lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(C(=O)c2ccc3c(ccn3S(=O)(=O)c3cccc(/C=C/C(=O)NO)c3)c2)cc1
InChIKey: DOVKZSHJPXDFRJ-KPKJPENVSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human HDAC10 using RHKKAc peptide as substrate
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 460.51, ALogP 3.94, HBA 6, HBD 2, PSA 105.47, QED 0.2
Compound (SMILES): Cc1cc2ncn(CC(=O)c3cc(S(N)(=O)=O)c(Cl)cc3Sc3ccccc3)c2cc1C
InChIKey: AGMAPYKKSIMHTM-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human N-terminal His6-tagged carbonic anhydrase 6 expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 83.4 nM (pChEMBL 7.079999923706055)
Descriptors: MW 486.02, ALogP 4.99, HBA 6, HBD 1, PSA 95.05, QED 0.39
Compound (SMILES): CCCCNc1nc(N)nc2cccc(C(=O)N[C@@H](C)c3ccccc3)c12
InChIKey: WDFAZLUMAXOURM-AWEZNQCLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.46, ALogP 3.92, HBA 5, HBD 3, PSA 92.93, QED 0.55
Compound (SMILES): C[C@@H]1SC(c2ccccc2O)=N[C@H]1CO
InChIKey: ZVWPMYHMXUXIMC-CBAPKCEASA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 223.3, ALogP 1.63, HBA 4, HBD 2, PSA 52.82, QED 0.8
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccccc2)o1)[C@@H](CC)N(O)C=O
InChIKey: PEIHYHWPPPLALT-RTBURBONSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP12 (unknown origin)
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 429.52, ALogP 3.57, HBA 5, HBD 3, PSA 111.88, QED 0.15
Compound (SMILES): CCCCCCOc1ccc(C2=N[C@@H](CO)[C@H](C)S2)cc1
InChIKey: BVZAVSLGIRKNFC-BBRMVZONSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from human 5-HT2C receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 307.46, ALogP 3.89, HBA 4, HBD 1, PSA 41.82, QED 0.74
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Nn2cnc3ccccc32)c(SC2CCCCC2)cc1Cl
InChIKey: KTMCVAZXKKRHMA-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5A expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 465, ALogP 4.15, HBA 6, HBD 2, PSA 107.08, QED 0.59
Compound (SMILES): CS(=O)(=O)c1ccc(N2CCC(F)(F)CC2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: RROASANFHJCPDA-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 504.53, ALogP 3.81, HBA 6, HBD 0, PSA 75.51, QED 0.54
Compound (SMILES): CC(Cc1cccc(-n2c(C(N)=O)cc3ccc(OC(F)(F)F)cc32)n1)C(=O)O
InChIKey: ASLSDJNSUCRUHC-UHFFFAOYSA-N
Target: Group 10 secretory phospholipase A2 (SINGLE PROTEIN), Homo sapiens
UniProt: O15496
Assay: Inhibition of recombinant human sPLA2-10 using human HDL as substrate pretreated for 20 mins followed by substrate addition and measured after 60 mins by NEFA based assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 407.35, ALogP 3.29, HBA 5, HBD 2, PSA 107.44, QED 0.65
Compound (SMILES): COc1ccc(N2CCN(CCCOc3c(C)cc(C)cc3C)CC2)cc1.Cl.Cl
InChIKey: PIDNTMJUJXPPFC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Antagonist activity at human 5-HT1A receptor expressed in CHO-K1 cells co-expressing Galpha16 assessed as decrease in serotonin calcium mobilization preincubated for 25 mins followed by serotonin challenge measured for 30 secs by aequorin-derived luminescence assay
Measurement: IC50 = 595 nM (pChEMBL 6.21999979019165)
Descriptors: MW 368.52, ALogP 4.21, HBA 4, HBD 0, PSA 24.94, QED 0.68
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: SGVATPANUQBIHA-LMOJIFKQSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC5R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 880.02, ALogP -0.3, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CN(C)C(=O)c1ccc(OCCCCC[C@H]2CC[C@]3(CC2)COC(C)(C)C3)cc1
InChIKey: NOJGRWVDPKFOQU-IHRKKFBRSA-N
Target: Glucose-dependent insulinotropic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDV5
Assay: Agonist activity at human GPR119 expressed in HEK293 cells assessed as increase in intracellular cAMP level after 30 mins
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 401.59, ALogP 5.7, HBA 3, HBD 0, PSA 38.77, QED 0.52
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(OCC(=O)NCCC4=C5C(C)=CC(C)=[N+]5[B-](F)(F)n5c(C)cc(C)c54)cc3)[nH]c2c1=O
InChIKey: XIMHBHBACDXPTB-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from recombinant human adenosine A1 receptor expressed in CHO cell membranes after 90 mins by liquid scintillation counting method
Measurement: Ki >= 10000 nM (pChEMBL 5)
Descriptors: MW 617.47
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1)C(F)(F)F
