lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc2c(=O)[nH]c(-c3ccc([C@](C)(O)CO)cc3)cn12
InChIKey: AOMPHWKJTUPEOB-QGZVFWFLSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 604 nM (pChEMBL 6.21999979019165)
Descriptors: MW 298.34, ALogP 1.8, HBA 4, HBD 3, PSA 77.73, QED 0.69
Compound (SMILES): Cc1cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n([C@@H]2CCC[C@@]2(C)O)c1=O
InChIKey: APLCQEOLIQVWQN-OXQOHEQNSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 435.55, ALogP 1.41, HBA 8, HBD 2, PSA 117.42, QED 0.75
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4ccc(OC)c(OC)c4)cs3)cs2)cc(OC)c1
InChIKey: UUPDTTCIJXOSCQ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 83753 nM (pChEMBL 4.079999923706055)
Descriptors: MW 455.56, ALogP 5.71, HBA 9, HBD 1, PSA 74.73, QED 0.36
Compound (SMILES): CC1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: VEWDWCKHTFNUTA-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta 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 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 479.43, ALogP 6.16, HBA 5, HBD 1, PSA 62.66, QED 0.44
Compound (SMILES): COc1cccc(S(=O)(=O)n2ccc3cnc(Nc4ccc(N5C[C@@H](C)N[C@@H](C)C5)cc4)nc32)c1
InChIKey: GLRBJDQXLPBXND-HDICACEKSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using TK as substrate incubated for 1 hr in presence of biotin/ATP by HTRF assay
Measurement: IC50 = 46.7 nM (pChEMBL 7.329999923706055)
Descriptors: MW 492.61, ALogP 3.61, HBA 9, HBD 2, PSA 101.38, QED 0.42
Compound (SMILES): CCOC(=O)c1cnc(Nc2ccc(N3CCN(C)CC3)cc2OC)nc1-c1cn(C)c2ccccc12
InChIKey: LOYONFSMCYGINB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/C797S mutant (unknown origin) using TK-substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 20 mins by HTRF assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 500.6, ALogP 4.32, HBA 9, HBD 1, PSA 84.75, QED 0.38
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(Cl)c3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: RWBHBQMJZIBEBQ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 432.89, ALogP 5.73, HBA 4, HBD 3, PSA 82.28, QED 0.33
Compound (SMILES): COc1ccc(/C=c2\c(=O)[nH]n3c(=O)c4ccccc4nc23)cc1
InChIKey: QNBMVIAVMRUVAY-UVTDQMKNSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human COX-1 using acetylcholinesterase as substrate preincubated for 10 mins followed by substrate addition and measured after 30 sec by Ellman's method
Measurement: IC50 = 1485 nM (pChEMBL 5.829999923706055)
Descriptors: MW 319.32, ALogP 1.09, HBA 5, HBD 1, PSA 76.46, QED 0.6
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCc5ccccn5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: NJQGZXLJDWIJDQ-MASCHLQQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 416.61, ALogP 5.98, HBA 3, HBD 0, PSA 25.36, QED 0.61
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(OC(F)(F)F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: PHEGERKTBZOREL-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 442.4, ALogP 4.64, HBA 5, HBD 2, PSA 93.21, QED 0.58
Compound (SMILES): O=C(OCCCN1CCN(c2ccncc2)CC1)c1cc2ccccc2o1
InChIKey: LHUNAHOZEVLINA-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Binding affinity to human H3 receptor assessed as inhibition constant incubated for 90 mins by scintillation counting method
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 365.43, ALogP 3.2, HBA 6, HBD 0, PSA 58.81, QED 0.49
Compound (SMILES): COCCn1cc(-c2n[nH]c3cnc(N4C5CCC4C(=O)N(C)C5)nc23)cn1
InChIKey: AVXYKYUDFKFQSI-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 382.43, ALogP 0.67, HBA 8, HBD 1, PSA 105.06, QED 0.69
Compound (SMILES): Cc1sc(-c2csc(Nc3ccc(N4CCOCC4)cc3)n2)nc1-c1ccncc1
