lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N[C@@H](CCP(=O)(O)C(O)c1ccc(O)c([N+](=O)[O-])c1)C(=O)O
InChIKey: GAGSUJFFXBSIDN-RGENBBCFSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Agonist activity at mGlu7 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method
Measurement: EC50 = 69000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 334.22, ALogP 0.36, HBA 7, HBD 5, PSA 184.22, QED 0.27
Compound (SMILES): CC(=O)c1ccc(NC(=O)Nc2cccc(S(N)(=O)=O)c2)cc1
InChIKey: ARFXMDAGWKFAIX-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 333.37, ALogP 2.18, HBA 4, HBD 3, PSA 118.36, QED 0.74
Compound (SMILES): O=C(NC1CCN(Cc2ccccc2)CC1)c1ccc(Cl)nc1Cl
InChIKey: FGUUNZVMTXKKDT-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse BGT1 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 364.28, ALogP 3.78, HBA 3, HBD 1, PSA 45.23, QED 0.84
Compound (SMILES): CSCC[C@@H]1N=C(c2ccccc2)c2ccccc2NC1=O
InChIKey: NFFFRNVSWUATIJ-INIZCTEOSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 310.42, ALogP 3.6, HBA 3, HBD 1, PSA 41.46, QED 0.94
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CS)C(N)=O
InChIKey: RQZHKEFEFWSLOK-PHNIDTBTSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC5R LBD expressed in HEK293 cell membranes incubated for 16 to 23 hrs in dark by scintillation proximity assay
Measurement: IC50 = 1905.46 nM (pChEMBL 5.71999979019165)
Descriptors: MW 1119.35
Compound (SMILES): Nc1nc(N)c2c(n1)[nH]c1cccc(Sc3ccc4ccccc4c3)c12
InChIKey: WRYJHTYXYDBSCF-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of human DHFR using dihydrofolate as substrate by spectrophotometric method
Measurement: IC50 > 28000 nM (pChEMBL 4.552999973297119)
Descriptors: MW 357.44, ALogP 4.58, HBA 5, HBD 3, PSA 93.61, QED 0.43
Compound (SMILES): Cc1nn2c(O)cc(C3CCN(C(=O)OCc4ccccc4)CC3)nc2c1-c1ccc(Cl)cc1
InChIKey: AAUMHOWAFCZIFJ-UHFFFAOYSA-N
Target: Short transient receptor potential channel 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCX4
Assay: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay
Measurement: EC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 476.96, ALogP 5.58, HBA 6, HBD 1, PSA 79.96, QED 0.42
Compound (SMILES): CC[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(C#CCCCC(=O)N3CCCC3)c2c(=O)n1-c1ccccc1
InChIKey: ZKNJZOFGGQYXQG-DEOSSOPVSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 575.68, ALogP 3.92, HBA 10, HBD 3, PSA 168.84, QED 0.21
Compound (SMILES): Cc1c(C#N)c(=O)oc2cc(OCc3ccc(Cl)cc3)ccc12
InChIKey: NPFLYKNCEWYOLO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using S-butylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 325.75, ALogP 4.21, HBA 4, HBD 0, PSA 63.23, QED 0.68
Compound (SMILES): Cc1nn2c(O)cc(C3CCN(C(=O)OCc4ccccc4)CC3)nc2c1-c1ccc(F)cc1
InChIKey: DQKIDQKOAUUVAT-UHFFFAOYSA-N
Target: Short transient receptor potential channel 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCX4
Assay: Agonist activity at human TRPC7 expressed in HEK293 cells assessed as increase in intracellular calcium level measured for 2.5 mins in presence of 2 mM Ca2+ by Fluo8-AM dye-based fluorescence assay
Measurement: EC50 = 314 nM (pChEMBL 6.5)
Descriptors: MW 460.51, ALogP 5.07, HBA 6, HBD 1, PSA 79.96, QED 0.46
Compound (SMILES): O=C(c1ccccc1)c1ccc2n1CCC2C(=O)NCCOc1ccc2oc(=O)ccc2c1
InChIKey: HREFIMOFGJMXJB-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human CA7 preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 442.47, ALogP 3.51, HBA 6, HBD 1, PSA 90.54, QED 0.27
Compound (SMILES): O=Cc1cnn2ccc(NC(=O)CCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc12
InChIKey: PMBZPLQKUNCRDH-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human Dopamine D3 receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 460.37, ALogP 3.99, HBA 6, HBD 1, PSA 69.95, QED 0.54
Compound (SMILES): Cc1ccc(-c2cc3c(N[C@@H]4CC[C@](C)(N)C4(C)C)c(C(N)=O)cnn3c2)cn1
InChIKey: YLPRMWFQNIEVDO-GCJKJVERSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged JAK2 (unknown origin) after 3 hrs by Caliper assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 392.51, ALogP 3.12, HBA 6, HBD 3, PSA 111.33, QED 0.63