InChIKey: DMRVMJNKRAGVQH-LBPRGKRZSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.38, ALogP 3.76, HBA 6, HBD 0, PSA 84.04, QED 0.57
Compound (SMILES): NC1=N[C@@]2(c3cc(NC(=O)c4ccc(F)cn4)ccc3F)CCC[C@H]2CS1
InChIKey: UIAVKAKVAXWNHJ-WLRWDXFRSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2
Measurement: IC50 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 388.44, ALogP 3.67, HBA 5, HBD 2, PSA 80.37, QED 0.84
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: LEGQBTRPHGOTTN-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.51, ALogP 4.38, HBA 5, HBD 0, PSA 72.27, QED 0.44
Compound (SMILES): COCCOc1cc2ncnc(N3CCN(c4ncc(Cc5ccccc5)cn4)CC3)c2cc1OCCOC
InChIKey: GWVUCXTYNJIWGK-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Binding affinity to KIT V559D/T670I mutant (unknown origin)
Measurement: Kd = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 530.63, ALogP 3.39, HBA 10, HBD 0, PSA 94.96, QED 0.25
Compound (SMILES): C[C@H]1C[C@@H](n2c(Nc3ccc(OC(F)(F)F)cc3)nc3cc(CCC(=O)O)ccc32)CC(C)(C)C1
InChIKey: RNMAUIMMNAHKQR-QFBILLFUSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of full length FLAG-tagged human recombinant wild type IDH1 expressed in Sf9 cells
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 489.54, ALogP 7.08, HBA 5, HBD 2, PSA 76.38, QED 0.37
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN4CCN(C)CC4)C5)ncc3F)cc2n1C(C)C
InChIKey: KZZDDXBCJROTIP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100×, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1×reaction buffer to prepare 5×compound for use; 2 μL 5×compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1×reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1× reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5×enzyme/substrate mixture and 2.5×ATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 80 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50 μM; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 15 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20 μM; 2.5×enzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5×ATP solution, reacted at room temperature for 30 minutes.3. LANCE® Detection Buffer was used, 1× to prepare 2×LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM×10000 was used as the final data for analysis.
Measurement: IC50 = 801 nM (pChEMBL 6.099999904632568)
Descriptors: MW 575.67, ALogP 3.93, HBA 9, HBD 1, PSA 95.31, QED 0.37
Compound (SMILES): Cc1cccc(-n2cc3c(n2)CN(C(=O)c2cc(S(C)(=O)=O)ccc2O[C@@H](C)C(F)(F)F)C3)c1
InChIKey: IAIFDVUVYFIYKI-HNNXBMFYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.51, ALogP 4.07, HBA 6, HBD 0, PSA 81.5, QED 0.54
Compound (SMILES): FC(F)(F)CCc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: ZLOMTQBPDHCEQU-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant 5-HT2A receptor (unknown origin) expressed in HEK293 cells assessed as increase in [3H]-inositol phosphate accumulation by scintillation counting method
Measurement: EC50 = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 285.31, ALogP 2.3, HBA 3, HBD 1, PSA 28.16, QED 0.9
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: YCYOWXTYVQGGHS-XKGNXMRFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human natural killer cells assessed as reduction in IL23/IL18-induced IFNgamma production incubated for 20 to 24 hrs by ELISA
Measurement: IC50 <= 25 nM (pChEMBL 7.6020002365112305)
Descriptors: MW 1623.82
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2-c2ccc(C3(C#N)CC3)cc2)CC1
InChIKey: WIXZFNIBMHEUJH-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of paclitaxel-mediated cytotoxicity by measuring paclitaxel IC50 at 10 uM after 4 days by CellTiter-Glo assay (Rvb = 1202 nM)
Measurement: IC50 = 411 nM (pChEMBL 6.389999866485596)
Descriptors: MW 478.55, ALogP 3.31, HBA 5, HBD 0, PSA 94.37, QED 0.57
Compound (SMILES): CC(C)(O)CNC(=O)CC1CSc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: DUBUCROMSYFQOW-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at GAL4-tagged human LXRalpha assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 792 nM (pChEMBL 6.099999904632568)
Descriptors: MW 604.57, ALogP 4.08, HBA 6, HBD 3, PSA 106.94, QED 0.41
Compound (SMILES): CCS(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4ccnc(C)c4)nc3C2)c1
