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]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)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: DRTISZFZZALDJX-VLSRZGDXSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Antagonist activity at human alpha9alpha10 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 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 3452.96
Compound (SMILES): O=C(C1CCCCC1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: FDUHADIZUWTWAZ-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 = 61000 nM (pChEMBL 4.210000038146973)
Descriptors: MW 393.53, ALogP 4.02, HBA 4, HBD 1, PSA 58.36, QED 0.85
Compound (SMILES): Cc1cc(C)n(NC(=O)C2CC(=O)N(c3cc(C)c(S(N)(=O)=O)c(C)c3Cl)C2)n1
InChIKey: SQIXPRUJAUUIMS-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 439.93, ALogP 1.54, HBA 6, HBD 2, PSA 127.39, QED 0.75
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3cc(Cl)c(F)cc3B(O)O2)cc1OCc1cccnc1
InChIKey: LYGOCJOSRHVHRY-UHFFFAOYSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human N-terminal Met and 6-His-tagged matriptase (G596 to V855 residues) expressed in Escherichia coli using Boc-QAR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 425.66
Compound (SMILES): N#Cc1cc(F)cc(NC(=O)Nc2ccc(Cl)cn2)c1
InChIKey: KDANLHLWAYNCMV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Inhibition of mGluR7 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 290.69, ALogP 3.39, HBA 3, HBD 2, PSA 77.81, QED 0.89
Compound (SMILES): CN(C)CCCOc1ccc(-c2cc(NCCCn3cccn3)nc(S(C)(=O)=O)n2)cc1
InChIKey: MSIJJXOWLFOYIN-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Affinity On-target Cellular interaction: (NanoBRET assay (NL-FL CERC2 in HEK293 cells)) EUB0000233b CECR2
Measurement: EC50 = 289 nM (pChEMBL 6.539999961853027)
Descriptors: MW 458.59, ALogP 2.58, HBA 9, HBD 1, PSA 102.24, QED 0.33
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RAFNWGJYLZVXFV-VIFPVBQESA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Antagonist activity at alpha5beta1 in human K562 cells assessed as reduction in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 248.24, ALogP 1.21, HBA 3, HBD 2, PSA 86.71, QED 0.77
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1cccc(C(F)(F)F)c1
InChIKey: PHBWEBASHGNHMO-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 = 57000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 418.4, ALogP 5.31, HBA 4, HBD 1, PSA 72.2, QED 0.49
Compound (SMILES): O=C(O)CC1CC(=O)N1
InChIKey: PFYZSIGLKDYGAG-UHFFFAOYSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha5beta1 in human K562 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 = 1031 nM (pChEMBL 5.989999771118164)
Descriptors: MW 129.11, ALogP -0.65, HBA 2, HBD 2, PSA 66.4, QED 0.49
Compound (SMILES): O=C1N(c2cccnc2C(F)(F)F)CC2(CCN(CCc3ccccc3F)CC2)OC12CC2
InChIKey: QNSPFRSAEHVDGL-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain membranes by microbeta scintillation counting method
Measurement: Ki = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 463.48, ALogP 4.21, HBA 4, HBD 0, PSA 45.67, QED 0.64
Compound (SMILES): Cc1ccc2c(c1)SC(=S)N1CCCN=C21
InChIKey: UZLFDAINHMGSAJ-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human C-terminal His-tagged N-terminal GST-tagged HDAC7 (518 to end residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 248.38, ALogP 2.84, HBA 3, HBD 0, PSA 15.6, QED 0.66
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(N(CC)CC)cc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: GIVANBDIGIBKKJ-AJWFRBGYSA-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) 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 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 1069.33
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccc(F)c(C(F)(F)F)c1
InChIKey: CAJHJZPMGCTMKB-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 436.39, ALogP 5.45, HBA 4, HBD 1, PSA 72.2, QED 0.43
Compound (SMILES): COc1ccc(Oc2nc(Nc3ccc(N4CCOCC4)nc3)ncc2NC(=O)c2cc(OC)cc(OC)c2)cc1