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CN1CCc2c(Cl)cc(C(OC)C3CCOC3)c(Cl)c2C1=O
InChIKey: AZFROWZIMGUVBM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 Y641N mutant (unknown origin) using oligonucleosomes as substrate after 60 mins in presence of [3H]SAM by scintillation counting analysis
Measurement: Ki < 0.1 nM (pChEMBL 10)
Descriptors: MW 481.38, ALogP 3.92, HBA 5, HBD 1, PSA 80.86, QED 0.68
Compound (SMILES): COc1ccccc1N1CCN(CCCCOc2ccn3ncc(/C=N/O)c3c2)CC1
InChIKey: BZCYPHOOPXOADD-XIEYBQDHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]spiperone from human Dopamine D2L receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 423.52, ALogP 3.13, HBA 8, HBD 1, PSA 74.83, QED 0.25
Compound (SMILES): Nc1c(-c2n[nH]c(=S)o2)sc2ncc(-c3ccsc3)cc12
InChIKey: MJWLCXWVFUXXNZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17B (SINGLE PROTEIN), Homo sapiens
UniProt: O94768
Assay: Binding affinity to DRAK2 (unknown origin) assessed as dissociation constant
Measurement: Kd = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 332.44, ALogP 4.32, HBA 7, HBD 2, PSA 80.73, QED 0.53
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)Nc3cncc(C(=O)O)c3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: UJBDBUQHMJYLGN-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 7 nM (pChEMBL 8.154999732971191)
Descriptors: MW 620.54, ALogP 7.47, HBA 6, HBD 3, PSA 122.13, QED 0.15
Compound (SMILES): COC[C@H](C(=O)Nc1cccc2c(-c3nc(Nc4cn(C)nc4C)ncc3F)c[nH]c12)N1CCN(C)CC1
InChIKey: KRLOGMJQWZWUCD-JOCHJYFZSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of N-terminal GST fused human recombinant JAK1 (866 to 1154 amino acids) expressed in insect cells using ATP and peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 521.6, ALogP 2.75, HBA 9, HBD 3, PSA 116.23, QED 0.32
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1NC(=O)C1(c2cc(NCCN3CCCCC3)ncn2)CC1
InChIKey: MHYLKHNGFDIZID-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of CRAF (unknown origin) using human His6-tagged MEK1 K97R mutant as substrate pretreated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter binding method
Measurement: IC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 601.07, ALogP 6.28, HBA 6, HBD 3, PSA 99.25, QED 0.27
Compound (SMILES): Cc1ccc(-c2cc3c(N[C@@H]4CC[C@](C)(N)C4(C)C)c(C(N)=O)cnn3c2)cc1
InChIKey: RKRKQDQJBAZLNK-XXBNENTESA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged JAK2 (unknown origin) after 3 hrs by Caliper assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 391.52, ALogP 3.73, HBA 5, HBD 3, PSA 98.44, QED 0.63
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(N4CCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: JJFZFULVGZVWGT-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of recombinant human His-tagged c-kit cytoplasmic domain (544 to 976 residues) expressed in baculovirus expression system using Ser/Thr 6 as substrate measured after 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.56, ALogP 4.62, HBA 6, HBD 1, PSA 64.6, QED 0.55
Compound (SMILES): O=C(c1ccccc1)N1CCc2oc(-c3ccc(F)cn3)nc2C1
InChIKey: FOPJMYBQTFPHTL-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 323.33, ALogP 3.07, HBA 4, HBD 0, PSA 59.23, QED 0.73
Compound (SMILES): N[C@@]1(C(=O)O)C[C@H](NC(=O)C2CCCCC2)[C@H]2[C@H](C(=O)O)[C@H]21
InChIKey: URPILZHDNHGJFA-DMZJWBPISA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Antagonist activity at human mGlu2 receptor expressed in HEK cells assessed as reversal of DCG-4 inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 310.35, ALogP 0.18, HBA 4, HBD 4, PSA 129.72, QED 0.59
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)c(F)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: HNKNKWOBIYGMKR-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Inhibition of human Nav1.1 expressed in HEK293 cells assessed as reduction in peak inward current by ionworks quattro electrophysiology assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 543.5, ALogP 6.52, HBA 6, HBD 1, PSA 94.32, QED 0.25