InChIKey: WWXURZJVUUIGAA-HNNXBMFYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 508.52, ALogP 3.85, HBA 7, HBD 0, PSA 94.39, QED 0.5
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCCC2)NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: YUKODIVVRQEHLF-UBLLTGQXSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC5R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 866, ALogP -0.69, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): C[C@@H]1SC(c2ccccc2)=N[C@H]1CO
InChIKey: YNQFPPQZWZBEHD-WPRPVWTQSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]-GR65630 from human 5-HT3 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 207.3, ALogP 1.93, HBA 3, HBD 1, PSA 32.59, QED 0.8
Compound (SMILES): COc1cc2c(cc1OC1CCCC1)CN(S(=O)(=O)c1ccc(NC(C)=O)cc1)CC2
InChIKey: MATVLUWHSFXXRL-UHFFFAOYSA-N
Target: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P51160
Assay: Inhibition of human PDE6C
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 444.55, ALogP 3.72, HBA 5, HBD 1, PSA 84.94, QED 0.73
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc2ccc([C@H]3CC[C@H](c4ccc5nc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c5c4)N3c3ccc(N4CCOCC4)cc3)cc2[nH]1)C(C)C
InChIKey: NLTMESNPGKZGSV-CNGYLHDYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Con1) (HCV)
UniProt: Q9WMX2
Assay: Inhibition of HCV genotype 1b Con1 NS5A expressed in HuH7 cell infected HCV genotype 3a assessed as decrease in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 917.12, ALogP 7.45, HBA 11, HBD 4, PSA 190.35, QED 0.1
Compound (SMILES): C=CC(=O)N1CC[C@]2(C1)C[C@H](n1c(NC(=O)c3ccc(C(F)F)s3)nc3cc(CN[C@@H](C)C(C)(C)C)ccc31)C2
InChIKey: CRYRQUNNVGZTRP-QTBKOHNUSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Inhibition Assay: The in vitro kinase assays were performed at Nanosyn (Santa Clara, Calif.) utilizing microfluidic detection technology. The test compounds were serially pre-diluted in DMSO and added, by the acoustic dispensing (Labcyte 550), directly to 384 well assay plates into 10 uL of a buffer with enzyme (ITK, TXK, BTK or TEC) comprising: 100 mM HEPES, pH7.5, 5 mM MgCl2, 0.1% bovine serum albumin, 1 mM DTT, 0.01% Triton X-100 and the enzyme. Final DMSO concentration was maintained at 1% in all samples, including the controls. The reactions were initiated by addition of ATP (1 mM final concentration) and the fluorescently labeled peptide substrate to a final concentration of 1 uM, and incubated for 3 hours at 25° C. Following incubation, the reactions were quenched by addition of 40 μL of termination buffer (100 mM HEPES, pH7.5, 0.01% Triton X-100, 50 mM EDTA). Terminated plates were analyzed using Caliper LabChip 3000 microfluidic electrophoresis instrument (Caliper Life Sciences/Perkin Elmer). The enzymatic modification of the peptide substrate (phosphorylation) results in a change of net charge enabling electrophoretic separation of product from substrate. As substrate and product are separated by electrophoresis, two peaks of fluorescence are observed. Change in the relative fluorescence intensity of the substrate and product peaks was the parameter measured, reflecting enzyme activity. In the presence of inhibitor, the ratio between product and substrate is altered: signal of the product decreases, while the signal of the substrate increases. Activity in each test sample was determined as the product to sum ratio (PSR): P/(S+P), where P is the peak height of the product and S is the peak height of the FAM-cAMP substrate. For each compound, enzyme activity was measured at 12 concentrations spaced by 3× dilution intervals. Negative control samples (0%-inhibition in the absence of inhibitor, DMSO only) and positive control samples (100%-inhibition, in the absence of enzyme or in the presence of control inhibitor) were assembled in replicates of four and were used to calculate %-inhibition values in the presence of compounds. Percent inhibition (Pinh) was determined using the following equation: Pinh=(PSR0%−PSRinh)/(PSR0%−PSR100%)*100, where PSRinh is the product sum ratio in the presence of inhibitor, PSR0% is the product sum ratio in the absence of inhibitor and PSR100% is the product sum ratio in 100%-inhibition control samples. To determine IC50 values, the inhibition curves (Pinh versus inhibitor concentration) were fitted by 4 parameter sigmoid dose-response model using XLfit software (IDBS).
