lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](N)[C@@H](C)O)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: DMUCPCOXWVUTMX-VLSRZGDXSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P04757
Assay: Antagonist activity at rat alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 8410 nM (pChEMBL 5.079999923706055)
Descriptors: MW 3422.84
Compound (SMILES): COc1ccc(Cl)cc1S(=O)(=O)Nc1ccc2oc(-c3ccc(NS(=O)(=O)c4ccc(Cl)s4)cc3)nc2c1
InChIKey: LZBFCHWAVQXCHZ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 610.52, ALogP 6.47, HBA 8, HBD 2, PSA 127.6, QED 0.21
Compound (SMILES): Cn1cncc1-c1c[nH]c2ccc(Br)cc12
InChIKey: NGEGVUWXHYDOQM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human recombinant 5-HT7B receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 276.14, ALogP 3.33, HBA 2, HBD 1, PSA 33.61, QED 0.73
Compound (SMILES): Cn1cc(Nc2nccc(N3C[C@H]4CC[C@H](C3)N4C(=O)NCC(F)(F)F)n2)cn1
InChIKey: CEDPCXUZXQKZKH-CHWSQXEVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 using fluorescence labeled peptide as substrate and using 1 mM ATP by microfluidic based mobility shift assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 410.4, ALogP 1.88, HBA 7, HBD 2, PSA 91.21, QED 0.8
Compound (SMILES): COc1nc(N[C@@H](C)c2cc3cc(Cl)c(OC(C)C)cc3[nH]c2=O)ncc1C#N
InChIKey: PVBTVTWQUGLJJL-NSHDSACASA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 413.87, ALogP 3.81, HBA 7, HBD 2, PSA 112.92, QED 0.63
Compound (SMILES): Cn1cc(-c2ccc(N3CCC([C@H]4c5c(F)cccc5-c5cncn54)CC3)cc2)cn1
InChIKey: UJGQDAMZVUNFBQ-VWLOTQADSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta measured after 1 hr microplate reader analysis
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 413.5, ALogP 4.91, HBA 5, HBD 0, PSA 38.88, QED 0.48
Compound (SMILES): CCC(F)(F)c1cc(N2CCC(S(C)(=O)=O)CC2)nc2sc(C(N)=O)c(N)c12
InChIKey: IYHHRZBKXXKDDY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0001492b DRD3
Measurement: Ki = 428.07 nM (pChEMBL 6.369999885559082)
Descriptors: MW 432.52, ALogP 2.49, HBA 7, HBD 2, PSA 119.38, QED 0.75
Compound (SMILES): CCn1c(=O)c2c(C)c(C(=O)N3CCC(O)CC3)sc2n(CCC(F)(F)F)c1=O
InChIKey: NTYVAKNEYLJAPT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate after 15 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 433.45, ALogP 2.1, HBA 7, HBD 1, PSA 84.54, QED 0.8
Compound (SMILES): Cl.Nc1ncccc1-c1nc2ccc(-c3ccccc3)nc2n1-c1ccc(C2(N)CCC2)cc1
InChIKey: DRHSWSSVIKDJME-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Inhibition of full length unphosphorylated AKT2 (1 to 481 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by Alphascreen assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 432.53, ALogP 5.07, HBA 6, HBD 2, PSA 95.64, QED 0.41
Compound (SMILES): CC(=O)Oc1c(C)cc2c(c1OC(C)=O)-c1cccc3c1[C@@H](C2)N(C)CC3
InChIKey: IYCVIMNLFPKSNJ-GOSISDBHSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at D1R (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: EC50 = 1548.82 nM (pChEMBL 5.809999942779541)
Descriptors: MW 365.43, ALogP 3.6, HBA 5, HBD 0, PSA 55.84, QED 0.6
Compound (SMILES): CC1=C[C@@H]2Cc3nc4cc(F)ccc4c(N)c3[C@H](C1)C2
InChIKey: CPGLYAIYMGVIIO-WDEREUQCSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of butyrylcholinesterase (BChE) activity in human serum
Measurement: IC50 = 2930 nM (pChEMBL 5.53000020980835)
Descriptors: MW 268.33, ALogP 3.95, HBA 2, HBD 1, PSA 38.91, QED 0.73
Compound (SMILES): O=C(NO)[C@@]1(NS(=O)(=O)c2ccc(Oc3ccc(F)cc3)cc2)C[C@H]2CC[C@@H](C1)O2
InChIKey: REZSPXZZCJTZIK-XEMDLRDOSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of matrix metalloprotease-9
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 436.46, ALogP 2.48, HBA 6, HBD 3, PSA 113.96, QED 0.47
