lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)[C@H]1CCN(c2nn(C(=O)c3c(Cl)cccc3C(F)(F)F)c3cccc(F)c23)C[C@@H]1O
InChIKey: GZMOOCYTZMPTMH-BONVTDFDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Biological Assay: The compounds of the invention inhibit RORgammaT activity. Activation of RORgammaT activity can be measured using, e.g., biochemical TR-FRET assay. In such an assay, interaction of cofactor-derived peptides with human RORgammaT-Ligand Binding Domain (LBD) can be measured. The TR-FRET technique is a sensitive biochemical proximity assay that will give information concerning the interaction of a ligand with the LBD, in the presence of cofactor-derived peptides (Zhou et al., Methods 25:54-61, 2001).To identify novel antagonists of RORgammaT, an assay was developed which employs the interaction of RORgammaT with its co-activator peptide SRC1_2. This peptide mimics the recruitment of co-activators to RORgammaT through its interaction with the LXXLL (SEQ ID NO:1) (e.g., NR box) motifs (Xie et al., J. Immunol. 175: 3800-09, 2005; Kurebayashi et al., Biochem. Biophys. Res. Commun. 315: 919-27, 2004; Jin et al., Mol. Endocrinology 24:923-29, 2010). The RORγ-Ligand Binding Domain TR-FRET Assay was run according to the following protocol.HIS-tagged RORγ-LBD protein was expressed in SF9 cells using a baculovirus expression system. The RORγ-LBD protein was purified by glutathione sepharose chromatography. Separately, SF9 cells not expressing any recombinant protein were lysed and the lysate was added to the purified RORγ-LBD at 0.25 μl lysate (from 10,000 SF9 cells)/nM purified protein. The mixture was then diluted in assay buffer (50 mM Tris pH 7.0, 50 mM KCl, 1 mM EDTA, 0.1 mM DTT) to obtain RORγ-LBD final concentration of 3 nM in 384-well assay plate.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 485.82, ALogP 3.81, HBA 6, HBD 2, PSA 95.66, QED 0.55
Compound (SMILES): Cc1cc(NC(=O)Nc2cc(C(C)(C)C)nn2-c2ccccc2)ccc1-c1cnc(NC2CC2)c2nccn12
InChIKey: LEVZCGPPIDIGHW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in liver microsomes (unknown origin) using alpha-naphthoflavone as substrate preincubated for 5 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 520.64, ALogP 6.41, HBA 7, HBD 3, PSA 101.17, QED 0.24
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(OC3CCN(C)CC3)c(C(F)(F)F)c2)cc1NC(=O)C1(c2ncnc3[nH]ccc23)CC1
InChIKey: DQCLAIYABKFDCU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF (unknown origin)
Measurement: IC50 = 43.1 nM (pChEMBL 7.369999885559082)
Descriptors: MW 592.62, ALogP 5.68, HBA 6, HBD 3, PSA 112.24, QED 0.25
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2ccc(N)c(C(=O)O)c2)o1
InChIKey: FEGGHDNFYOHIAS-OAHLLOKOSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 460.49, ALogP 2.07, HBA 7, HBD 5, PSA 175.2, QED 0.08
Compound (SMILES): COc1ccc(-c2ccc(Nc3cc(=O)n(O)c(=O)n3C)cc2)cc1
InChIKey: WUSZKBHMAGTNLD-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of RNase H activity of full length recombinant HIV1 reverse transcriptase assessed as reduction in RNA 5'-end directed cleavage using HTS3 substrate
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 339.35, ALogP 2.2, HBA 7, HBD 2, PSA 85.49, QED 0.71
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@H](C)c3ccc(N4CC5CCC(C4)N5)cc3F)sc2n1
InChIKey: VFGWBSOLIAYSQU-JEYLPNPQSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 453.59, ALogP 3.8, HBA 6, HBD 3, PSA 83.28, QED 0.55
Compound (SMILES): CCSc1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: MINMBWMRXQZRGS-JTFADIMSSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay relative to control
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 406.45, ALogP -1.64, HBA 12, HBD 4, PSA 188.7, QED 0.4
Compound (SMILES): COc1cc(C)c2[nH]cc(/C=N/NC(=N)NCCc3ccc(Cl)c(Cl)c3)c2c1