InChIKey: RYJMAXSFHOPKJH-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of human CSF1R using poly[Glu:Tyr] (4:1) as substrate after 120 mins in presence of 100 uM [gamma-33P]-ATP by filtration method
Measurement: IC50 = 273 nM (pChEMBL 6.559999942779541)
Descriptors: MW 558.6, ALogP 4.52, HBA 11, HBD 2, PSA 129.19, QED 0.28
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCOC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: WQWHBQYUWSARDT-INIZCTEOSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full-length C-terminal his-tagged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N\"-triacetylchitotrioside as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 376.89, ALogP 1.95, HBA 6, HBD 2, PSA 83.3, QED 0.85
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3cccc(C(F)(F)F)n3)cc21
InChIKey: MNKQUDROCZIINF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 348.33, ALogP 3.21, HBA 4, HBD 0, PSA 51.02, QED 0.73
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3ccc(Cl)cn3)CC2)cc1
InChIKey: HHVQGHMBHYXHGF-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting
Measurement: Ki = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 347.87, ALogP 4.02, HBA 3, HBD 0, PSA 19.37, QED 0.74
Compound (SMILES): CCCOc1ccc(NC(=O)CN2CCN(C)CC2)cc1-c1nc(CC)c(CC)c(=O)[nH]1
InChIKey: PIOIVHHIGWTEJQ-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of N-terminal GST-tagged human PDE10A expressed in baculovirus infected sf9 cells using [3H]cAMP as substrate measured after 30 mins by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 441.58, ALogP 2.54, HBA 6, HBD 2, PSA 90.56, QED 0.62
Compound (SMILES): Cc1cccc(S(=O)(=O)Nc2ccc3oc(-c4ccccc4)nc3c2)c1
InChIKey: LJBFMMFROOECPM-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 364.43, ALogP 4.6, HBA 4, HBD 1, PSA 72.2, QED 0.57
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4c(F)cccc4F)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: OOMBFNDWQIGHEK-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Binding affinity to ACVR1 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay
Measurement: Kd > 70 nM (pChEMBL 7.15500020980835)
Descriptors: MW 616.66, ALogP 5.27, HBA 8, HBD 1, PSA 93.23, QED 0.23
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ncc(Cl)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: JJICHOVZOJORFF-CQSZACIVSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR cytoplasmic domain expressed in baculovirus expression system using FITC-C6-KKAEEEEYFELVAKK-NH2 as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 455.88, ALogP 3.33, HBA 8, HBD 2, PSA 136.08, QED 0.56
Compound (SMILES): Cc1cccc2c1SC(=S)N1CCN=C21
InChIKey: JCHNUJLNFOMCKL-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 234.35, ALogP 2.45, HBA 3, HBD 0, PSA 15.6, QED 0.64
Compound (SMILES): COc1cc(N(C)c2ccnc3ccc(C(F)(F)F)cc23)cc(OC)c1OC
InChIKey: PVTQCCFMFWASHK-UHFFFAOYSA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Binding affinity to C-terminal AVI-tagged BMP2K (unknown origin) (38 to 345 residues) expressed in Escherichia coli after 1.5 hrs by TR-FRET assay
Measurement: Ki = 95000 nM (pChEMBL 4.019999980926514)
Descriptors: MW 392.38, ALogP 5.05, HBA 5, HBD 0, PSA 43.82, QED 0.61
Compound (SMILES): CCCn1c(=O)c2c(nc3cc(OC)ccn32)n(CCCNC(=O)c2ccc(S(C)(=O)=O)cc2)c1=O
InChIKey: AASXHCGIIQCKEE-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Competitive surmountable antagonist activity at human A3 adenosine receptor expressed in CHO cell membranes assessed as inhibition of 2-Cl-IB-MECA-induced [35S]-GTPgammaS binding preincubated for 60 mins followed by 2-Cl-IB-MECA and [35S]-GTPgammaS addition and measured after 30 mins
Measurement: Kd = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 513.58, ALogP 1.45, HBA 10, HBD 1, PSA 133.77, QED 0.33
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CC(=O)N(c3cccc(Br)c3)C2)cc1
InChIKey: XRVRIYCPWZRODG-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 = 56 nM (pChEMBL 7.25)
