lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOC(=O)N1CCC(=CC#Cc2cccc(C)c2)CC1
InChIKey: DZXSEYITFJOIRX-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Displacement of [3H]MPEP from human mGlu5 receptor expressed in CHO-TREx cell membranes after 60 mins by liquid scintillation spectrometric analysis
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 283.37, ALogP 3.53, HBA 2, HBD 0, PSA 29.54, QED 0.74
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(C(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: QIEKHLDZKRQLLN-FOIQADDNSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/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 = 1.25 nM (pChEMBL 8.899999618530273)
Descriptors: MW 471.53, ALogP 2.04, HBA 8, HBD 2, PSA 117.42, QED 0.69
Compound (SMILES): O=C(CC(=O)Nc1ccc2c(/C=C/c3ccccn3)n[nH]c2c1)Nc1cccc(F)c1
InChIKey: OLZDZYHEIBZXCI-CSKARUKUSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of TEL fused wild type c-KIT (unknown origin) transfected in mouse BaF3 cells assessed as reduction in phosphorylation at Y703 residue after 2 hrs by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 415.43, ALogP 4.23, HBA 4, HBD 3, PSA 99.77, QED 0.41
Compound (SMILES): O=C(NNS(=O)(=O)c1ccccc1)c1cc(-c2ccnnc2)ccc1F
InChIKey: WYMCVPPNOFFNGE-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT6A (SINGLE PROTEIN), Homo sapiens
UniProt: Q92794
Assay: Affinity Biochemical interaction (AlphaScreen (HAT activity assay)) EUB0000327a MYST3
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 372.38, ALogP 1.91, HBA 5, HBD 2, PSA 101.05, QED 0.67
Compound (SMILES): CS(=O)(=O)c1cc(C(=O)NS(=O)(=O)c2ccc(N[C@H](CCN3CCOCC3)CSc3ccccc3)c([N+](=O)[O-])c2)ccc1-c1ccc(F)cc1
InChIKey: SHBJYYFMMRJMMJ-HHHXNRCGSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of Bcl-xl in human U266B1 cells assessed as caspase 3/7 activation in presence of 10 % serum for 6 hrs by Caspase 3/7-Glo luminescence assay
Measurement: EC50 > 31500 nM (pChEMBL 4.501999855041504)
Descriptors: MW 742.87, ALogP 5.22, HBA 11, HBD 2, PSA 165.02, QED 0.1
Compound (SMILES): CO[C@H]1/C=C/C[C@H](C)[C@@H](C)S(=O)(=O)NC(=O)c2ccc3c(c2)N(C[C@@H]2CC[C@H]21)C[C@@]1(CCCc2cc(Cl)ccc21)CO3
InChIKey: JQNINBDKGLWYMU-GEAQBIRJSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of human Biotin-DMRPEIWIAQELRRIGDEFNAYYARR peptide binding to recombinant 10His-tagged human Bcl2 (2 to 211 residues) expressed in Escherichia coli cells after 120 mins by fluorescence polarization assay
Measurement: Ki = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 613.22, ALogP 5.9, HBA 6, HBD 1, PSA 84.94, QED 0.4
Compound (SMILES): CC(C)NC[C@H](O)COc1ccccc1CCCNC(=O)NCCCc1ccccc1OC[C@@H](O)CNC(C)C
InChIKey: LJWNNXVLKPPMLD-NSOVKSMOSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Displacement of [3H]DHA from beta2 adrenergic receptor (unknown origin) stably expressed in HEK293 cell membranes measured after 90 mins by scintillation counting analysis
Measurement: Kd = 1.905 nM (pChEMBL 8.720000267028809)
Descriptors: MW 558.76, ALogP 3.03, HBA 7, HBD 6, PSA 124.11, QED 0.14
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c3c(cc(-n4cnc(C)c4)nc13)C(=O)N2C
InChIKey: FSMTUHGXWGJNKK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from BRD2 BD2 (unknown origin) incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 21450 nM (pChEMBL 4.670000076293945)
Descriptors: MW 449.49, ALogP 3.13, HBA 7, HBD 1, PSA 106.42, QED 0.5
Compound (SMILES): COc1cc(Br)cc2[nH]cc(-c3cnc(-c4ccc[nH]4)o3)c12
InChIKey: HCBIATVCCJRSKR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase SIK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K2