InChIKey: JGIPHTRWXCTQHW-KBKYJPHKSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHOK1 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation preincubated for 30 mins followed by forskolin-stimulation and measured after 30 mins by HTRF assay
Measurement: EC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 418.33, ALogP 4.48, HBA 3, HBD 4, PSA 85.29, QED 0.27
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCOCCn4cc(CN5CCN(Cc6cn(CCOCCOCCOc7ccc(-c8oc9ccccc9c(=O)c8OCc8cccc(C(=O)OC)c8)cc7)nn6)CC5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: LOCAHSWELXZHMU-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1281.39
Compound (SMILES): C[C@@H]1SC(N)=N[C@@H]1CC(=O)O
InChIKey: MQFCGOLHKFXDRZ-IUYQGCFVSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30531
Assay: Inhibition of human GAT1 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 174.22, ALogP 0.28, HBA 4, HBD 2, PSA 75.68, QED 0.63
Compound (SMILES): N#CN1CCC(NC(=O)c2ccc(N3CCCC3c3cccnc3)nc2)C1
InChIKey: MTJXHXNNDCGFDT-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 362.44, ALogP 2.1, HBA 6, HBD 1, PSA 85.15, QED 0.84
Compound (SMILES): CC(C)n1cc(C(=O)Nc2cc3cn[nH]c3cc2F)c2ncc(-c3ccc(N)cc3)cc21
InChIKey: NWKPQWAZOMCVOH-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of ACC1 in human HCT116 cells assessed as reduction in [14C]acetate uptake preincubated for 60 mins followed by [14C]acetate addition and measured after 2 hrs by top count scintillation counting method
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 428.47, ALogP 5.13, HBA 5, HBD 3, PSA 101.62, QED 0.35
Compound (SMILES): Fc1cccc2c1C(C1CCCCC1)n1cncc1-2
InChIKey: QATDUWMUWYMNES-UHFFFAOYSA-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 = 568 nM (pChEMBL 6.25)
Descriptors: MW 256.32, ALogP 4.17, HBA 2, HBD 0, PSA 17.82, QED 0.75
Compound (SMILES): Cc1cc2ccc(OCC3CCN(Cc4ccc(CO)cc4)CC3)cc2oc1=O
InChIKey: DLNHNGYHCSSOLK-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate by Ellman's method
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 393.48, ALogP 3.88, HBA 5, HBD 1, PSA 62.91, QED 0.64
Compound (SMILES): COc1ccc2c(Nc3cc(OC)c(OC)c(OC)c3)ccnc2c1
InChIKey: GRKVQPWSPUXGKV-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Binding affinity to biotinylated human GAK (13 to 338 residues) expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 340.38, ALogP 4.01, HBA 6, HBD 1, PSA 61.84, QED 0.73
Compound (SMILES): Cl.Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(N2CCN(C3CCCCC3)CC2)cc1)c1ccccc1
InChIKey: XAPXVYSMBUGLID-BZAYTVMESA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to GST-tagged ERRgamma LBD (unknown origin) using fluorescein-conjugated coactivator PGC-1alpha incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 99 nM (pChEMBL 7)
Descriptors: MW 496.7, ALogP 6.58, HBA 4, HBD 2, PSA 46.94, QED 0.35
Compound (SMILES): CCCCCCC(Sc1nc2ccc(NCc3ccccc3)cc2s1)C(=O)O
InChIKey: IQXYNQBOHVNJHU-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Partial agonist activity at Gal4-fused PPARdelta LBD (unknown origin) expressed in HEK293T cells after 14 to 16 hrs by dual-Glo luciferase assay
Measurement: EC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 414.6, ALogP 6.42, HBA 5, HBD 2, PSA 62.22, QED 0.28
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2ccc(C)c(C(=O)O)c2)o1
InChIKey: VYNLFBJOPSEBLC-QGZVFWFLSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 459.5, ALogP 2.8, HBA 6, HBD 4, PSA 149.18, QED 0.12
Compound (SMILES): CCc1ccc(C(=O)Nc2cccc(C(F)(F)F)c2)cc1-c1cccc(-c2cnc3cnccn23)c1C
InChIKey: XGAYALCZXPVWQM-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of human recombinant full length His-tagged Bcr-Abl expressed in baculovirus expression system using tyrosine-2 peptide as substrate after 1 hr in presence of 10 mM ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 1813 nM (pChEMBL 5.739999771118164)
Descriptors: MW 500.52, ALogP 7.21, HBA 4, HBD 1, PSA 59.29, QED 0.28
Compound (SMILES): CC(C)(C)c1ccc(-c2nc3ccc(F)cc3c(=O)[nH]2)cc1