Measurement: IC50 = 1.01 nM (pChEMBL 9)
Descriptors: MW 569.72, ALogP 6.55, HBA 6, HBD 2, PSA 79.26, QED 0.3
Compound (SMILES): CCOC(=O)N1CCc2c(c3cc(OC)ccc3n2CC(=O)O)C1
InChIKey: DCDAZZGJAFXXQQ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in Wistar rat eye lens assessed as reduction in NADPH consumption preincubated for 1 min followed by D,L-glyceraldehyde addition measured after 4 mins by spectrophotometric analysis
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 332.36, ALogP 2.25, HBA 5, HBD 1, PSA 81, QED 0.93
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1)C(F)(F)F
InChIKey: AAMMWJACZPQZNL-LBPRGKRZSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.46, ALogP 3.3, HBA 7, HBD 0, PSA 94.39, QED 0.5
Compound (SMILES): N#Cc1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: LZOXZIGBRAVWHE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.41, ALogP 4.24, HBA 5, HBD 0, PSA 74.81, QED 0.49
Compound (SMILES): Cc1nn(-c2ccccc2)c(C)c1NC(=O)COC(=O)Cc1c(C)[nH]c2cc(C(=N)N)ccc12
InChIKey: FVOAURGQNYSTPO-UHFFFAOYSA-N
Target: Kallikrein-14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0G3
Assay: Inhibition of KLK14 (unknown origin) expressed in Pichia pastoris pre-incubated for 10 mins before Boc-ValProArg-AMC substrate addition and measured after 30 mins by fluorescence based assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 458.52, ALogP 3.29, HBA 6, HBD 4, PSA 138.88, QED 0.19
Compound (SMILES): CO[C@H]1CNC[C@@H](OCC2CCC(F)(F)CC2)[C@@H]1Nc1ncc(-c2cncc(C)c2)c2cc(C)c(=O)[nH]c12
InChIKey: YDPMMWAOCCOULO-JBRSBNLGSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) by TR-FRET assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 527.62, ALogP 4.21, HBA 7, HBD 3, PSA 101.16, QED 0.42
Compound (SMILES): COc1cc2c(cc1OC)C1CC(O)C(CC(C)C)CN1CC2
InChIKey: WEQLWGNDNRARGE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [125I]DOI from human 5HT2A receptor expressed in HEK293 cell membranes
Measurement: Ki = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 319.45, ALogP 3.03, HBA 4, HBD 1, PSA 41.93, QED 0.93
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)Nc2ccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)cc2)cc1
InChIKey: KGXBCWANASZZQG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00444
Assay: Inhibition of GST-tagged human PLK4 (1 to 836 residues) by Lanthascreen binding assay
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 535.61, ALogP 5.49, HBA 7, HBD 3, PSA 119.56, QED 0.3
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2N2CCC(C#N)(c3ccccc3)CC2)CC1
InChIKey: XMNLWOQHMQRHDV-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of paclitaxel-mediated cytotoxicity by measuring paclitaxel IC50 at 10 uM after 4 days by CellTiter-Glo assay (Rvb = 1202 nM)
Measurement: IC50 = 25.2 nM (pChEMBL 7.599999904632568)
Descriptors: MW 521.62, ALogP 3.15, HBA 6, HBD 0, PSA 97.61, QED 0.52
Compound (SMILES): C[C@@H]1SC(c2cccs2)=N[C@H]1CO
InChIKey: ZUJITGFVHDARMS-BQBZGAKWSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]-GR65630 from human 5-HT3 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 213.33, ALogP 1.99, HBA 4, HBD 1, PSA 32.59, QED 0.81
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCN(C(=O)C(C)(C)C)CC4)nc3)nn(Cc3cn(Cc4ccccc4)nn3)c2n1
InChIKey: AKGTYUDYJSLFDE-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of wild-type human partial length MET (D1010 to S1367 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 565.69, ALogP 3.31, HBA 11, HBD 1, PSA 122.78, QED 0.32
Compound (SMILES): CC(C)[C@H](NC(=O)C(C)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(=O)n(C)c2)c1)c1cc(F)cc(F)c1
InChIKey: ROGXRBIZXSSLJN-LOSJGSFVSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: GRE Antagonist Assay: A reporter cell line (ChagoK1 18:7:2 s4/GRE) was established by stable transfection of the human bronchogenic carcinoma celline, ChaGo K1 (ATCC: HTB 168) with a MMTV-GRE-LacZ reporter construct. The generated cell line allows for identification of compounds showing antagonist activity at the human glucocorticoid receptor (GR) via reduction of LacZ gene expression. Dexamethasone-activated GR binds to the Glucocorticoid Response Element (GRE) in the promoter of the LacZ gene and transcription is initiated. Antagonistic properties of compounds are