lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Enzyme Assay: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z′-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen Biochemical Kinase Profiling Service. The Z′-LYTE biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophore on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(Cc2ccccc2)C3)n(C)c1=O
InChIKey: BZDHUIDJDDKOMY-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human A2B receptor expressed in CHO cell membrane measured after 75 mins by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 325.37, ALogP 0.45, HBA 7, HBD 0, PSA 65.06, QED 0.69
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CCCCCCCCCCCCCCC(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: ISOOOILKNZMRMU-YNNVFSJPSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled rat calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.011 nM (pChEMBL 10.960000038146973)
Descriptors: MW 3490.96
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in goat anti-human IgM F(ab')2-stimulated human B cells assessed as reduction in cell proliferation pretreated for 30 mins followed by goat anti-human IgM F(ab')2-stimulation and measured after 3 days by [3H]-thymidine incorporation assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): Cc1c(Cl)cccc1OCc1cc(=O)n2nc(-c3ccccc3)nc2[nH]1
InChIKey: DHVPJCVPOZYDTH-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Displacement of BODIPY 500/510 C4 from human FABP3 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 366.81, ALogP 3.63, HBA 5, HBD 1, PSA 72.28, QED 0.6
Compound (SMILES): NCc1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)c4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: HVEXWDUPQQGDSO-BYQQZPSGSA-N
Target: Trypsin (SINGLE PROTEIN), Sus scrofa
UniProt: P00761
Assay: Inhibition of porcine trypsin using Mes-DArg-Gly-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 1541 nM (pChEMBL 5.809999942779541)
Descriptors: MW 794.98, ALogP 2.37, HBA 9, HBD 6, PSA 195.07, QED 0.16
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChIKey: IPUJINDWAGRAHN-KNXBSLHKSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 473.51, ALogP 2.7, HBA 8, HBD 2, PSA 111.72, QED 0.59
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Affinity Biochemical interaction (Enzymatic assay) EUB0000706a LRRK2
Measurement: IC50 = 6480 nM (pChEMBL 5.190000057220459)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOCC2)CSc2ccccc2)c([N+](=O)[O-])c1)c1ccc(-c2ccc(F)cc2)c(S(=O)(=O)O)c1
InChIKey: LCBYEMBRULUYAU-AREMUKBSSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of Bcl-xl in human U266B1 cells assessed as caspase 3/7 activation in presence of 10 % serum for 6 hrs by Caspase 3/7-Glo luminescence assay
Measurement: EC50 > 31500 nM (pChEMBL 4.501999855041504)
Descriptors: MW 744.84, ALogP 5.06, HBA 11, HBD 3, PSA 185.25, QED 0.07
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human CA7 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CCCCN1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)[C@@H]2[C@@H](N3CCCC3)CCC[C@@H]21
InChIKey: QZYMRJVVDVLWFH-WPFOTENUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]diprenorphine from human KOR expressed in HEK293T cell membranes after 120 mins by scintillation counting method
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 452.47, ALogP 4.87, HBA 3, HBD 0, PSA 26.79, QED 0.62
Compound (SMILES): Nc1cc(F)ccc1NC(=O)c1ccc(CNC(=O)/C=C2\NC(=O)c3ccccc32)cc1
InChIKey: NESNIDDWICBBQX-MTJSOVHGSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of HDAC11 (unknown origin) using Fluor de Lys substrate by fluorescence assay relative to control
Measurement: IC50 = 632 nM (pChEMBL 6.199999809265137)
Descriptors: MW 430.44, ALogP 3.06, HBA 4, HBD 4, PSA 113.32, QED 0.37
Compound (SMILES): CN(CC(F)(F)F)S(=O)(=O)NCc1cccc(-c2ccc3c(NC(=O)C4CC4)n[nH]c3c2)c1
InChIKey: MCYCSSJHDPRHBZ-UHFFFAOYSA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Inhibition of tracer K5 binding to N-terminal nano luciferase-fused BMP2K (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition and measured within 10 mins by NanoBRET assay
Measurement: IC50 = 3030 nM (pChEMBL 5.519999980926514)
Descriptors: MW 481.5, ALogP 3.41, HBA 4, HBD 3, PSA 107.19, QED 0.46
Compound (SMILES): COCCS(=O)(=O)Nc1cc(-c2cc3c(c(OC[C@H](C)N4CCC(C(C)(C)O)CC4)c2)COC3)cnc1OC