InChIKey: YWNDUCFQXOXSHW-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS2 (873 to 1166 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 60 mins in presence of bio-NAD as co-substrate by ELISA
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 296.35, ALogP 4.03, HBA 2, HBD 1, PSA 45.75, QED 0.74
Compound (SMILES): CCCN(CCCCNC(=O)c1cc2ccccc2[nH]1)C[C@H]1C[C@@H]1c1cccc(Cl)c1Cl.Cl
InChIKey: SUJXBDJLOIDKBO-DGXMUYMBSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D3 receptor (unknown origin) measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 472.46, ALogP 6.5, HBA 2, HBD 2, PSA 48.13, QED 0.31
Compound (SMILES): CCCN1C(=O)/C(=N\c2ccc(NC(=O)Nc3ccc(S(N)(=O)=O)cc3)cc2)c2ccccc21
InChIKey: QKYUTWNCIPAGNF-ROMGYVFFSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped flow CO2 hydration assay
Measurement: Ki = 19.6 nM (pChEMBL 7.710000038146973)
Descriptors: MW 477.55, ALogP 3.86, HBA 5, HBD 3, PSA 133.96, QED 0.5
Compound (SMILES): COc1cc(Nc2ccnc3ccccc23)cc(OC)c1OC
InChIKey: YUFKUUNLQBRXJX-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43353
Assay: Binding affinity to biotinylated human RIPK2 (1 to 310 residues) expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 310.35, ALogP 4, HBA 5, HBD 1, PSA 52.61, QED 0.77
Compound (SMILES): CC(C)(C)CNc1nccc(NCCN)n1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: IDMSKUFQFIZZEM-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of 20 nM [3H]UR-DE257 from human H2R expressed in Sf9 cell membranes co-expressing GsalphaS by competition binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 223.32, ALogP 1.31, HBA 5, HBD 3, PSA 75.86, QED 0.7
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCC(N(CCCN3CCOCC3)S(C)(=O)=O)CC2)n1
InChIKey: ZRYVMWWFILNTSK-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal p110alpha/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 665.77, ALogP 1.95, HBA 13, HBD 0, PSA 131.28, QED 0.3
Compound (SMILES): CC(C)C(=O)CN1c2nc(N3CCOC[C@H]3C)cc(=O)n2CC[C@H]1C(F)(F)F
InChIKey: ITCIAOUZMPREOO-OCCSQVGLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K p110delta (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.42, ALogP 1.83, HBA 7, HBD 0, PSA 67.67, QED 0.77
Compound (SMILES): C[C@@H](Oc1cc(-c2ccn(C)c(=O)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: APENINWAKNLZAY-SNVBAGLBSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human N-terminal GST-tagged ALK G1202R mutant (1058 to 1620 residues) expressed in baculovirus expression system using Srctide as substrate incubated with enzyme and substrate for 5 mins followed by ATP addition followed by further incubation for 30 mins by HTRF assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 408.26, ALogP 4.62, HBA 5, HBD 1, PSA 70.14, QED 0.64
Compound (SMILES): Cc1c(C(=O)N2CCN(c3ccc(C(F)(F)F)cn3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: HIHSCXZQCPFJRD-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 472.43, ALogP 1.89, HBA 8, HBD 1, PSA 104.42, QED 0.49
Compound (SMILES): NS(=O)(=O)c1ccc(N2C(=O)C[C@H](C(=O)NCCCN3CCCC3)[C@H]2c2ccc(Cl)cc2)cc1
InChIKey: KZFHHLGLHNFERJ-JTHBVZDNSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.89 nM (pChEMBL 9.050000190734863)
Descriptors: MW 505.04, ALogP 2.68, HBA 5, HBD 2, PSA 112.81, QED 0.54
Compound (SMILES): CCCCCCCNCC12c3ccccc3C(c3ccccc31)C1C(=O)NC(=O)C12
InChIKey: FPWIRYVKZNCSQX-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant cannabinoid CB2 receptor expressed in HEK293 cell membranes incubated for 90 mins
Measurement: IC50 = 3930 nM (pChEMBL 5.409999847412109)
Descriptors: MW 402.54, ALogP 3.88, HBA 3, HBD 2, PSA 58.2, QED 0.52
Compound (SMILES): CC(C)(C)c1cc(C(=O)NCCC(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)cc(C(C)(C)C)c1O
InChIKey: GNROHNFPJCPGCQ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 621.74, ALogP 5.19, HBA 9, HBD 4, PSA 156.64, QED 0.19
Compound (SMILES): O=C(NCc1ncccn1)c1csc(CCNCc2nc3ccccc3[nH]2)n1