Descriptors: MW 438.3, ALogP 2.09, HBA 4, HBD 2, PSA 109.57, QED 0.76
Compound (SMILES): CCC(CC)n1c(C)nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc21
InChIKey: POTKDJWRAMHALZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
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 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 534.66, ALogP 5.5, HBA 8, HBD 1, PSA 75, QED 0.3
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(Cl)cn2)C1
InChIKey: AVIWDYSJSPOOAR-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Reversible inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA Polymerase 2 CTD phosphorylation at Ser2 residues preincubated for 6 hrs followed by compound washout and measured after 2 hrs by immunofluorescence assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 429.95, ALogP 3.81, HBA 5, HBD 2, PSA 88.91, QED 0.77
Compound (SMILES): COc1ccc(-c2cc(OCCN(C)c3ncc(C(=O)NO)cn3)c3ncnc(C)c3c2)cn1
InChIKey: GVPYBTYCSMGVJF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human full length HDAC2 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 461.48, ALogP 2.43, HBA 10, HBD 2, PSA 135.48, QED 0.3
Compound (SMILES): S=C1Sc2cc(Br)ccc2C2=NCCN12
InChIKey: KJYDOYMIBGLEAG-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human C-terminal His-tagged N-terminal GST-tagged HDAC7 (518 to end residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 299.22, ALogP 2.9, HBA 3, HBD 0, PSA 15.6, QED 0.69
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cncc(C(=O)N5CCN(C)CC5)c4)c3c2)cn1
InChIKey: VNHWGUFFQWQQFS-UHFFFAOYSA-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 CD86 expression preincubated for 1 hr followed by anti-IgM stimulation for 24 hrs by flow cytometry
Measurement: IC50 = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 440.51, ALogP 3.15, HBA 7, HBD 0, PSA 84.34, QED 0.48
Compound (SMILES): C=CCn1cc(-c2cccc(C(=O)N(C)C)c2)c2cc[nH]c2c1=O
InChIKey: SPSRAFOXVSNAJA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant His-tagged BRD4 bromodomain1 (unknown origin) using biotinylated ligand incubated for 10 mins by TR-FRET assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 321.38, ALogP 2.88, HBA 3, HBD 1, PSA 58.1, QED 0.75
Compound (SMILES): Cn1cc(-c2cc(F)cc(S(=O)(=O)c3cnc(CN)s3)c2)cn1
InChIKey: SNKUHRMTDUIGHD-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells by Qpatch electrophysiological assay
Measurement: IC50 = 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 352.42, ALogP 1.97, HBA 7, HBD 1, PSA 90.87, QED 0.78
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]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)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: DRTISZFZZALDJX-VLSRZGDXSA-N
Target: Nicotinic acetylcholine receptor alpha9/alpha10 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q9JLB5
Assay: Antagonist activity at rat alpha9alpha10 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 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 3452.96
Compound (SMILES): Cc1cc(C)n(NC(=O)C2CC(=O)N(c3cc(C)c(S(N)(=O)=O)c(C)c3Cl)C2)n1
InChIKey: SQIXPRUJAUUIMS-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 10 nM (pChEMBL 8)
Descriptors: MW 439.93, ALogP 1.54, HBA 6, HBD 2, PSA 127.39, QED 0.75
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3cc(Cl)c(F)cc3B(O)O2)cc1OCc1cccnc1
InChIKey: LYGOCJOSRHVHRY-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human recombinant C-terminal 10-His-tagged thrombin (M1 to E622 residues) expressed in mouse NS0 cells using BOC-VPR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 425.66
Compound (SMILES): CN(C)CCCOc1ccc(-c2cc(NCCCn3cccn3)nc(S(C)(=O)=O)n2)cc1
InChIKey: MSIJJXOWLFOYIN-UHFFFAOYSA-N
Target: Nucleosome-remodeling factor subunit BPTF (SINGLE PROTEIN), Homo sapiens
UniProt: Q12830
Assay: Affinity Biochemical interaction: (AlphaScreen assay) EUB0000233b BPTF
Measurement: IC50 = 30350 nM (pChEMBL 4.519999980926514)
