and had an IC50 of 0.562 μM using the WT STING protein and 0.098 M using the AQ STING protein.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 634.51, ALogP 2.41, HBA 15, HBD 4, PSA 200.59, QED 0.18
Compound (SMILES): Cn1cc2c(n1)C(=O)NCCCOc1ccc(=O)n(n1)Cc1cccc(n1)C(=O)N2
InChIKey: JTDOHCWXAJEHMM-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51617
Assay: Enzymatic Assay: IRAK1 is a human purified recombinant enzyme (His-TEV-IRAK1 (194-712)) In this assay, IRAK1 hydrolyses ATP and autophosphorylates. Measurement of IRAK-1 inhibition is performed in 384-well format based on luminescence assay (ADP-Glo Kinase Assay from Promega). Purified human recombinant IRAK1 (0.3 ug/ml) and serial diluted compounds in DMSO (range of concentration from 10 uM to 0.5 nM) or controls (1% DMSO) are incubated for 15 minutes at RT in assay buffer containing 50 mM Hepes pH 7.0, Fatty acid-free BSA 0.1%, Dithiothreitol (DTT) 2 mM, MgCl2 10 mM, EGTA 0.5 mM, Triton X-100 0.01%. The kinase reaction is then initiated by the addition of ATP at a concentration of 1 uM. After 2 hours of incubation at RT, the reaction is stopped and the unconsumed ATP depleted by the addition of ADP-Glo Reagent according to supplier instructions. After 40 minutes of incubation at RT, the Kinase Detection Reagent is then added to the assay plate according to supplier instructions. After 20 minutes of incubation at RT, the luminescence signal is measured with a luminometer (PerkinElmer Envision or equivalent reader).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 409.41, ALogP 0.18, HBA 9, HBD 2, PSA 133.03, QED 0.54
Compound (SMILES): CN(C)C(=O)[C@@H]1CN(C2CCCCC2)CC[C@H]1NC(=O)c1cn(-c2ccc(F)cc2F)nn1
InChIKey: PIOBCFUJVLPSHS-IEBWSBKVSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: In Vitro Assay: Tango CXCR7-bla U2OS cells are detached from culture dishes with 0.05% trypsin-EDTA and collected in growing medium (McCoy's 5A 90% (v/v), dialyzed FCS 10% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), 1 mM sodium pyruvate, P/S 1% (v/v) 50 μg/ml Hygromycin, 100 μg/ml Geneticin, 200 μg/ml Zeocin), spinned down and resuspended in assay medium (McCoy's 5A 90% (v/v), dialyzed FCS 1% (v/v), 0.1 mM NEAA, 25 mM HEPES (pH7.3), P/S 1% (v/v)). 10′000 cells per well (in 30 μl) are seeded in a 384 well plate (black-walled, clear bottom). The plate is incubated at 37° C./5% CO2 for 24 hours. Test compounds are dissolved to 10 mM in DMSO and serially diluted in DMSO to 500× of the final concentration for dose response curves. Compounds are then diluted 1:100 in assay medium to 5× of the final concentration. 10 μl/well of diluted compounds are added to the assay plate and incubated for 15 minutes at 37° C. Thereafter CXCL12/SDF1-α is diluted in assay medium to 5× of the final concentration (its EC80 value for receptor activation) and 10 μl/well are added to the assay plate. The agonist leads to activation of the receptor and therefore to b-arrestin recruitment. Compounds acting as antagonists reduce this activation. The plate is incubated for 22 hrs at 37° C. 10 μl/well of detection reagent (LiveBLAzer-FRET BIG (CCF4-AM) substrate) is transferred to the assay plate and the plate is incubated for 2 hours at room temperature protected from light. Fluorescent counts are determined (Scan1: Ex 409/20 nm, Em 460/30 nm, Scan 2: Ex 409/20 nm, Em 530/30 nm).
