lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(Cl)cc1F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: IOLLWTLQKNSFOR-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 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 410.84, ALogP 4.54, HBA 4, HBD 2, PSA 83.98, QED 0.65
Compound (SMILES): COc1ccc2c(c1)C/C(=C\c1ccc(Br)o1)C2=O
InChIKey: UJKXUNOFSDTDGU-CSKARUKUSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 319.15, ALogP 3.87, HBA 3, HBD 0, PSA 39.44, QED 0.79
Compound (SMILES): O=C1CC2Cc3ccsc3C2=NN1CCCCCCCN1CCN(Cc2cccc3c2ccn3S(=O)(=O)c2ccccc2)CC1
InChIKey: UHZOUSUGNFTACG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis
Measurement: Ki = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 643.88, ALogP 5.82, HBA 8, HBD 0, PSA 78.22, QED 0.18
Compound (SMILES): O=C(NO)c1cn(C2CCN(C(=O)Cc3ccc4ccccc4c3)CC2)nn1
InChIKey: VDICYJQVOFOYHC-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 379.42, ALogP 1.96, HBA 6, HBD 2, PSA 100.35, QED 0.53
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@]1(C)Cc2c([nH]c3ccccc23)CN([C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C1=O
InChIKey: TVDHJWHHMJAOCK-QOSLDAFVSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Inhibition of human somatostatin receptor type 3
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 647.78, ALogP 0.52, HBA 7, HBD 7, PSA 212.74, QED 0.12
Compound (SMILES): CCOc1ccc(F)c(N2CC[C@@H](Oc3ccc(N4C[C@H](OCCCOC)[C@@H](C)[C@@H]4CC(=O)O)cc3)[C@H](C)C2)c1
InChIKey: NZLOVHNRCBOONY-FTYUDISHSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q76JU9
Assay: Positive allosteric modulation of mouse GPR40
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 558.69, ALogP 5.24, HBA 7, HBD 1, PSA 80.7, QED 0.33
Compound (SMILES): Cn1c2ccccc2c2cc[n+](-c3ccc(Cl)cc3)cc21
InChIKey: AYDVADIGEZQAHF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE (unknown origin)
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 293.78, ALogP 4.26, HBA 1, HBD 0, PSA 8.81, QED 0.46
Compound (SMILES): C[C@H]1CCC[C@H]1n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: ZUVPRDWNBVOFCM-XJKSGUPXSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (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 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 405.52, ALogP 1.99, HBA 7, HBD 1, PSA 97.19, QED 0.84
Compound (SMILES): CC1=CC(C)=[N+]2C1=C(c1ccc(OCCn3cc(CCCCOc4cc(C(=O)O)nc5c(C)c6nc(C(=O)O)cc(O)c6cc45)nn3)cc1)c1nc(C)cn1[B-]2(F)F
InChIKey: OZMINXGQAXYZSF-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Agonist activity at GPR-35 in human HT-29 cells assessed as desensitization of zaprinast induced DMR response incubated for 1 hr followed by zaprinast stimulation in presence of ML-145
Measurement: IC50 = 542.2 nM (pChEMBL 6.269999980926514)
Descriptors: MW 790.59
Compound (SMILES): CC(=O)C1CCN(CCCOc2ccc3c(c2)CC[C@@H]2[C@@H]3CC[C@]3(C)[C@@H](N4CCCC4)CC[C@@H]23)CC1
InChIKey: JZHDMAKZPRQFAR-KQLGDFJMSA-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 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 492.75, ALogP 6.08, HBA 4, HBD 0, PSA 32.78, QED 0.43
Compound (SMILES): Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc(-c2ccccc2)c1C(=O)NC1CCCCC1
InChIKey: YOHLTWMPXNQOAA-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 2290.87 nM (pChEMBL 5.639999866485596)
Descriptors: MW 554.57, ALogP 6.21, HBA 5, HBD 1, PSA 53.4, QED 0.36
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H]2CCC(=O)N2)C(=O)N1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: HLUXTGTURXBMGU-DCBLBBIQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 1090.35
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(OC)c1
InChIKey: GUUQXMDBAHSFGF-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TrkA (unknown origin) in presence of ATP
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 366.4, ALogP 2.89, HBA 6, HBD 2, PSA 80.65, QED 0.57