Descriptors: MW 458.59, ALogP 2.58, HBA 9, HBD 1, PSA 102.24, QED 0.33
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RAFNWGJYLZVXFV-VIFPVBQESA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Agonist activity at alpha2bbeta3 in human HEL cells assessed as increase in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 248.24, ALogP 1.21, HBA 3, HBD 2, PSA 86.71, QED 0.77
Compound (SMILES): O=C(O)CC1CC(=O)N1
InChIKey: PFYZSIGLKDYGAG-UHFFFAOYSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Agonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as increase in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 129.11, ALogP -0.65, HBA 2, HBD 2, PSA 66.4, QED 0.49
Compound (SMILES): O=C1N(c2cccnc2C(F)(F)F)CC2(CCN(CCc3ccccc3F)CC2)OC12CC2
InChIKey: QNSPFRSAEHVDGL-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHO-K1 cell membranes incubated for 90 mins measured by MicroBeta scintillation counter method
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 463.48, ALogP 4.21, HBA 4, HBD 0, PSA 45.67, QED 0.64
Compound (SMILES): Cc1ccc2c(c1)SC(=S)N1CCCN=C21
InChIKey: UZLFDAINHMGSAJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 248.38, ALogP 2.84, HBA 3, HBD 0, PSA 15.6, QED 0.66
Compound (SMILES): COc1ccc(Oc2nc(Nc3ccc(N4CCOCC4)nc3)ncc2NC(=O)c2cc(OC)cc(OC)c2)cc1
InChIKey: RYJMAXSFHOPKJH-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of human CSF1R using poly[Glu:Tyr] (4:1) as substrate after 120 mins in presence of [gamma-33P]-ATP by filtration method
Measurement: Ki = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 558.6, ALogP 4.52, HBA 11, HBD 2, PSA 129.19, QED 0.28
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCOC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: WQWHBQYUWSARDT-INIZCTEOSA-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 376.89, ALogP 1.95, HBA 6, HBD 2, PSA 83.3, QED 0.85
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3cccc(C(F)(F)F)n3)cc21
InChIKey: MNKQUDROCZIINF-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: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 348.33, ALogP 3.21, HBA 4, HBD 0, PSA 51.02, QED 0.73
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3ccc(Cl)cn3)CC2)cc1
InChIKey: HHVQGHMBHYXHGF-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting
Measurement: Ki = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 347.87, ALogP 4.02, HBA 3, HBD 0, PSA 19.37, QED 0.74
Compound (SMILES): CCCOc1ccc(NC(=O)CN2CCN(C)CC2)cc1-c1nc(CC)c(CC)c(=O)[nH]1
InChIKey: PIOIVHHIGWTEJQ-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of N-terminal GST-tagged human PDE11A4 expressed in baculovirus infected sf9 cells using [3H]cGMP as substrate measured after 30 mins by scintillation proximity assay
Measurement: IC50 = 998 nM (pChEMBL 6)
Descriptors: MW 441.58, ALogP 2.54, HBA 6, HBD 2, PSA 90.56, QED 0.62
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4c(F)cccc4F)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: OOMBFNDWQIGHEK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00444
Assay: Binding affinity to PLK4 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay
Measurement: Kd = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 616.66, ALogP 5.27, HBA 8, HBD 1, PSA 93.23, QED 0.23
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ncc(Cl)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: JJICHOVZOJORFF-CQSZACIVSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full-length human C-terminal His6-tagged BTK C481S mutant expressed in Sf9 insect cells using FAM-Srctide peptide as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 455.88, ALogP 3.33, HBA 8, HBD 2, PSA 136.08, QED 0.56
Compound (SMILES): COc1cc(N(C)c2ccnc3ccc(C(F)(F)F)cc23)cc(OC)c1OC
InChIKey: PVTQCCFMFWASHK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 16 (SINGLE PROTEIN), Homo sapiens
UniProt: O75716
Assay: Binding affinity to C-terminal AVI-tagged STK16 (unknown origin) (13 to 305 residues) expressed in Escherichia coli after 1.5 hrs by TR-FRET assay