Compound (SMILES): COC[C@@H](NC(=O)N1CC(=O)Nc2cc(OC)cnc21)c1ccc(OC(F)(F)F)c(F)c1
InChIKey: AWJSRXUQLSPAOI-CQSZACIVSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE4D2 (2 to 507 residues) expressed in baculovirus infected fall armyworm Sf9 cells using [3H]cAMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by scintillation counting
Measurement: IC50 = 14882 nM (pChEMBL 4.829999923706055)
Descriptors: MW 458.37, ALogP 2.98, HBA 6, HBD 2, PSA 102.02, QED 0.65
Compound (SMILES): CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O
InChIKey: FEEFNUHNOXJGEG-QVWIHFFISA-N
Target: Neuromedin-U receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BZ39
Assay: Agonist activity at mouse NMUR2 expressed in CHO cells assessed as induction of Ca2+ flux measured for 180 secs by Fluo 4-AM dye-based FLIPR assay
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 1168.42
Compound (SMILES): Cn1nc(-c2cnc(N)c(-n3ncc4ccccc43)n2)nc1C1(c2ccccc2)CC1
InChIKey: GGJRDLXDHZPLTA-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human His6-tagged PI3K p110beta/p85alpha using DiC8-PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 < 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 408.47, ALogP 3.27, HBA 8, HBD 1, PSA 100.33, QED 0.49
Compound (SMILES): O=C(CCCCCn1cc(-c2ncnc3[nH]ccc23)cn1)NO
InChIKey: RNGSAWKSEBQCHM-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of C-terminal FLAG His tagged full length human recombinant HDAC1 (1 to 482 residues) expressed in baculovirus infected sf21 cells using RHKKAc as substrate in presence of ATP
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 314.35, ALogP 1.89, HBA 6, HBD 3, PSA 108.72, QED 0.35
Compound (SMILES): O=C(C(=S)N1CCOCC1)c1ccc(F)cc1
InChIKey: LQWLWWYWWKQSBQ-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human HL60 cells assessed as reduction in cell viability in serine repleted medium after 5 days by presto blue assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 253.3, ALogP 1.67, HBA 3, HBD 0, PSA 29.54, QED 0.59
Compound (SMILES): Cc1cccc(S(=O)(=O)NCCCN2CC=C(c3c[nH]c4ccc(F)cc34)CC2)c1
InChIKey: DCQKCNGVYBRKSC-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]-imipramine from human serotonin transporter expressed in HEK-293 cell membranes after 30 mins by scintillation counting
Measurement: Ki = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 427.55, ALogP 4.07, HBA 3, HBD 2, PSA 65.2, QED 0.56
Compound (SMILES): CS[C@H]1O[C@@H](c2ccc(C)c(Cc3ccc(CCCCNCC(C)(C)C(N)=O)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: MGCZCTGKMFIXJU-IONQDRQYSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: In Vitro Human SGLT2 Inhibition Assay: Human sodium/glucose co-transporter type 2 (SGLT2; accession number P31639; GI:400337) was cloned into pIRESpuro2 vector for mammalian expression (construct: HA-SGLT2-pIRESpuro2). HEK293 cells were transfected with the human HA-SGLT2-pIRESpuro2 vector and the bulk stable cell line was selected in presence of 0.5 μg/mL of puromycin. Human HA-SGLT2 cells were maintained in DMEM media containing 10% FBS, 1% GPS and 0.5 μg/mL of puromycin. The HEK293 cells expressing the human HA-SGLT2 were seeded in 384 well plates (30,000 cells/well) in DMEM media containing 10% FBS, 1% GPS and 0.5 μg/mL of puromycin, then incubated overnight at 37 C, 5% CO2. Cells were then washed with uptake buffer (140 mM NaCl, 2 mM KCl, 1 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 5 mM Tris, 1 mg/mL bovine serum albumin (BSA), pH 7.3). Twenty microliters of uptake buffer with or without testing compounds were added to the cells. Then, 20 microliters of uptake buffer containing 14C-AMG (100 nCi) were added to the cells. The cell plates were incubated at 37° C., 5% CO2 for 1-2 hours. After washing the cells with uptake buffer, scintillation fluid was added (40 microliters/well) and 14C-AMG uptake was measured by counting radioactivity using a scintillation coulter (TopCoulter NXT; Packard Instruments).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 530.73, ALogP 2.85, HBA 7, HBD 5, PSA 125.04, QED 0.27