InChIKey: XASYLEIOLRXCJP-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 1257 nM (pChEMBL 5.900000095367432)
Descriptors: MW 435.58, ALogP 5.22, HBA 8, HBD 1, PSA 63.17, QED 0.46
Compound (SMILES): COc1ccc(S(=O)(=O)N(c2c(C)cc(-c3cccc(C(F)(F)F)c3)cc2C(=O)NO)N(C)C)cc1
InChIKey: IPKOKUIXGDZGRK-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin)
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 523.53, ALogP 4.48, HBA 6, HBD 2, PSA 99.18, QED 0.35
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCN(C)Cc1ccc(O)cc1
InChIKey: VSDNNQHHKUMUKF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 450.62, ALogP 6.42, HBA 5, HBD 1, PSA 54.7, QED 0.21
Compound (SMILES): NC[C@@H](NC(=O)c1ccc(-c2ccncc2)cc1)c1ccccc1
InChIKey: MLGGUGPIWDHBAI-LJQANCHMSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Inhibition of PRKG1 (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 317.39, ALogP 3.18, HBA 3, HBD 2, PSA 68.01, QED 0.76
Compound (SMILES): O=C(CCCCCCNCc1ccc2ccccc2c1)NO
InChIKey: ZTHTYSUCXALYGC-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 300.4, ALogP 3.39, HBA 3, HBD 3, PSA 61.36, QED 0.38
Compound (SMILES): Cc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: WUECJPFZZOZFNC-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 54.5 nM (pChEMBL 7.260000228881836)
Descriptors: MW 431.47, ALogP 2.56, HBA 7, HBD 1, PSA 132.84, QED 0.58
Compound (SMILES): CC(C)(C)c1ccc(-c2ccncc2NC(=O)c2ccnc(NC(=O)C3CC3)c2)cc1
InChIKey: VCAIGCKZZLIJFZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 414.51, ALogP 5.04, HBA 4, HBD 2, PSA 83.98, QED 0.61
Compound (SMILES): N#Cc1[nH]c2ccccc2c1CN1CCN(c2ccccc2)CC1
InChIKey: GEVFMRRCRSTMJH-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-spiperone from human D4 receptor expressed in CHO cells assessed as inhibition constant
Measurement: Ki = 0.76 nM (pChEMBL 9.119999885559082)
Descriptors: MW 316.41, ALogP 3.36, HBA 3, HBD 1, PSA 46.06, QED 0.81
Compound (SMILES): N#C/C(=C/c1cccc(-c2ncnc3[nH]ccc23)c1)C(N)=O
InChIKey: PBACTZXZNFJQGT-GHXNOFRVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) incubated for 45 mins by LC-MS/MS analysis
Measurement: IC50 = 55.9 nM (pChEMBL 7.25)
Descriptors: MW 289.3, ALogP 2.02, HBA 4, HBD 2, PSA 108.45, QED 0.57
Compound (SMILES): C[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KPLTXOWOJNWKCJ-AWEZNQCLSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human 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 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): C[C@@H]1CCN(c2ccc(C#N)cn2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
InChIKey: RJQGZZJLHCOKLX-WBMJQRKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 373.42, ALogP 2.56, HBA 6, HBD 2, PSA 106.39, QED 0.56
Compound (SMILES): Fc1cccc(Nc2nc(-c3nccs3)cs2)c1
InChIKey: IALVPYOIIOBVIK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 249.2 nM (pChEMBL 6.599999904632568)
Descriptors: MW 277.35, ALogP 4.15, HBA 5, HBD 1, PSA 37.81, QED 0.78
Compound (SMILES): O=C(Nc1ccccc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: PNZZNNLKSKJYFE-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 297.36, ALogP 2.75, HBA 3, HBD 2, PSA 55.81, QED 0.9
Compound (SMILES): CC(C)N1C[C@H](C)[C@H](NC(=O)c2cc3ccc(Br)cc3[nH]2)C1
InChIKey: LOSOPIVYJSAUGK-MEDUHNTESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-methylspiperone from D4 (unknown origin) receptor expressed in HEK293T cells assessed as inhibition constant
Measurement: Ki = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 364.29, ALogP 3.39, HBA 2, HBD 2, PSA 48.13, QED 0.88
Compound (SMILES): Nc1ccc(/N=N/c2ccc(/C=C/c3ccc(/N=N/c4ccc(N)c5ccccc45)cc3S(=O)(=O)O)c(S(=O)(=O)O)c2)c2ccccc12
InChIKey: BEOHKTZPLVXCFG-NKPXSSHVSA-N
