lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CC4)c3)c2n1
InChIKey: HBAQYPYDRFILMT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 364.41, ALogP 1.36, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): COc1ccc(Nc2ncnc3c2cnn3-c2ccc(Cl)cc2C)cc1Cl
InChIKey: RNJQSVZFLIHBSM-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of PI5P4Kalpha in human HEK293 cells incubated for 60 mins by luminescence based analysis
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 400.27, ALogP 5.18, HBA 6, HBD 1, PSA 64.86, QED 0.51
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: CDRHMFVWJYVLGL-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P28593
Assay: Inhibition of HIS-tagged recombinant Trypanosoma cruzi TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 48500 nM (pChEMBL 4.309999942779541)
Descriptors: MW 546.72, ALogP 3.29, HBA 7, HBD 2, PSA 102.18, QED 0.2
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSC(C(=O)NC(C)C(N)=O)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NC(=O)C(C(C)O)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(C)NC(=O)C2CCCN2C(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(CCCNC(=N)N)NC1=O
InChIKey: SJBURJCQSMMNIC-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human fXIa using Boc-FSR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1879.19
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: NAUMQOWVCNOPGB-INIZCTEOSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin)
Measurement: IC50 = 0.96 nM (pChEMBL 9.020000457763672)
Descriptors: MW 547.41, ALogP 5.54, HBA 7, HBD 1, PSA 85.81, QED 0.31
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5c(F)cccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: WXVYORSFYSHIOF-ZDUSSCGKSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Positive allosteric modulation of human mGluR4
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.4, ALogP 2.88, HBA 7, HBD 0, PSA 74.51, QED 0.64
Compound (SMILES): CSc1c(C#N)c(=O)c2ccc(F)cc2n1-c1c(Cl)cccc1Cl
InChIKey: AWQZXHDLUBADMM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of recombinant hERG in the presence of dofetilide by competitive binding assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 379.24, ALogP 5.03, HBA 4, HBD 0, PSA 45.79, QED 0.59
Compound (SMILES): CC(C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: NSIQQHYATFPGEC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR T790M/L858R double mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as peptide substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki < 0.6 nM (pChEMBL 9.222000122070312)
Descriptors: MW 537.65, ALogP 2.96, HBA 12, HBD 2, PSA 143.95, QED 0.34
Compound (SMILES): C=CCn1c(=O)c2cnc(Nc3ccc4c(c3)CNCC4(C)C)nc2n1-c1cccc(C(C)(C)O)n1
InChIKey: WOBLPQMIMKNCIR-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: LanthaScreen TR-FRET Assay: IC50 values of compounds against WEE1 kinase enzyme were determined by LanthaScreen Terbium Labeled TR-FRET assay. Kinase assays were performed in 1× kinase buffer (#PV6135, Invitrogen, Life Technologies Grand Island, N.Y.) where total reaction volume was 10 μL in low-volume 384-well plates (#4511, Corning). Serially diluted compounds (3-fold) were incubated with WEE1 Enzyme (1 nM) (#PR7373A, Invitrogen, Life Technologies Grand Island, N.Y.) for 10 min, following which a mixture of ATP (10 μM) (#A1852, Sigma, St-Louis, Mo.) and fluorescent-PolyGT substrate (200 nM) (#PV3610, Invitrogen, Life Technologies Grand Island, N.Y.) was added and incubated in dark at room temperature for 1 h. After 1 h, 10 L stop solution containing Terbium labeled antibody (4 nM) (#PV3529, Invitrogen, Life Technologies Grand Island, N.Y.) and EDTA (#E5134, Sigma, St-Louis, Mo.) (20 mM) in TR-FRET dilution buffer (#PV3574, Invitrogen, Life Technologies Grand Island, N.Y.) was added. Readings were taken in a Synergy Neo Plate reader (BioTek, Winooski) at single excitation of 340 nm and Dual emission at 495 nm and 520 nm respectively.