Assay: Inhibition of SIK3 (unknown origin) by [33P]-ATP filter binding kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.2, ALogP 4.59, HBA 3, HBD 2, PSA 66.84, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)Cc1ccc(/N=N/c2ccc(O)cc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: CYSDVHNALKAECX-NMUVOBAGSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of recombinant human SIRT3 (118 to 399 residues) defatty-acylase activity expressed in Escherichia coli using SFP3 as substrate measured at 5 mins interval for 60 mins in presence of NAD+ by fluorescence assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 1014.2
Compound (SMILES): CC(C)OP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: PEQTVDTVQHQBMY-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 355.35, ALogP 2.66, HBA 5, HBD 1, PSA 95.69, QED 0.8
Compound (SMILES): COC(=O)c1ccc(CS(=O)(=O)c2ccc3nc(N)sc3c2)cc1
InChIKey: OXCYJIKKVMXIOQ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 362.43, ALogP 2.64, HBA 7, HBD 1, PSA 99.35, QED 0.72
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)CN)CSSC[C@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: LCMSWGVHKJDKHX-ZFWCQMGFSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin) using Ac-ATPRpNA as substrate incubated for 30 mins measured for 7 mins by morrison plot analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 3517.98
Compound (SMILES): O[C@@H](C[C@H]1c2c(F)cccc2-c2cncn21)[C@H]1CC[C@H](O)CC1
InChIKey: YGACXVRLDHEXKY-HJXMPXNTSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 316.38, ALogP 2.89, HBA 4, HBD 2, PSA 58.28, QED 0.92
Compound (SMILES): O=c1oc2ccccc2cc1CO[C@H]1[C@@H](O)[C@@H](CO)O[C@@H](S[C@@H]2O[C@H](CO)[C@H](O)[C@H](OCc3cc4ccccc4oc3=O)[C@H]2O)[C@@H]1O
InChIKey: NUVVBMDSAGKGGC-PBGHOUHASA-N
Target: Galectin-8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00214
Assay: Competitive binding affinity to recombinant human galectin-8 N-terminal after 5 mins in presence of fluorescent probe 2-(fluorescein-5-yl-carbonylamino)ethyl beta-D-galactopyranosyl(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl(1-3)-beta-D-galactopyranosyl(1-4)-beta-D-glucopyranoside by fluorescence polarization assay
Measurement: Kd = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 674.68, ALogP -0.02, HBA 15, HBD 6, PSA 218.72, QED 0.12
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc2n1C1CCCC1
InChIKey: CZQMPFCNIINMMC-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: LANCE Ultra ULight 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 100x, 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 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE 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 x10000 was used as the final data for analysis.
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 532.64, ALogP 5.25, HBA 8, HBD 1, PSA 75, QED 0.35
Compound (SMILES): CN(CCc1ccc(-c2ccccc2)cc1)Cc1cn(C)c2ccc(C(=O)Nc3ccc(F)cc3)cc12
InChIKey: XYNOVGMRAYSMEO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13233
Assay: Inhibition of recombinant human N-terminal 4xFLAG-tagged/C-terminal His8 fused MAP3K1 C-terminal domain (M1193 to W1512 residues) expressed in Sf9 insect cells using Bio-RS-Peptide as substrate measured after 60 mins in presence of [gamma-33P]-ATP by scintillation counting method
Measurement: IC50 = 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 491.61, ALogP 6.91, HBA 3, HBD 1, PSA 37.27, QED 0.26
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3Cl)c3c(F)cccc32)cc1
InChIKey: VQSPTRMJQBBPEN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 428.25, ALogP 6.01, HBA 3, HBD 1, PSA 59.3, QED 0.41
Compound (SMILES): Cc1cc(-c2cnc3ccn(CC4CCOC4)c3c2)ccc1F
InChIKey: QOOQJPOGMSVFBK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG expressed in HEK293 cell membranes measured after 80 mins by TopCount scintillation analysis