Target: Sentrin-specific protease 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC62
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 678.75, ALogP 8.65, HBA 10, HBD 4, PSA 210.22, QED 0.05
Compound (SMILES): COc1ccc(-c2nc(N3CCOCC3)c3sc(CN(C)c4ccc(C(=O)NO)cc4)cc3n2)cn1
InChIKey: ZPDSADGKXLOVPB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta by ADP-Glo luminescent kinase assay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 506.59, ALogP 3.35, HBA 10, HBD 2, PSA 112.94, QED 0.29
Compound (SMILES): Cc1cnc(NC(=O)N[C@@H]2CCCN(c3ccc(-c4ccccc4NS(C)(=O)=O)cc3F)C2=O)cn1
InChIKey: LPEZWOPFRXAYNB-HXUWFJFHSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays: A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 flurorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 512.57, ALogP 3.28, HBA 6, HBD 3, PSA 133.39, QED 0.46
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)N(C(=O)c1ccco1)CCC2
InChIKey: KXCBTFVHUFFVNM-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 460.94, ALogP 4.64, HBA 5, HBD 1, PSA 88.85, QED 0.6
Compound (SMILES): O=C1NC(=O)C(=NNc2cccc(-c3nc4ccccc4[nH]3)c2)C(=O)N1
InChIKey: FHKZZINQCMHAGZ-UHFFFAOYSA-N
Target: Phospholipase A2, membrane associated (SINGLE PROTEIN), Homo sapiens
UniProt: P14555
Assay: Inhibition of recombinant human sPLA2-V
Measurement: IC50 = 7510 nM (pChEMBL 5.119999885559082)
Descriptors: MW 348.32, ALogP 1.36, HBA 6, HBD 4, PSA 128.34, QED 0.53
Compound (SMILES): Cc1c(C(=O)N[C@@H](CCC2CC2)C(=O)Nc2ccc(C#N)cc2)[nH]c2c1C(=O)CC(C)(C)C2
InChIKey: OWORSODZTADOQX-IBGZPJMESA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Binding affinity to G9a (unknown origin) assessed as dissociation constant by SPR analysis
Measurement: Kd = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 446.55, ALogP 4.28, HBA 4, HBD 3, PSA 114.85, QED 0.59
Compound (SMILES): CC(O)(CC#Cc1ccccc1)c1cc(C(=O)N2Cc3ccccc3C2)ccc1O
InChIKey: MHSIPJGKEHUWFL-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Binding affinity to Grp94 (unknown origin) incubated for 24 hrs by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 397.47, ALogP 4.2, HBA 3, HBD 2, PSA 60.77, QED 0.65
Compound (SMILES): CC1(C)CCN(Cc2ccc(C(=O)NC[C@]3(O)CCCN(c4cc(NCc5ccccc5)ncn4)C3)c(O)c2)CC1
InChIKey: PWYRDVXYAOGDNK-JGCGQSQUSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9HCE5
Assay: Inhibition of recombinant METTL3 (354 to 580 residues)/METTL14 (106 to 396 residues) (unknown origin) using m6A oligonucleotide as substrate by HTRF assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 558.73, ALogP 4.18, HBA 8, HBD 4, PSA 113.85, QED 0.31
Compound (SMILES): CCOc1ccc(S(=O)(=O)Nc2ccccc2C#Cc2ccc(C(=O)O)nc2)c2ncccc12
InChIKey: ZGUSMMUTIWZXMZ-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Binding affinity to full-length C-terminal GFP-tagged human MCT4 incubated for 1 hrs by fluorescence cross-correlation spectroscopy analysis
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 473.51, ALogP 3.93, HBA 6, HBD 2, PSA 118.48, QED 0.41
Compound (SMILES): C[C@@H]1Cc2cc(OCCCN3CCCC3)ccc2[C@H]2CC[C@]3(C)[C@@H](N4CCCC4)CC[C@H]3[C@H]12
InChIKey: SORNPDADRIGIFO-LSVBPWPTSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 450.71, ALogP 6.12, HBA 3, HBD 0, PSA 15.71, QED 0.49
Compound (SMILES): Fc1ccc(Nc2nc(-c3nccs3)cs2)cc1
InChIKey: JKLORPQQXDJLFW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 303.5 nM (pChEMBL 6.519999980926514)
Descriptors: MW 277.35, ALogP 4.15, HBA 5, HBD 1, PSA 37.81, QED 0.78
Compound (SMILES): O=C(Cc1ccc(Cl)cc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: ZVWPAJGWVHTYOY-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 330.82, ALogP 2.94, HBA 3, HBD 1, PSA 43.78, QED 0.94
