lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)C(=O)CCC3)cc1
InChIKey: ZDXQXBYRSSKFPO-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant HDAC4 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 334.38, ALogP 3.33, HBA 4, HBD 2, PSA 71.33, QED 0.57
Compound (SMILES): Nc1nc2cccc(-c3ccc(C(F)(F)F)c(S(N)(=O)=O)c3-c3nn[nH]n3)c2[nH]1
InChIKey: KFPSHECGQIXYEL-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 channel (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.37, ALogP 1.66, HBA 7, HBD 4, PSA 169.32, QED 0.39
Compound (SMILES): CCOc1ccc(-c2nc(C(=O)NCc3ccc(C(=O)NO)cc3)c3[nH]c(=O)n(-c4cccnc4OC)c3n2)cn1
InChIKey: GUMHZCBUHIIKRC-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using acetylated luminogenic substrate incubated for 10 mins by ultra-glo recombinant firefly luciferase based luminescence assay
Measurement: IC50 = 10.8 nM (pChEMBL 7.96999979019165)
Descriptors: MW 556.54, ALogP 2.02, HBA 11, HBD 4, PSA 186.24, QED 0.15
Compound (SMILES): CC(=O)N[C@H]1Cc2ccc(cc2)OC/C=C\CNC(=O)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: PIYDBRKFQAMHCU-LVTIVQEQSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of recombinant thrombin (unknown origin) using D-Phe-Pip-Arg-pNA as chromogenic substrate preincubated for 30 mins followed by substrate addition by absorbance based analysis
Measurement: IC50 = 3180 nM (pChEMBL 5.5)
Descriptors: MW 775.93, ALogP 1.45, HBA 10, HBD 8, PSA 246.59, QED 0.05
Compound (SMILES): CCC1CCc2c(sc(NC(=O)CCCC(=O)Nc3sc4c(c3C(N)=O)CCC(CC)C4)c2C(N)=O)C1
InChIKey: SEZSJALNCORZIQ-UHFFFAOYSA-N
Target: DnaJ homolog subfamily C member 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99615
Assay: Inhibition of GST-tagged human DNAJC7 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 544.74, ALogP 4.78, HBA 6, HBD 4, PSA 144.38, QED 0.34
Compound (SMILES): CC(C)n1nnc2ccc(-c3ccnc(Nc4cc(C(=O)N5CCCC5)ccn4)c3)cc21
InChIKey: UVSZGHBPMOAFSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin)
Measurement: IC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 427.51, ALogP 4.45, HBA 7, HBD 1, PSA 88.83, QED 0.51
Compound (SMILES): O=c1c(Oc2ccc(I)cc2)coc2cc(O)ccc12
InChIKey: XXZKJJYWINSUMJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Antagonist activity against LSP4-202-induced wild type rat mGlu7 assessed as decrease in LSP4-202 potency by measuring LSP4-202 pEC50 at 3 uM
Measurement: EC50 = 43400 nM (pChEMBL 4.360000133514404)
Descriptors: MW 380.14, ALogP 3.9, HBA 4, HBD 1, PSA 59.67, QED 0.69
Compound (SMILES): C=C1C(=O)[C@]23[C@H](O)[C@H]1CC[C@H]2[C@]12C=CCC(C)(C)[C@H]1[C@H](O)[C@@]3(OCc1cncs1)OC2
InChIKey: DQVDXXLRESFSRM-ZYRCWTSVSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using dextromethorphan as substrate preincubated for 5 min followed by NADPH addition and measured after 15 mins
Measurement: IC50 = 29.2 nM (pChEMBL 7.539999961853027)
Descriptors: MW 443.57, ALogP 2.86, HBA 7, HBD 2, PSA 88.88, QED 0.55
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclinE1 (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 31.38 nM (pChEMBL 7.5)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@H](C)F)n1)c1ccc(-c2ccc(NC(=O)COc3cccnc3)cc2)cc1
InChIKey: NGXVQQDDOXHWSX-CUVVAGTFSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R172K mutant (unknown origin) using alpha-ketoglutarate as substrate incubated in presence of NADPH by Envision multimode plate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 556.6, ALogP 5.41, HBA 8, HBD 2, PSA 118.57, QED 0.27
Compound (SMILES): CN(C(=O)CCc1ccoc1)[C@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5.Cl
InChIKey: WBIGRZFMPUSILZ-XLOOZMJBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 137.3 nM (pChEMBL 6.860000133514404)
Descriptors: MW 462.59, ALogP 3.3, HBA 5, HBD 1, PSA 66.15, QED 0.71
Compound (SMILES): CCOc1cc([C@H]2Oc3c(OCC)cc(CCCO)cc3[C@@H]2CO)ccc1OC
InChIKey: NWARZTAQZRDFKR-PGRDOPGGSA-N
Target: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P51160