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccc(Cl)cc1
InChIKey: QATIKBIGSDAPRI-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 23700 nM (pChEMBL 4.619999885559082)
Descriptors: MW 233.7, ALogP 3.32, HBA 2, HBD 1, PSA 35.25, QED 0.83
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)[C@H](C)CN(c2cc(C(=O)O)cc4c2OCO4)C3=O)cc(C)c1Cl
InChIKey: HEVVLFVAUFXERT-HXUWFJFHSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Fluorescence Polarization Anisotropy Competition Assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2)that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207 A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. For the FITC-BAK assay 2.5 uL compound is added to 47.5 μL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 μM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. For the FITC-Bim assay, compound is added to 40 uL of assay buffer containing protein, 15 minutes prior to addition of 10 μL of the FITC-Bim peptide, for a final DMSO concentration of 0.165% and a top concentration of 200 nM. A FITC-Bim peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature.
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 703.62, ALogP 8.24, HBA 8, HBD 1, PSA 108.05, QED 0.16
Compound (SMILES): CCOP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: SKWKPUDZFINNSN-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human recombinant carbonic anhydrase 5B preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 40.1 nM (pChEMBL 7.400000095367432)
Descriptors: MW 341.33, ALogP 2.27, HBA 5, HBD 1, PSA 95.69, QED 0.81
Compound (SMILES): CNC(=O)CN(CCc1ccc(Cl)cc1)C1CCN(c2nc(N)n[nH]2)CC1
InChIKey: WMSNBGASPSHJJO-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human acidic mammalian chitinase expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 391.91, ALogP 1.3, HBA 6, HBD 3, PSA 103.17, QED 0.66
Compound (SMILES): CCCCCCCC(=O)SCC/C=C(\F)[C@@H]1CC(=O)NCc2nc(cs2)C2=N[C@@](C)(CS2)C(=O)N[C@@H](C(C)C)C(=O)O1
InChIKey: SFAXIIRLEIWVMY-DYFJFAIHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length C-terminal His-tagged human HDAC8 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 240 mins by fluorescence based assay
Measurement: IC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 640.87, ALogP 5.33, HBA 10, HBD 2, PSA 126.82, QED 0.25
Compound (SMILES): CC(=O)N1CCCn2c1nc(C)c2-c1cn(S(=O)(=O)c2ccccc2)c2ccccc12
InChIKey: QHDSLCOANJPNLJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 434.52, ALogP 3.81, HBA 6, HBD 0, PSA 77.2, QED 0.49
Compound (SMILES): COc1nc(N[C@@H](C)c2cc3cc(Cl)c(F)cc3[nH]c2=O)ncc1C#N
InChIKey: UCQMQHNCVXBAFQ-QMMMGPOBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 M Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 373.78, ALogP 3.16, HBA 6, HBD 2, PSA 103.69, QED 0.73
Compound (SMILES): CCOP(=O)(OCC)N(C)CCN1CCc2nc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)ccc2C1
InChIKey: SAIXTBXXQWMWMW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
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 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 628.67, ALogP 6.27, HBA 10, HBD 1, PSA 110.53, QED 0.18
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2C[C@H]1CCCN1C[C@@H]1CO1
InChIKey: LXURGGKEOPHREO-DENIHFKCSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Inhibition of human recombinant TXK using Ulight-Poly GAT[EAY(1:1:1) as substrate measured after 30 mins in the presence of ATP by LANCE method
Measurement: IC50 = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 441.54, ALogP 4.34, HBA 7, HBD 1, PSA 81.73, QED 0.43
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)Cn2ccnc2C(N)=N1