assessed as beta-galactosidase intensity reduction from pre-stimulation with dexamethasone through a colour reaction (change in absorbance).Cryo-preserved ChagoK1 18:7:2 s4/GRE cells were suspended in RPMI medium with 10% FBS, 1% NEAA and 1% sodium pyruvate, and seeded as 50000 cells/200 ul/well in 96-well plates and cultured at 37° C. with 5% CO2 and 95% humidity for 24 hr. Cells were pre-stimulated with 2 μl dexamethasone (70 nM final conc) for 4-5 hr, before addition of 1 μl compound at different concentrations and incubation for an additional 24 hr. Cells were washed once in PBS and lysed with 50 μl of 0.1% Triton-X for 10 min at room temperature. 40 μl of reaction mixture (2.5 mM MgCl2, 0.1 M β-mercapto ethanol, 1.7 mg/ml ONPG and 42.5 mM sodium phosphate, pH 7.5), was added to each well and kept at 37° C. for 60 min. The reaction was then terminated by addition of 100 μl stop solution (300 mM glycine, 15 mM EDTA, pH 11.3, adjusted with NaOH). The plates were measured at 420 nm for absorbance in a SpectraMax reader (Molecular Device).The relative efficacy (% effect) of a compound is calculated based on the full antagonist effect of the reference compound Mifepristone (RU486): % Effect=((Sample abs−min abs)/(max abs−min abs))×100To calculate IC50, max, min and slope factor for each compound, a concentration response curve is fitted by plotting % Effect versus compound concentration using the 4 parameter logistic equation: y=A+(B−A)/(1+((10C)/x)D)Where A=min Y, B=max Y, C=log IC50 and D=Slope factor.
Measurement: IC50 = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 530.52, ALogP 4.92, HBA 6, HBD 1, PSA 78.15, QED 0.33
Compound (SMILES): CNC(=O)c1cnc(N)c(O[C@H]2CN(C(=O)Cc3ccc(OC(F)(F)F)cc3)CC2(F)F)c1
InChIKey: FTAFQADCGCSJAH-HNNXBMFYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Binding affinity to un phosphorylated C-terminal His6/N-terminal BAP-tagged TrkA (441 to 796 residues) (unknown origin) by SPR assay
Measurement: Kd = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 474.39, ALogP 2.39, HBA 6, HBD 2, PSA 106.78, QED 0.62
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Cn2cnc3ccccc32)c(Cl)cc1Cl
InChIKey: YAIQQAHCNJQINN-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5B (40 to 317 residues) expressed in Escherichia coli Rosetta 2 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 23.8 nM (pChEMBL 7.619999885559082)
Descriptors: MW 384.24, ALogP 2.87, HBA 5, HBD 1, PSA 95.05, QED 0.7
Compound (SMILES): Cc1cc(-n2cc3c(n2)CN(C(=O)c2cc(C#N)ccc2OC(C)C)C3)ccn1
InChIKey: CIEHAYBWEMOJMN-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 387.44, ALogP 3.39, HBA 6, HBD 0, PSA 84.04, QED 0.69
Compound (SMILES): Cc1cc2ncn(CC(=O)c3cc(S(N)(=O)=O)c(Cl)cc3Sc3ccccc3)c2cc1C
InChIKey: AGMAPYKKSIMHTM-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human full length N-terminal His6-tagged mitochondrial carbonic anhydrase 5B (40 to 317 residues) expressed in Escherichia coli Rosetta 2 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 194 nM (pChEMBL 6.710000038146973)
Descriptors: MW 486.02, ALogP 4.99, HBA 6, HBD 1, PSA 95.05, QED 0.39
Compound (SMILES): C[C@@H]1SC(c2ccccc2O)=N[C@H]1CO
InChIKey: ZVWPMYHMXUXIMC-CBAPKCEASA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A (unknown origin) receptor after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10 nM (pChEMBL 8)
Descriptors: MW 223.3, ALogP 1.63, HBA 4, HBD 2, PSA 52.82, QED 0.8
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccccc2)o1)[C@@H](CC)N(O)C=O
InChIKey: PEIHYHWPPPLALT-RTBURBONSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human full length TLL1 using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 429.52, ALogP 3.57, HBA 5, HBD 3, PSA 111.88, QED 0.15
Compound (SMILES): CCCCCCOc1ccc(C2=N[C@@H](CO)[C@H](C)S2)cc1
InChIKey: BVZAVSLGIRKNFC-BBRMVZONSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Displacement of [3H]-GR65630 from human 5-HT3 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 307.46, ALogP 3.89, HBA 4, HBD 1, PSA 41.82, QED 0.74
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)Nn2cnc3ccccc32)c(SC2CCCCC2)cc1Cl
InChIKey: KTMCVAZXKKRHMA-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human N-terminal His6-tagged carbonic anhydrase 4 expressed in Escherichia coli BL21 (DE3) assessed as intrinsic dissociation constant in presence of ANS by fluorescent thermal shift assay