Assay: Inhibition of full length human PDE6C expressed in Escherichia coli BL21 (DE3) using [3H]-cAMP/cGMP as substrate incubated for 10 mins by MicroBeta scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.49, ALogP 3.63, HBA 6, HBD 2, PSA 77.38, QED 0.63
Compound (SMILES): CC(=O)N[C@H]1C/C=C/COc2ccc(cc2)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: CMECINVDWRULPU-QJLKIGBLSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of recombinant thrombin (unknown origin) using D-Phe-Pip-Arg-pNA as chromogenic substrate preincubated for 30 mins followed by substrate addition by absorbance based analysis
Measurement: IC50 = 8810 nM (pChEMBL 5.050000190734863)
Descriptors: MW 718.88, ALogP 2.33, HBA 9, HBD 7, PSA 217.49, QED 0.05
Compound (SMILES): CN(C(=O)CCc1ccco1)[C@@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5.Cl
InChIKey: XRAIFDBVCRNCMI-CYZBAFPSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 1105 nM (pChEMBL 5.960000038146973)
Descriptors: MW 462.59, ALogP 3.3, HBA 5, HBD 1, PSA 66.15, QED 0.71
Compound (SMILES): CCOCC1(COCC)CCC(Oc2ccccc2CN(C)C[C@@H](O)CNC)CC1
InChIKey: MOPCOJLFDMFKCS-NRFANRHFSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) by AlphaLISA assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 422.61, ALogP 3.08, HBA 6, HBD 2, PSA 63.19, QED 0.48
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: KVJYMIYOBIVPHB-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human PBMCs assessed as reduction in IL-2 induced STAT5 phosphorylation preincubated for 30 mins followed by IIL-2 addition and measured after 30 mins by FACS cytometer analysis
Measurement: IC50 = 882 nM (pChEMBL 6.050000190734863)
Descriptors: MW 470.49, ALogP 2.95, HBA 10, HBD 1, PSA 131.08, QED 0.47
Compound (SMILES): CC(=O)c1cc2ccc(OCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: AWKSRJLNZWGCOO-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant CA7 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 373.39, ALogP 2.22, HBA 6, HBD 1, PSA 116.67, QED 0.54
Compound (SMILES): OC[C@H]1CN(C2CCN(c3ccccn3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: JUASDJMEXFDEHC-LEWJYISDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG incubated for 2 to 6 hrs by fluorescence polarization assay
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 401.94, ALogP 3.01, HBA 5, HBD 1, PSA 48.83, QED 0.83
Compound (SMILES): COc1cccc2c(N3CCC(CCP(=O)(O)O)CC3)ncnc12
InChIKey: IXXUGBPAQOKGTM-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Mus musculus
UniProt: P06802
Assay: Inhibition of ENPP1 in mouse EL4 cells using cGAMP as substrate incubated for 3 hrs followed by incubation in R1 reaction buffer for 1 hr and R2 reaction buffer for 1 hr by luminescence based analysis
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 351.34, ALogP 2.42, HBA 5, HBD 2, PSA 95.78, QED 0.8
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: CLRIOMZLSLAWHG-WBCKFURZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 = 21100 nM (pChEMBL 4.679999828338623)
Descriptors: MW 862.07, ALogP 8.93, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CNCc1ccccc1-c1csc(C(C)Nc2nc(C)nc3cc(OC)c(OC)cc23)c1
InChIKey: WEGLOYDTDILXDA-UHFFFAOYSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: P01116
Assay: Inhibition of N-terminal GST-tagged recombinant human KRAS G12C mutant (1 to 169 residues) expressed in Escherichia coli/N-terminal His10-tagged wild-type recombinant human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli protein-protein interaction preincubated for 2 mins with KRAS followed by SOS1 addition measured after 60 mins in presence of anti-6His-XL665 by HTRF analysis
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 448.59, ALogP 5.58, HBA 7, HBD 2, PSA 68.3, QED 0.37
Compound (SMILES): CN(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: PTNFJBUKNHJEPL-RWYGWLOXSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 0.023 nM (pChEMBL 10.640000343322754)