Compound (SMILES): COc1ccc(-c2ccc(Oc3cccc4c3CCCC4)c(NC(=O)Nc3cccc(C)c3)c2)cc1C(=O)O
InChIKey: SSUQEFNUCUXHQL-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 522.6, ALogP 7.68, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccc(C#N)c3)CC2)nc2ccsc12
InChIKey: MWXHRAPYPDVMJW-QPJJXVBHSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase Y188L mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 520.66, ALogP 6.59, HBA 8, HBD 1, PSA 97.86, QED 0.27
Compound (SMILES): COc1cc(Br)c(C[C@@H]2C[C@H]2C(=O)O)c(Br)c1OC
InChIKey: JYYXECVMEBTPHQ-NKWVEPMBSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow CO2 hydration method
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 394.06, ALogP 3.49, HBA 3, HBD 1, PSA 55.76, QED 0.83
Compound (SMILES): Cc1csc2cc([C@H](C)Nc3ncnc(N)c3C#N)c(Cc3cccc(CNCCCCOCCc4ccccc4)c3)c(=O)n12
InChIKey: RHJYRDFGTODYSM-VWLOTQADSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human His6-tagged PI3Kgamma (144 to 1102 residues) using DiC8-PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 621.81, ALogP 5.81, HBA 10, HBD 3, PSA 130.36, QED 0.13
Compound (SMILES): Nc1nccn2c([C@H]3CN(C4CCOCC4)CCO3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3F)c12
InChIKey: GZYUJXFTHLKPAK-OAQYLSRUSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC assessed as reduction in anti-IgM-induced MIP1beta
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 585.56, ALogP 4.34, HBA 9, HBD 2, PSA 119.9, QED 0.33
Compound (SMILES): O=C(c1cc([C@H]2CCCN2c2cc(F)cc(F)c2)c2oc(N3CCOCC3)cc(=O)c2c1)N1CCOCC1
InChIKey: CPFXYHKMOTWOFK-XMMPIXPASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human PI3Kgamma using PIP2 as substrate preincubated for 20 mins followed by substrate addition measured after 80 mins in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 525.55, ALogP 3.72, HBA 7, HBD 0, PSA 75.46, QED 0.51
Compound (SMILES): NS(=O)(=O)c1ccc(CC/N=C2\NC(=O)/C(=C3/C(=O)Nc4ccc(Br)cc43)S2)cc1
InChIKey: WYTBMDUZQWLZPT-NXVVXOECSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 79.3 nM (pChEMBL 7.099999904632568)
Descriptors: MW 507.39, ALogP 2.22, HBA 6, HBD 3, PSA 130.72, QED 0.55
Compound (SMILES): Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: GCXKULANKFAPOX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): COc1ccc(S(=O)(=O)N(C(C)=O)c2ccccc2/C=C/c2cc[n+]([O-])cc2)cc1
InChIKey: OCKHRKSTDPOHEN-BQYQJAHWSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.48, ALogP 3.24, HBA 5, HBD 0, PSA 90.62, QED 0.45
Compound (SMILES): CCS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1.Cl
InChIKey: IYULGYKOHUAYCG-UHFFFAOYSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 445.55, ALogP 1.37, HBA 8, HBD 3, PSA 133.55, QED 0.55
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: KSUDUUBCXJUFRL-SFHVURJKSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.51, ALogP 3.31, HBA 8, HBD 1, PSA 108.27, QED 0.46
Compound (SMILES): Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)NCc2cc(F)ccc2Oc2ccc3c(cnn3CCO)c2)cc1
InChIKey: LNMRSSIMGCDUTP-UHFFFAOYSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 556.64, ALogP 6.07, HBA 7, HBD 3, PSA 106.23, QED 0.22
Compound (SMILES): Cc1nc2cc(-c3nn(C(C)C)c4ncnc(N)c34)ccc2o1
InChIKey: JUUFLLKHNYWHKP-UHFFFAOYSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 308.35, ALogP 3.11, HBA 7, HBD 1, PSA 95.65, QED 0.61
Compound (SMILES): COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)c2c(N)ncnn2c1CN1CCOCC1
InChIKey: GZPJCJKUZPUFAL-UHFFFAOYSA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.54, ALogP 4.9, HBA 8, HBD 3, PSA 119.04, QED 0.26
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO.Cl
InChIKey: OOVTUOCTLAERQD-OJMBIDBESA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.85, ALogP 3.3, HBA 6, HBD 3, PSA 94.14, QED 0.62
Compound (SMILES): CN(C)c1nc2ccc(C(O)(c3ccncc3)c3cncn3C)cc2c(Cl)c1-c1ccccc1
InChIKey: SEJAMGYPDDPTHR-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4 DBD-fused human RORgammat expressed in HEK293T cells assessed as inhibition of transcriptional activity after 24 hrs by Dual-glo luciferase reporter gene assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 469.98, ALogP 5.03, HBA 6, HBD 1, PSA 67.07, QED 0.39