Measurement: Ki = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 310.37, ALogP 4.19, HBA 3, HBD 0, PSA 27.05, QED 0.73
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)NC1CCCc2ccccc21
InChIKey: IBDVKPRUZGKSPR-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as decrease in CP55940-induced beta-arrestin recruitment pretreated with non-selective cannabinoid receptor agonist CP55940 for 30 mins and measured after 20 mins by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 348.47, ALogP 4.93, HBA 3, HBD 1, PSA 41.99, QED 0.73
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccccc1Cl
InChIKey: JRMTVHPMEDOUHD-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 86000 nM (pChEMBL 4.070000171661377)
Descriptors: MW 384.84, ALogP 4.95, HBA 4, HBD 1, PSA 72.2, QED 0.54
Compound (SMILES): COc1ccc(NC(=O)C2CCN(c3ncccc3C)CC2)cc1Cl
InChIKey: LYNICYGLTYJRMV-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 in human OCI-LY3 cells assessed as reduction in Rel-b cleavage
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 359.86, ALogP 3.91, HBA 4, HBD 1, PSA 54.46, QED 0.9
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: DHWJFHNJLLGOEU-YGPXUFAZSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 3966.5
Compound (SMILES): C=CC(=O)Nc1ccc(-n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)cc1
InChIKey: HKMTYQNMRIBAHX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of human VEGFR1 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.46, ALogP 3.85, HBA 7, HBD 3, PSA 131.83, QED 0.36
Compound (SMILES): Cc1nn(CC(F)(F)F)cc1Nc1ncc(Br)c(NCc2ccc(S(N)(=O)=O)cc2)n1
InChIKey: FFPHMUIGESPOTK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of recombinant human TBK1 using MBP as substrate in presence of gamma-33P]-ATP by Hotspot assay
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 520.34, ALogP 3.31, HBA 8, HBD 3, PSA 127.82, QED 0.44
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@@H]1CCN(C(=O)C2CC2)c2ccc(Cc3ccc4ccccc4c3)cc21.O=C(O)C(F)(F)F
InChIKey: CIBYNSHRIWRSKF-XJEPUKKESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 1 hr
Measurement: EC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 547.7, ALogP 5.63, HBA 4, HBD 3, PSA 95.66, QED 0.28
Compound (SMILES): N#CC(C(=O)NCC(=O)NC1COC1)c1nc2ccc(-c3ccc(F)nc3)cc2s1
InChIKey: XNXVLLZYFKJWLJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 425.45, ALogP 1.74, HBA 7, HBD 2, PSA 117, QED 0.58
Compound (SMILES): COc1cc2c(Oc3ccc(C4SCC(=O)N4NC(=O)Nc4ccc(F)cc4F)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: MDXPQQJSGHVAGT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using FAM-labelled peptide as substrate measured after 10 mins by mobility shift assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 696.75, ALogP 5.78, HBA 9, HBD 2, PSA 108.5, QED 0.19
Compound (SMILES): COC[C@H](C(=O)Nc1cccc2c(-c3nc(Nc4cccc(S(C)(=O)=O)c4F)ncc3F)c[nH]c12)N1CCN(C)CC1
InChIKey: JNUZADQZHYFJGW-JOCHJYFZSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Inhibition Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132, AstraZeneca R&D Boston), or JAK3 (amino acids 781-1124, AstraZeneca R&D Boston) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 μg/ml BSA, and 10 mM MgCl2. JAK enzyme was expressed as N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed at their approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations.For JAK1, 4 nM of enzyme was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.3 nM enzyme was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.), For JAK3, 0.1 nM enzyme was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NII2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphotylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition.