Compound (SMILES): CC(C)C[C@@H](NC(=O)C1(C(F)(F)F)CCCCC1)C(=O)Nc1nnc(Cc2ccc(C#N)cc2)s1
InChIKey: LXRBPWHQMGKMRT-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 21 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK80
Assay: Binding affinity to recombinant human N-terminal His6-tagged USP21 (209 to 563 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by SPR analysis
Measurement: Kd = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 507.58, ALogP 4.98, HBA 6, HBD 2, PSA 107.77, QED 0.52
Compound (SMILES): Cc1onc(-c2ccccc2)c1C=CCCCCCNC(=O)C(C)(C)S
InChIKey: ZGHBHVXMFJZHBU-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 372.53, ALogP 5.05, HBA 4, HBD 2, PSA 55.13, QED 0.48
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(N)c(C(=O)NCc3cccnc3)cc21
InChIKey: PKTAJMUNQBHIIP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 362.39, ALogP 1.58, HBA 7, HBD 2, PSA 107.31, QED 0.54
Compound (SMILES): CC(C)(O)C#Cc1ccc2[nH]nc(-c3ccnc(N)n3)c2c1
InChIKey: YYDZERROCWRVDT-UHFFFAOYSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay
Measurement: IC50 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 293.33, ALogP 1.72, HBA 5, HBD 3, PSA 100.71, QED 0.59
Compound (SMILES): C#CCCCCCN1CCC(COC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1
InChIKey: IJPOIHRHFSVJOM-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 474.98, ALogP 6.74, HBA 3, HBD 1, PSA 41.57, QED 0.32
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(OC)c2)c2cc(C)[nH]c2c1=O
InChIKey: AVBQIZYXLUVYRI-SNAWJCMRSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 17400 nM (pChEMBL 4.760000228881836)
Descriptors: MW 421.5, ALogP 3.36, HBA 5, HBD 1, PSA 76.56, QED 0.64
Compound (SMILES): CC(C)(O)c1ccc(-c2cn3cccc3c(=O)[nH]2)cc1
InChIKey: WADUGMWGTNMWRD-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 268.32, ALogP 2.52, HBA 3, HBD 2, PSA 57.5, QED 0.75
Compound (SMILES): O=C(COc1ccccc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: SOKWAQDMVUMRKD-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 312.37, ALogP 2.12, HBA 4, HBD 1, PSA 53.01, QED 0.94
Compound (SMILES): CCc1c(F)ccc2cc(O)cc(-c3ncc4c(N5CCCC6(CCO6)C5)nc(OC[C@@]56CCCN5C[C@H](F)C6)nc4c3F)c12
InChIKey: IUFLRSMAQREKRN-UIICDIJFSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human ASPC1 cells assessed as reduction in ERK1/2 phosphorylation level incubated for 2 hrs by MSD assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 619.69, ALogP 6.11, HBA 8, HBD 1, PSA 83.84, QED 0.28
Compound (SMILES): COc1nc2ccc([C@](O)(c3ccc(C)nc3C)c3cnnn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
InChIKey: HVSWHSCHDKSPHW-NDEPHWFRSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibition of human RORgammmat LBD expressed in HEK293T by two-hybrid reporter assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 568, ALogP 5.93, HBA 7, HBD 1, PSA 85.95, QED 0.27
Compound (SMILES): CC(C)n1cc(C(=O)NC2CCOCC2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: DJHWPKSBDIEQGY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 peptide as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 550.65, ALogP 3.26, HBA 11, HBD 2, PSA 145.92, QED 0.34
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)c(Cc1cccc(C(F)(F)F)c1)cn2CCCCCCC(=O)NO
InChIKey: ZEWRQBNFEANYQN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 using human HeLa cell nuclear extract at 1 uM measured after 60 mins by fluorescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 513.56, ALogP 6.98, HBA 5, HBD 2, PSA 80.29, QED 0.14
Compound (SMILES): COCCCN1CCC(c2nnc(-c3nn(C(C)C)c4ccccc34)o2)CC1.O=C(O)C(=O)O