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 485.59, ALogP 3.52, HBA 9, HBD 3, PSA 109.89, QED 0.36
Compound (SMILES): COC1CCN(c2nccc(Nc3cc4c(cn3)c(C(N)=O)cn4C(C)C)n2)CC1
InChIKey: GBQZWJZYHRNIFT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type human EGFR assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 409.49, ALogP 2.86, HBA 8, HBD 2, PSA 111.19, QED 0.64
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2Cl)CCC1(O)c1cccc(O)c1
InChIKey: VZKYGOFDBBGOOF-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at DOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 548.6 nM (pChEMBL 6.260000228881836)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(N)=O)c2C#N)cc1
InChIKey: KIWBVAQAICXQKZ-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 436.52, ALogP 4.9, HBA 5, HBD 1, PSA 101.89, QED 0.44
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis partial length PknB (M1 to G279 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 180 nM (pChEMBL 6.75)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): O=C1CCc2cc(OCCN3CCCC3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition of full length human ALDH2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): Cc1cccc2c(C(=O)N3CCN(Cc4ccc(C(=O)NO)cc4)CC3)c[nH]c12
InChIKey: LOYLSJNIQXFWSL-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin) using trifluoroacetyl lysine as substrate by fluorescence-based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 392.46, ALogP 2.55, HBA 4, HBD 3, PSA 88.67, QED 0.47
Compound (SMILES): CCC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1C
InChIKey: YKDZIFFKQUNVHH-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of recombinant human CK2alpha extracted from Escherichia coli C41 (DE3) cells
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 375.44, ALogP 3.58, HBA 7, HBD 3, PSA 107.14, QED 0.61
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cn1)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: CZIDGRDZSFIUHX-UHFFFAOYSA-N
Target: CTP synthase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P70303
Assay: Inhibition of mouse CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 512.54, ALogP 3.83, HBA 8, HBD 2, PSA 126.83, QED 0.49
Compound (SMILES): COc1ccc(S(=O)(=O)N2CCN(c3cccnc3)CC2C(=O)NO)cc1
InChIKey: LHPNKVRYCBRQPZ-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 using Mca-Pro-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 20 to 30 mins by fluorescence microplate reader analysis
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 392.44, ALogP 0.48, HBA 7, HBD 2, PSA 112.07, QED 0.56
Compound (SMILES): O=C(NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO)c1cccc(C(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1
InChIKey: LJOOWNHZCTUDSG-XRSDMRJBSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP12 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 1232.62
Compound (SMILES): COc1ccc(C(c2c(-c3ccccc3)n(O)c3ccccc23)N2CCN(C)CC2)cc1
InChIKey: BBAJRFXAJHAPJE-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Inhibition of GST-tagged Bfl-1 (unknown origin) incubated for 60 min by TR-FRET assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 427.55, ALogP 4.89, HBA 5, HBD 1, PSA 40.87, QED 0.46
Compound (SMILES): CC1(C)c2ccccc2N(Cc2ccc(C(=O)NO)cc2)C1c1cccnc1
InChIKey: HGCZGYHCBRKJNB-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of C-terminal His-tagged recombinant human HDAC5 catalytic domain (656 to 1122 residues) expressed in baculovirus infected Sf9 insect cells using a fluorogenic substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.46, ALogP 4.24, HBA 4, HBD 2, PSA 65.46, QED 0.53
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccnc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: UWDRPHXOMMPVSE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis partial length PknB (M1 to G279 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 448.88, ALogP 4.71, HBA 6, HBD 1, PSA 57.18, QED 0.58
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(O)c4)cc23)CC1
InChIKey: ZTBPVQXPLLMZGW-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(ccn2-c2ccnc(N)n2)cn1
InChIKey: ISYRCGISNANONJ-KRWDZBQOSA-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 307.36, ALogP 1.91, HBA 6, HBD 2, PSA 89.85, QED 0.71
Compound (SMILES): Cc1ccc(S(=O)(=O)O)cc1.Cc1ccsc1C(=O)Nc1cc(CN2CCN(C(=O)CO)CC2)ccc1/C=C/c1n[nH]c2ccccc12
InChIKey: SIJKXSMUXNJNQM-HRNDJLQDSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human IGF1R expressed in MDA-MB-468 cells
Measurement: IC50 < 2 nM (pChEMBL 8.699000358581543)
Descriptors: MW 515.64, ALogP 3.99, HBA 6, HBD 3, PSA 101.56, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccccc4)n3)cc2C(F)(F)F)CC1
InChIKey: CWFRZEJQFAQELA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis partial length PknB (M1 to G279 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 413.45, ALogP 4.66, HBA 5, HBD 1, PSA 44.29, QED 0.67
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCN1CCN(Cc2ccccc2)CC1
InChIKey: BNGICRROXYSOFL-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 408.57, ALogP 3.06, HBA 5, HBD 0, PSA 39.15, QED 0.76
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1Cc1ccc(CN2CCN(Cc3ccccc3)CC2)cc1
