lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl IKBKB
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: GPCRScan assay: inhibition of NET
Measurement: Ki = 1935.54 nM (pChEMBL 5.710000038146973)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of recombinant wild type tyrosine phosphorylated C-terminal 6His tagged human STAT3 C426A mutant (127 to 711 residues) DNA-binding activity transfected in v-Src transformed mouse NIH3T3 cell nuclear extract preincubated for 30 mins followed by addition of radiolabeled hSIE and measured after 30 mins by EMSA analysis
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2occc12
InChIKey: JMBNFFBZCFTGQK-XQKZEKTMSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Agonist activity at MT1 (unknown origin) expressed in HEK293T cells incubated for 15 mins by melatonin Gi/o-mediated cAMP inhibition GloSensor assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 249.28, ALogP 2.84, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): CC(C)S(=O)(=O)c1ccc2nccc(Nc3ccc4scnc4c3)c2c1
InChIKey: ZCDBTQNFAPKACC-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Inhibition of recombinant human RIP3 kinase activity by ADP-glo assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 383.5, ALogP 4.77, HBA 6, HBD 1, PSA 71.95, QED 0.55
Compound (SMILES): Cc1nc2cc(F)c(-c3cnc(C(C)(C)O)nc3)nc2c(N[C@H](C)c2cc(C#N)ccc2F)c1Cl
InChIKey: UDLNDXDUOBMZIQ-GFCCVEGCSA-N
Target: Tumor necrosis factor ligand superfamily member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P48023
Assay: Inhibition of FasL (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 494.93, ALogP 5.6, HBA 7, HBD 2, PSA 107.61, QED 0.37
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Antagonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human full length C-terminal Flag tagged HDAC4 expressed in HEK293T cells using H3K9-myristoyl peptide as substrate by HPLC method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin) by LANCE ULight TR-FRET assay
Measurement: IC50 = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): C=CC(=O)N1CC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cn2)CC1
InChIKey: AYGSWHUBBRQXAY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using ULight -mylein basic protein as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 391.48, ALogP 3.23, HBA 4, HBD 2, PSA 90.98, QED 0.74
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O95382
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl MAP3K6
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: GPCRScan assay: inhibition of NET
Measurement: Ki = 1905.46 nM (pChEMBL 5.71999979019165)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of recombinant wild type tyrosine phosphorylated C-terminal 6His tagged human STAT3 C468A mutant (127 to 711 residues) DNA-binding activity transfected in v-Src transformed mouse NIH3T3 cell nuclear extract preincubated for 30 mins followed by addition of radiolabeled hSIE and measured after 30 mins by EMSA analysis
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCCF)ccc2occc12
InChIKey: JMBNFFBZCFTGQK-XQKZEKTMSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at MT2(unknown origin) expressed in HEK293T cells incubated for 15 mins by melatonin Gi/o-mediated cAMP inhibition GloSensor assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 249.28, ALogP 2.84, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): CC(C)S(=O)(=O)c1ccc2nccc(Nc3ccc4scnc4c3)c2c1
InChIKey: ZCDBTQNFAPKACC-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Inhibition of RIPK3 (unknown origin) by ADP-Glo reagent based assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 383.5, ALogP 4.77, HBA 6, HBD 1, PSA 71.95, QED 0.55
Compound (SMILES): Cc1nc2cc(F)c(-c3cnc(C(C)(C)O)nc3)nc2c(N[C@H](C)c2cc(C#N)ccc2F)c1Cl
InChIKey: UDLNDXDUOBMZIQ-GFCCVEGCSA-N
Target: Lymphotoxin-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q06643
Assay: Inhibition of LTbeta (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 494.93, ALogP 5.6, HBA 7, HBD 2, PSA 107.61, QED 0.37
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P05107
Assay: Agonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as increase in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) by LANCE ULight TR-FRET assay
Measurement: IC50 = 14400 nM (pChEMBL 4.840000152587891)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of CLK3 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl MERTK
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: GPCRScan assay: inhibition of 5-HT1D
Measurement: Ki = 417.5 nM (pChEMBL 6.380000114440918)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of recombinant wild type tyrosine phosphorylated C-terminal 6His tagged human STAT3 C542S mutant (127 to 711 residues) DNA-binding activity transfected in v-Src transformed mouse NIH3T3 cell nuclear extract preincubated for 30 mins followed by addition of radiolabeled hSIE and measured after 30 mins by EMSA analysis