Measurement: IC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 460.53, ALogP 2.39, HBA 6, HBD 1, PSA 83.36, QED 0.74
Compound (SMILES): C=CC(=O)N1CC(NC(=O)Cn2cc(Cl)c3cc(Br)ccc32)C1
InChIKey: MQXOZSCNPCFYGJ-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Coupled Nucleotide Exchange Assay (2 hours): Purified GDP-bound KRAS protein (aa 1-169), containing both G12C and C118A amino acid substitutions and an N-terminal His-tag, was pre-incubated in assay buffer (25 mM HEPES pH 7.4, 10 mM MgCl2, and 0.01% Triton X-100) with a compound dose-response titration for either 2 hours. Following compound pre-incubation, purified SOS protein (aa 564-1049) and GTP (Roche 10106399001) were added to the assay wells and incubated for an additional 30 min (for 5 min compound pre-incubation) or 1 hour (for 2 hour compound pre-incubation). To determine the extent of inhibition of SOS-mediated nucleotide exchange, purified GST-tagged cRAF (aa 1-149), nickel chelate AlphaLISA acceptor beads (PerkinElmer AL108R), and AlphaScreen glutathione donor beads (PerkinElmer 6765302) were added to the assay wells and incubated for 10 minutes. The assay plates were then read on a PerkinElmer EnVision Multilabel Reader, using AlphaScreen® technology, and data were analyzed using a 4-parameter logistic model to calculate IC50 values.
Measurement: IC50 = 5120 nM (pChEMBL 5.289999961853027)
Descriptors: MW 396.67, ALogP 2.57, HBA 3, HBD 1, PSA 54.34, QED 0.81
Compound (SMILES): COC1CCN(c2cc(C(=O)N3CC(c4ccccc4)C3)no2)CC1
InChIKey: BGNZTDZSJZZITP-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86SK9
Assay: Compound Profiling Methods: Strains expressing SCD1 or SCD5 as the sole desaturase, the human SCD1 and SCD5 genes were used to evaluate inhibition of SCD1/SCD5 using reduced growth as a surrogate for SCD inhibition. These yeast strains express human SCD1 or SCD5 from a plasmid harbored in a strain in which the yeast OLE1 gene is deleted.All compound profiling experiments were performed using the same basic protocol. Yeast were cultured using standard techniques in complete synthetic media lacking uracil and containing yeast nitrogen base supplemented with 2% (w/v) glucose (SD-Ura) Starter cultures were inoculated in 3 mL SD-Ura media containing 0.01% tween and 0.2 mM palmitoleic and oleic acid. Cultures were incubated overnight in a 30° C. shaker incubator (225 rpm). Saturated morning cultures were centrifuged, washed in SD-Ura media lacking TWEEN-20 and fatty acids, and then diluted 1:20 in fresh SD-Ura media also lacking TWEEN-20 and fatty acids. Cells were grown for 6 h to an  (optical density) of 0.4-0.8 at 30° C. with shaking.Compound stocks (10 mM in 100% DMSO) were arrayed into 384-round well, v-bottom polypropylene plates and diluted according to indicated dilution factors. Compound administration was performed in two separate steps. First, 15 μL of SD-Ura was dispensed into clear 384-well assay plates using a MULTIDROP Combi reagent dispenser. The diluted compound stock plates were then applied to the assay plates using an automated workstation (Perkin Elmer JANUS) outfitted with a 384-pin tool containing slotted pins that deliver 100 nL of compound. The cultures described above were centrifuged and washed with media lacking TWEEN-20 or oleic and palmitoleic acids. Cultures were then resuspended at a 2-fold concentrated  of 0.02 (final  of 0.0.01) in SD-Ura. 15 μL of diluted culture was then dispensed into the pinned assay plate to achieve 30 μL of the 1× culture (0.01) and a top drug concentration of 33.3 μM.After yeast delivery, assay plates were incubated under humidified conditions at 30° C. for 40 h. Yeast growth was monitored by reading the  of each well using a microplate reader (Perkin Elmer EnVision). Data were analyzed as follows. Raw data were processed by background subtracting and converting values to a percent of the nontreated condition for that strain [(EXP-0.035)/(DMSO-0.035)×100%].
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 341.41, ALogP 2.53, HBA 5, HBD 0, PSA 58.81, QED 0.86
Compound (SMILES): C#CCOc1cc(C(=O)NCc2cnc(C)cn2)cc(-c2ncc(C)s2)c1
InChIKey: HKQDCIZFKBUDQD-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Intracellular Calcium Measurement to Assess Antagonist Activity : A fluorescent imaging plate reader (FLEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Fluo-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C. The final assay DMSO concentration is 1%.The agonist, α,β-Me-ATP, was added in a volume of 20 μl at a concentration representing the EC80 value. The fluorescence was measured for an interval of 90 sec at 2 sec intervals and analyzed based on the increase in peak relative fluorescence units (RFU) compared to the basal fluorescence. Peak fluorescence was used to determine the response to agonist obtained at each concentration of test compound by the following equation: % Response=100*(RFU(test compound)−RFU(control))/(RFU(DMSO)−RFU(control)).
Measurement: IC50 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 378.46, ALogP 3.16, HBA 6, HBD 1, PSA 77, QED 0.67