InChIKey: DHKNWWNHNHJFPH-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human HL60 cell extract measured after 2 hrs by kinobeads based pull down assay
Measurement: IC50 = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 563.72, ALogP 3.43, HBA 9, HBD 2, PSA 119.45, QED 0.4
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant full length N-terminal GST His6 fused CDK9 (M1 to F372 residues/ N-terminal His6 tagged Cyclin T1 (M1 to K726 residues) expressed in sf9 cells using RBER-IRStide as substrate incubated for 90 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccc(Cl)c(Cl)c1
InChIKey: PBZNCQQGLHOIGW-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 8110 nM (pChEMBL 5.090000152587891)
Descriptors: MW 268.14, ALogP 3.97, HBA 2, HBD 1, PSA 35.25, QED 0.85
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2OCO[C@H]21
InChIKey: JUSWNBNJCUGXNH-WHEJUCFXSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7R transfected in human 1321N1 cells assessed as inhibition of Bz-ATP-induced calcium influx
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 519.19, ALogP -0.61, HBA 14, HBD 5, PSA 257.13, QED 0.27
Compound (SMILES): COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OCC(=O)NC1CCCCC1
InChIKey: VAWMVQAKEDXTNH-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 expressed in baker's yeast-derived microsomes using 7-ethoxyresorufin as substrate by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 407.47, ALogP 3.43, HBA 5, HBD 2, PSA 93.31, QED 0.65
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin)
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (SPR) EUB0000230b CARM1
Measurement: Kd = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccc(Cl)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N2
InChIKey: KKRGXDSPEUYYKM-XIQIEEFNSA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibition of recombinant human chymase expressed in Pichia pastoris X-33 cells assessed as decrease in angiotensin 1 cleavage to angiotensin 2 incubated for 120 mins at 298 K by UPLC-MS analysis
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 1626.19
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of human HeLa cell-derived full length DNA-PK catalytic subunit using fluorescein-EPPLSQEAFADLWKK as substrate preincubated for 30 mins followed by substrate addition and measured after 40 mins TR-FRET assay
Measurement: IC50 = 0.1585 nM (pChEMBL 9.800000190734863)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(Cc2ccccc2)C3)n(C)c1=O
InChIKey: BZDHUIDJDDKOMY-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human A3 receptor expressed in CHO cell membrane by liquid scintillation counting method relative to control
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 325.37, ALogP 0.45, HBA 7, HBD 0, PSA 65.06, QED 0.69
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of full-length recombinant human C-terminal His-tagged SRC cytoplasmic domain expressed in baculovirus expression system using FAM-Srctide peptide as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 1630 nM (pChEMBL 5.789999961853027)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): Cc1c(Cl)cccc1OCc1cc(=O)n2nc(-c3ccccc3)nc2[nH]1
InChIKey: DHVPJCVPOZYDTH-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of BODIPY 500/510 C4 from human FABP4 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 366.81, ALogP 3.63, HBA 5, HBD 1, PSA 72.28, QED 0.6
Compound (SMILES): NCc1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NS(=O)(=O)c4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: HVEXWDUPQQGDSO-BYQQZPSGSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Binding affinity to human plasmin assessed as slow binding constant in presence of Mes-DArg-Phe-Arg-AMC after 20 mins by Dixon plot analysis
Measurement: Ki = 0.54 nM (pChEMBL 9.270000457763672)
Descriptors: MW 794.98, ALogP 2.37, HBA 9, HBD 6, PSA 195.07, QED 0.16
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChIKey: IPUJINDWAGRAHN-KNXBSLHKSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 473.51, ALogP 2.7, HBA 8, HBD 2, PSA 111.72, QED 0.59
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000706a SIGMAR1