InChIKey: FMHFUABJEGMXDA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 3650 nM (pChEMBL 5.440000057220459)
Descriptors: MW 484.67, ALogP 4.76, HBA 5, HBD 0, PSA 39.15, QED 0.51
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cncnc5)ccc4n3)cn2)CC1
InChIKey: QQIQOMIKWUAMAA-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) in presence of 600 uM ATP
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 457.54, ALogP 3.62, HBA 10, HBD 1, PSA 106.77, QED 0.46
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C)c2)n1
InChIKey: QYMHHIWJCCQYPU-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.47, ALogP 5.09, HBA 5, HBD 2, PSA 71.42, QED 0.42
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(OC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: OYXCACHCXKHEOC-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 1025.6
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3cccc5ccccc35)C4=O)nn2)cc1
InChIKey: MWWVNAOGVSRMHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human transmembrane carbonic anhydrase 12 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 9.22 nM (pChEMBL 8.039999961853027)
Descriptors: MW 553.56, ALogP 3.23, HBA 9, HBD 1, PSA 154.55, QED 0.25
Compound (SMILES): COc1cc(/C=C/C(=O)[N-]S(=O)(=O)c2ccc(-n3nc(C(F)(F)F)cc3-c3ccc(C)cc3)cc2)ccc1[O-].[Na+].[Na+]
InChIKey: NMSJRWUGJMSTET-UHFFFAOYSA-L
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Inhibition of TRPV1 (unknown origin)
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 557.55, ALogP 5.1, HBA 7, HBD 2, PSA 110.52, QED 0.31
Compound (SMILES): CC#CCOc1ccc2cc(C(O)(c3ccc(Br)cc3)c3cccnc3)oc2c1
InChIKey: GZWXDDIEDPOAKI-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 448.32, ALogP 5.28, HBA 4, HBD 1, PSA 55.49, QED 0.42
Compound (SMILES): O=C1NC(NC2CCCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: HJEKFRDOAYXXRU-DHDCSXOGSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Escherichia coli using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 340.45, ALogP 3.44, HBA 5, HBD 2, PSA 66.38, QED 0.65
Compound (SMILES): CC1C(=O)N(C)CCN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: OJGOVIODTPNPDG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(C(F)(F)F)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: HCKWZGBREFFBGT-KRWDZBQOSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 528, ALogP 5.58, HBA 6, HBD 1, PSA 65.9, QED 0.41
Compound (SMILES): COCCCC(=O)N(C)CCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: FKEYBQUXJBIQQC-GNAFDRTKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in CHO-K1 cell membrane measured after 45 mins by topcount scintillation counting method
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 511.07, ALogP 3.99, HBA 6, HBD 0, PSA 67.67, QED 0.36
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc(C)[nH]c2c1=O
InChIKey: POICMTYCJMMADL-ONEGZZNKSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 391.47, ALogP 3.35, HBA 4, HBD 1, PSA 67.33, QED 0.69
Compound (SMILES): O=C1NCCc2c1cnn2-c1ccnc(Cc2cc(F)cc(C(F)(F)F)c2)c1
InChIKey: VASPFLVEEOBQOS-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 390.34, ALogP 3.3, HBA 4, HBD 1, PSA 59.81, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3ncccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: HENRITOGWFFGGA-PMACEKPBSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 1479 nM (pChEMBL 5.829999923706055)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: RXAZQWJCOUIOPS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGR-induced EGFR phosphorylation in human A549 cells pretreated for 2 hrs followed by EGF stimulation by immune assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 557.66, ALogP 4.3, HBA 10, HBD 2, PSA 113.85, QED 0.21
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)c1csc(Nc2ccccc2)n1
InChIKey: CYVGSDYVNUNREA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.39, ALogP 4.02, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CC4)c3)c2n1
InChIKey: HBAQYPYDRFILMT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 364.41, ALogP 1.36, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: CDRHMFVWJYVLGL-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma congolense
UniProt: P13110
Assay: Inhibition of HIS-tagged recombinant Trypanosoma congolense TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 18700 nM (pChEMBL 4.730000019073486)
Descriptors: MW 546.72, ALogP 3.29, HBA 7, HBD 2, PSA 102.18, QED 0.2
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSC(C(=O)NC(C)C(N)=O)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NC(=O)C(C(C)O)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(C)NC(=O)C2CCCN2C(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(CCCNC(=N)N)NC1=O
InChIKey: SJBURJCQSMMNIC-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human fXIIa using Z-GGR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1879.19
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: NAUMQOWVCNOPGB-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR A763-Y764 ins FQEA mutant (unknown origin)
Measurement: IC50 = 0.097 nM (pChEMBL 10.010000228881836)
Descriptors: MW 547.41, ALogP 5.54, HBA 7, HBD 1, PSA 85.81, QED 0.31