Descriptors: MW 863.05, ALogP 7.87, HBA 12, HBD 3, PSA 175.27, QED 0.08
Compound (SMILES): CN1CCN(CC2CCc3c(c4cc(F)ccc4n3Cc3ccc(C(=O)NO)cc3)C2=O)CC1
InChIKey: IPQWNMYTXBPMAT-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human recombinant HDAC5 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 = 4270 nM (pChEMBL 5.369999885559082)
Descriptors: MW 464.54, ALogP 2.94, HBA 6, HBD 2, PSA 77.81, QED 0.45
Compound (SMILES): CCCCC#Cc1nc2c(N)nc(-c3ccco3)nc2[nH]1
InChIKey: CUXKGZJSDUHGOJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes in presence of NADPH incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 281.32, ALogP 2.74, HBA 5, HBD 2, PSA 93.62, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: COVOAONOMYHKDP-TXAVNGFNSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P32214
Assay: Displacement of 125I-rat amylin from rat AMY3R complex of CTR/RAMP3 expressed in Baby hamster kidney cell membrane incubated for 120 mins by SPA method
Measurement: IC50 = 0.92 nM (pChEMBL 9.039999961853027)
Descriptors: MW 3942.42
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human ABL
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(OCc3ccc(/C=C/C(=O)NO)cc3)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: BIFMDHUVYGGFCU-GHOSXJJBSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 (1 to 347 residues) preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 > 1250 nM (pChEMBL 5.9029998779296875)
Descriptors: MW 646.63, ALogP 2.23, HBA 11, HBD 4, PSA 174.9, QED 0.09
Compound (SMILES): FC(F)(F)c1ccc(-c2ccc3nccc(N[C@@H]4CCNC4)c3n2)cn1
InChIKey: JAJSIWPSPROYAQ-GFCCVEGCSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.36, ALogP 3.48, HBA 5, HBD 2, PSA 62.73, QED 0.75
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)C(=O)CCC3)cc1
InChIKey: ZDXQXBYRSSKFPO-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human recombinant HDAC5 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 334.38, ALogP 3.33, HBA 4, HBD 2, PSA 71.33, QED 0.57
Compound (SMILES): Nc1nc2cccc(-c3ccc(C(F)(F)F)c(S(N)(=O)=O)c3-c3nn[nH]n3)c2[nH]1
InChIKey: KFPSHECGQIXYEL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.37, ALogP 1.66, HBA 7, HBD 4, PSA 169.32, QED 0.39
Compound (SMILES): CCOc1ccc(-c2nc(C(=O)NCc3ccc(C(=O)NO)cc3)c3[nH]c(=O)n(-c4cccnc4OC)c3n2)cn1
InChIKey: GUMHZCBUHIIKRC-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human HDAC7 using acetylated luminogenic substrate incubated for 10 mins by ultra-glo recombinant firefly luciferase based luminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 556.54, ALogP 2.02, HBA 11, HBD 4, PSA 186.24, QED 0.15
Compound (SMILES): CCC1CCc2c(sc(NC(=O)CCCC(=O)Nc3sc4c(c3C(N)=O)CCC(CC)C4)c2C(N)=O)C1
InChIKey: SEZSJALNCORZIQ-UHFFFAOYSA-N
Target: Mitochondrial import receptor subunit TOM70 (SINGLE PROTEIN), Homo sapiens
UniProt: O94826
Assay: Inhibition of GST-tagged human TOM70 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 544.74, ALogP 4.78, HBA 6, HBD 4, PSA 144.38, QED 0.34
Compound (SMILES): CC(C)n1nnc2ccc(-c3ccnc(Nc4cc(C(=O)N5CCCC5)ccn4)c3)cc21
InChIKey: UVSZGHBPMOAFSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin)
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 427.51, ALogP 4.45, HBA 7, HBD 1, PSA 88.83, QED 0.51
Compound (SMILES): O=c1c(Oc2ccc(I)cc2)coc2cc(O)ccc12
InChIKey: XXZKJJYWINSUMJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Antagonist activity against LSP4-202-induced wild type rat mGlu7 assessed as decrease in LSP4-202 potency by measuring LSP4-202 pEC50 at 3 uM
Measurement: EC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 380.14, ALogP 3.9, HBA 4, HBD 1, PSA 59.67, QED 0.69
Compound (SMILES): C=C1C(=O)[C@]23[C@H](O)[C@H]1CC[C@H]2[C@]12C=CCC(C)(C)[C@H]1[C@H](O)[C@@]3(OCc1cncs1)OC2
InChIKey: DQVDXXLRESFSRM-ZYRCWTSVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using midazolam as substrate preincubated for 5 min followed by NADPH addition and measured after 5 mins