InChIKey: PURBTYQRCRLUGF-FQEVSTJZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in HEK293 cells at -80 mV holding potential by automated patch-clamp method
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 389.39, ALogP 2.18, HBA 7, HBD 2, PSA 121.98, QED 0.71
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(C4CCN(CC5CCC5)CC4)cn3)nccc12
InChIKey: FQYVJQRHNLIPIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay
Measurement: IC50 = 559 nM (pChEMBL 6.25)
Descriptors: MW 364.45, ALogP 2.48, HBA 6, HBD 1, PSA 79.7, QED 0.77
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2OC3(CCCCC3)O[C@H]21
InChIKey: MYODNHHKQWEUOO-GLBHFFKESA-N
Target: P2X purinoceptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99571
Assay: Antagonist activity at human P2X4R transfected in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx
Measurement: IC50 = 29600 nM (pChEMBL 4.53000020980835)
Descriptors: MW 587.31, ALogP 1.09, HBA 14, HBD 5, PSA 257.13, QED 0.27
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC1CC1CCNC(=O)c1cc2ccccc2[nH]1
InChIKey: JQBHQHNVJCDNEL-ZCLRBYCSSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEK293 cell membranes measured after 60 mins by scintillation counting method
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 433.56, ALogP 3.36, HBA 5, HBD 3, PSA 96.27, QED 0.53
Compound (SMILES): CN1CCC(CNC(=O)c2cccc(-c3noc(C(F)(F)F)n3)c2)(c2nc(-c3ccccc3)cs2)CC1
InChIKey: BQFISAUAZNJOEG-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: Ki > 23000 nM (pChEMBL 4.638000011444092)
Descriptors: MW 527.57, ALogP 5.27, HBA 7, HBD 1, PSA 84.15, QED 0.37
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)[C@H](C)CN(c2cccc4c(C(=O)O)cccc24)C3=O)cc(C)c1Cl
InChIKey: RRWFCNKYNKGARG-HSZRJFAPSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Fluorescence Polarization Anisotropy Competition Assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2)that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207 A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. For the FITC-BAK assay 2.5 uL compound is added to 47.5 μL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 μM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. For the FITC-Bim assay, compound is added to 40 uL of assay buffer containing protein, 15 minutes prior to addition of 10 μL of the FITC-Bim peptide, for a final DMSO concentration of 0.165% and a top concentration of 200 nM. A FITC-Bim peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature.
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 709.67, ALogP 9.67, HBA 6, HBD 1, PSA 89.59, QED 0.16
Compound (SMILES): CNCCNC(=O)c1c(-c2ccccn2)c([C@H](C)Nc2ncnc(N)c2C#N)nc2ccc(F)cc12
InChIKey: XGWXHMIKUSFVER-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Mus musculus
UniProt: O35904
Assay: Inhibition of PI3Kdelta in BALB/c mouse B cells assessed as reduction in Anti-IgM induced AKT Ser473 phosphorylation pre-incubated for 45 mins before Anti-IgM stimulation
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 485.53, ALogP 2.8, HBA 9, HBD 4, PSA 154.53, QED 0.28
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(Cl)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: ASSZTGFDWPKORU-NIULTJEISA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Activity at RORbeta (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 670.04, ALogP 6.74, HBA 4, HBD 1, PSA 91.75, QED 0.36
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc3c(c2)S(=O)(=O)NC3=O)cc1
InChIKey: YFCUDZKVJVWEAU-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human carbonic anhydrase 7 preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 316.34, ALogP 1.68, HBA 4, HBD 2, PSA 92.34, QED 0.88