Measurement: IC50 = 1220 nM (pChEMBL 5.909999847412109)
Descriptors: MW 599.66, ALogP 3.25, HBA 9, HBD 3, PSA 132.55, QED 0.27
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4ccccc4C(F)(F)F)cc3F)ccnc2cc1OCCCN1CCC(C)CC1
InChIKey: DGKPSIOJHHBXOP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 647.69, ALogP 7.5, HBA 7, HBD 1, PSA 89.99, QED 0.13
Compound (SMILES): C#CCOP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: QPPDZAQVRNMGGM-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 351.32, ALogP 1.88, HBA 5, HBD 1, PSA 95.69, QED 0.63
Compound (SMILES): CCn1ncc(-c2nc3c(N4CCC(n5c(=O)[nH]c6ncccc65)CC4)ncnc3n2C)c1C
InChIKey: WRPLWRLROFHFJF-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of PDE2 (unknown origin)
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 458.53, ALogP 2.43, HBA 10, HBD 1, PSA 115.34, QED 0.44
Compound (SMILES): CC1=C(c2cccc(O)c2)[C@H](c2ccc(OCCN3CC(CF)C3)cc2)Oc2ccc(O)cc21
InChIKey: KJAAPZIFCQQQKX-NDEPHWFRSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 461.53, ALogP 5.44, HBA 5, HBD 2, PSA 62.16, QED 0.49
Compound (SMILES): O=C(Nc1n[nH]c2cc(-c3cccc(CNS(=O)(=O)CCC(F)(F)F)c3)ccc12)C1CC1
InChIKey: NTOMZGNNDKIPEH-UHFFFAOYSA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Inhibition of tracer K5 binding to N-terminal nano luciferase-fused BMP2K (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition and measured within 10 mins by NanoBRET assay
Measurement: IC50 = 1890 nM (pChEMBL 5.71999979019165)
Descriptors: MW 466.49, ALogP 3.95, HBA 4, HBD 3, PSA 103.95, QED 0.47
Compound (SMILES): CC(Oc1ccccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: CSWAXADHPUYFGC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor expressed in CHO-K1 cells incubated for 1 hr by microbeta counting method
Measurement: Ki = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 348.84, ALogP 2, HBA 7, HBD 1, PSA 80.4, QED 0.9
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccccc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: SXKKMGOPECZXNY-JJMBJGOUSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Activity at LXRalpha (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 635.6, ALogP 6.08, HBA 4, HBD 1, PSA 91.75, QED 0.4
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)NC34CCC(C(N)=O)(CC3)CC4)nc3cnc4[nH]ccc4c32)CC1
InChIKey: VGQGFYCOZCNACG-RWSJPRBTSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 487.61, ALogP 3.79, HBA 6, HBD 3, PSA 142.48, QED 0.48
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cccc(F)c5)CC4)cn3)nccc12
InChIKey: FJLXFYHDLHZPQK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4C1
Assay: Inhibition of KDM3A (unknown origin) by Alphascreen assay
Measurement: IC50 = 6420 nM (pChEMBL 5.190000057220459)
Descriptors: MW 418.48, ALogP 3.07, HBA 6, HBD 1, PSA 79.7, QED 0.54
Compound (SMILES): Cc1cc(-c2ccc(C(F)(F)F)cn2)[nH]c1C(=O)N[C@@H](CN)c1ncc(CO)s1
InChIKey: BILBXEUAJZPBIW-AWEZNQCLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 425.44, ALogP 2.78, HBA 6, HBD 4, PSA 116.92, QED 0.48
Compound (SMILES): O=S(=O)(Nc1ccc2oc(-c3ccccc3)nc2c1)c1ccc(F)cc1
InChIKey: ZWOGDTJABZSCJD-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 368.39, ALogP 4.43, HBA 4, HBD 1, PSA 72.2, QED 0.58
Compound (SMILES): CCSP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: DPWUIFSNYYMDBQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant carbonic anhydrase 7 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 357.39, ALogP 2.98, HBA 5, HBD 1, PSA 86.46, QED 0.8
Compound (SMILES): Cc1cnc(Nc2ccc(N3CCC(N(C)CCO)CC3)c(F)c2)nc1-c1cnn(C(C)C)c1
InChIKey: CVLXNRIQVFIVGY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 467.59, ALogP 4.01, HBA 8, HBD 2, PSA 82.34, QED 0.52
Compound (SMILES): COc1cccc(S(=O)(=O)Nc2ccc(-c3nc4ccccc4o3)cc2)c1