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 443.57, ALogP 2.86, HBA 7, HBD 2, PSA 88.88, QED 0.55
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of CDK5/p25NCK (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 87.43 nM (pChEMBL 7.059999942779541)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@H](C)F)n1)c1ccc(-c2ccc(NC(=O)COc3cccnc3)cc2)cc1
InChIKey: NGXVQQDDOXHWSX-CUVVAGTFSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of wildtype IDH2 (unknown origin) using alpha-ketoglutarate as substrate incubated in presence of NADPH by Envision multimode plate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 556.6, ALogP 5.41, HBA 8, HBD 2, PSA 118.57, QED 0.27
Compound (SMILES): CCOc1cc([C@H]2Oc3c(OCC)cc(CCCO)cc3[C@@H]2CO)ccc1OC
InChIKey: NWARZTAQZRDFKR-PGRDOPGGSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of human PDE7A catalytic domain (S130 to S482 residues) expressed in Escherichia coli BL21 (DE3) using [3H]-cAMP/cGMP as substrate incubated for 10 mins by MicroBeta scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.49, ALogP 3.63, HBA 6, HBD 2, PSA 77.38, QED 0.63
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: KVJYMIYOBIVPHB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 in human PBMCs assessed as reduction in GM/CSF induced STAT5 phosphorylation preincubated for 30 mins followed by IFNalpha addition and measured after 30 mins by FACS cytometer analysis
Measurement: IC50 = 1794 nM (pChEMBL 5.75)
Descriptors: MW 470.49, ALogP 2.95, HBA 10, HBD 1, PSA 131.08, QED 0.47
Compound (SMILES): CC(=O)c1cc2ccc(OCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: AWKSRJLNZWGCOO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant CA12 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 39.4 nM (pChEMBL 7.409999847412109)
Descriptors: MW 373.39, ALogP 2.22, HBA 6, HBD 1, PSA 116.67, QED 0.54
Compound (SMILES): COc1cccc2c(N3CCC(CCP(=O)(O)O)CC3)ncnc12
InChIKey: IXXUGBPAQOKGTM-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22413
Assay: ENPP1 Activity Assay: Selected compounds of Table 1, Table 2 and other derivatives were prepared and assessed in an ENPP1 activity assay using thymidine monophosphate paranitrophenol (TMP-pNP) as a substrate. Enzyme reactions were prepared with TMP-pNP (2 μM), 5-fold dilutions of ENPP1 inhibitor, and purified recombinant mouse ENPP1 (0.5 nM) in 100 mM Tris, 150 mM NaCl, 2 mM CaCl2, 200 μM ZnCl2, pH 7.5 at room temperature. Reaction progress was monitored by measuring absorbance at 400 nm of paranitrophenolate produced by the reaction for 20 minutes. Slopes of product formation were extracted, plotted, and fit to obtain IC50 values with Graphpad Prism 7.03. Compounds were also assessed in an ENPP1 enzyme activity assay using 32P cGAMP as a substrate. Radiolabeled32P cGAMP was synthesized by incubating unlabeled ATP (1 mM) and GTP (1 mM) doped with 32P-ATP with 2 μM purified recombinant porcine cGAS in 20 mM Tris pH 7.5, 2 mM MgCl2, 100 μg/mL herring testes DNA overnight at room temperature, and the remaining nucleotide starting materials were degraded with alkaline phosphatase for 4 h at 37° C. The probe 32P-cGAMP (5 μM) was incubated with purified recombinant mouse ENPP1 (20 nM) in 100 mM Tris, 150 mM NaCl, 2 mM CaCl2, 200 μM ZnCl2, pH 7.5 at room temperature for 5 hours. To generate enzyme inhibition curves, 5-fold dilutions of ENPP1 inhibitor were included in the reaction. Degradation was evaluated by TLC (as described by Li et al. Nat. Chem. Biol. (2014) 10:1043-8). Plates were exposed on a phosphor screen (Molecular Dynamics) and imaged on a Typhoon 9400 and the 32P signal was quantified using ImageJ. Inhibition curves were fit to obtain IC50 values using Graphpad Prism 7.03.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 351.34, ALogP 2.42, HBA 5, HBD 2, PSA 95.78, QED 0.8