Compound (SMILES): O=C(O)[C@H]1CNC[C@@H](CN/N=C/c2ccc(-c3cccc4ccccc34)o2)C1
InChIKey: LJBVJKRYRCGTBC-NBWFOSRTSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30531
Assay: Non-competitive inhibition of human GAT1 expressed in COS cells assessed as reduction in [2H6]GABA uptake by measuring [2H6]GABA Kd(app) at 1 uM preincubated for 25 mins followed by [2H6]GABA addition and measured after 4 mins by liquid scintillation counting method (Rvb = 28.3 +/- 1.5 nM)
Measurement: Kd = 56 nM (pChEMBL 7.25)
Descriptors: MW 377.44, ALogP 3.33, HBA 5, HBD 3, PSA 86.86, QED 0.45
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cccc(Cl)c1.Cl
InChIKey: WMZQIFSWRNNLKA-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH23390 from recombinant human D5 receptor transiently expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 8670 nM (pChEMBL 5.059999942779541)
Descriptors: MW 449.04, ALogP 6.52, HBA 2, HBD 1, PSA 32.34, QED 0.34
Compound (SMILES): CCc1cc(F)c2nc(N3CCC(N[C@H]4CCOC4)CC3)c(-c3nc(C)no3)cc2c1
InChIKey: MUONIRNLLGRCTP-SFHVURJKSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: OPR Mu Antagonist Assay: The purpose of this assay is to confirm the potency and selectivity of compounds synthesized to be OPRK1 Antagonists. This assay monitors the OPRMu1 activation, in membrane recruitment of β-arrestin. The assay monitors GPCR-β-arrestin proximity using low affinity fragment complementation of beta-galactosidase (beta-gal). It employs U20S cells which express OPRMu1 fused to the complementary beta-gal fragment (enzyme acceptor). As designed, compounds that act as antagonists will prevent receptor activation resulting in reduce well luminescence. Compounds were tested in triplicate using a 10-point, 1:3 dilution series starting at a nominal concentration of 10 micromolar.The Discover X OPRMu1-U20S cell line was routinely cultured in T175 flasks at 37° C., 5% CO2 and 95% relative humidity (RH). The growth media consisted of DMEM/F12 1:1 Media supplemented with 10% v/v heat inactivated fetal bovine serum, 25 mM HEPES, Non-essential amino acids, 1 mM Sodium Pyruvate, 1× antibiotic mix (penicillin streptomycin) plus 500 ug/mL Geneticin and 300 ug/mL Hygromycin (selection antibiotics).On Day 1 of the assay, 5000 cells in 20 ul of assay buffer (Discover X's Cell Plating Reagent 5) were seeded into each well of a 384 Corning 3570 standard white plate, and incubated 16-24 hours at 37° C., 5% CO2 and 95% (RH). On Day 2, 100 nl of test compound in DMSO was added to the appropriate wells, 100 nl of DMSO added to control wells and plates were incubated for 30 min at 37° C., 5% CO2 and 95% (RH). Next 100 nl of DAMGO OPRMu1 or DMSO in assay media (EC80 Challenge consists of 100 nl of 50 uM DAMGO, final assay concentration=250 nM, 100% Response wells receive 100 nl 200 uM DAMGO). After incubation for 3 hours at 37° C., 5% CO2 and 95% (RH), 10 ul of Path Hunter Detection Mix is added to each well, plate placed on a plate rotator/mixer for 10 minutes and then incubated at room temperature, in the dark for 1 hour. Well luminescence was measured on Perkin Elmer's Envision.The Percent Inhibition was calculated from the median ratio as follows:% ⁢ ⁢ Inhibition = 100 - ( 100 ⁢ ( Compound ⁢ ⁢ Well - 0 ⁢ % ⁢ ⁢ Response ⁢ ⁢ Well EC ⁢ ⁢ 80 ⁢ ⁢ Control ⁢ ⁢ Well - 0 ⁢ % ⁢ ⁢ Response ⁢ ⁢ Well ) )where:    COMPOUND WELL is defined as the well containing test compound;    EC80 CONTROL WELL is defined as wells containing DAMGO challenge (250 nM final)=0% inhibition; and    0% RESPONSE WELL is defined as wells containing DMSO=100% inhibition.    IC50 is defined as the concentration of compound required to achieve 50% inhibition.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 425.51, ALogP 3.64, HBA 7, HBD 1, PSA 76.31, QED 0.67