Measurement: Ki = 1593.68 nM (pChEMBL 5.800000190734863)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CCCCN1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)[C@@H]2[C@@H](N3CCCC3)CCC[C@@H]21
InChIKey: QZYMRJVVDVLWFH-WPFOTENUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in HEK293T cells assessed as inhibition of Galphai-mediated cAMP accumulation after 15 mins by microbeta counting assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 452.47, ALogP 4.87, HBA 3, HBD 0, PSA 26.79, QED 0.62
Compound (SMILES): CN(CC(F)(F)F)S(=O)(=O)NCc1cccc(-c2ccc3c(NC(=O)C4CC4)n[nH]c3c2)c1
InChIKey: MCYCSSJHDPRHBZ-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Inhibition of tracer K5 binding to N-terminal nano luciferase-fused GAK (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition and measured within 10 mins by NanoBRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.5, ALogP 3.41, HBA 4, HBD 3, PSA 107.19, QED 0.46
Compound (SMILES): COCCS(=O)(=O)Nc1cc(-c2cc3c(c(OC[C@H](C)N4CCC(C(C)(C)O)CC4)c2)COC3)cnc1OC
InChIKey: DHKNWWNHNHJFPH-IBGZPJMESA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NEB9
Assay: Inhibition of VPS34 in human HL60 cell extract measured after 2 hrs by kinobeads based pull down assay
Measurement: IC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 563.72, ALogP 3.43, HBA 9, HBD 2, PSA 119.45, QED 0.4
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/Cyclin E (unknown origin) incubated for 30 to 120 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OCC(=O)NC1CCCCC1
InChIKey: VAWMVQAKEDXTNH-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 expressed in baker's yeast-derived microsomes using 3-cyano-7-ethoxycoumarin as substrate by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 407.47, ALogP 3.43, HBA 5, HBD 2, PSA 93.31, QED 0.65
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 JH1 domain (unknown origin)
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Scintillation proximity assays) EUB0000230b CARM1
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human A549 cells assessed as reduction in irradiation-induced autophosphorylation at S2056 residue preincubated for 1 hr followed by 8 Gy irradiation and measured after 1 hr by ELISA
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR cytoplasmic domain expressed in baculovirus expression system using FITC-C6-KKAEEEEYFELVAKK-NH2 as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 16800 nM (pChEMBL 4.78000020980835)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChIKey: IPUJINDWAGRAHN-KNXBSLHKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 473.51, ALogP 2.7, HBA 8, HBD 2, PSA 111.72, QED 0.59
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000706a TMEM97
Measurement: Ki = 1074.98 nM (pChEMBL 5.96999979019165)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CCCCN1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)[C@@H]2[C@@H](N3CCCC3)CCC[C@@H]21
InChIKey: QZYMRJVVDVLWFH-WPFOTENUSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at Tango-KOR (unknown origin) expressed in HTLA cells harboring TEV-fused-beta-arrestin 2 assessed as increase in beta arrestin 2 recruitment after overnight incubation by BrightGlo reagent based assay
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 452.47, ALogP 4.87, HBA 3, HBD 0, PSA 26.79, QED 0.62
Compound (SMILES): CN(CC(F)(F)F)S(=O)(=O)NCc1cccc(-c2ccc3c(NC(=O)C4CC4)n[nH]c3c2)c1
InChIKey: MCYCSSJHDPRHBZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: O75716
Assay: Inhibition of tracer K5 binding to N-terminal nano luciferase-fused STK16 (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition and measured within 10 mins by NanoBRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.5, ALogP 3.41, HBA 4, HBD 3, PSA 107.19, QED 0.46
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclinH/MAT1 (unknown origin) using RBER-IRStide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OCC(=O)NC1CCCCC1
InChIKey: VAWMVQAKEDXTNH-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 expressed in baker's yeast-derived microsomes using 7-ethoxyresorufin as substrate by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 407.47, ALogP 3.43, HBA 5, HBD 2, PSA 93.31, QED 0.65
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: JAK2/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2/JAK2 in IL23-stimulated human Kit225 cells by steady-glo luciferase assay