Compound (SMILES): COc1ccc2c(c1)CN(c1nccc(Nc3ccc(-c4ccncc4)cc3)n1)C2
InChIKey: IWWPOKDCCFPYFJ-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Rho-kinase inhibition assay for ROC2 and ROCK1: Dose response curves for Rho-kinase inhibition were derived from a Invitrogen Z′-LYTE Kinase Assay Kit (Invitrogen catalog number PV3793). Purified active ROCK1 and ROCK2 were obtained from Invitrogen (catalog numbers ROCK1, PV3691 and ROCK2, PV3759). The kit components include a coumarin and fluorescein labeled peptide based on myosin light chain 2 (KKRPQRRYSNVF), a proprietary protease containing development reagent and a proprietary Stop buffer used to terminate the development reaction. The inhibitory activities of compounds are measured according to the manufactures protocol. Briefly, decreasing concentrations of test compounds or the known ROCK inhibitor Y-27963, are added, from 10 uM to 2.56×10−5 uM to reaction buffer containing 50 mM HEPES pH 7.5, 10 mM MgCl2, 5 mM EGTA, and 0.05% Brij-35 and of ROCK1 at 0.18 ug/mL or ROCK2 at 0.8 ug/mL in assay dilution buffer. This mixture is overlayed into a white 96-well half area plate and the reaction is initiated with the addition of 5 uM ATP for ROCK1 or 12 uM ATP for ROCK2. The assay proceeds at room temperature for 1 hour followed by the addition of development reagent, and further incubation for 1 hour at room temperature. STOP reagent is then added and the reaction and immediately the coumarin and fluorescein emission signals are read on a Tecan Infinite M1000 fluorescence plate reader (excitation: 400 nm; emission 445 and 520 nm, respectively). By comparing the emission ratios of the test samples against control samples, percent phosphorylation values are calculated and the concentration of inhibitor that produces ½ inhibition of kinase activity (IC50) is determined using Prism. Table 1 provides IC50 concentrations for compounds of the above examples. Several of the compounds also demonstrated activity in a preliminary assay that measured inhibition of myosin light chain phosphorylation (pMLC). For compounds marked ND, activity was not determinable under the test conditions employed.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 395.47, ALogP 4.81, HBA 6, HBD 1, PSA 63.17, QED 0.52
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-KAYWLYCHSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: AVRXPWHNFRJKJJ-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 539.68, ALogP 5.04, HBA 9, HBD 2, PSA 101.1, QED 0.33
Compound (SMILES): COc1cc(/C=C2\SC(=O)N(CCNC(=O)Nc3c(C)n(C)n(-c4ccccc4)c3=O)C2=O)cc(OC)c1OC
InChIKey: FDSDNMJXILQXBF-QNGOZBTKSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) by ELISA assay
Measurement: IC50 = 344 nM (pChEMBL 6.460000038146973)
Descriptors: MW 567.62, ALogP 3.37, HBA 10, HBD 2, PSA 133.13, QED 0.38
Compound (SMILES): COc1ccc(S(=O)(=O)N(Cc2ccccc2)c2c(C(=O)NO)ccc3c(C(C)(C)C)cccc23)cc1
InChIKey: FOTKISDMFBTXGP-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of MMP-13 (unknown origin)
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 518.64, ALogP 5.66, HBA 5, HBD 2, PSA 95.94, QED 0.24
Compound (SMILES): Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc(-c2ccccc2)c1C(=O)NCc1ccccc1
InChIKey: RDAMHUJTGOWZOX-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 3467.37 nM (pChEMBL 5.460000038146973)
Descriptors: MW 562.55, ALogP 6.08, HBA 5, HBD 1, PSA 53.4, QED 0.27
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-IIBYNOLFSA-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 = 0.064 nM (pChEMBL 10.1899995803833)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): Cc1ccccc1CC(=O)N1CCC(O)(c2cccc(O)c2)C(CN(C)C)C1
InChIKey: PBDPQNYBBXZGBB-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 227.4 nM (pChEMBL 6.639999866485596)