Compound (SMILES): CCc1cc2cc(NS(=O)(=O)c3ccc(C#N)cc3)ccc2n(CC)c1=O
InChIKey: QTIVTZLLONAWRR-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 381.46, ALogP 3.26, HBA 5, HBD 1, PSA 91.96, QED 0.73
Compound (SMILES): CCCN[C@@H]1Cc2cccc3c2n(c(=O)n3CCCCOCCCCc2ccccc2)C1
InChIKey: HMBLGIYYEVWFCT-XMMPIXPASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human dopamine D2 receptor expressed in HEK293 cells coexpressing renilla luciferase-fused Galphai1/GFP10-fused Ggamma2 by BRET assay
Measurement: EC50 = 194.5 nM (pChEMBL 6.710000038146973)
Descriptors: MW 435.61, ALogP 4.55, HBA 5, HBD 1, PSA 48.19, QED 0.4
Compound (SMILES): O=C1CCc2ccc(OCCCN3CCN(Cc4ccccc4)CC3)cc2N1
InChIKey: RRBYJBJQLCHSIT-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 21800 nM (pChEMBL 4.659999847412109)
Descriptors: MW 379.5, ALogP 3.16, HBA 4, HBD 1, PSA 44.81, QED 0.75
Compound (SMILES): CC(C)c1cc(C(=O)N2CCC(NC(=O)C3CCC3)C2)n[nH]1
InChIKey: WFZQSICPYNAMNU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: KDM5 Enzyme Assay: Full length KDM5A enzyme was expressed and purified inhouse. Biotin-H3K4me3 peptide was purchased from New England Biolabs. HTRF reagents (containing Eu-labeled H3K4me1-2 antibody, and streptavidin-XL665) were purchased from Cis-Bio International. Plates were read on an Envision multi-label plate reader (Perkin Elmer).The HTRF assay mixture contained 2 nM full length KDM5A enzyme, 100 nM H3K4Me3 peptide substrate, 1 uM 2-OG, 100 uM Fe2+, 500 uM ascorbate. 50 mM HEPES pH 7.0 buffer, 0.01% Triton-X 100, 2 mM DTT, 0.25% DMSO at a final volume of 10 uL.The enzyme reaction was carried out at room temperature in black Proxiplate 384-Plus plate (Corning. Costar) within 30 minutes, in the presence of varying concentration of a test compound. At the end of enzyme reaction, 5 uL of 1 mM EDTA were added to quench the reaction and then the detection reagents (5 uL) were added to give final concentrations of 0.5 nM Eu-labeled H3K4me1-2 antibody, and 50 nM streptavidin-XL665. The plates were incubated at room temperature for 60 minutes and then read in the Envision plate reader. The readouts were transformed into % inhibition, and IC50 value of a test compounds was generated by using four parameters curve fitting (Model 205 in XLFIT5, iDBS).
Measurement: IC50 = 0.083 nM (pChEMBL 10.079999923706055)
Descriptors: MW 304.39, ALogP 1.66, HBA 3, HBD 2, PSA 78.09, QED 0.89
Compound (SMILES): Cc1cc2c(cc1N1C(=O)c3cccc4c(CCCCO)ccc(c34)C1=O)n(C)c(=O)n2C
InChIKey: LGZFUXSDGGGPHG-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD2 (unknown origin) preincubated for 15 mins followed by addition of C-terminal biotinylated synthetic K5,8,12,16 tetra-acetylated histone H4 (1 to 20 residues) peptide as substrate measured after 1 hr by TR-FRET assay
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 443.5, ALogP 3.45, HBA 6, HBD 1, PSA 84.54, QED 0.38
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1C[C@@H](NS(=O)(=O)C2CC2)C1
InChIKey: FEWYOEFWRYEMQU-AOOOYVTPSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using FITC-KGGEEEEYFELVKK as substrate in presence of 1 mM ATP by mobility shift assay
Measurement: IC50 >= 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 321.41, ALogP 1.01, HBA 5, HBD 2, PSA 90.98, QED 0.86
Compound (SMILES): O=C(/C=C/c1ccc2ccccc2c1)c1cccnc1
InChIKey: VWBDGXJRQZDLRV-CSKARUKUSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human liver CYP2D6 expressed in Saccharomyces cerevisiae YY7 microsomal membranes using EOMCC as substrate after 10 mins by fluorescence assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 259.31, ALogP 4.13, HBA 2, HBD 0, PSA 29.96, QED 0.52
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccnc3)CC2)nc2ccsc12
InChIKey: RTUZYZMEIYLNIT-HWKANZROSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase E138K mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 6.59 nM (pChEMBL 8.180000305175781)
Descriptors: MW 496.64, ALogP 6.11, HBA 8, HBD 1, PSA 86.96, QED 0.31