InChIKey: XHXCJKNEBFAUSE-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 2 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 383.5, ALogP 3.88, HBA 7, HBD 0, PSA 69.21, QED 0.58
Compound (SMILES): C[C@H]1CN(C2COC2)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: XQGSCOPKLHKANW-AWEZNQCLSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 24.4 nM (pChEMBL 7.610000133514404)
Descriptors: MW 643.05, ALogP 2.08, HBA 11, HBD 3, PSA 160.84, QED 0.27
Compound (SMILES): Cc1ncn(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(C(F)(F)F)nc3)C[C@H]2CCO)n1
InChIKey: FDZFVXKCJKOSRC-CYBMUJFWSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Mus musculus
UniProt: O88410
Assay: Antagonist activity at mouse CXCR3-mediated chemotaxis expressed in CD3/CD28-activated primary mouse T cells assessed as inhibition of CXCLI1 mediated cell migration incubated for 45 mins by Boyden chamber assay
Measurement: IC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 550.49, ALogP 2.64, HBA 10, HBD 1, PSA 113.16, QED 0.47
Compound (SMILES): O=C(CCCCCCNCc1ccc(-c2ccccc2)s1)NO
InChIKey: SGDSORAAJXVVRX-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 332.47, ALogP 3.96, HBA 4, HBD 3, PSA 61.36, QED 0.35
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(C(N)=O)c(O)c(F)c3F)c3c(=O)n4c(nc32)CCC4)c(Cl)c(F)n1
InChIKey: LGAFZGSECXDYIR-ZDUSSCGKSA-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 645.04, ALogP 2.86, HBA 10, HBD 3, PSA 151.61, QED 0.27
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)Cn2nnnc2N1C
InChIKey: XFCIWMKGBAWFGT-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of N-terminal GST-fused human LRRK2 G2019S mutant using fluorescein-labeled LRRKtide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 310.32, ALogP 0.91, HBA 7, HBD 2, PSA 104.62, QED 0.73
Compound (SMILES): O=C(c1ccc2c(c1)OCCO2)C1CCN(c2ncnc3sccc23)CC1
InChIKey: UJJCDSDROQBQQE-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Inhibition of GST/His-tagged human recombinant DDR2 N456S mutant (422 to 855 residues) expressed in baculovirus expression system
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 381.46, ALogP 3.56, HBA 7, HBD 0, PSA 64.55, QED 0.65
Compound (SMILES): CCN1CCN(Cc2cccc3ccccc23)[C@@H](CCO)C1
InChIKey: FDUWKETXXFSWBN-SFHVURJKSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Binding affinity to sigma 1 receptor (unknown origin) expressed in human RPMI-8226 cells
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 298.43, ALogP 2.73, HBA 3, HBD 1, PSA 26.71, QED 0.92
Compound (SMILES): CCN(c1ccc(C(=O)O)cc1)c1ccc(C(C)C)c(OC(C)C)c1
InChIKey: NHPGPVYPYBWTBU-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Inhibition of RXRgamma (unknown origin)
Measurement: EC50 = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 341.45, ALogP 5.45, HBA 3, HBD 1, PSA 49.77, QED 0.73
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3cnccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: XCAXLCSQKKQKHA-PMACEKPBSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of MAP4K2 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 242 nM (pChEMBL 6.619999885559082)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2N=C(c3ccc(F)cc3)CC2c2ccccc2)cc1
InChIKey: ZZKBTLUZRLLDBE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9
Measurement: Ki = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 423.47, ALogP 3.46, HBA 4, HBD 1, PSA 92.83, QED 0.7
Compound (SMILES): C=CC1(C=C)Oc2c(NC(=O)Nc3ccc(C)cc3)cc(-c3ccccc3-c3nn[nH]n3)cc2[C@@H]1c1ccccc1
InChIKey: ZHVHMEOMIDRYBQ-LJAQVGFWSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 540.63, ALogP 7.12, HBA 5, HBD 3, PSA 104.82, QED 0.19
Compound (SMILES): N#C[C@@H]1C[C@H]2[C@H](CC2(F)F)N1C(=O)[C@@H](N)C12CC3CC(CC(O)(C3)C1)C2