Descriptors: MW 382.5, ALogP 2.54, HBA 4, HBD 2, PSA 64.01, QED 0.83
Compound (SMILES): CC(C)(O)c1ccc(-c2cn3c(CO)ccc3c(=O)[nH]2)cc1
InChIKey: XPFCXDCYIAOOBE-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 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 298.34, ALogP 2.01, HBA 4, HBD 3, PSA 77.73, QED 0.69
Compound (SMILES): Nc1cnc(-c2cc(N3C[C@@H]4C[C@H]3CO4)nc(N3CC4CC3C4)n2)cn1
InChIKey: XGFVOKJJQCQLJX-TYUFSLCMSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 1072 nM (pChEMBL 5.96999979019165)
Descriptors: MW 351.41, ALogP 1.09, HBA 8, HBD 1, PSA 93.29, QED 0.88
Compound (SMILES): Cc1onc(-c2ccccc2)c1/C=C/c1ccc(CNC(=O)C(C)S)cc1
InChIKey: DGOYOCWNRBRVGP-OUKQBFOZSA-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 378.5, ALogP 4.75, HBA 4, HBD 2, PSA 55.13, QED 0.61
Compound (SMILES): C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCCN4CCOCC4)cc23)c1
InChIKey: WBKHQQZRHCECKK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R mutant using 5-FAM-EEPLYWSFPAKKKCONH2 as substrate incubated for 30 mins in presence of ATP
Measurement: IC50 = 1.05 nM (pChEMBL 8.979999542236328)
Descriptors: MW 418.5, ALogP 3.46, HBA 7, HBD 1, PSA 68.74, QED 0.44
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)c1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: BBRIVIRAAPNZBF-JREFTJHFSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 1016.27
Compound (SMILES): CC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)SCCCCCNC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2c(sc(C)c2C)-n2c(C)nnc21
InChIKey: FNDFWBANYDEWBA-MVIMOGLESA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 BD1 domain (unknown origin)
Measurement: Kd = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 958.68, ALogP 7.2, HBA 13, HBD 4, PSA 183.8, QED 0.07
Compound (SMILES): Clc1cc(Cl)cc(Nc2nc(-c3nc(-c4ccccc4)cs3)cs2)c1
InChIKey: CNIUXHFXCOLCIK-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 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 404.35, ALogP 6.98, HBA 5, HBD 1, PSA 37.81, QED 0.4
Compound (SMILES): COc1ccc2c(c1)CN(c1nccc(Nc3ccc(-c4cn[nH]c4)cc3)n1)C2
InChIKey: QWVKCTINPBKQMS-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: ROCK1 and ROCK2 Compound Selectivity: Dose response curves for Rho-kinase inhibition were derived from a Invitrogen Z′-LYTE Kinase Assay Kit (Invitrogen catalog number PV3793). Purified active ROCK1 and ROCK2 were obtained from Invitrogen (catalog numbers ROCK1, PV3691 and ROCK2, PV3759). The kit components include a coumarin and fluorescein labeled peptide based on myosin light chain 2 (KKRPQRRYSNVF), a proprietary protease containing development reagent and a proprietary Stop buffer used to terminate the development reaction. The inhibitory activities of compounds are measured according to the manufactures protocol. Briefly, decreasing concentrations of test compounds or the known ROCK inhibitor Y-27963, are added, from 10 uM to 2.56×10−5 uM to reaction buffer containing 50 mM HEPES pH 7.5, 10 mM MgCl2, 5 mM EGTA, and 0.05% Brij-35 and of ROCK1 at 0.18 ug/mL or ROCK2 at 0.8 ug/mL in assay dilution buffer. This mixture is overlayed into a white 96-well half area plate and the reaction is initiated with the addition of 5 uM ATP for ROCK1 or 12 uM ATP for ROCK2. The assay proceeds at room temperature for 1 hour followed by the addition of development reagent, and further incubation for 1 hour at room temperature. STOP reagent is then added and the reaction and immediately the coumarin and fluorescein emission signals are read on a Tecan Infinite M1000 fluorescence plate reader (excitation: 400 nm; emission 445 and 520 nm, respectively). By comparing the emission ratios of the test samples against control samples, percent phosphorylation values are calculated and the concentration of inhibitor that produces ½ inhibition of kinase activity (IC50) is determined using Prism.