Measurement: Ki = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 392.38, ALogP 5.05, HBA 5, HBD 0, PSA 43.82, QED 0.61
Compound (SMILES): CCCn1c(=O)c2c(nc3cc(OC)ccn32)n(CCCNC(=O)c2ccc(S(C)(=O)=O)cc2)c1=O
InChIKey: AASXHCGIIQCKEE-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Competitive surmountable antagonist activity at human A3 adenosine receptor expressed in CHO cell membranes assessed as inhibition of 2-Cl-IB-MECA-induced [35S]-GTPgammaS binding measured after 30 mins
Measurement: Kd = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 513.58, ALogP 1.45, HBA 10, HBD 1, PSA 133.77, QED 0.33
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CC(=O)N(c3cccc(Br)c3)C2)cc1
InChIKey: XRVRIYCPWZRODG-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 10000 nM (pChEMBL 5)
Descriptors: MW 438.3, ALogP 2.09, HBA 4, HBD 2, PSA 109.57, QED 0.76
Compound (SMILES): CCC(CC)n1c(C)nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc21
InChIKey: POTKDJWRAMHALZ-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CDK4 (1 to 303 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay
Measurement: IC50 = 1.08 nM (pChEMBL 8.970000267028809)
Descriptors: MW 534.66, ALogP 5.5, HBA 8, HBD 1, PSA 75, QED 0.3
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(Cl)cn2)C1
InChIKey: AVIWDYSJSPOOAR-LSDHHAIUSA-N
Target: Casein kinase I isoform gamma-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCP0
Assay: Inhibition of CK1gamma1 (unknown origin) in presence of 5 mM ATP
Measurement: IC50 = 5520 nM (pChEMBL 5.260000228881836)
Descriptors: MW 429.95, ALogP 3.81, HBA 5, HBD 2, PSA 88.91, QED 0.77
Compound (SMILES): COc1ccc(-c2cc(OCCN(C)c3ncc(C(=O)NO)cn3)c3ncnc(C)c3c2)cn1
InChIKey: GVPYBTYCSMGVJF-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human full length HDAC4 expressed in baculovirus infected Sf9 insect cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr
Measurement: IC50 = 972 nM (pChEMBL 6.010000228881836)
Descriptors: MW 461.48, ALogP 2.43, HBA 10, HBD 2, PSA 135.48, QED 0.3
Compound (SMILES): S=C1Sc2cc(Br)ccc2C2=NCCN12
InChIKey: KJYDOYMIBGLEAG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length N-terminal His6/SUMO-tagged HDAC8 expressed in Escherichia coli BL21 DE3 using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 299.22, ALogP 2.9, HBA 3, HBD 0, PSA 15.6, QED 0.69
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cncc(C(=O)N5CCN(C)CC5)c4)c3c2)cn1
InChIKey: VNHWGUFFQWQQFS-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 transfected in HEK293 cell membranes after 60 mins by scintillation counting
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 440.51, ALogP 3.15, HBA 7, HBD 0, PSA 84.34, QED 0.48
Compound (SMILES): C=CCn1cc(-c2cccc(C(=O)N(C)C)c2)c2cc[nH]c2c1=O
InChIKey: SPSRAFOXVSNAJA-UHFFFAOYSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: IC50 Measurements for Inhibitors Using CECR2 TR-FRET Binding Assay: His/Flag epitope tagged CECR2424-538 was cloned, expressed, and purified to homogeneity. CECR2 binding and inhibition was assessed by monitoring the engagement of a biotinylated small molecule compound 1001 (Example 125) with the target using the TR-FRET assay technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate CECR2 (1.5 nM final) was combined with biotin-ligand (25 nM final) in 50 mM HEPES (pH 7.5), 50 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.2% DMSO) or compound dilution series in DMSO. After 15 minutes incubation at room temperature, a mixture Eu-W1024 Anti-6×His antibody (Perkin Elmer AD0110) and SureLight¿ Allophycocyanin-Streptavidin (APC-SA, Perkin Elmer CR130-100) were added to a final concentrations of 0.2 nMolar antibody and 12.5 nMolar APC-SA, respectively. After forty minutes of equilibration, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit. Novel compound 1001 and the CECR2 TR-FRET Binding Assay described above represent additional embodiments of the invention.