InChIKey: NVNKICRJZZVDMB-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 76000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 380.43, ALogP 4.3, HBA 5, HBD 1, PSA 81.43, QED 0.56
Compound (SMILES): CC(C)(C)c1cc(NC(=O)COC(=O)c2ccc(-n3cnnn3)cc2)n(-c2ccccc2)n1
InChIKey: PRZQRZSCFWKYBL-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of inactive recombinant human His-tagged TrkB expressed in baculovirus expression system preincubated for 20 mins followed by ATP/SRCtide substarte addition further incubated for 2 hrs by caliper microfluidic mobility shift assay
Measurement: IC50 = 47.1 nM (pChEMBL 7.329999923706055)
Descriptors: MW 445.48, ALogP 2.94, HBA 9, HBD 1, PSA 116.82, QED 0.45
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2ccc(Cl)c(Cl)c2)cc1
InChIKey: ARSRPMMXCDOZIA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 expressed in HEK293T/17 cells using Ac-GAK(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 339.18, ALogP 3.04, HBA 3, HBD 3, PSA 78.43, QED 0.59
Compound (SMILES): O=C1Nc2cccc(n2)-c2nncn2CCCCCOc2ccccc21
InChIKey: LYYWIICEGIMSTN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: TR-FRET Assay: Table 1: Briefly, 20 μL aliquots of a 1.5× stock of ASK1, STK Substrate 3 and Assay Buffer were distributed in the wells of a white 384 well Optiplate, prior to addition of 0.3 μL of a 100× compound stock in DMSO, or DMSO alone in Blank and 100% Activity Controls. After a 10 minute pre-incubation, ASK1 protein kinase activity was initiated by addition of 10 μL of 300 μM ATP. After 5 hours, the kinase activity was quenched by addition of 30 μL of CisBio Kit 62ST3PEJ components: 0.5 μM of Streptavidin XL665; and 100×STK Antibody-Eu Cryptate; in Detection Buffer containing sufficient EDTA to chelate Mg2+ in the assay buffer. The plates were read after 65 minutes in an Envision Plate reader, with the following components and settings: Top Mirror, Lance Delfia Dual (662); UV Ex Filter, 320 nm (111); Emission Filter for donor, 615 nm (203); Emission Filter for Acceptor; 665 nM (205); and 100 usec delay, with 665/615 ratio output.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 349.39, ALogP 3.16, HBA 6, HBD 1, PSA 81.93, QED 0.67
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3ccc(C(F)(F)F)cc3B(O)O2)cc1OCc1cccnc1
InChIKey: DFCWVDGZBOIYOG-UHFFFAOYSA-N
Target: Kallikrein-14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0G3
Assay: Inhibition of recombinant human C-terminal 10-His-tagged KLK14 (Q19 to M248 residues) expressed in mouse NS0 cells using BOC-VPR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 441.22
Compound (SMILES): COCCS(=O)(=O)Nc1cc(-c2cc3c(c(O[C@@H](C)CN4CCC(C(C)(C)O)CC4)c2)COC3)cnc1OC
InChIKey: RPZIXRBMHRKWST-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human HL60 cell extract measured after 2 hrs by kinobeads based pull down assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 563.72, ALogP 3.43, HBA 9, HBD 2, PSA 119.45, QED 0.4
Compound (SMILES): Nc1nc2[nH]c(CCOc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1
InChIKey: VFYUKZOGWIMWFW-AWEZNQCLSA-N
Target: Folate receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P14207
Assay: Inhibition of human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue fluorescence analysis
Measurement: IC50 = 2.59 nM (pChEMBL 8.59000015258789)
Descriptors: MW 443.42, ALogP 0.5, HBA 7, HBD 6, PSA 200.49, QED 0.26
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)Cc1ccc(/N=N/c2ccccc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: WPBXUCGYRGXSCG-LVFYHKNWSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 998.2, ALogP 1.38, HBA 12, HBD 14, PSA 386.44, QED 0.02
Compound (SMILES): COc1ccc2c(c1)c(C1=CCNCC1)cn2S(=O)(=O)c1ccc2cccnc2c1
InChIKey: YMLDFYDEWIBRLP-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 HEK293 cells by microbeta liquid scintillation counting