Measurement: IC50 = 7066 nM (pChEMBL 5.150000095367432)
Descriptors: MW 384.44, ALogP 4.14, HBA 6, HBD 2, PSA 78.96, QED 0.54
Compound (SMILES): COC(=O)/C=C/c1ccc(OCCCNc2cc3c([nH]c4ccccc43)c(-c3ccc(OC)cc3)n2)c(OC)c1
InChIKey: GYNSNDXSMWEHDL-MHWRWJLKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Boc-Lys (Ac)-AMC as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 537.62, ALogP 6.47, HBA 7, HBD 2, PSA 94.7, QED 0.11
Compound (SMILES): CC(C)CN(c1ccc(O)c(C(=O)O)c1)S(=O)(=O)c1ccc2ccccc2c1
InChIKey: QYLHXALODXJWDE-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 = 44636 nM (pChEMBL 4.349999904632568)
Descriptors: MW 399.47, ALogP 4.09, HBA 4, HBD 2, PSA 94.91, QED 0.65
Compound (SMILES): O=C(CCCCCCNCc1cc2ccccc2[nH]1)NO
InChIKey: KZPHOMXAZIKWEU-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 289.38, ALogP 2.71, HBA 3, HBD 4, PSA 77.15, QED 0.33
Compound (SMILES): CCN(CCCCCCCCCCCCn1cc(C=O)c2cc(OC)ccc21)Cc1cccc(O)c1
InChIKey: OESTWNDKVZPZBM-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 = 42490 nM (pChEMBL 4.369999885559082)
Descriptors: MW 492.7, ALogP 7.59, HBA 5, HBD 1, PSA 54.7, QED 0.15
Compound (SMILES): Cn1ncc2cc(CN3CCO[C@H](COc4ccc(F)c(F)c4)C3)ccc21
InChIKey: JAKIOOTWQGBKAJ-KRWDZBQOSA-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 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 373.4, ALogP 3.13, HBA 5, HBD 0, PSA 39.52, QED 0.69
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C12CCN(CC1)CC2)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: NBVPHNBDESFHFB-VWLOTQADSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3 expressed in baculovirus infected insect cells using FLUOR DE LYS-SIRT1 as fluorogenic substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by spectrophotometer based analysis
Measurement: IC50 < 3.5 nM (pChEMBL 8.456000328063965)
Descriptors: MW 518.66, ALogP 5.47, HBA 7, HBD 1, PSA 97.56, QED 0.32
Compound (SMILES): COc1cccc(CN2C(=O)CN(Cc3ccc(C(=O)NO)cc3)C(=O)[C@H]2Cc2ccccc2)c1
InChIKey: WPNBQZUEGUZARL-XMMPIXPASA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 473.53, ALogP 2.8, HBA 5, HBD 2, PSA 99.18, QED 0.39
Compound (SMILES): CC[C@H](C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: RDWYRIOEHIKPRE-INIZCTEOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/del (746 to 750 residues) mutant autophosphorylation in human PC-9/ER1 cells harboring harboring EGFR T790M/del (746 to 750 residues) mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 551.68, ALogP 3.35, HBA 12, HBD 2, PSA 143.95, QED 0.32
Compound (SMILES): Cc1n[nH]c2cc(N(C(=O)NCCCn3cncc3C)C3CCCCC3)ccc12
InChIKey: DWKOIVNSZJZOOM-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXS2
Assay: Inhibition of isoQC (unknown origin)
Measurement: IC50 = 106.1 nM (pChEMBL 6.96999979019165)
Descriptors: MW 394.52, ALogP 4.32, HBA 4, HBD 2, PSA 78.84, QED 0.61
Compound (SMILES): COc1ccc(S(=O)(=O)N(c2ccc3c(c2)CCCN3C(=O)c2ccco2)S(=O)(=O)c2ccc(OC)cc2)cc1
InChIKey: BWZWPDAHMTYUOQ-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 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 582.66, ALogP 4.47, HBA 8, HBD 0, PSA 123.43, QED 0.3
Compound (SMILES): CCC(=O)CNC(=O)Nc1nc2ccc(-c3oc4c(OC)c(O)c(O)c(OC)c4c(=O)c3O)cc2s1
InChIKey: MRGBLPQQHOOJIK-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 515.5, ALogP 3.3, HBA 11, HBD 5, PSA 180.45, QED 0.23
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc([N+](=O)[O-])c4)n3)cc2C(F)(F)F)CC1
InChIKey: QZAFKCISRNOJGA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis recombinant N-terminal His-tagged PknB (1 to 331 residues) expressed in Escherichia coli DH5alpha cells by microscale thermophoresis analysis
Measurement: Kd = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 458.44, ALogP 4.57, HBA 7, HBD 1, PSA 87.43, QED 0.44