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 321.38, ALogP 2.88, HBA 3, HBD 1, PSA 58.1, QED 0.75
Compound (SMILES): Cn1cc(-c2cc(F)cc(S(=O)(=O)c3cnc(CN)s3)c2)cn1
InChIKey: SNKUHRMTDUIGHD-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P14920
Assay: Diamine Oxidase (DAO) Selectivity Assay: ReagentsPromega ROS-Glo H2O2 Assay Kit, 50 ml. Cat No. G8821Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.Positive Control (Aminoguanidine):1 mM stock diluted to 1 to 0.0001 and 0.00003 mM in drug plate, resulting in a concentration of 3 to 0.001 and 0.0003 uM in the assay.DAO:DAO batch is obtained from Sigma Enzyme is reconstituted in sodium phosphate buffer at 10 mg/mLAssay Plates: 96 well white polystyrene, flat bottom plates: Fisher, Cat No. DPS-134-050AProcedure:1. Dilute 400 ul DAO enzyme in 4 mL Assay Buffer (enough for one plate). Add 40 ul DAO enzyme to all wells (excluding G+H 12, assay buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of Aminoguanidine down column 11 and to E+F 125. Add 0.5 μl DMSO (100% activity control) to C+D 126. Cover plate and incubate for 20 minutes at room temp on a plate shaker7. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final ConcnAssay Buffer 2 ml 3 ml —8.5M Cadaverine 23 μl 34.5 μl 97.8 mMH2O2 Substrate (1:80) 25 μl 37.5 μl 125 μM8. Add 10 μl Start Mix to all wells9. Incubate for 60 min at room temp on a plate shaker10. Prepare Detection Reagent: Volume Reagent 1 × plate 2 × plate Luciferin 5 ml 10 ml D-cysteine (1:100) 50 μl 100 μl Signal Enhancer (1:100) 50 μl 100 μl11. Add 50 μl Detection Regent to each well EXCEPT No Luciferin controls (A+B 12, add 50 μl assay buffer)12. Incubate for 20 min at room temp on a plate shaker, protected from light13. Measure luminescence using a plate reader (integration 500 ms)Values for the blank (no DAO controls) are subtracted from all samples. DMSO controls are set as 100% activity and samples are calculated as a % of the DMSO control. Data is plotted using Graphpad Prism software, and a non-linear regression line is calculated using a variable slope sigmoidal dose response equation.:Y=Bottom+(Top-Bottom)/(1+10{circumflex over ( )}((LogIC50−X)*HillSlope)).Where X is the logarithm of concentration and Y is the response. The IC50 is the concentration of the drug that produces a percentage control fluorescence value midway between the saturation and zero effect plateaus. Two independent assays are usually performed, and the mean IC50 is reported.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 352.42, ALogP 1.97, HBA 7, HBD 1, PSA 90.87, QED 0.78
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]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)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: DRTISZFZZALDJX-VLSRZGDXSA-N
Target: Nicotinic acetylcholine receptor alpha9/alpha10 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q9JLB5
Assay: Antagonist activity at rat alpha9alpha10 nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 3452.96
Compound (SMILES): Cc1cc(C)n(NC(=O)C2CC(=O)N(c3cc(C)c(S(N)(=O)=O)c(C)c3Cl)C2)n1
InChIKey: SQIXPRUJAUUIMS-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 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 439.93, ALogP 1.54, HBA 6, HBD 2, PSA 127.39, QED 0.75
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3cc(Cl)c(F)cc3B(O)O2)cc1OCc1cccnc1
InChIKey: LYGOCJOSRHVHRY-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using MeOSuc-AAPV-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 425.66
Compound (SMILES): CN(C)CCCOc1ccc(-c2cc(NCCCn3cccn3)nc(S(C)(=O)=O)n2)cc1
InChIKey: MSIJJXOWLFOYIN-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Affinity Biochemical interaction: (AlphaScreen assay) EUB0000233b CECR2
Measurement: IC50 = 30350 nM (pChEMBL 4.519999980926514)
Descriptors: MW 458.59, ALogP 2.58, HBA 9, HBD 1, PSA 102.24, QED 0.33
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RAFNWGJYLZVXFV-VIFPVBQESA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Antagonist activity at alpha2bbeta3 in human HEL cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 248.24, ALogP 1.21, HBA 3, HBD 2, PSA 86.71, QED 0.77
Compound (SMILES): O=C(O)CC1CC(=O)N1