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P05107
Assay: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin) by LANCE ULight TR-FRET assay
Measurement: IC50 = 1610 nM (pChEMBL 5.789999961853027)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of CLK4 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl EGFR
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: GPCRScan assay: inhibition of 5-HT1D
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Displacement of 5-carboxyfluorescein GpYLPQTV-NH2 probe from C-terminal 6His-tagged recombinant human STAT3 (127 to 711 residues) SH2 domain extracted from Escherichia coli BL21 (DE3) assessed as inhibition of dimerization preincubated for 10 mins followed by probe addition and measured after 30 mins by fluorescence polarization assay
Measurement: IC50 = 27900 nM (pChEMBL 4.550000190734863)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of fibronectin binding to human recombinant alphaVbeta3 expressed in HEK293 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl ERBB4
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: Enzymatic OGA assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Displacement of 5-carboxyfluorescein GpYLPQTV-NH2 probe from C-terminal 6His-tagged recombinant human STAT3 (127 to 711 residues) SH2 domain extracted from Escherichia coli BL21 (DE3) assessed as inhibition of dimerization preincubated for 30 mins followed by probe addition and measured after 30 mins by fluorescence polarization assay
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of fibrinogen binding to alphaVbeta5 isolated form human mCf7 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin)
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of DYRK1B (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Ephrin type-A receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29320
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl EPHA3
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Beta-hexosaminidase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P07686
Assay: Enzymatic HEXB assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): O=C(O)c1ccc(N(Cc2ccc(C3CCCCC3)cn2)C(=O)[C@H]2CCN2S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1O
InChIKey: PRLVPYXUDLHWQA-HXUWFJFHSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Displacement of 5-carboxyfluorescein GpYLPQTV-NH2 probe from C-terminal 6His-tagged recombinant human STAT3 (127 to 711 residues) SH2 domain extracted from Escherichia coli BL21 (DE3) assessed as inhibition of dimerization preincubated for 60 mins followed by probe addition and measured after 30 mins by fluorescence polarization assay
Measurement: IC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 639.6, ALogP 5.23, HBA 6, HBD 2, PSA 128.11, QED 0.2
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of fibronectin binding to alphaVbeta6 isolated form human HT-29 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CCCCCCCCCCCCCCCCNNC(=O)c1cccs1
InChIKey: HSHXDCVZWHOWCS-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.62, ALogP 6.46, HBA 3, HBD 2, PSA 41.13, QED 0.25
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of DYRK2 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl MST1R
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC1CCN(c2ccnc(NCc3cn(C)cn3)n2)CC1
InChIKey: PWKAYICUBVNJAZ-UHFFFAOYSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Homo sapiens
UniProt: O60502
Assay: In-cell western assay
Measurement: EC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 286.38, ALogP 2.06, HBA 6, HBD 1, PSA 58.87, QED 0.93
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of fibronectin binding to alpha4bbeta1 isolated from human Jurkat E6.1 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P80192
Assay: Inhibition of MLK1 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl RET
Measurement: IC50 = 11500 nM (pChEMBL 4.940000057220459)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02779
Assay: Inhibition of MLK2 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl ITK
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16584
Assay: Inhibition of MLK3 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl MAP3K7
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cn[nH]n4)nc23)cc1
InChIKey: KTGZHJWTKLQHBK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase-like 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVW4
Assay: Inhibition of CDKL3 (unknown origin) by NanoBRET cellular target engagement assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 318.38, ALogP 4.58, HBA 4, HBD 1, PSA 67.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl ROCK1
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(C(=O)Nc2cn3cc(-n4ccnc4)ccc3n2)cc1.Cl.Cl
InChIKey: IKKLFEDUYFZNBO-UHFFFAOYSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Selectivity interaction (Kinase panel (Invitrogen, enzymatic assay)) EUB0000623aCl PRKCQ