Compound (SMILES): Cc1ccc(S(=O)(=O)N(c2ccc3c(c2)CCCN3C(=O)c2ccco2)S(=O)(=O)c2ccc(C)cc2)cc1
InChIKey: KWRQTKAOLXKOHO-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 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 550.66, ALogP 5.07, HBA 6, HBD 0, PSA 104.97, QED 0.33
Compound (SMILES): Cc1cn(-c2ccccc2F)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: OBHFQERJBPUJPO-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 346.38, ALogP 2.77, HBA 4, HBD 1, PSA 68.17, QED 0.79
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3ccc(Cl)c([N+](=O)[O-])c3)ccc21
InChIKey: WZTHHXBUGHRRQX-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 461.88, ALogP 4.24, HBA 6, HBD 1, PSA 122.76, QED 0.45
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
InChIKey: YQXARSVRDPJIEQ-RCJYHZQCSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.56, ALogP 4.43, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): O=C1c2ccccc2C(=O)N1c1nc2cc([N+](=O)[O-])ccc2n1Cc1ccc(-c2ccccc2)cc1
InChIKey: FMXPLCOPRJODRZ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 by EIA method
Measurement: IC50 = 9850 nM (pChEMBL 5.010000228881836)
Descriptors: MW 474.48, ALogP 5.46, HBA 6, HBD 0, PSA 98.34, QED 0.19
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccccc3F)cc2)nc2cnccc12)C(N)=O
InChIKey: UAFHHPALEOOBTA-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 425.47, ALogP 4.65, HBA 5, HBD 2, PSA 104.69, QED 0.47
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(C(F)(F)F)c(Nc4ccc5[nH]ccc5c4)n3)cc2)CC1
InChIKey: MSQGPWMOQMTFAA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) expressed in baculovirus expression system by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.5, ALogP 5.22, HBA 6, HBD 3, PSA 72.11, QED 0.37
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(C)(C)O)cc2OC)c2cc[nH]c2c1=O
InChIKey: GVJYOLRRZZUUOE-AATRIKPKSA-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 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 352.43, ALogP 3.81, HBA 4, HBD 2, PSA 67.25, QED 0.69
Compound (SMILES): COc1cccc(Cl)c1NCc1cc(=O)n2nc(-c3ccccc3)nc2[nH]1
InChIKey: PEPOAHRJJMETTF-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Displacement of BODIPY 500/510 C4 from human FABP3 expressed in Escherichia coli incubated for 30 mins by FP assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 381.82, ALogP 3.36, HBA 6, HBD 2, PSA 84.31, QED 0.55
Compound (SMILES): CCCCc1ccc(S(=O)(=O)Nc2ccc3c(c2)CCCN3C(=O)c2ccco2)cc1
InChIKey: HLMMTQCQDCOGLJ-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 = 3690 nM (pChEMBL 5.429999828338623)
Descriptors: MW 438.55, ALogP 5.02, HBA 4, HBD 1, PSA 79.62, QED 0.56
Compound (SMILES): COc1ccc(-c2ccc(Oc3ccccc3C(C)(C)C)c(NC(=O)Nc3ccccc3F)c2)cc1C(=O)O
InChIKey: XAJOXNWLUKPUDW-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR (unknown origin)
Measurement: EC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 528.58, ALogP 7.93, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): COc1ccc(-c2ccc3nc(C)c(-c4cnc(N)c(C(F)(F)F)c4)n3n2)cc1OC
InChIKey: ZMTTVTGSKOFZGH-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)
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 429.4, ALogP 4.38, HBA 7, HBD 1, PSA 87.56, QED 0.52
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4cccc(OC)c4)cs3)cs2)cc(OC)c1
InChIKey: WYFQLTFGHOLASO-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 = 1321 nM (pChEMBL 5.880000114440918)
Descriptors: MW 425.54, ALogP 5.7, HBA 8, HBD 1, PSA 65.5, QED 0.41
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccc(F)cc1
InChIKey: ITGWQDKBZORLFI-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 = 2730 nM (pChEMBL 5.559999942779541)
Descriptors: MW 488.97, ALogP 5.19, HBA 4, HBD 1, PSA 75.71, QED 0.54
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)c1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O)C1CCCCC1