InChIKey: BHPATRIWBRAYHP-GBFWRCQXSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of DPP-9 (unknown origin)
Measurement: IC50 = 1660 nM (pChEMBL 5.78000020980835)
Descriptors: MW 365.42, ALogP 1.79, HBA 4, HBD 2, PSA 90.35, QED 0.78
Compound (SMILES): CN(C)CC(=O)Nc1cc(Nc2ncc(F)c(Nc3c(F)cccc3F)n2)ccc1F
InChIKey: VMZGYYCCAWUCHJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 434.4, ALogP 4.02, HBA 6, HBD 3, PSA 82.18, QED 0.49
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@@H](CC(C)C)C2)c1
InChIKey: IQGGLJZCPWVYHD-NRFANRHFSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta 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 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 505.61, ALogP 5.99, HBA 5, HBD 1, PSA 56.67, QED 0.43
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)C[C@@H]2C)c1
InChIKey: HUAKZZAZJGNQFD-HNNXBMFYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human 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 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): O=C(CCc1cccs1)N1CCN(c2ccc(O)cn2)CC1
InChIKey: ZQZACIKLLIUJCK-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 317.41, ALogP 2.13, HBA 5, HBD 1, PSA 56.67, QED 0.94
Compound (SMILES): CC(C)(O)C12CC(C1)N(c1cc(-n3ncc4ccc(-c5ccn[nH]5)cc43)ncn1)C2
InChIKey: VGHHZMPDXMQZDE-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 in human PBMCs assessed as reduction in Ser95 phosphorylation
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 401.47, ALogP 2.95, HBA 7, HBD 2, PSA 95.75, QED 0.55
Compound (SMILES): O=C(c1cccnc1Oc1cccc(C(F)(F)F)c1)N1CCCc2ccccc21
InChIKey: ARQDIVACZSGTEC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 398.38, ALogP 5.49, HBA 3, HBD 0, PSA 42.43, QED 0.59
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3ccc4ccccc4c3)ccc21
InChIKey: DFEFXHCMMQBARM-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 2080 nM (pChEMBL 5.679999828338623)
Descriptors: MW 432.5, ALogP 4.83, HBA 4, HBD 1, PSA 79.62, QED 0.5
Compound (SMILES): CNc1ccc(NC(=O)c2nnn(-c3cc(OC)ccc3OC)c2C)cc1C(C)(C)C
InChIKey: DGNSIKFPHNMBML-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 14100 nM (pChEMBL 4.849999904632568)
Descriptors: MW 423.52, ALogP 4.18, HBA 7, HBD 2, PSA 90.3, QED 0.62
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(C(=O)Nc2ccc(-c3ncn(C4CC4)n3)cc2)c1OC
InChIKey: UKJLHSUFJRYTMJ-FIBGUPNXSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/3 dependent IL-2 stimulated STAT5 phosphorylation in CD3-positive T cells (unknown origin)
Measurement: IC50 = 972 nM (pChEMBL 6.010000228881836)
Descriptors: MW 567.61, ALogP 3.78, HBA 10, HBD 4, PSA 165.05, QED 0.22
Compound (SMILES): CCc1cccc2cc(O)cc(-c3ncc4c(N5CCCC6(CCO6)C5)nc(OC[C@@]56CCCN5C[C@H](F)C6)nc4c3F)c12
InChIKey: NNBQBCOFWYNOFV-LZZYYUTMSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human ASPC1 cells assessed as reduction in ERK1/2 phosphorylation level incubated for 2 hrs by MSD assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 601.7, ALogP 5.97, HBA 8, HBD 1, PSA 83.84, QED 0.29
Compound (SMILES): c1cn(-c2ccc(Nc3nc(-c4nccs4)cs3)cc2)cn1
InChIKey: XWXSDNPGIFGIES-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 0.125 nM (pChEMBL 9.899999618530273)
Descriptors: MW 325.42, ALogP 4.2, HBA 7, HBD 1, PSA 55.63, QED 0.61
Compound (SMILES): NS(=O)(=O)c1nccc(-c2ccc(CO)cc2)c1-c1nn[nH]n1
InChIKey: ZLLPEJMJTQBWDI-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 332.35, ALogP 0.07, HBA 7, HBD 3, PSA 147.74, QED 0.61
Compound (SMILES): Cc1csc(OC[C@@H]2CN(Cc3ccc4c(cnn4C)c3)CCO2)n1
InChIKey: TZQHMBLLYPEOFM-INIZCTEOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 557 nM (pChEMBL 6.25)
Descriptors: MW 358.47, ALogP 2.62, HBA 7, HBD 0, PSA 52.41, QED 0.7