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: CLRIOMZLSLAWHG-WBCKFURZSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 0.036 nM (pChEMBL 10.4399995803833)
Descriptors: MW 862.07, ALogP 8.93, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CN(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: PTNFJBUKNHJEPL-RWYGWLOXSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 863.05, ALogP 7.87, HBA 12, HBD 3, PSA 175.27, QED 0.08
Compound (SMILES): CN1CCN(CC2CCc3c(c4cc(F)ccc4n3Cc3ccc(C(=O)NO)cc3)C2=O)CC1
InChIKey: IPQWNMYTXBPMAT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using fluorescent peptide p53 (379 to 382 residues) RHKK(Ac) as substrate by fluorescence based analysis
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 464.54, ALogP 2.94, HBA 6, HBD 2, PSA 77.81, QED 0.45
Compound (SMILES): CCCCC#Cc1nc2c(N)nc(-c3ccco3)nc2[nH]1
InChIKey: CUXKGZJSDUHGOJ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes in presence of NADPH incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 281.32, ALogP 2.74, HBA 5, HBD 2, PSA 93.62, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: COVOAONOMYHKDP-TXAVNGFNSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32214
Assay: Displacement of 125I-Calcitonin from rat CTR expressed in Baby hamster kidney cell membrane incubated for 120 mins by SPA method
Measurement: IC50 = 55.64 nM (pChEMBL 7.25)
Descriptors: MW 3942.42
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase BRSK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWQ3
Assay: Inhibition of human BRSK2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(OCc3ccc(/C=C/C(=O)NO)cc3)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: BIFMDHUVYGGFCU-GHOSXJJBSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of N-terminal GST tagged human recombinant PARP1 (2 to 1014 residues) preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 82.3 nM (pChEMBL 7.079999923706055)
Descriptors: MW 646.63, ALogP 2.23, HBA 11, HBD 4, PSA 174.9, QED 0.09
Compound (SMILES): FC(F)(F)c1ccc(-c2ccc3nccc(N[C@@H]4CCNC4)c3n2)cn1
InChIKey: JAJSIWPSPROYAQ-GFCCVEGCSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.36, ALogP 3.48, HBA 5, HBD 2, PSA 62.73, QED 0.75
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)C(=O)CCC3)cc1
InChIKey: ZDXQXBYRSSKFPO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using fluorescent peptide p53 (379 to 382 residues) RHKK(Ac) as substrate by fluorescence based analysis
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 334.38, ALogP 3.33, HBA 4, HBD 2, PSA 71.33, QED 0.57
Compound (SMILES): Nc1nc2cccc(-c3ccc(C(F)(F)F)c(S(N)(=O)=O)c3-c3nn[nH]n3)c2[nH]1
InChIKey: KFPSHECGQIXYEL-UHFFFAOYSA-N
Target: Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK) (PROTEIN COMPLEX), Homo sapiens
UniProt: P15382
Assay: Inhibition of KCNQ1/KCNE1 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.37, ALogP 1.66, HBA 7, HBD 4, PSA 169.32, QED 0.39
Compound (SMILES): CCOc1ccc(-c2nc(C(=O)NCc3ccc(C(=O)NO)cc3)c3[nH]c(=O)n(-c4cccnc4OC)c3n2)cn1
InChIKey: GUMHZCBUHIIKRC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using acetylated luminogenic substrate incubated for 10 mins by ultra-glo recombinant firefly luciferase based luminescence assay
Measurement: IC50 = 138.5 nM (pChEMBL 6.860000133514404)
Descriptors: MW 556.54, ALogP 2.02, HBA 11, HBD 4, PSA 186.24, QED 0.15
Compound (SMILES): CC(C)n1nnc2ccc(-c3ccnc(Nc4cc(C(=O)N5CCCC5)ccn4)c3)cc21
InChIKey: UVSZGHBPMOAFSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin)
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 427.51, ALogP 4.45, HBA 7, HBD 1, PSA 88.83, QED 0.51
Compound (SMILES): O=c1c(Oc2ccc(I)cc2)coc2cc(O)ccc12
InChIKey: XXZKJJYWINSUMJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Antagonist activity against LSP4-202-induced wild type rat mGlu7 assessed as decrease in LSP4-202 potency by measuring LSP4-202 pEC50 at 10 uM
Measurement: EC50 = 66200 nM (pChEMBL 4.179999828338623)