InChIKey: DSRIHZWECPNXKK-JRADREEXSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 1002.24
Compound (SMILES): COCCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: RCOSLDFGEVGMJF-VZYDHVRKSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist potency at human H1 receptor
Measurement: Kd = 0.182 nM (pChEMBL 9.739999771118164)
Descriptors: MW 497.04, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.41
Compound (SMILES): CC(C)n1cc(C(=O)NC2COC2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: ZKEOBSJWSQXRIH-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 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 522.59, ALogP 2.48, HBA 11, HBD 2, PSA 145.92, QED 0.36
Compound (SMILES): Cc1ccc(-c2nc(N(c3ccccc3)c3ccccc3)sc2C(=O)c2cccs2)cc1
InChIKey: FWGZRKOIYICETM-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin) using linoleic acid as substrate preincubated for 5 mins followed by substrate addition by absorbance based analysis
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 452.6, ALogP 7.88, HBA 5, HBD 0, PSA 33.2, QED 0.25
Compound (SMILES): OC(Cn1ccnc1)Cn1c2ccc(Cl)cc2c2cc(Cl)ccc21
InChIKey: BKMVULRFIQMMNO-UHFFFAOYSA-N
Target: Plasma membrane ATPase 1 (SINGLE PROTEIN), Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
UniProt: P05030
Assay: Allosteric inhibition of H+ ATPase pma1 isoform by measuring NADP-coupled ATPase activity in presence of 10 mM ATP by spectrophotometry method
Measurement: IC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 360.24, ALogP 4.36, HBA 4, HBD 1, PSA 42.98, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(N2N=C(c3ccc(O)cc3)CC2c2cccs2)cc1
InChIKey: IPSZZGQBFIICSX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 53.5 nM (pChEMBL 7.269999980926514)
Descriptors: MW 399.5, ALogP 3.46, HBA 6, HBD 2, PSA 95.99, QED 0.7
Compound (SMILES): O=C(CCc1ccc(F)cc1)N1CCN(c2ccc(O)cn2)CC1
InChIKey: HISYQGYAJLHNDD-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 = 1740 nM (pChEMBL 5.760000228881836)
Descriptors: MW 329.38, ALogP 2.21, HBA 4, HBD 1, PSA 56.67, QED 0.93
Compound (SMILES): O=C(Nc1cccc(S(=O)(=O)C2CCCC2)c1)c1cccnc1N1CCCCC1
InChIKey: PGNDBHSSJBNDJL-UHFFFAOYSA-N
Target: Centromere-associated protein E (SINGLE PROTEIN), Homo sapiens
UniProt: Q02224
Assay: Inhibition of recombinant GST-tagged human CENP-E assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 413.54, ALogP 4.04, HBA 5, HBD 1, PSA 79.37, QED 0.8
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H]2Cc3ccccc3CN2C1=O
InChIKey: UVUOMESIOOEXGA-MATBRXERSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human melanocortin receptor 5
Measurement: EC50 = 2.05 nM (pChEMBL 8.6899995803833)
Descriptors: MW 1096.3
Compound (SMILES): Cn1c2ccccc2c2cc[n+](-c3ccc(I)cc3)cc21
InChIKey: PFXJDWFVKKAJGD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE (unknown origin)
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 385.23, ALogP 4.21, HBA 1, HBD 0, PSA 8.81, QED 0.34
Compound (SMILES): O=[N+]([O-])c1ccccc1-n1cc(COc2cccc3cnc(Nc4cccc(Cl)c4)nc23)nn1
InChIKey: XYFHSCKRPLMJIO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 473.88, ALogP 5.09, HBA 9, HBD 1, PSA 120.89, QED 0.26
Compound (SMILES): Cc1ccccc1CCc1cn(CCCCCC(=O)NO)c2ccc(-c3c(C)noc3C)cc12
InChIKey: FSVKCBFELANYQU-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 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 459.59, ALogP 6.07, HBA 5, HBD 2, PSA 80.29, QED 0.17
Compound (SMILES): O=C(c1cccc(-c2n[nH]c3ncc(Cc4cc(F)ccc4F)cc23)c1)N1CCCC(O)C1
InChIKey: JRLOPMVTMMPZMV-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 448.47, ALogP 4.09, HBA 4, HBD 2, PSA 82.11, QED 0.49
Compound (SMILES): Cc1nc(N2CCCN(C(=O)c3ccco3)CC2)c2c3c(sc2n1)CC(C)(C)CC3
InChIKey: HQSFJZSVDOXKCM-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membranes assessed as inhibition constant incubated for 90 mins by liquid scintillation spectrometry analysis