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 419.51, ALogP 3.81, HBA 6, HBD 1, PSA 73.22, QED 0.54
Compound (SMILES): N#Cc1ccc(S(=O)(=O)Nc2cccc(-c3ccc(C(=O)c4cc(F)c(F)c(O)c4F)s3)c2)cc1
InChIKey: KHIRYSLWKHQOIK-UHFFFAOYSA-N
Target: Estradiol 17-beta-dehydrogenase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P51657
Assay: Inhibition of recombinant rat 17beta-HSD1 expressed in HEK293 cells using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis
Measurement: IC50 = 1334 nM (pChEMBL 5.880000114440918)
Descriptors: MW 514.51, ALogP 5.44, HBA 6, HBD 2, PSA 107.26, QED 0.26
Compound (SMILES): COc1cc(OC)c2c(c1)OC[C@@]1(C)NCC[C@@H]21
InChIKey: NYBQQHJGLBCUBL-IINYFYTJSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Displacement of [3H]5-CT from human recombinant 5-HT1B receptor expressed in stable HEK cells after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 249.31, ALogP 1.93, HBA 4, HBD 1, PSA 39.72, QED 0.87
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@H](O)CC1)c(=O)n2C
InChIKey: XGWVDWGXBYRXIX-JOCQHMNTSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Enzyme Assay: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z′-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen Biochemical Kinase Profiling Service. The Z′-LYTE biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophore on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 394.44, ALogP 1.7, HBA 10, HBD 2, PSA 115.16, QED 0.54
Compound (SMILES): Nc1nc(-c2ccc(OCCNC(=O)CCCCC3CCSS3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: QUUSOCIUFGWWEB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]NECA from rat adenosine A2A receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 550.71, ALogP 4.34, HBA 10, HBD 2, PSA 116.54, QED 0.21
Compound (SMILES): O=S(=O)(Nc1ccc2oc(-c3ccccc3)nc2c1)c1ccc(C(F)(F)F)cc1
InChIKey: WVOXPLQUMVLIKP-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 64000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 418.4, ALogP 5.31, HBA 4, HBD 1, PSA 72.2, QED 0.49
Compound (SMILES): CC1(C)CCN1Cc1cccc(F)c1CNc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1Cl
InChIKey: RGBIVRJIERNIRK-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 513.04, ALogP 5.47, HBA 6, HBD 2, PSA 74.33, QED 0.42
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(F)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: MLXUDJPUEMLBKJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR exon19 deletion mutant (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 585.71, ALogP 4.42, HBA 10, HBD 3, PSA 128.79, QED 0.25
Compound (SMILES): Cc1cc(NC(=O)C2CC(=O)N(c3ccccc3)C2)cc(C)c1S(N)(=O)=O
InChIKey: XKSNHXULXLMTSO-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 387.46, ALogP 1.94, HBA 4, HBD 2, PSA 109.57, QED 0.84
Compound (SMILES): O=C(O)C[C@H](CN1CC[C@@](F)(CCc2ccc3c(n2)NCCC3)C1)c1cccc(N2CCOCC2)c1
InChIKey: HKDUWRRLEDNORE-LXFBAYGMSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Binding affinity to Integrin alphaVbeta6 (unknown origin)
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 496.63, ALogP 3.88, HBA 6, HBD 2, PSA 77.93, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC(C(=O)O)CC2=O)cc1
InChIKey: PQTYDOPYQOAELL-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 284.29, ALogP -0.23, HBA 4, HBD 2, PSA 117.77, QED 0.79
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(C(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: QIEKHLDZKRQLLN-FOIQADDNSA-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 = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 471.53, ALogP 2.04, HBA 8, HBD 2, PSA 117.42, QED 0.69
Compound (SMILES): O=C(CC(=O)Nc1ccc2c(/C=C/c3ccccn3)n[nH]c2c1)Nc1cccc(F)c1