Measurement: Kd = 1.07 nM (pChEMBL 8.970000267028809)
Descriptors: MW 465, ALogP 4.15, HBA 6, HBD 2, PSA 107.08, QED 0.59
Compound (SMILES): CS(=O)(=O)c1ccc(N2CCC(F)(F)CC2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: RROASANFHJCPDA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 504.53, ALogP 3.81, HBA 6, HBD 0, PSA 75.51, QED 0.54
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCCCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: SGVATPANUQBIHA-LMOJIFKQSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human MC5R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins
Measurement: EC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 880.02, ALogP -0.3, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(OCC(=O)NCCC4=C5C(C)=CC(C)=[N+]5[B-](F)(F)n5c(C)cc(C)c54)cc3)[nH]c2c1=O
InChIKey: XIMHBHBACDXPTB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX-2 from recombinant human adenosine A2A receptor expressed in HEK cell membranes after 30 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 617.47
Compound (SMILES): C[C@H](Oc1ccc(C#N)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1)C(F)(F)F
InChIKey: DMRVMJNKRAGVQH-LBPRGKRZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.38, ALogP 3.76, HBA 6, HBD 0, PSA 84.04, QED 0.57
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4ccccc4F)nc3C2)c1
InChIKey: LEGQBTRPHGOTTN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.51, ALogP 4.38, HBA 5, HBD 0, PSA 72.27, QED 0.44
Compound (SMILES): COCCOc1cc2ncnc(N3CCN(c4ncc(Cc5ccccc5)cn4)CC3)c2cc1OCCOC
InChIKey: GWVUCXTYNJIWGK-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Biochemical Activity Assay: Kit wild type assay: In each well of a 384-well plate, 0.2 ng/ul final (2 nM) of wild type Kit (Carna Bioscience 08-156) was incubated in a total of 12.5 ul of buffer (100 mM HEPES pH 7.5, 0.015% Brij 35, 10 mM MgCl2, 1 mM DTT) with 1 uM Srctide (5-FAM-GEEPLYWSFPAKKK-NH2) and 400 uM ATP at 25 C for 90 minutes in the presence or absence of a dosed concentration series of compound (1% DMSO final concentration). The reaction was stopped by the addition of 70 ul of Stop buffer (100 mM HEPES pH 7.5, 0.015% Brij 35, 35 mM EDTA and 0.2% of Coating Reagent 3 (Caliper Lifesciences)). The plate was then read on a Caliper EZReader 2 (protocol settings: −1.9 psi, upstream voltage −700, downstream voltage −3000, post sample sip 35 s). Data was normalized to 0% and 100% inhibition controls and the IC50 or EC50 calculated using a 4-parameter fit using GraphPad Prism.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 530.63, ALogP 3.39, HBA 10, HBD 0, PSA 94.96, QED 0.25
Compound (SMILES): C[C@H]1C[C@@H](n2c(Nc3ccc(OC(F)(F)F)cc3)nc3cc(CCC(=O)O)ccc32)CC(C)(C)C1
InChIKey: RNMAUIMMNAHKQR-QFBILLFUSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of human N-terminal TEV cleavable/strep tagged IDH1 R132H mutant expressed in Escherichia coli BL21(DE3) using alpha KG as substrate preincubated with compound for 30 mins followed by substrate addition measured after 1.5 hrs by HTS assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 489.54, ALogP 7.08, HBA 5, HBD 2, PSA 76.38, QED 0.37
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(C(=O)CN4CCN(C)CC4)C5)ncc3F)cc2n1C(C)C
InChIKey: KZZDDXBCJROTIP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100×, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1×reaction buffer to prepare 5×compound for use; 2 μL 5×compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1×reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1× reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5×enzyme/substrate mixture and 2.5×ATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 80 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50 μM; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 15 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20 μM; 2.5×enzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5×ATP solution, reacted at room temperature for 30 minutes.3. LANCE® Detection Buffer was used, 1× to prepare 2×LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE® Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM×10000 was used as the final data for analysis.