Compound (SMILES): Cn1cc(-c2cc(C(=O)/N=c3\[nH]c4ccccc4n3CC(C)(C)O)ccn2)cn1
InChIKey: RBNXRNXSQJWDFU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of phosphorylated EGFR del19/T790M/C797S triple mutant (unknown origin) expressed in mouse BaF3 cells incubated for 4 hrs by Alphascreen assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 390.45, ALogP 2.28, HBA 6, HBD 2, PSA 101.09, QED 0.56
Compound (SMILES): CC[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H]2CN1C(=O)[C@H](C(C)(C)C)NC(=O)OCC(C)(C)CCCCc1cccc3c1CN(C3)C(=O)O2)C(=O)NS(=O)(=O)C1CC1
InChIKey: KUQWGLQLLVFLSM-ONAXAZCASA-N
Target: Cathepsin L2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60911
Assay: Inhibition of human Cathepsin V
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 757.95, ALogP 3.9, HBA 9, HBD 3, PSA 180.52, QED 0.39
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](N)[C@@H](C)O)CSSC[C@@H](C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: DMUCPCOXWVUTMX-VLSRZGDXSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha2beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 9060 nM (pChEMBL 5.039999961853027)
Descriptors: MW 3422.84
Compound (SMILES): Cn1cncc1-c1c[nH]c2ccc(Br)cc12
InChIKey: NGEGVUWXHYDOQM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H] raclopride from human recombinant D2L receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 1862 nM (pChEMBL 5.730000019073486)
Descriptors: MW 276.14, ALogP 3.33, HBA 2, HBD 1, PSA 33.61, QED 0.73
Compound (SMILES): Cn1cc(Nc2nccc(N3C[C@H]4CC[C@H](C3)N4C(=O)NCC(F)(F)F)n2)cn1
InChIKey: CEDPCXUZXQKZKH-CHWSQXEVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using fluorescence labeled peptide as substrate and using 1 mM ATP by microfluidic based mobility shift assay
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 410.4, ALogP 1.88, HBA 7, HBD 2, PSA 91.21, QED 0.8
Compound (SMILES): COc1nc(N[C@@H](C)c2cc3cc(Cl)c(OC(C)C)cc3[nH]c2=O)ncc1C#N
InChIKey: PVBTVTWQUGLJJL-NSHDSACASA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 M Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 413.87, ALogP 3.81, HBA 7, HBD 2, PSA 112.92, QED 0.63
Compound (SMILES): Cn1cc(-c2ccc(N3CCC([C@H]4c5c(F)cccc5-c5cncn54)CC3)cc2)cn1
InChIKey: UJGQDAMZVUNFBQ-VWLOTQADSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO in human HeLa cells using tryptophan as substrate measured after 48 hrs in presence of INF gamma microplate reader analysis
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 413.5, ALogP 4.91, HBA 5, HBD 0, PSA 38.88, QED 0.48
Compound (SMILES): CCC(F)(F)c1cc(N2CCC(S(C)(=O)=O)CC2)nc2sc(C(N)=O)c(N)c12
InChIKey: IYHHRZBKXXKDDY-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Selectivity interaction (Kinase panel (enzymatic assay, literature)) EUB0001492b GAK
Measurement: IC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 432.52, ALogP 2.49, HBA 7, HBD 2, PSA 119.38, QED 0.75
Compound (SMILES): CCn1c(=O)c2c(C)c(C(=O)N3CCC(O)CC3)sc2n(CCC(F)(F)F)c1=O
InChIKey: NTYVAKNEYLJAPT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 30 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 433.45, ALogP 2.1, HBA 7, HBD 1, PSA 84.54, QED 0.8
Compound (SMILES): Cl.Nc1ncccc1-c1nc2ccc(-c3ccccc3)nc2n1-c1ccc(C2(N)CCC2)cc1
InChIKey: DRHSWSSVIKDJME-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of full length unphosphorylated AKT3 (1 to 479 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by Alphascreen assay
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 432.53, ALogP 5.07, HBA 6, HBD 2, PSA 95.64, QED 0.41