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 424.57, ALogP 4.46, HBA 6, HBD 0, PSA 62.47, QED 0.61
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H]1Cc2c([nH]c3ccccc23)CN([C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C1=O
InChIKey: YTCWEYGKGQOXIE-LAHIFKPXSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30938
Assay: Inhibition of rat somatostatin receptor type 5
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 633.75, ALogP 0.13, HBA 7, HBD 7, PSA 212.74, QED 0.12
Compound (SMILES): CC(C)(C)NC(=O)Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc2cc(Br)c(Br)cc21
InChIKey: ISJJKHYAKDKZNA-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 2630.27 nM (pChEMBL 5.579999923706055)
Descriptors: MW 660.28, ALogP 6.54, HBA 5, HBD 1, PSA 53.4, QED 0.31
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)C1CC1
InChIKey: ZQLQFWNFWSRBRS-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 = 2220 nM (pChEMBL 5.650000095367432)
Descriptors: MW 434.95, ALogP 4.15, HBA 4, HBD 1, PSA 75.71, QED 0.77
Compound (SMILES): CC[C@@H](C)n1nc(N2CC(C(C)(C)O)C2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: RDWYRIOEHIKPRE-MRXNPFEDSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells harboring harboring EGFR L858R/T790M double mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 551.68, ALogP 3.35, HBA 12, HBD 2, PSA 143.95, QED 0.32
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C)c2)c2cc(C)[nH]c2c1=O
InChIKey: WHKOQEHRVJBOCH-SNAWJCMRSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.5, ALogP 3.66, HBA 4, HBD 1, PSA 67.33, QED 0.67
Compound (SMILES): COC(=O)[C@]1(c2ccccc2)C[C@@H]1CN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: ZQZLNUMNWMAXIZ-USIGFJHISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from KOR receptor (unknown origin) assessed as inhibition constant
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 405.54, ALogP 4.05, HBA 4, HBD 1, PSA 49.77, QED 0.78
Compound (SMILES): CCCCCCN(C)CC(=O)C(CC(=O)O)NC(=O)[C@H](CC)n1cc(C(C)(C)C)nc(NCc2nonc2C)c1=O
InChIKey: XIMITGPWYYFUQF-QWAKEFERSA-N
Target: Caspase-8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14790
Assay: Inhibition of caspase-8 (unknown origin)
Measurement: IC50 = 6480 nM (pChEMBL 5.190000057220459)
Descriptors: MW 575.71, ALogP 2.84, HBA 11, HBD 3, PSA 172.55, QED 0.24
Compound (SMILES): O=C1Nc2cc(S(=O)(=O)Cc3c(Cl)cccc3Cl)ccc2S/C1=C\c1ccc(O)c([N+](=O)[O-])c1
InChIKey: DOMBZVXKSRQDOJ-NKVSQWTQSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 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 537.4, ALogP 5.67, HBA 7, HBD 2, PSA 126.61, QED 0.24
Compound (SMILES): O=C(CCCCCCNC(=O)C(O)(O)C(F)(F)F)Nc1ccc(-c2ccccc2)cc1
InChIKey: ALWAFPQKUFSFNP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) incubated for 3 hrs by chemiluminescent assay
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 438.45, ALogP 3.6, HBA 4, HBD 4, PSA 98.66, QED 0.34
Compound (SMILES): CN(C)c1ccc(NC(=O)NCCCCNC(=O)CS)cc1
InChIKey: FYIWSBSEDMXMFQ-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of HDAC10 (unknown origin)
Measurement: IC50 = 4610 nM (pChEMBL 5.340000152587891)
Descriptors: MW 324.45, ALogP 1.7, HBA 4, HBD 4, PSA 73.47, QED 0.43
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC(=O)N1CCC(CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: IHOAJHDGKCNHMA-MMQQLJCSSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylscopolamine from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 2410 nM (pChEMBL 5.619999885559082)
Descriptors: MW 476.58, ALogP 2.19, HBA 6, HBD 3, PSA 116.58, QED 0.5
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)c3c(cnn3C)c2N2C[C@@H](O)C[C@H]2CN)n1