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5c(F)cccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: WXVYORSFYSHIOF-ZDUSSCGKSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Positive allosteric modulation of human mGluR5
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.4, ALogP 2.88, HBA 7, HBD 0, PSA 74.51, QED 0.64
Compound (SMILES): CC(C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: NSIQQHYATFPGEC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type human EGFR assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 537.65, ALogP 2.96, HBA 12, HBD 2, PSA 143.95, QED 0.34
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Binding affinity to human full length CDK4 (M1 to E303 residues) expressed in mammalian expression system/CyclinD3 by KdELECT kinase assay
Measurement: Kd = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): Cc1cccc2c(C(=O)N3CCN(Cc4ccc(C(=O)NO)cc4)CC3)c[nH]c12
InChIKey: LOYLSJNIQXFWSL-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC3 (unknown origin) using fluorogenic peptide RHKAcKAc-AMC as substrate by fluorescence-based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 392.46, ALogP 2.55, HBA 4, HBD 3, PSA 88.67, QED 0.47
Compound (SMILES): CCC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1C
InChIKey: YKDZIFFKQUNVHH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UEE5
Assay: Inhibition of DRAK1 (unknown origin)
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 375.44, ALogP 3.58, HBA 7, HBD 3, PSA 107.14, QED 0.61
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cn1)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: CZIDGRDZSFIUHX-UHFFFAOYSA-N
Target: CTP synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P70698
Assay: Inhibition of mouse CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 512.54, ALogP 3.83, HBA 8, HBD 2, PSA 126.83, QED 0.49
Compound (SMILES): O=C(NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO)c1cccc(C(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1
InChIKey: LJOOWNHZCTUDSG-XRSDMRJBSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of human recombinant MMP14 catalytic domain using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 1232.62
Compound (SMILES): CC1(C)c2ccccc2N(Cc2ccc(C(=O)NO)cc2)C1c1cccnc1
InChIKey: HGCZGYHCBRKJNB-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full-length recombinant human HDAC11 (1 to 347 residues) extracted from Sf9 insect cells using a fluorogenic substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by fluorescence based assay
Measurement: IC50 = 695 nM (pChEMBL 6.159999847412109)
Descriptors: MW 373.46, ALogP 4.24, HBA 4, HBD 2, PSA 65.46, QED 0.53
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccnc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: UWDRPHXOMMPVSE-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Binding affinity to human full length CDK4 (M1 to E303 residues) expressed in mammalian expression system/CyclinD3 by KdELECT kinase assay
Measurement: Kd = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 448.88, ALogP 4.71, HBA 6, HBD 1, PSA 57.18, QED 0.58
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(O)c4)cc23)CC1
InChIKey: ZTBPVQXPLLMZGW-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Agonist activity at human SST5 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): Cc1ccc(S(=O)(=O)O)cc1.Cc1ccsc1C(=O)Nc1cc(CN2CCN(C(=O)CO)CC2)ccc1/C=C/c1n[nH]c2ccccc12
InChIKey: SIJKXSMUXNJNQM-HRNDJLQDSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human IGF1R expressed in SUM149 cells
Measurement: IC50 < 2 nM (pChEMBL 8.699000358581543)
Descriptors: MW 515.64, ALogP 3.99, HBA 6, HBD 3, PSA 101.56, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccccc4)n3)cc2C(F)(F)F)CC1
InChIKey: CWFRZEJQFAQELA-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Binding affinity to human full length CDK4 (M1 to E303 residues) expressed in mammalian expression system/CyclinD3 by KdELECT kinase assay
Measurement: Kd = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 413.45, ALogP 4.66, HBA 5, HBD 1, PSA 44.29, QED 0.67
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cncnc5)ccc4n3)cn2)CC1
InChIKey: QQIQOMIKWUAMAA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) in presence of 75 uM ATP
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 457.54, ALogP 3.62, HBA 10, HBD 1, PSA 106.77, QED 0.46
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C)c2)n1
InChIKey: QYMHHIWJCCQYPU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.47, ALogP 5.09, HBA 5, HBD 2, PSA 71.42, QED 0.42
Compound (SMILES): CC#CCOc1ccc2cc(C(O)(c3ccc(Br)cc3)c3cccnc3)oc2c1
InChIKey: GZWXDDIEDPOAKI-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam/testosterone as substrate by LC-MS/MS analysis
Measurement: IC50 = 3380 nM (pChEMBL 5.46999979019165)
Descriptors: MW 448.32, ALogP 5.28, HBA 4, HBD 1, PSA 55.49, QED 0.42
Compound (SMILES): O=C1NC(NC2CCCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: HJEKFRDOAYXXRU-DHDCSXOGSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 13.9 nM (pChEMBL 7.860000133514404)
Descriptors: MW 340.45, ALogP 3.44, HBA 5, HBD 2, PSA 66.38, QED 0.65