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Western Blot (dimethylation of BAF155 (BAF155me2a/BAF155) in HEK293T cells)) EUB0000230b CARM1
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Nuclear receptor subfamily 4 group A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92570
Assay: Inhibition of TEC (unknown origin)
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LRRK2 Biochemical Assay
Measurement: IC50 = 6480 nM (pChEMBL 5.190000057220459)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human recombinant full length GST-fused/His-tagged FLT3 ITD mutant expressed in Sf9 cells using poly (Glu,Tyr) as substrate incubated for 80 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2/JAK1 in IFNalpha-stimulated human Kit225 cells by steady-glo luciferase assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Western Blot (dimethylation of BAF155 (BAF155me2a/BAF155) in NCI-H929 cells)) EUB0000230b CARM1
Measurement: IC50 = 716 nM (pChEMBL 6.139999866485596)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of BMX (unknown origin)
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): C[C@@H]1CN(c2cc(-c3nn(C)c4ccc(OC5(C)CC5)cc34)ncn2)C[C@H](C)O1
InChIKey: YGCZGTCXWBPTDC-GASCZTMLSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Cellular assay monitoring dephosphorylation of pSer935 LRRK2
Measurement: IC50 = 5439 nM (pChEMBL 5.260000228881836)
Descriptors: MW 393.49, ALogP 3.58, HBA 7, HBD 0, PSA 65.3, QED 0.68
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 (unknown origin) in IL-2 stimulated cells by cell based assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Western Blot (dimethylation of BAF155 (BAF155me2a/BAF155) in KMS-27 cells)) EUB0000230b CARM1
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ccc(F)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: SQFDBQCBXUWICP-OAHLLOKOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) One-hour enzymatic assay without pre-incubation
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 438.44, ALogP 3.42, HBA 7, HBD 2, PSA 123.19, QED 0.59
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK2 (unknown origin) in GM-CSF stimulated cells by cell based assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Western Blot (dimethylation of BAF155 (BAF155me2a/BAF155) in U266B1 cells)) EUB0000230b CARM1
Measurement: IC50 = 486 nM (pChEMBL 6.309999942779541)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCCCC1)c(=O)n2C
InChIKey: PCTWMWBDQSWVBE-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.44, ALogP 2.73, HBA 9, HBD 1, PSA 94.93, QED 0.59
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 (unknown origin) by morrison titration assay
Measurement: Ki = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Selectivity interaction (Cell viability assay (CellTiter-Glo assay in RPM8226 cells)) EUB0000230b CARM1
Measurement: IC50 = 886 nM (pChEMBL 6.050000190734863)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant full length N-terminal His6x-tagged human CA5B expressed in Escherichia coli Rosetta 2 (DE3) assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.033 nM (pChEMBL 10.479999542236328)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 (unknown origin) by Scintillation proximity assay
Measurement: EC50 = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Selectivity interaction (Scintillation proximity assays) EUB0000230b PRMT1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human CA6 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O60678
Assay: Selectivity interaction (Scintillation proximity assays) EUB0000230b PRMT3
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human CA7 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Selectivity interaction (Scintillation proximity assays) EUB0000230b PRMT6
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.093 nM (pChEMBL 10.029999732971191)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Selectivity interaction (Scintillation proximity assays) EUB0000230b PRMT7
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccc([N+](=O)[O-])cc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: YFQTYSFYANGBFX-LSHDLFTRSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 459.48, ALogP 1.36, HBA 7, HBD 2, PSA 165.07, QED 0.38