Measurement: IC50 = 8.21 nM (pChEMBL 8.09000015258789)
Descriptors: MW 575.67, ALogP 3.93, HBA 9, HBD 1, PSA 95.31, QED 0.37
Compound (SMILES): Cc1cccc(-n2cc3c(n2)CN(C(=O)c2cc(S(C)(=O)=O)ccc2O[C@@H](C)C(F)(F)F)C3)c1
InChIKey: IAIFDVUVYFIYKI-HNNXBMFYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 493.51, ALogP 4.07, HBA 6, HBD 0, PSA 81.5, QED 0.54
Compound (SMILES): FC(F)(F)CCc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: ZLOMTQBPDHCEQU-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant 5-HT2B receptor (unknown origin) expressed in HEK293 cells assessed as increase in [3H]-inositol phosphate accumulation by scintillation counting method
Measurement: EC50 = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 285.31, ALogP 2.3, HBA 3, HBD 1, PSA 28.16, QED 0.9
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: YCYOWXTYVQGGHS-XKGNXMRFSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Binding affinity to human recombinant interleukin-23 receptor by SPR assay
Measurement: Kd = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 1623.82
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2-c2ccc(C3(C#N)CC3)cc2)CC1
InChIKey: WIXZFNIBMHEUJH-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of paclitaxel-mediated cytotoxicity by measuring paclitaxel IC50 at 20 uM after 4 days by CellTiter-Glo assay (Rvb = 1202 nM)
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 478.55, ALogP 3.31, HBA 5, HBD 0, PSA 94.37, QED 0.57
Compound (SMILES): CC(C)(O)CNC(=O)CC1CSc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1S(=O)(=O)c1ccc(F)cc1
InChIKey: DUBUCROMSYFQOW-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at GAL4-tagged human LXRalpha assessed as receptor activation expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 604.57, ALogP 4.08, HBA 6, HBD 3, PSA 106.94, QED 0.41
Compound (SMILES): CCS(=O)(=O)c1ccc(O[C@@H](C)C(F)(F)F)c(C(=O)N2Cc3cn(-c4ccnc(C)c4)nc3C2)c1
InChIKey: WWXURZJVUUIGAA-HNNXBMFYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 508.52, ALogP 3.85, HBA 7, HBD 0, PSA 94.39, QED 0.5
Compound (SMILES): C[C@@H]1SC(c2ccccc2)=N[C@H]1CO
InChIKey: YNQFPPQZWZBEHD-WPRPVWTQSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Displacement of [3H]-LSD from human 5-HT5A receptor expressed in Flp-In CHO cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 207.3, ALogP 1.93, HBA 3, HBD 1, PSA 32.59, QED 0.8
Compound (SMILES): COc1cc2c(cc1OC1CCCC1)CN(S(=O)(=O)c1ccc(NC(C)=O)cc1)CC2
InChIKey: MATVLUWHSFXXRL-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of human PDE7A
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 444.55, ALogP 3.72, HBA 5, HBD 1, PSA 84.94, QED 0.73
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc2ccc([C@H]3CC[C@H](c4ccc5nc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c5c4)N3c3ccc(N4CCOCC4)cc3)cc2[nH]1)C(C)C
InChIKey: NLTMESNPGKZGSV-CNGYLHDYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), Hepatitis C virus genotype 1b (isolate Con1) (HCV)
UniProt: Q9WMX2
Assay: Inhibition of HCV genotype 1b Con1 NS5A expressed in HuH7 cell infected HCV genotype 4a assessed as decrease in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.316 nM (pChEMBL 9.5)
Descriptors: MW 917.12, ALogP 7.45, HBA 11, HBD 4, PSA 190.35, QED 0.1
Compound (SMILES): C=CC(=O)N1CC[C@]2(C1)C[C@H](n1c(NC(=O)c3ccc(C(F)F)s3)nc3cc(CN[C@@H](C)C(C)(C)C)ccc31)C2
InChIKey: CRYRQUNNVGZTRP-QTBKOHNUSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Kinase Inhibition Assay: The in vitro kinase assays were performed at Nanosyn (Santa Clara, Calif.) utilizing microfluidic detection technology. The test compounds were serially pre-diluted in DMSO and added, by the acoustic dispensing (Labcyte 550), directly to 384 well assay plates into 10 uL of a buffer with enzyme (ITK, TXK, BTK or TEC) comprising: 100 mM HEPES, pH7.5, 5 mM MgCl2, 0.1% bovine serum albumin, 1 mM DTT, 0.01% Triton X-100 and the enzyme. Final DMSO concentration was maintained at 1% in all samples, including the controls. The reactions were initiated by addition of ATP (1 mM final concentration) and the fluorescently labeled peptide substrate to a final concentration of 1 uM, and incubated for 3 hours at 25° C. Following incubation, the reactions were quenched by addition of 40 μL of termination buffer (100 mM HEPES, pH7.5, 0.01% Triton X-100, 50 mM EDTA). Terminated plates