InChIKey: PFYZSIGLKDYGAG-UHFFFAOYSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Agonist activity at alpha2bbeta3 in human HEL cells assessed as increase in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 = 311 nM (pChEMBL 6.510000228881836)
Descriptors: MW 129.11, ALogP -0.65, HBA 2, HBD 2, PSA 66.4, QED 0.49
Compound (SMILES): COc1ccc(Oc2nc(Nc3ccc(N4CCOCC4)nc3)ncc2NC(=O)c2cc(OC)cc(OC)c2)cc1
InChIKey: RYJMAXSFHOPKJH-UHFFFAOYSA-N
Target: Death-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53355
Assay: Inhibition of DAPK1 in HEK293 tau-BiFC cells assessed as reduction in forskolin-induced tau aggregation after 48 hrs by Hoechst staining based HCS analysis
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 558.6, ALogP 4.52, HBA 11, HBD 2, PSA 129.19, QED 0.28
Compound (SMILES): Nc1n[nH]c(N2CCC(N3CCOC[C@@H]3Cc3ccc(Cl)cc3)CC2)n1
InChIKey: WQWHBQYUWSARDT-INIZCTEOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: ERG Channel Binding Assay: Fluorescence polarization assay based on the principle of fluorescence polarization where a red-shifted fluorescent tracer is displaced from the hERG channel by compounds that bind to the channel was used to establish the binding of the compounds to hERG channel. Briefly, the compounds in serial dilutions were incubated with a membrane fraction containing hERG channel protein and a high-affinity red fluorescent hERG channel ligand in black 384-well plate. The reaction was incubated for 4 h at room temperature followed by the measurement of the fluorescence polarization using Tecan Spark multimode plate reader at excitation wavelength of 535 nm and emission wavelength 590 nm. The IC50 values were calculated using GraphPad Prism.
Measurement: IC50 = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 376.89, ALogP 1.95, HBA 6, HBD 2, PSA 83.3, QED 0.85
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3ccc(Cl)cn3)CC2)cc1
InChIKey: HHVQGHMBHYXHGF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 347.87, ALogP 4.02, HBA 3, HBD 0, PSA 19.37, QED 0.74
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4c(F)cccc4F)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: OOMBFNDWQIGHEK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: Binding affinity to FYN in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay
Measurement: Kd = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 616.66, ALogP 5.27, HBA 8, HBD 1, PSA 93.23, QED 0.23
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4ncc(Cl)cc4F)cc3)c(C(N)=O)c2N)C1
InChIKey: JJICHOVZOJORFF-CQSZACIVSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Human EGFR LanthaScreen Selectivity Assay: TR-FRET LanthaScreen assays were performed by incubating a dilution series of inhibitor concentrations with 20 μM ATP, 100 nM peptide substrate (FITC-C6-KKAEEEEYFELVAKK-NH2 (SEQ ID NO.: 2, American Peptide, #333778) and 600 μM of human EGFR kinase domain (Invitrogen). The assays were performed with and without pre-incubating the inhibitors with the enzyme for 60 minutes before starting the kinase reaction by adding ATP and the peptide substrate. Samples containing enzyme but no inhibitor were included to determine the maximal extent of reaction. Samples containing no enzyme served as the negative control. The kinase reaction mixtures were incubated at room temperature for 60 minutes before stopping the kinase activity by the addition of 15 mM EDTA. The extent of peptide phosphorylation by EGFR was detected using a Terbium-conjugated anti-phospho-Tyrosine antibody (Tb-PT66 antibody, invitrogen # PV3557). Phosphorylation of peptide substrate was measured by determining the ratio of 520/495 nm on an Envision Multi-label Reader (Perkin Elmer) and IC50 values were calculated by fitting the data to a four-parameter equation using XLFIt4 (IDBS).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 455.88, ALogP 3.33, HBA 8, HBD 2, PSA 136.08, QED 0.56
Compound (SMILES): COc1cc(N(C)c2ccnc3ccc(C(F)(F)F)cc23)cc(OC)c1OC
InChIKey: PVTQCCFMFWASHK-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y616
Assay: Binding affinity to human IRAK3 (147 to 596 residues) expressed in bacterial expression system by KINOMEscan assay