Compound (SMILES): CC(=O)Oc1c(C)cc2c(c1OC(C)=O)-c1cccc3c1[C@@H](C2)N(C)CC3
InChIKey: IYCVIMNLFPKSNJ-GOSISDBHSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at D1R (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: EC50 = 1555 nM (pChEMBL 5.809999942779541)
Descriptors: MW 365.43, ALogP 3.6, HBA 5, HBD 0, PSA 55.84, QED 0.6
Compound (SMILES): CC1=C[C@@H]2Cc3nc4cc(F)ccc4c(N)c3[C@H](C1)C2
InChIKey: CPGLYAIYMGVIIO-WDEREUQCSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Bos taurus
UniProt: P23795
Assay: Inhibition of acetylcholinesterase (AChE)activity in bovine erythrocytes
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 268.33, ALogP 3.95, HBA 2, HBD 1, PSA 38.91, QED 0.73
Compound (SMILES): O=C(NO)[C@@]1(NS(=O)(=O)c2ccc(Oc3ccc(F)cc3)cc2)C[C@H]2CC[C@@H](C1)O2
InChIKey: REZSPXZZCJTZIK-XEMDLRDOSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of matrix metalloprotease-3
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 436.46, ALogP 2.48, HBA 6, HBD 3, PSA 113.96, QED 0.47
Compound (SMILES): CCOP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: SKWKPUDZFINNSN-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 = 38.2 nM (pChEMBL 7.420000076293945)
Descriptors: MW 341.33, ALogP 2.27, HBA 5, HBD 1, PSA 95.69, QED 0.81
Compound (SMILES): COc1nc(N[C@@H](C)c2cc3cc(Cl)c(F)cc3[nH]c2=O)ncc1C#N
InChIKey: UCQMQHNCVXBAFQ-QMMMGPOBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 M Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 373.78, ALogP 3.16, HBA 6, HBD 2, PSA 103.69, QED 0.73
Compound (SMILES): CCOP(=O)(OCC)N(C)CCN1CCc2nc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)ccc2C1
InChIKey: SAIXTBXXQWMWMW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
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 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 628.67, ALogP 6.27, HBA 10, HBD 1, PSA 110.53, QED 0.18
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2C[C@H]1CCCN1C[C@@H]1CO1
InChIKey: LXURGGKEOPHREO-DENIHFKCSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human recombinant SRC using Ulight-Poly GAT[EAY(1:1:1) as substrate measured after 10 mins in the presence of ATP by LANCE method
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 441.54, ALogP 4.34, HBA 7, HBD 1, PSA 81.73, QED 0.43
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(C4CCN(CC5CCC5)CC4)cn3)nccc12
InChIKey: FQYVJQRHNLIPIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 364.45, ALogP 2.48, HBA 6, HBD 1, PSA 79.7, QED 0.77
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2OC3(CCCCC3)O[C@H]21
InChIKey: MYODNHHKQWEUOO-GLBHFFKESA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7R transfected in human 1321N1 cells assessed as inhibition of Bz-ATP-induced calcium influx
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 587.31, ALogP 1.09, HBA 14, HBD 5, PSA 257.13, QED 0.27
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC1CC1CCNC(=O)c1cc2ccccc2[nH]1
InChIKey: JQBHQHNVJCDNEL-ZCLRBYCSSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293 cell membranes measured after 60 mins by scintillation counting method
Measurement: Ki = 6650 nM (pChEMBL 5.179999828338623)
Descriptors: MW 433.56, ALogP 3.36, HBA 5, HBD 3, PSA 96.27, QED 0.53
Compound (SMILES): CN1CCC(CNC(=O)c2cccc(-c3noc(C(F)(F)F)n3)c2)(c2nc(-c3ccccc3)cs2)CC1
InChIKey: BQFISAUAZNJOEG-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: Ki > 19000 nM (pChEMBL 4.7210001945495605)
Descriptors: MW 527.57, ALogP 5.27, HBA 7, HBD 1, PSA 84.15, QED 0.37
Compound (SMILES): CNCCNC(=O)c1c(-c2ccccn2)c([C@H](C)Nc2ncnc(N)c2C#N)nc2ccc(F)cc12
InChIKey: XGWXHMIKUSFVER-AWEZNQCLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) at 3 uM using midazolam substrate by LC-MS method