were analyzed using Caliper LabChip 3000 microfluidic electrophoresis instrument (Caliper Life Sciences/Perkin Elmer). The enzymatic modification of the peptide substrate (phosphorylation) results in a change of net charge enabling electrophoretic separation of product from substrate. As substrate and product are separated by electrophoresis, two peaks of fluorescence are observed. Change in the relative fluorescence intensity of the substrate and product peaks was the parameter measured, reflecting enzyme activity. In the presence of inhibitor, the ratio between product and substrate is altered: signal of the product decreases, while the signal of the substrate increases. Activity in each test sample was determined as the product to sum ratio (PSR): P/(S+P), where P is the peak height of the product and S is the peak height of the FAM-cAMP substrate. For each compound, enzyme activity was measured at 12 concentrations spaced by 3× dilution intervals. Negative control samples (0%-inhibition in the absence of inhibitor, DMSO only) and positive control samples (100%-inhibition, in the absence of enzyme or in the presence of control inhibitor) were assembled in replicates of four and were used to calculate %-inhibition values in the presence of compounds. Percent inhibition (Pinh) was determined using the following equation: Pinh=(PSR0%−PSRinh)/(PSR0%−PSR100%)*100, where PSRinh is the product sum ratio in the presence of inhibitor, PSR0% is the product sum ratio in the absence of inhibitor and PSR100% is the product sum ratio in 100%-inhibition control samples. To determine IC50 values, the inhibition curves (Pinh versus inhibitor concentration) were fitted by 4 parameter sigmoid dose-response model using XLfit software (IDBS).
Measurement: IC50 = 2.36 nM (pChEMBL 8.630000114440918)
Descriptors: MW 569.72, ALogP 6.55, HBA 6, HBD 2, PSA 79.26, QED 0.3
Compound (SMILES): C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3cncc(F)c3)nc2C1)C(F)(F)F
InChIKey: AAMMWJACZPQZNL-LBPRGKRZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 498.46, ALogP 3.3, HBA 7, HBD 0, PSA 94.39, QED 0.5
Compound (SMILES): N#Cc1ccc(-c2cccc(F)c2)c(C(=O)N2Cc3cn(-c4cncc(F)c4)nc3C2)c1
InChIKey: LZOXZIGBRAVWHE-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.41, ALogP 4.24, HBA 5, HBD 0, PSA 74.81, QED 0.49
Compound (SMILES): CO[C@H]1CNC[C@@H](OCC2CCC(F)(F)CC2)[C@@H]1Nc1ncc(-c2cncc(C)c2)c2cc(C)c(=O)[nH]c12
InChIKey: YDPMMWAOCCOULO-JBRSBNLGSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Displacement of Halo-tagged Histone H3.3 from Nanoluc-ATAD2A BD (962 to 1119 residues) (unknown origin) transfected in human HCT116 cells incubated for 18 hrs by NanoBRET assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 527.62, ALogP 4.21, HBA 7, HBD 3, PSA 101.16, QED 0.42
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)Nc2ccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)cc2)cc1
InChIKey: KGXBCWANASZZQG-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant GST-tagged human LRRK2 (970 to 2527 residues) catalytic domain expressed in baculovirus expression system by ADAPTA assay
Measurement: IC50 = 714 nM (pChEMBL 6.150000095367432)
Descriptors: MW 535.61, ALogP 5.49, HBA 7, HBD 3, PSA 119.56, QED 0.3
Compound (SMILES): CS(=O)(=O)N1CCN(C(=O)c2cnc3ccc(F)cc3c2N2CCC(C#N)(c3ccccc3)CC2)CC1
InChIKey: XMNLWOQHMQRHDV-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 in human SKOV3TR cells assessed as potentiation of paclitaxel-mediated cytotoxicity by measuring paclitaxel IC50 at 20 uM after 4 days by CellTiter-Glo assay (Rvb = 1202 nM)
Measurement: IC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 521.62, ALogP 3.15, HBA 6, HBD 0, PSA 97.61, QED 0.52
Compound (SMILES): C[C@@H]1SC(c2cccs2)=N[C@H]1CO
InChIKey: ZUJITGFVHDARMS-BQBZGAKWSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Displacement of [3H]-LSD from human 5-HT5A receptor expressed in Flp-In CHO cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 213.33, ALogP 1.99, HBA 4, HBD 1, PSA 32.59, QED 0.81
Compound (SMILES): CNc1ncc2c(-c3ccc(N4CCN(C(=O)C(C)(C)C)CC4)nc3)nn(Cc3cn(Cc4ccccc4)nn3)c2n1
InChIKey: AKGTYUDYJSLFDE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of wild-type human partial length MER (R557 to L884 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 565.69, ALogP 3.31, HBA 11, HBD 1, PSA 122.78, QED 0.32