Measurement: Kd = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 392.38, ALogP 5.05, HBA 5, HBD 0, PSA 43.82, QED 0.61
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CC(=O)N(c3cccc(Br)c3)C2)cc1
InChIKey: XRVRIYCPWZRODG-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 438.3, ALogP 2.09, HBA 4, HBD 2, PSA 109.57, QED 0.76
Compound (SMILES): CCC(CC)n1c(C)nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc21
InChIKey: POTKDJWRAMHALZ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay
Measurement: IC50 = 1.55 nM (pChEMBL 8.8100004196167)
Descriptors: MW 534.66, ALogP 5.5, HBA 8, HBD 1, PSA 75, QED 0.3
Compound (SMILES): COc1ccc(-c2cc(OCCN(C)c3ncc(C(=O)NO)cn3)c3ncnc(C)c3c2)cn1
InChIKey: GVPYBTYCSMGVJF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Ac-peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 461.48, ALogP 2.43, HBA 10, HBD 2, PSA 135.48, QED 0.3
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]2CSSC[C@H](NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N2)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: DRTISZFZZALDJX-VLSRZGDXSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Antagonist activity at human alpha9alpha10 nACh receptor expressed in Xenopus oocyte assessed as inhibition of acetylcholine-induced response at -70 mV holding potential by voltage-clamp based electrophysiological assay
Measurement: IC50 = 20.3 nM (pChEMBL 7.690000057220459)
Descriptors: MW 3452.96
Compound (SMILES): Cc1cc(C)n(NC(=O)C2CC(=O)N(c3cc(C)c(S(N)(=O)=O)c(C)c3Cl)C2)n1
InChIKey: SQIXPRUJAUUIMS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.011 nM (pChEMBL 10.960000038146973)
Descriptors: MW 439.93, ALogP 1.54, HBA 6, HBD 2, PSA 127.39, QED 0.75
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3cc(Cl)c(F)cc3B(O)O2)cc1OCc1cccnc1
InChIKey: LYGOCJOSRHVHRY-UHFFFAOYSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of recombinant human C-terminal 10-His-tagged urokinase (M1 to L431 residues) expressed in mouse NS0 cells using Z-GGR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 79432.82 nM (pChEMBL 4.099999904632568)
Descriptors: MW 425.66
Compound (SMILES): CN(C)CCCOc1ccc(-c2cc(NCCCn3cccn3)nc(S(C)(=O)=O)n2)cc1
InChIKey: MSIJJXOWLFOYIN-UHFFFAOYSA-N
Target: Nucleosome-remodeling factor subunit BPTF (SINGLE PROTEIN), Homo sapiens
UniProt: Q12830
Assay: Selectivity interaction (ITC measurement) EUB0000233b BPTF
Measurement: Kd = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 458.59, ALogP 2.58, HBA 9, HBD 1, PSA 102.24, QED 0.33
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RAFNWGJYLZVXFV-VIFPVBQESA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Antagonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 = 1.39 nM (pChEMBL 8.859999656677246)
Descriptors: MW 248.24, ALogP 1.21, HBA 3, HBD 2, PSA 86.71, QED 0.77
Compound (SMILES): O=C(O)CC1CC(=O)N1
InChIKey: PFYZSIGLKDYGAG-UHFFFAOYSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Antagonist activity at alpha4beta1 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to VCAM1 pre-incubated for 30 mins before VCAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 129.11, ALogP -0.65, HBA 2, HBD 2, PSA 66.4, QED 0.49
Compound (SMILES): COc1ccc(Oc2nc(Nc3ccc(N4CCOCC4)nc3)ncc2NC(=O)c2cc(OC)cc(OC)c2)cc1
InChIKey: RYJMAXSFHOPKJH-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of red tracer binding to human ERG expressed in membranes preincubated for 10 to 15 mins followed by tracer addition measured after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 17100 nM (pChEMBL 4.769999980926514)
Descriptors: MW 558.6, ALogP 4.52, HBA 11, HBD 2, PSA 129.19, QED 0.28
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3ccc(Cl)cn3)CC2)cc1
InChIKey: HHVQGHMBHYXHGF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 347.87, ALogP 4.02, HBA 3, HBD 0, PSA 19.37, QED 0.74
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4c(F)cccc4F)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: OOMBFNDWQIGHEK-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Binding affinity to AURKB in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay
Measurement: Kd = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 616.66, ALogP 5.27, HBA 8, HBD 1, PSA 93.23, QED 0.23