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)CCc3cccc(Cl)c3)nc2C2(CCCCC2)C1(C)C
InChIKey: PRNNNUJEBJXVGU-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 440.98, ALogP 5.05, HBA 4, HBD 1, PSA 75.19, QED 0.72
Compound (SMILES): CCCCCn1c(-c2ccc(NC(=O)Cc3ccc(S(=O)(=O)CC)cc3)cc2)nc2ccc(C)cc21
InChIKey: GBDJRIWHDOPRIC-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Inverse agonist activity at human GAL4-fused LXRalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 503.67, ALogP 6.18, HBA 5, HBD 1, PSA 81.06, QED 0.26
Compound (SMILES): Cc1cc(C(F)(F)F)nc(Nc2ccccc2-c2nnn[nH]2)n1
InChIKey: XXKGCSWBGJTTJM-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]methylspiperone from human D3 receptor stably expressed in HEK293T cells by Cheng-Prusoff equation analysis
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 321.27, ALogP 2.73, HBA 6, HBD 2, PSA 92.27, QED 0.77
Compound (SMILES): c1ccc(CCN2CCN(c3ncnc4c3[nH]c3ccccc34)CC2)cc1
InChIKey: WSQDGWOFRGACTF-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) expressed in dog MDCK-II cells using pheophorbide A as substrate preincubated for 20 mins followed by substrate addition and measured after 120 mins by flow cytometry analysis
Measurement: IC50 = 839 nM (pChEMBL 6.079999923706055)
Descriptors: MW 357.46, ALogP 3.48, HBA 4, HBD 1, PSA 48.05, QED 0.61
Compound (SMILES): COC1=CC2C(=O)NC3=Cc4ccc(OC)cc4C(=C1OC)C32
InChIKey: CGRDYMCBGXJNLR-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 311.34, ALogP 2.31, HBA 4, HBD 1, PSA 56.79, QED 0.93
Compound (SMILES): Cc1csc2c(=O)[nH]c(-c3ccc(C(C)(C)O)cc3)nc12
InChIKey: ZJHLKLRWORVGKO-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 300.38, ALogP 3.19, HBA 4, HBD 2, PSA 65.98, QED 0.76
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3ccc(-c4ccc5[nH]ccc5c4)nn3)C3CCN2CC3)c1
InChIKey: ALGQHHHCUISTSF-NOZRDPDXSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Binding affinity to alpha3beta4 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 1210 nM (pChEMBL 5.920000076293945)
Descriptors: MW 411.51, ALogP 4.1, HBA 5, HBD 1, PSA 66.93, QED 0.54
Compound (SMILES): CC(C)CN(c1ccc(C(=O)O)c(O)c1)S(=O)(=O)c1ccc(-c2ccccc2)cc1
InChIKey: GESPQVXZLMHYFH-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 10781 nM (pChEMBL 4.96999979019165)
Descriptors: MW 425.51, ALogP 4.61, HBA 4, HBD 2, PSA 94.91, QED 0.58
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2ccc(Cl)c(C(=O)N(C)C)c2)c1=O
InChIKey: CQDKWYPGWAEELX-QGZVFWFLSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of human recombinant DPP-9
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 457.96, ALogP 1.36, HBA 7, HBD 1, PSA 93.57, QED 0.68
Compound (SMILES): O=[N+]([O-])C1=Cc2cc(Cl)ccc2OC1C(F)(F)F
InChIKey: MZKIMVRXOFRAQO-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to dopamine 3 receptor (unknown origin)
Measurement: Ki = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 279.6, ALogP 3.28, HBA 3, HBD 0, PSA 52.37, QED 0.59
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(NC)c(C(=O)NCc3cccnc3)cc21
InChIKey: RQPADNQUANMUPN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 = 4890 nM (pChEMBL 5.309999942779541)
Descriptors: MW 376.42, ALogP 2.04, HBA 7, HBD 2, PSA 93.32, QED 0.56
Compound (SMILES): CCOC(=O)Oc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: LGYAXXBEAXZUNZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-fused JAK1 (866 to 1154 residues)(unknown origin) using FITC-Ahr-KKSRGDYMTMQIG-NH2 peptide as substrate incubated for 30 mins in presence of ATP by caliper microfluidic mobility shift assay
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 427.85, ALogP 4.25, HBA 8, HBD 3, PSA 128.46, QED 0.48