Compound (SMILES): CCC(=O)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: SADFFAQSWHTWLL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]UNSW-MK259 from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cells after 3 hrs by liquid scintillation counting assay
Measurement: Ki = 1.096 nM (pChEMBL 8.960000038146973)
Descriptors: MW 627.79, ALogP 4.27, HBA 7, HBD 3, PSA 128.67, QED 0.23
Compound (SMILES): NC(=O)c1cccc(C2C[C@H]3CC[C@H](C2)N3CCCc2ccccc2)c1
InChIKey: KHPUWLSETPQJPL-FGZHOGPDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]DPN from guinea pig kappa opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 0.1585 nM (pChEMBL 9.800000190734863)
Descriptors: MW 348.49, ALogP 4.13, HBA 2, HBD 1, PSA 46.33, QED 0.85
Compound (SMILES): O=C1SCCc2nc(-c3ccc(C(F)(F)F)cc3)[nH]c(=O)c21
InChIKey: YAAIOGGCMLWOPM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of recombinant human N-terminal His-GST-tagged TNKS2 (849 to 1166 residues) expressed in baculovirus infected Sf9 cells using biotinylated NAD+ as substrate measured after 2 hrs
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 326.3, ALogP 2.89, HBA 4, HBD 1, PSA 62.82, QED 0.88
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccc(F)cc3F)ncn2)CC1)N1CCc2ccccc2C1
InChIKey: RGKNMWKLNOOSDH-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at recombinant human M5 receptor expressed in CHO cells co-expressing Gqi5 by calcium mobilization assay
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 450.49, ALogP 4.35, HBA 5, HBD 0, PSA 58.56, QED 0.59
Compound (SMILES): CC[C@@H](NC(=O)c1cnn2cc(C)cnc12)c1ccc(OC(F)(F)F)cc1
InChIKey: CXEGBNQZVKLHTO-OAHLLOKOSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PDE5A1 expressed in baculovirus infected Sf9 cell expression system using [3H]cGMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.35, ALogP 3.82, HBA 5, HBD 1, PSA 68.52, QED 0.73
Compound (SMILES): CC(=O)N1CCN(c2cccc(-c3cc(-c4ccnn4CC(F)(F)F)c4c(N)ncnn34)c2)C(=O)C1(C)C
InChIKey: KSAKMNJFOKNIAA-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 526.52, ALogP 3.38, HBA 8, HBD 1, PSA 114.65, QED 0.44
Compound (SMILES): Cl.NCc1cc(Oc2cccc(C(=O)Nc3ccccc3)c2)nc(C(F)(F)F)c1
InChIKey: KKQUMMOVFCDMIK-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of recombinant human LOXL2 expressed in human whole blood assessed as reduction of H2O2 production from oxidative deamination of DAP preincubated for 2 hrs followed by substrate addition measured every 2 mins for 1 hr by amplex red reagent-based fluorescence assay
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 387.36, ALogP 4.6, HBA 4, HBD 2, PSA 77.24, QED 0.67
Compound (SMILES): O=[N+]([O-])c1ccccc1[Se][Se]c1ccccc1[N+](=O)[O-]
InChIKey: QUTPYNJBIHTIGA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human cytosolic carbonic anhydrase 2 pretreated for 15 mins prior to testing measured for 10 to 100 secs by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 402.13
Compound (SMILES): CCn1nnc([C@H]2O[C@@H](n3cnc4c(NCc5cccc(Br)c5)nc(Cl)nc43)[C@H](O)[C@@H]2O)n1
InChIKey: WTSRCKFFAWSKBH-MOROJQBDSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Agonist activity at recombinant human adenosine A2A receptor expressed in CHO cell membranes assessed as stimulation of adenylyl cyclase activity by [alpha-32P]ATP assay
Measurement: EC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 536.78, ALogP 1.85, HBA 12, HBD 3, PSA 148.92, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccccc3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1
InChIKey: YECANFWMOCZDPE-UHFFFAOYSA-N
Target: L-lactate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: V9HWB9
Assay: Inhibition of LDH in human A673 cells assessed as reduction in lactate production preincubated for 2 hrs measured after 30 mins by high throughput fluorescence assay
Measurement: IC50 = 3370 nM (pChEMBL 5.46999979019165)
Descriptors: MW 494.6, ALogP 3.88, HBA 7, HBD 2, PSA 128.17, QED 0.38