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.43, ALogP 4.07, HBA 5, HBD 1, PSA 64.22, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta5 in human MCF7 cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Inhibition of alphavbeta3 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCNCC4)cc3)nc2n2cc(C(C)C)nc12
InChIKey: DEVYXOKAXWLJRC-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 = 94.7 nM (pChEMBL 7.019999980926514)
Descriptors: MW 443.56, ALogP 4.07, HBA 8, HBD 2, PSA 87.45, QED 0.45
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Agonist activity at alphaVbeta6 in human HT-29 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta5 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 = 3002 nM (pChEMBL 5.519999980926514)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Antagonist activity at alphaVbeta6 in human HT-29 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Inhibition of alphavbeta6 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 = 2762 nM (pChEMBL 5.559999942779541)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Antagonist activity at alpha5beta1 in human K562 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-8 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta8 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Agonist activity at alpha2bbeta3 in human HEL cells assessed as increase in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P13612
Assay: Inhibition of alpha4beta1 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Antagonist activity at alpha2bbeta3 in human HEL cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PTCMVGOQRMWOTP-MVBWARRXSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 821.96, ALogP 1.31, HBA 9, HBD 9, PSA 282.08, QED 0.06
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P13612
Assay: Antagonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 8.8 nM (pChEMBL 8.0600004196167)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P20701
Assay: Agonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as increase in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-L/beta-2 (LFA-1) (PROTEIN COMPLEX), Homo sapiens
UniProt: P20701
Assay: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Inhibition of fibronectin binding to human recombinant alphaVbeta3 expressed in HEK293 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN([C@H]4CC[C@H](C(=O)O)CC4)CC3)cc12
InChIKey: RYPUWZOEFAAXRB-SAABIXHNSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 467.52, ALogP 5.25, HBA 4, HBD 2, PSA 78.45, QED 0.54
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of fibrinogen binding to alphaVbeta5 isolated form human mCf7 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Inhibition of fibronectin binding to alphaVbeta6 isolated form human HT-29 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): Nc1ccc(CNC(=O)N2C(=O)C[C@H]2C(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: PBDSUCKUKNOMFW-FVGYRXGTSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P13612
Assay: Inhibition of fibronectin binding to alpha4bbeta1 isolated from human Jurkat E6.1 cells incubated for 1 hr by scintillation-proximity assay based competitive solid-phase binding assay
Measurement: IC50 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 263.25, ALogP 0.16, HBA 4, HBD 3, PSA 112.73, QED 0.53
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)n(C(C)C)c4n3)C2)cc1
InChIKey: BYNXYHOKVMMMKC-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 446.51, ALogP 2.82, HBA 7, HBD 2, PSA 109.22, QED 0.56
Compound (SMILES): O=c1ccoc2ccc(OCCCN3CCOCC3)cc12
InChIKey: NZDIHDNMUCUHGB-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]pentazocine from human sigma 1 receptor expressed in HEK293 cell membrane incubated for 2 hrs by liquid scintillation counting method
Measurement: Ki = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 289.33, ALogP 1.89, HBA 5, HBD 0, PSA 51.91, QED 0.79
Compound (SMILES): C/C(=N\NC(=S)Nc1cccc(Br)c1)c1ccc2c(c1)NC(=O)CO2
InChIKey: NLCNOTRUDXVTON-UFFVCSGVSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15121
Assay: Inhibition of ALR2 (unknown origin)
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 419.3, ALogP 3.49, HBA 4, HBD 3, PSA 74.75, QED 0.4
Compound (SMILES): CCS(=O)(=O)N1CC(n2cc3cc(NC(=O)c4cccc(C(F)(F)F)n4)c(C(C)(C)O)cc3n2)C1
InChIKey: BXRSHPLJLHEUPU-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin)
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 511.53, ALogP 3.14, HBA 7, HBD 2, PSA 117.42, QED 0.53
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cc1
InChIKey: CGWPUJBNBZHNQO-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 in human HeLa nuclear extract using Boc-Lys(Ac)-AMC as substrate measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 517.61, ALogP 2.16, HBA 10, HBD 3, PSA 151.57, QED 0.2