InChIKey: OHKSBENCBXMGAT-KBPBESRZSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μL of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 509.52, ALogP 2.47, HBA 9, HBD 3, PSA 131.42, QED 0.36
Compound (SMILES): O=C(c1ccc(Oc2ccccc2)cc1Cl)c1c[nH]c2ncnc(NC3CC[C@@H](CO)OC3)c12
InChIKey: JSFCZQSJQXFJDS-PKHIMPSTSA-N
Target: Tyrosine-protein kinase Yes (SINGLE PROTEIN), Homo sapiens
UniProt: P07947
Assay: Inhibition of YES (unknown origin)
Measurement: IC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 478.94, ALogP 4.59, HBA 7, HBD 3, PSA 109.36, QED 0.33
Compound (SMILES): COc1ccnc(Nc2nn3c(C)cc(C)nc3c2C#N)c1
InChIKey: MWJHAGJIVBGATF-UHFFFAOYSA-N
Target: Phospholipase A2, membrane associated (SINGLE PROTEIN), Homo sapiens
UniProt: P14555
Assay: Inhibition of recombinant human sPLA2-V
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 294.32, ALogP 2.37, HBA 7, HBD 1, PSA 88.13, QED 0.8
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2ccc3cccc(OCc4ccc(F)cc4)c3n2)cc1
InChIKey: TYJQMXUZTVSEOB-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Boc-Lys(Ac)-AMC or Boc-Lys(Tfa)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.45, ALogP 4, HBA 5, HBD 3, PSA 100.55, QED 0.29
Compound (SMILES): CC(=O)c1c(C)c2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n(C2CCCC2)c1=O
InChIKey: BMHDAQPPVLYLRR-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (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 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 447.56, ALogP 2.25, HBA 8, HBD 1, PSA 114.26, QED 0.7
Compound (SMILES): Cc1cccc(COC2CCN(Cc3cn4ccccc4n3)CC2)n1
InChIKey: HELVAYSYFPKPOV-UHFFFAOYSA-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 = 323.59 nM (pChEMBL 6.489999771118164)
Descriptors: MW 336.44, ALogP 3.22, HBA 5, HBD 0, PSA 42.66, QED 0.72
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc3c(ncn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: ORQCQXMGDYAIOI-CQSZACIVSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of Lck (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 461.5, ALogP 2.97, HBA 8, HBD 2, PSA 111.19, QED 0.47
Compound (SMILES): O=C(CCCCCCN(Cc1ccc2ccccc2c1)Cc1ccc2ccccc2c1)NO
InChIKey: CIXQTRDAEWYSSH-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 440.59, ALogP 6.45, HBA 3, HBD 2, PSA 52.57, QED 0.16
Compound (SMILES): c1ccc2c(c1)[nH]c1cnc3c4ccncc4[nH]c3c12
InChIKey: RZXWKGHDRQNABH-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Binding affinity to human recombinant GABAA alpha5 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 258.28, ALogP 3.75, HBA 2, HBD 2, PSA 57.36, QED 0.44
Compound (SMILES): N#Cc1nc2c(nc1C#N)-c1ccc(F)cc1C2=O
InChIKey: MLVYMHCKGZRDFG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of USP8 (unknown origin)
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 250.19, ALogP 1.57, HBA 5, HBD 0, PSA 90.43, QED 0.6
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccnc(N5CCOCC5)c4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: SLIDWZKKXCTTPU-OAHLLOKOSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 486.54, ALogP 2.37, HBA 10, HBD 2, PSA 129.98, QED 0.45
Compound (SMILES): O=C(Nc1nnn[nH]1)c1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
InChIKey: KVASBUNZQLUXCB-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at TGR5 (unknown origin) expressed in HEK293 cells
Measurement: EC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 551.39, ALogP 4.58, HBA 8, HBD 2, PSA 129.23, QED 0.36
Compound (SMILES): Cn1nccc1-n1c([C@@H]2CSCN2c2ncnc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: ODXCALFCFKOJLD-AWEZNQCLSA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O88763
Assay: Inhibition of PI3Kalpha in rat Rat1 cells reduction in phosphorylation of AKT at Ser473 residue incubated for 2 hrs by alpha screen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 465.93, ALogP 2.27, HBA 11, HBD 1, PSA 131.54, QED 0.48