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 485.53, ALogP 2.8, HBA 9, HBD 4, PSA 154.53, QED 0.28
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(Cl)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4CC[C@@H]23)CC1
InChIKey: ASSZTGFDWPKORU-NIULTJEISA-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 670.04, ALogP 6.74, HBA 4, HBD 1, PSA 91.75, QED 0.36
Compound (SMILES): O=C(O)[C@H]1CNC[C@@H](CN/N=C/c2ccc(-c3cccc4ccccc34)o2)C1
InChIKey: LJBVJKRYRCGTBC-NBWFOSRTSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30531
Assay: Non-competitive inhibition of human GAT1 expressed in COS cells assessed as reduction in [2H6]GABA uptake by measuring [2H6]GABA Kd(app) at 10 uM preincubated for 25 mins followed by [2H6]GABA addition and measured after 4 mins by liquid scintillation counting method (Rvb = 28.3 +/- 1.5 nM)
Measurement: Kd = 111.9 nM (pChEMBL 6.949999809265137)
Descriptors: MW 377.44, ALogP 3.33, HBA 5, HBD 3, PSA 86.86, QED 0.45
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cccc(Cl)c1.Cl
InChIKey: WMZQIFSWRNNLKA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from recombinant human 5HT2C receptor expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 449.04, ALogP 6.52, HBA 2, HBD 1, PSA 32.34, QED 0.34
Compound (SMILES): Cn1cc(-c2cc(C(=O)/N=c3\[nH]c4ccccc4n3CC(C)(C)O)ccn2)cn1
InChIKey: RBNXRNXSQJWDFU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Biochemical EGFR Inhibition Assays (5 mM ATP): 5 μL of EGFR enzyme form in assay buffer (50 mM HEPES pH 7.3, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween 20, 2 mM DTT) are dispensed into columns 1-23, than 5 μL of ATP and ULight-poly-GT substrate (PerkinElmer; TRF0100-M) mix in assay buffer is added to all wells (final assay concentration of the ULight-poly-GT substrate 200 nM). Each of the different EGFR enzyme form assays is available at low ATP (final assay concentration 5 μM). After 90 minutes incubation at room temperature 5 μL EDTA (final assay concentration 50 mM) and LANCE Eu-anti-P-Tyr (PT66) antibody (PerkinElmer, AD0069) (final assay concentration 6 nM) mix are added to stop the reaction and start the binding of the antibody. After additional 60 minutes incubation at room temperature the signal is measured in a PerkinElmer Envision HTS Multilabel Reader using the TR-FRET LANCE Ultra specs of PerkinElmer (used wavelengths: excitation 320 nm, emission 1 665 nm, emission 2 615 nm). Each plate contains 16 wells of a negative control (diluted DMSO instead of test compound; w EGFR enzyme form; column 23) and 16 wells of a positive control (diluted DMSO instead of test compound; w/o EGFR enzyme form; column 24). Negative and positive control values are used for normalization and IC50 values are calculated and analysed using a 4 parametric logistic model.
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 390.45, ALogP 2.28, HBA 6, HBD 2, PSA 101.09, QED 0.56
Compound (SMILES): CC[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H]2CN1C(=O)[C@H](C(C)(C)C)NC(=O)OCC(C)(C)CCCCc1cccc3c1CN(C3)C(=O)O2)C(=O)NS(=O)(=O)C1CC1
InChIKey: KUQWGLQLLVFLSM-ONAXAZCASA-N
Target: Chymase (SINGLE PROTEIN), Homo sapiens
UniProt: P23946
Assay: Inhibition of human Chymase
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 757.95, ALogP 3.9, HBA 9, HBD 3, PSA 180.52, QED 0.39
Compound (SMILES): Cn1cc(Nc2nccc(N3C[C@H]4CC[C@H](C3)N4C(=O)NCC(F)(F)F)n2)cn1
InChIKey: CEDPCXUZXQKZKH-CHWSQXEVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 using fluorescence labeled peptide as substrate and using 1 mM ATP by microfluidic based mobility shift assay