Descriptors: MW 380.14, ALogP 3.9, HBA 4, HBD 1, PSA 59.67, QED 0.69
Compound (SMILES): C=C1C(=O)[C@]23[C@H](O)[C@H]1CC[C@H]2[C@]12C=CCC(C)(C)[C@H]1[C@H](O)[C@@]3(OCc1cncs1)OC2
InChIKey: DQVDXXLRESFSRM-ZYRCWTSVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using testosterone as substrate preincubated for 5 min followed by NADPH addition and measured after 10 mins
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 443.57, ALogP 2.86, HBA 7, HBD 2, PSA 88.88, QED 0.55
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of CDK5/p35NCK (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 193.8 nM (pChEMBL 6.710000038146973)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@H](C)F)n1)c1ccc(-c2ccc(NC(=O)COc3cccnc3)cc2)cc1
InChIKey: NGXVQQDDOXHWSX-CUVVAGTFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG in CHO cells incubated for 2.5 mins by Qpatch electrogram analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 556.6, ALogP 5.41, HBA 8, HBD 2, PSA 118.57, QED 0.27
Compound (SMILES): CCOc1cc([C@H]2Oc3c(OCC)cc(CCCO)cc3[C@@H]2CO)ccc1OC
InChIKey: NWARZTAQZRDFKR-PGRDOPGGSA-N
Target: High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (SINGLE PROTEIN), Homo sapiens
UniProt: O60658
Assay: Inhibition of full length human PDE8A expressed in Escherichia coli BL21 (DE3) using [3H]-cAMP/cGMP as substrate incubated for 10 mins by MicroBeta scintillation proximity assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 402.49, ALogP 3.63, HBA 6, HBD 2, PSA 77.38, QED 0.63
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: KVJYMIYOBIVPHB-UHFFFAOYSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as reduction in IFNalpha induced STAT1 phosphorylation preincubated for 30 mins followed by IFNalpha addition and measured after 20 mins by flow cytometer analysis
Measurement: IC50 = 478 nM (pChEMBL 6.320000171661377)
Descriptors: MW 470.49, ALogP 2.95, HBA 10, HBD 1, PSA 131.08, QED 0.47
Compound (SMILES): CC(=O)c1cc2ccc(OCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: AWKSRJLNZWGCOO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI-TN-5B1-4 insect cells using kynuramine as substrate incubated for 10 10 mins by spectrophotometric assay
Measurement: IC50 = 51.9 nM (pChEMBL 7.289999961853027)
Descriptors: MW 373.39, ALogP 2.22, HBA 6, HBD 1, PSA 116.67, QED 0.54
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCC5CCOCC5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: CLRIOMZLSLAWHG-WBCKFURZSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 862.07, ALogP 8.93, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CNCc1ccccc1-c1csc(C(C)Nc2nc(C)nc3cc(OC)c(OC)cc23)c1
InChIKey: WEGLOYDTDILXDA-UHFFFAOYSA-N
Target: Guanine nucleotide exchange factor DBS (SINGLE PROTEIN), Homo sapiens
UniProt: O15068
Assay: Inhibition of human DBS assessed as reduction in CDC42 activation preincubated for 1 min with CDC42 followed by DBS addition measured after 20 mins in presence of EDA-GTP-DY-647P1 by HTRF analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 448.59, ALogP 5.58, HBA 7, HBD 2, PSA 68.3, QED 0.37
Compound (SMILES): CN1CCN(CC2CCc3c(c4cc(F)ccc4n3Cc3ccc(C(=O)NO)cc3)C2=O)CC1
InChIKey: IPQWNMYTXBPMAT-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human recombinant HDAC7 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 = 4520 nM (pChEMBL 5.340000152587891)
Descriptors: MW 464.54, ALogP 2.94, HBA 6, HBD 2, PSA 77.81, QED 0.45
Compound (SMILES): CCCCC#Cc1nc2c(N)nc(-c3ccco3)nc2[nH]1
InChIKey: CUXKGZJSDUHGOJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes in presence of NADPH incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 281.32, ALogP 2.74, HBA 5, HBD 2, PSA 93.62, QED 0.57
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of human IRAK4