Compound (SMILES): CC(=O)N[C@H]1CSCc2cc3cc(c2)CSC[C@H](C(=O)N[C@@H](C)C(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2c[nH]c4ccccc24)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CSC3)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: OHOYFNPMBCNOTR-QFZQKJJLSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of recombinant human alpha thrombin using fluorogenic peptide as substrate by fluorescence based assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 2558.96
Compound (SMILES): CC(C)(C)OC[C@@H]1N=C(c2ccccc2)c2ccccc2NC1=O
InChIKey: MCCWPRRTKDOMRT-KRWDZBQOSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Schistosoma mansoni
UniProt: A5H660
Assay: Inhibition of Schistosoma mansoni KDAC8 using (FAM)-labeled peptide as substrate after 60 mins by microfluidic assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 322.41, ALogP 3.66, HBA 3, HBD 1, PSA 50.69, QED 0.94
Compound (SMILES): CC1(N)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: YGUFCDOEKKVKJK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by Q-patch assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 352.27, ALogP 3.35, HBA 5, HBD 2, PSA 81.06, QED 0.87
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3cc(-c4cccc5ccccc45)ccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: OYXSSEAGSFYOGN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR delE746_A750 mutant in human HCC827 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 534.66, ALogP 6.26, HBA 6, HBD 3, PSA 85.52, QED 0.18
Compound (SMILES): O=C(O)CCCCN1C(=O)[C@H](CC(=O)O)N=C(c2ccccc2)c2ccccc21
InChIKey: AQWXALQNWXWYLI-KRWDZBQOSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human KDAC8 after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 394.43, ALogP 2.97, HBA 4, HBD 2, PSA 107.27, QED 0.67
Compound (SMILES): COCCN1C(=O)c2cc(-c3ccnc(Nc4ccnn4C)n3)[nH]c2C[C@@H]1C
InChIKey: QLNRHZIAMVVOMQ-LBPRGKRZSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin) in the presence of 60 uM ATP
Measurement: IC50 < 0.3 nM (pChEMBL 9.52299976348877)
Descriptors: MW 381.44, ALogP 1.98, HBA 7, HBD 2, PSA 100.96, QED 0.68
Compound (SMILES): CC(C)CN1CCC23c4cc(O)ccc4CC1C21CCC2C3[C@@H](CN2C(=O)c2ccccc2)O1
InChIKey: TWGYRBSROHRNIC-BTNQZZBKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 458.6, ALogP 3.99, HBA 4, HBD 1, PSA 53.01, QED 0.76
Compound (SMILES): COc1ccc(-c2ccc(Oc3cccc4c3CCCC4)c(NC(=O)Nc3ccccc3Cl)c2)cc1C(=O)O
InChIKey: OLUVZKHXNIKBIS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 543.02, ALogP 8.03, HBA 4, HBD 3, PSA 96.89, QED 0.22
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3cc(-c4ccc(F)cc4)ccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: BUVGSBCMNREXAL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR delE746_A750 mutant in human HCC827 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 765 nM (pChEMBL 6.119999885559082)
Descriptors: MW 502.59, ALogP 5.24, HBA 6, HBD 3, PSA 85.52, QED 0.26
Compound (SMILES): C[C@@H]1CN(c2nc(N3CCOCC3)c3sc(-c4cnc(N)nc4)cc3n2)C[C@H](C)O1
InChIKey: XIGIJFUSWMTGMS-BETUJISGSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant full length human N-terminal His6-tagged PI3K p110delta/p85alpha expressed in baculovirus infected Sf21 cells using PIP2 as substrate after 1 hr by kinase-glo luminescence assay
Measurement: IC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 427.53, ALogP 2.18, HBA 10, HBD 1, PSA 102.52, QED 0.67
Compound (SMILES): Cn1cnc(C(=O)N2CCN(C(=O)c3ccc(Nc4nc5ccccc5n5nnnc45)cc3)CC2)c1
InChIKey: YFNNDVKJUPAWSW-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Binding affinity to PARP14 in human Jurkat cell extract after 45 mins by mass spectrometric analysis
Measurement: IC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 482.51, ALogP 1.75, HBA 10, HBD 1, PSA 126.44, QED 0.41
Compound (SMILES): CNC(=O)[C@H](NC(=O)c1ccc(-c2ccc(CSc3nc4c(c(=O)[nH]3)CCC4)c(F)c2)o1)C1CCCCC1
InChIKey: VAUVOKSOLZDEJH-XMMPIXPASA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of MMP9 (unknown origin) using fTHP-15 as substrate preincubated for 30 mins followed by substrate addition measured immediately by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 538.65, ALogP 4.37, HBA 6, HBD 3, PSA 117.09, QED 0.29