Measurement: IC50 = 6872 nM (pChEMBL 5.159999847412109)
Descriptors: MW 410.4, ALogP 1.88, HBA 7, HBD 2, PSA 91.21, QED 0.8
Compound (SMILES): Cn1cc(-c2ccc(N3CCC([C@H]4c5c(F)cccc5-c5cncn54)CC3)cc2)cn1
InChIKey: UJGQDAMZVUNFBQ-VWLOTQADSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate measured after 10 mins in presence of NADPH by UHPLC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 413.5, ALogP 4.91, HBA 5, HBD 0, PSA 38.88, QED 0.48
Compound (SMILES): CCC(F)(F)c1cc(N2CCC(S(C)(=O)=O)CC2)nc2sc(C(N)=O)c(N)c12
InChIKey: IYHHRZBKXXKDDY-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Selectivity interaction (NanoBRET assay (in HEK293T cells)) EUB0001492b GAK
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 432.52, ALogP 2.49, HBA 7, HBD 2, PSA 119.38, QED 0.75
Compound (SMILES): CCn1c(=O)c2c(C)c(C(=O)N3CCC(O)CC3)sc2n(CCC(F)(F)F)c1=O
InChIKey: NTYVAKNEYLJAPT-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human A1 adenosine receptor expressed in CHO cell membranes after 60 mins by radioligand displacement assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 433.45, ALogP 2.1, HBA 7, HBD 1, PSA 84.54, QED 0.8
Compound (SMILES): Cl.Nc1ncccc1-c1nc2ccc(-c3ccccc3)nc2n1-c1ccc(C2(N)CCC2)cc1
InChIKey: DRHSWSSVIKDJME-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of AKT1 phosphorylation at Ser473 in EGF/insulin-stimulated human AN3CA cells incubated for 1 hr followed by stimulation for 15 mins by Western blot analysis
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 432.53, ALogP 5.07, HBA 6, HBD 2, PSA 95.64, QED 0.41
Compound (SMILES): CC(=O)Oc1c(C)cc2c(c1OC(C)=O)-c1cccc3c1[C@@H](C2)N(C)CC3
InChIKey: IYCVIMNLFPKSNJ-GOSISDBHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at D2 long receptor (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: EC50 = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 365.43, ALogP 3.6, HBA 5, HBD 0, PSA 55.84, QED 0.6
Compound (SMILES): CC1=C[C@@H]2Cc3nc4cc(F)ccc4c(N)c3[C@H](C1)C2
InChIKey: CPGLYAIYMGVIIO-WDEREUQCSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of butyrylcholinesterase (BChE) activity in human serum
Measurement: IC50 = 197 nM (pChEMBL 6.710000038146973)
Descriptors: MW 268.33, ALogP 3.95, HBA 2, HBD 1, PSA 38.91, QED 0.73
Compound (SMILES): O=C(NO)[C@@]1(NS(=O)(=O)c2ccc(Oc3ccc(F)cc3)cc2)C[C@H]2CC[C@@H](C1)O2
InChIKey: REZSPXZZCJTZIK-XEMDLRDOSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of human recombinant MMP2 by colorimetric analysis
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 436.46, ALogP 2.48, HBA 6, HBD 3, PSA 113.96, QED 0.47
Compound (SMILES): CCOP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: SKWKPUDZFINNSN-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 = 18.7 nM (pChEMBL 7.730000019073486)
Descriptors: MW 341.33, ALogP 2.27, HBA 5, HBD 1, PSA 95.69, QED 0.81
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2C[C@H]1CCCN1C[C@@H]1CO1
InChIKey: LXURGGKEOPHREO-DENIHFKCSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of BLK (unknown origin)
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 441.54, ALogP 4.34, HBA 7, HBD 1, PSA 81.73, QED 0.43
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(C4CCN(CC5CCC5)CC4)cn3)nccc12
InChIKey: FQYVJQRHNLIPIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 202 nM (pChEMBL 6.699999809265137)
Descriptors: MW 364.45, ALogP 2.48, HBA 6, HBD 1, PSA 79.7, QED 0.77
Compound (SMILES): CN1CCC(CNC(=O)c2cccc(-c3noc(C(F)(F)F)n3)c2)(c2nc(-c3ccccc3)cs2)CC1
InChIKey: BQFISAUAZNJOEG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: Ki > 43000 nM (pChEMBL 4.367000102996826)
Descriptors: MW 527.57, ALogP 5.27, HBA 7, HBD 1, PSA 84.15, QED 0.37