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(OCc3ccc(/C=C/C(=O)NO)cc3)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: BIFMDHUVYGGFCU-GHOSXJJBSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of N-terminal GST tagged human PARP2 (2 to 583 residues) infected in baculovirus infected Sf9 cells preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 646.63, ALogP 2.23, HBA 11, HBD 4, PSA 174.9, QED 0.09
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)C(=O)CCC3)cc1
InChIKey: ZDXQXBYRSSKFPO-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human recombinant HDAC7 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 334.38, ALogP 3.33, HBA 4, HBD 2, PSA 71.33, QED 0.57
Compound (SMILES): Nc1nc2cccc(-c3ccc(C(F)(F)F)c(S(N)(=O)=O)c3-c3nn[nH]n3)c2[nH]1
InChIKey: KFPSHECGQIXYEL-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacteria
UniProt: C7C422
Assay: Class B Enzyme Assay: The Class B enzyme activities were measured in the presence of the test inhibitor in a fluorescence assay against a commercially available substrate consisting of a cephalosporin core linking 7-hydroxycoumarin to fluorescein (CCF2-FA). The enzyme (NDM-1, IMP-1 or VIM-1) and the substrate were diluted in 100 mM KH2PO4 buffer (pH 7) containing 0.005% Tween-20 and 10 μM ZnSO4. In the assay, the final concentration of enzyme was 1 pM, 2 pM and 30 pM for NDM-1, IMP-1 and VIM-1, respectively, and the final concentration of CCF2-FA was 1.25 μM. The test inhibitor was dissolved in dimethylsulfoxide and diluted 1:50 in the assay, resulting in a final concentration range of 20 uM to 0.00063 uM. In a 384-well microplate, the test inhibitor was incubated with the metallo-β-lactamase enzyme and the substrate for 2 hours at 25° C. Fluorescence at 460 nm following excitation at 405 nm was measured. The IC50 value was determined from semi-logarithmic plots of enzyme inhibition versus inhibitor concentration, with a curve generated using a 4-parameter fit.
Measurement: IC50 = 0.142 nM (pChEMBL 9.850000381469727)
Descriptors: MW 424.37, ALogP 1.66, HBA 7, HBD 4, PSA 169.32, QED 0.39
Compound (SMILES): CCOc1ccc(-c2nc(C(=O)NCc3ccc(C(=O)NO)cc3)c3[nH]c(=O)n(-c4cccnc4OC)c3n2)cn1
InChIKey: GUMHZCBUHIIKRC-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human HDAC9 using acetylated luminogenic substrate incubated for 10 mins by ultra-glo recombinant firefly luciferase based luminescence assay
Measurement: IC50 = 19.7 nM (pChEMBL 7.710000038146973)
Descriptors: MW 556.54, ALogP 2.02, HBA 11, HBD 4, PSA 186.24, QED 0.15
Compound (SMILES): CC(C)n1nnc2ccc(-c3ccnc(Nc4cc(C(=O)N5CCCC5)ccn4)c3)cc21
InChIKey: UVSZGHBPMOAFSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 427.51, ALogP 4.45, HBA 7, HBD 1, PSA 88.83, QED 0.51
Compound (SMILES): O=c1c(Oc2ccc(I)cc2)coc2cc(O)ccc12
InChIKey: XXZKJJYWINSUMJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Antagonist activity against LSP4-202-induced wild type rat mGlu7 assessed as decrease in LSP4-202 potency by measuring LSP4-202 pEC50 at 10 uM
Measurement: EC50 = 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 380.14, ALogP 3.9, HBA 4, HBD 1, PSA 59.67, QED 0.69
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of CDK8/CyclinC (unknown origin) by ADP-Glo chemiluminescence assay
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): CCOc1cc([C@H]2Oc3c(OCC)cc(CCCO)cc3[C@@H]2CO)ccc1OC
InChIKey: NWARZTAQZRDFKR-PGRDOPGGSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of human PDE9A catalytic domain (P181 to K506 residues) expressed in Escherichia coli BL21 (DE3) using [3H]-cAMP/cGMP as substrate incubated for 10 mins by MicroBeta scintillation proximity assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 402.49, ALogP 3.63, HBA 6, HBD 2, PSA 77.38, QED 0.63
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: KVJYMIYOBIVPHB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 in human whole blood assessed as reduction in IL-6 induced STAT1 phosphorylation preincubated for 30 mins followed by IL-6 addition and measured after 20 mins by flow cytometer analysis
Measurement: IC50 = 3466 nM (pChEMBL 5.460000038146973)