Compound (SMILES): CC1C(=O)N(C)CCN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: OJGOVIODTPNPDG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(C(F)(F)F)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: HCKWZGBREFFBGT-KRWDZBQOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 528, ALogP 5.58, HBA 6, HBD 1, PSA 65.9, QED 0.41
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc(C)[nH]c2c1=O
InChIKey: POICMTYCJMMADL-ONEGZZNKSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 391.47, ALogP 3.35, HBA 4, HBD 1, PSA 67.33, QED 0.69
Compound (SMILES): O=C1NCCc2c1cnn2-c1ccnc(Cc2cc(F)cc(C(F)(F)F)c2)c1
InChIKey: VASPFLVEEOBQOS-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 390.34, ALogP 3.3, HBA 4, HBD 1, PSA 59.81, QED 0.7
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3ncccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: HENRITOGWFFGGA-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human whole blood assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 373 nM (pChEMBL 6.429999828338623)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)c1csc(Nc2ccccc2)n1
InChIKey: CYVGSDYVNUNREA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 335.39, ALogP 4.02, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: CDRHMFVWJYVLGL-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Inhibition of HIS-tagged recombinant human GR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 546.72, ALogP 3.29, HBA 7, HBD 2, PSA 102.18, QED 0.2
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: NAUMQOWVCNOPGB-INIZCTEOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding affinity to human ERG
Measurement: IC50 = 1135 nM (pChEMBL 5.949999809265137)
Descriptors: MW 547.41, ALogP 5.54, HBA 7, HBD 1, PSA 85.81, QED 0.31
Compound (SMILES): COc1cc(F)cc2c(N3CCN4c5c(F)cccc5OC[C@@H]4C3)c(C#N)nnc12
InChIKey: WXVYORSFYSHIOF-ZDUSSCGKSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Positive allosteric modulation of human mGluR8
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 409.4, ALogP 2.88, HBA 7, HBD 0, PSA 74.51, QED 0.64
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Binding affinity to human full length GSK-3 beta (M1 to T433 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): CCC(=O)Nc1cc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)ccc1C
InChIKey: YKDZIFFKQUNVHH-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Affinity Phenotypic Cellular interaction: (ProQinase broad tumor cell line profiling (CellTiterGlo assay, antiproliferative activity tested in U-937 blood cell line, 8-point dose-response)) EUB0001183a CSNK2A1
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 375.44, ALogP 3.58, HBA 7, HBD 3, PSA 107.14, QED 0.61
Compound (SMILES): O=C(NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO)c1cccc(C(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1
InChIKey: LJOOWNHZCTUDSG-XRSDMRJBSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O14672
Assay: Inhibition of human recombinant ADAM10 expressed in baculovorus-infected Sf21 cells using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 1232.62
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccnc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: UWDRPHXOMMPVSE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Binding affinity to human full length GSK-3 beta (M1 to T433 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 448.88, ALogP 4.71, HBA 6, HBD 1, PSA 57.18, QED 0.58
Compound (SMILES): NC1CCN(c2c(-c3cc(F)cc(F)c3)cnc3ccc(-c4cccc(O)c4)cc23)CC1
InChIKey: ZTBPVQXPLLMZGW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG by fluorescence polarization assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 431.49, ALogP 5.48, HBA 4, HBD 2, PSA 62.38, QED 0.45
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccccc4)n3)cc2C(F)(F)F)CC1
InChIKey: CWFRZEJQFAQELA-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Binding affinity to human full length GSK-3 beta (M1 to T433 residues) expressed in mammalian expression system by KdELECT kinase assay
Measurement: Kd = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 413.45, ALogP 4.66, HBA 5, HBD 1, PSA 44.29, QED 0.67
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cncnc5)ccc4n3)cn2)CC1
InChIKey: QQIQOMIKWUAMAA-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) in presence of 400 uM ATP
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 457.54, ALogP 3.62, HBA 10, HBD 1, PSA 106.77, QED 0.46
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C)c2)n1
InChIKey: QYMHHIWJCCQYPU-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human ALK2 by NanoBERT assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.47, ALogP 5.09, HBA 5, HBD 2, PSA 71.42, QED 0.42
Compound (SMILES): O=C1NC(NC2CCCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: HJEKFRDOAYXXRU-DHDCSXOGSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 2.602 nM (pChEMBL 8.59000015258789)
Descriptors: MW 340.45, ALogP 3.44, HBA 5, HBD 2, PSA 66.38, QED 0.65
Compound (SMILES): CC1C(=O)N(C)CCN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: OJGOVIODTPNPDG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73