InChIKey: OLZDZYHEIBZXCI-CSKARUKUSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of TEL fused wild type c-KIT (unknown origin) transfected in mouse BaF3 cells assessed as reduction in phosphorylation at Y719 residue after 2 hrs by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 415.43, ALogP 4.23, HBA 4, HBD 3, PSA 99.77, QED 0.41
Compound (SMILES): O=C(NNS(=O)(=O)c1ccccc1)c1cc(-c2ccnnc2)ccc1F
InChIKey: WYMCVPPNOFFNGE-UHFFFAOYSA-N
Target: Alpha-2A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08913
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000327a ADRA2A
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 372.38, ALogP 1.91, HBA 5, HBD 2, PSA 101.05, QED 0.67
Compound (SMILES): CO[C@H]1/C=C/C[C@H](C)[C@@H](C)S(=O)(=O)NC(=O)c2ccc3c(c2)N(C[C@@H]2CC[C@H]21)C[C@@]1(CCCc2cc(Cl)ccc21)CO3
InChIKey: JQNINBDKGLWYMU-GEAQBIRJSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of human Biotin-DMRPEIWIAQELRRIGDEFNAYYARR peptide binding to Bcl-xL (unknown origin) after 120 mins by fluorescence polarization assay
Measurement: Ki = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 613.22, ALogP 5.9, HBA 6, HBD 1, PSA 84.94, QED 0.4
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2c3c(cc(-n4cnc(C)c4)nc13)C(=O)N2C
InChIKey: FSMTUHGXWGJNKK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Displacement of tetra-acetylated histone H4 peptide (1-21) from BRD3 BD2 (unknown origin) incubated for 30 mins followed by further incubation with tetra-acetylated histone H4 peptide (1-21) for 30 mins by Alphascreen assay
Measurement: IC50 = 49770 nM (pChEMBL 4.300000190734863)
Descriptors: MW 449.49, ALogP 3.13, HBA 7, HBD 1, PSA 106.42, QED 0.5
Compound (SMILES): COc1cc(Br)cc2[nH]cc(-c3cnc(-c4ccc[nH]4)o3)c12
InChIKey: HCBIATVCCJRSKR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of GCK (unknown origin) by [33P]-ATP filter binding kinase assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 358.2, ALogP 4.59, HBA 3, HBD 2, PSA 66.84, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)Cc1ccc(/N=N/c2ccc(O)cc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: CYSDVHNALKAECX-NMUVOBAGSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1014.2
Compound (SMILES): CC(C)OP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: PEQTVDTVQHQBMY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 355.35, ALogP 2.66, HBA 5, HBD 1, PSA 95.69, QED 0.8
Compound (SMILES): COC(=O)c1ccc(CS(=O)(=O)c2ccc3nc(N)sc3c2)cc1
InChIKey: OXCYJIKKVMXIOQ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human CYP3A4 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 362.43, ALogP 2.64, HBA 7, HBD 1, PSA 99.35, QED 0.72
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)CN)CSSC[C@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: LCMSWGVHKJDKHX-ZFWCQMGFSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using Ac-RM(O2)YRpNA as substrate incubated for 30 mins measured for 7 mins by morrison plot analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 3517.98
Compound (SMILES): O[C@@H](C[C@H]1c2c(F)cccc2-c2cncn21)[C@H]1CC[C@H](O)CC1
InChIKey: YGACXVRLDHEXKY-HJXMPXNTSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 316.38, ALogP 2.89, HBA 4, HBD 2, PSA 58.28, QED 0.92
Compound (SMILES): O=c1oc2ccccc2cc1CO[C@H]1[C@@H](O)[C@@H](CO)O[C@@H](S[C@@H]2O[C@H](CO)[C@H](O)[C@H](OCc3cc4ccccc4oc3=O)[C@H]2O)[C@@H]1O
InChIKey: NUVVBMDSAGKGGC-PBGHOUHASA-N
Target: Galectin-9 (SINGLE PROTEIN), Homo sapiens
UniProt: O00182
Assay: Competitive binding affinity to recombinant human galectin-9 N-terminal after 5 mins in presence of fluorescent probe 2-(fluorescein-5-yl-carbonylamino)ethyl-beta-D-galactopyranosyl(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl(1-3)-beta-D-galactopyranosyl(1-4)-beta-D-glucopyranoside by fluorescence polarization assay
Measurement: Kd = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 674.68, ALogP -0.02, HBA 15, HBD 6, PSA 218.72, QED 0.12