Descriptors: MW 470.49, ALogP 2.95, HBA 10, HBD 1, PSA 131.08, QED 0.47
Compound (SMILES): CNCc1ccccc1-c1csc(C(C)Nc2nc(C)nc3cc(OC)c(OC)cc23)c1
InChIKey: WEGLOYDTDILXDA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR using biotin-aminohexyl-AEEEEYFELVAKKK as substrate preincubated for 15 mins followed by substrate/ATP addition measured after 20 mins by FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 448.59, ALogP 5.58, HBA 7, HBD 2, PSA 68.3, QED 0.37
Compound (SMILES): CN1CCN(CC2CCc3c(c4cc(F)ccc4n3Cc3ccc(C(=O)NO)cc3)C2=O)CC1
InChIKey: IPQWNMYTXBPMAT-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using fluorescent peptide p53 (379 to 382 residues) (RHK(Ac)K(Ac)) as substrate by fluorescence based analysis
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 464.54, ALogP 2.94, HBA 6, HBD 2, PSA 77.81, QED 0.45
Compound (SMILES): CCCCC#Cc1nc2c(N)nc(-c3ccco3)nc2[nH]1
InChIKey: CUXKGZJSDUHGOJ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 281.32, ALogP 2.74, HBA 5, HBD 2, PSA 93.62, QED 0.57
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cncc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: USZDDOBUMPPACY-GFCCVEGCSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora B
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN(c2ncc(OCc3ccc(/C=C/C(=O)NO)cc3)cn2)CC1)Nc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: BIFMDHUVYGGFCU-GHOSXJJBSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of N-terminal GST tagged human PARP5A (1001 to 1327 residues) infected in baculovirus infected Sf9 cells preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 1909 nM (pChEMBL 5.71999979019165)
Descriptors: MW 646.63, ALogP 2.23, HBA 11, HBD 4, PSA 174.9, QED 0.09
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)C(=O)CCC3)cc1
InChIKey: ZDXQXBYRSSKFPO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using fluorescent peptide p53 (379 to 382 residues) (RHK(Ac)K(Ac)) as substrate by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 334.38, ALogP 3.33, HBA 4, HBD 2, PSA 71.33, QED 0.57
Compound (SMILES): CCOc1ccc(-c2nc(C(=O)NCc3ccc(C(=O)NO)cc3)c3[nH]c(=O)n(-c4cccnc4OC)c3n2)cn1
InChIKey: GUMHZCBUHIIKRC-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of recombinant human HDAC10 using acetylated luminogenic substrate incubated for 10 mins by ultra-glo recombinant firefly luciferase based luminescence assay
Measurement: IC50 = 18.9 nM (pChEMBL 7.71999979019165)
Descriptors: MW 556.54, ALogP 2.02, HBA 11, HBD 4, PSA 186.24, QED 0.15
Compound (SMILES): CC(C)n1nnc2ccc(-c3ccnc(Nc4cc(C(=O)N5CCCC5)ccn4)c3)cc21
InChIKey: UVSZGHBPMOAFSS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin)
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 427.51, ALogP 4.45, HBA 7, HBD 1, PSA 88.83, QED 0.51
Compound (SMILES): FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1
InChIKey: YRFOQHHFWYWAST-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin) by ADP-Glo assay
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 494.18, ALogP 4.26, HBA 5, HBD 1, PSA 42.32, QED 0.69
Compound (SMILES): CCOc1cc([C@H]2Oc3c(OCC)cc(CCCO)cc3[C@@H]2CO)ccc1OC
InChIKey: NWARZTAQZRDFKR-PGRDOPGGSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of human PDE10A catalytic domain (S439 to A766 residues) expressed in Escherichia coli BL21 (DE3) using [3H]-cAMP/cGMP as substrate incubated for 10 mins by MicroBeta scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.49, ALogP 3.63, HBA 6, HBD 2, PSA 77.38, QED 0.63
Compound (SMILES): CNCc1ccccc1-c1csc(C(C)Nc2nc(C)nc3cc(OC)c(OC)cc23)c1
InChIKey: WEGLOYDTDILXDA-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to N-terminal His10-tagged wild-type recombinant human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli assessed as dissociation constant by ITC analysis
Measurement: Kd = 18 nM (pChEMBL 7.75)
Descriptors: MW 448.59, ALogP 5.58, HBA 7, HBD 2, PSA 68.3, QED 0.37