Compound (SMILES): C[C@@H]1CN(c2cncnc2)Cc2cc(NC(=O)c3cc(CN4CCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: FXWGWJNBGHQODS-LJQANCHMSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.59, ALogP 4.62, HBA 6, HBD 1, PSA 64.6, QED 0.53
Compound (SMILES): CCN(CC)CC1=Cc2cn(S(=O)(=O)c3ccccc3)c3cccc(c23)O1
InChIKey: YPUNCYRZMZDDIB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to 5HT2A receptor (unknown origin)
Measurement: Ki = 1703 nM (pChEMBL 5.769999980926514)
Descriptors: MW 382.49, ALogP 3.95, HBA 5, HBD 0, PSA 51.54, QED 0.65
Compound (SMILES): O=C(CCCCCCn1cc(-c2ncnc3[nH]ccc23)cn1)NO
InChIKey: YRRVLBINSXVLFM-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of C-terminal His tagged human recombinant HDAC5 (657 to 1123 residues) expressed in Baculovirus infected insect cells in presence of ATP
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 328.38, ALogP 2.28, HBA 6, HBD 3, PSA 108.72, QED 0.33
Compound (SMILES): CC(=O)NC(C)c1ccc2nc(-c3ccc(Oc4cccc(OCC5CC5)c4)nc3)oc2c1
InChIKey: ODPQVXKNLIIEJW-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Mus musculus
UniProt: E9Q4Z2
Assay: Inhibition of mouse His-tagged ACC2 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 443.5, ALogP 5.67, HBA 6, HBD 1, PSA 86.48, QED 0.38
Compound (SMILES): CC(C)(C)SC[C@H]1N=C(c2ccccc2)c2ccccc2N(CCCCC(=O)NO)C1=O
InChIKey: ZIAMUXVOAZMOPT-HXUWFJFHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Schistosoma mansoni
UniProt: A5H660
Assay: Inhibition of Schistosoma mansoni KDAC8 using (FAM)-labeled peptide as substrate after 60 mins by microfluidic assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 453.61, ALogP 4.45, HBA 5, HBD 2, PSA 82, QED 0.35
Compound (SMILES): CCNC(=O)c1noc(-c2cc(Cl)c(O)cc2O)c1-c1ccc(CN2CCOCC2)cc1C
InChIKey: RXSXHCNTLOATRW-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Fluorescence Polarization Assay: Fluorescence polarization {also known as fluorescence anisotropy} measures the rotation of a fluorescing species in solution, where the larger molecule the more polarized the fluorescence emission.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 471.94, ALogP 3.96, HBA 7, HBD 3, PSA 108.06, QED 0.5
Compound (SMILES): O=C(O)CC1CCC2(CCN(c3ccc(-c4nc5cc(C(F)(F)F)ccc5[nH]4)cn3)CC2)OC1
InChIKey: LFHXTDBDALXSLW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 20400 nM (pChEMBL 4.690000057220459)
Descriptors: MW 474.48, ALogP 4.88, HBA 5, HBD 2, PSA 91.34, QED 0.56
Compound (SMILES): N[C@@H](CCP(=O)(O)C(O)c1ccc(O)c([N+](=O)[O-])c1)C(=O)O
InChIKey: GAGSUJFFXBSIDN-RGENBBCFSA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O15303
Assay: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay
Measurement: EC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 334.22, ALogP 0.36, HBA 7, HBD 5, PSA 184.22, QED 0.27
Compound (SMILES): O=C(NC1CCN(Cc2ccccc2)CC1)c1ccc(Cl)nc1Cl
InChIKey: FGUUNZVMTXKKDT-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent betaine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P48065
Assay: Inhibition of human BGT1 Q299L mutant expressed in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 364.28, ALogP 3.78, HBA 3, HBD 1, PSA 45.23, QED 0.84
Compound (SMILES): CSCC[C@@H]1N=C(c2ccccc2)c2ccccc2NC1=O
InChIKey: NFFFRNVSWUATIJ-INIZCTEOSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human KDAC8 after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 310.42, ALogP 3.6, HBA 3, HBD 1, PSA 41.46, QED 0.94
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CS)C(N)=O
InChIKey: RQZHKEFEFWSLOK-PHNIDTBTSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in low doxycyclin-treated HEK293 cell membranes assessed as increase in cAMP production after 45 mins by HTRF method
Measurement: EC50 = 0.263 nM (pChEMBL 9.579999923706055)
Descriptors: MW 1119.35
Compound (SMILES): CC[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(C#CCCCC(=O)N3CCCC3)c2c(=O)n1-c1ccccc1
InChIKey: ZKNJZOFGGQYXQG-DEOSSOPVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 575.68, ALogP 3.92, HBA 10, HBD 3, PSA 168.84, QED 0.21