InChIKey: KHFWFPNHQURMTB-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 393.48, ALogP 2.07, HBA 7, HBD 3, PSA 108.48, QED 0.4
Compound (SMILES): Nc1c(C(=O)NCCc2ccc(N3CCNCC3)cc2)sc2nc(CO)ccc12
InChIKey: NZTRPFRDOXKWFY-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 411.53, ALogP 1.75, HBA 7, HBD 4, PSA 103.51, QED 0.49
Compound (SMILES): Cc1cc(-n2cc(C(=O)N3CCN(C)CC3)c3ccc(N[C@@H](C)c4ccc(F)cn4)nc32)[nH]n1
InChIKey: MFUMJAGTBAKMKI-INIZCTEOSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human ALK expressed in HEK293 cells assessed as reduction in ALK autophosphorylation at Tyr1604 residue incubated for 60 mins by sandwich ELISA
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 462.53, ALogP 3.15, HBA 7, HBD 2, PSA 94.97, QED 0.47
Compound (SMILES): NC/C=C/CO[C@H]1[C@H](O)[C@H](OCc2ccccc2)COC/C=C/c2cccc(O)c2C(=O)OC[C@@H]1NC(=O)Cc1c[nH]c2ccccc12
InChIKey: JFHISKSWYZGVAZ-SUSQNPOLSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]somatostatin-14 (Tyr11) from human SSTR5 expressed in African green monkey COS1 cell membranes after 2 hrs by scintillation counting method
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 655.75, ALogP 3.65, HBA 9, HBD 5, PSA 165.36, QED 0.13
Compound (SMILES): Cn1cncc1[C@](O)(COc1ccc(C#N)cc1-c1ccc(OC(F)(F)F)cc1)c1ccc(C#N)cc1
InChIKey: HEUVRFNVTLGKMZ-SANMLTNESA-N
Target: Protein farnesyltransferase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49356
Assay: Affinity Biochemical interaction (Scintillation proximity assay (SPA)) EUB0000289c FNTB
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 504.47, ALogP 5.04, HBA 7, HBD 1, PSA 104.09, QED 0.38
Compound (SMILES): CCCCCCCN1C(=O)C2C3c4ccccc4C(Cl)(c4ccccc43)C2C1=O
InChIKey: ANCDLQKPVSSDHS-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant cannabinoid CB2 receptor expressed in HEK293 cell membranes incubated for 90 mins
Measurement: IC50 = 9880 nM (pChEMBL 5)
Descriptors: MW 407.94, ALogP 5.2, HBA 2, HBD 0, PSA 37.38, QED 0.37
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)C[C@H](C)NC3=O)cc(C)c1Cl
InChIKey: UBNJFCRDLRILJW-KRWDZBQOSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a 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 1-207A96T,G110R, Î35-91, 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.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 539.51, ALogP 6.73, HBA 5, HBD 1, PSA 61.08, QED 0.28
Compound (SMILES): CN(C)CCCNC(=O)[C@H]1CC(=O)N(c2ccc(S(N)(=O)=O)cc2)[C@@H]1c1ccc(Cl)cc1
InChIKey: FKMBSEVMCQVMPX-PZJWPPBQSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 479, ALogP 2.15, HBA 5, HBD 2, PSA 112.81, QED 0.56
Compound (SMILES): O=c1c(-c2ccc(OCCN3CCCCC3)cc2)coc2cc(OCCN3CCCC3)ccc12
InChIKey: LKWBRFHBJPNBMM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: Q03311
Assay: Inhibition of mouse plasma BuChE using S-butyrylacetylthiocholine iodide as substrate measured after 30 mins by Ellman's method relative to control
Measurement: IC50 = 4550 nM (pChEMBL 5.340000152587891)
Descriptors: MW 462.59, ALogP 4.8, HBA 6, HBD 0, PSA 55.15, QED 0.46
Compound (SMILES): O=C(CCCCCn1cc(-c2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)nn1)NO
InChIKey: IKTSOHKYDYDWRP-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 542.62, ALogP 5.53, HBA 9, HBD 4, PSA 137.57, QED 0.08
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(C)=O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C
InChIKey: USEVPSVMTBETHD-YZJIJPGJSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 3905.64
Compound (SMILES): C=CC(=O)N1CCN(C(CC)c2ccc([C@H](C)Nc3nc(N)cc(N4C(=O)OCC4(C)C)n3)cc2)CC1
InChIKey: IRYXPSUOUWFUGU-YMXDCFFPSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of N-terminal His-tagged IDH1 R132C mutant (unknown origin) expressed in Escherichia coli using alpha-KG and NADPH substrate assessed as suppression of 2-HG production incubated for 40 mins by LC-MS analysis
Measurement: IC50 = 8.89 nM (pChEMBL 8.050000190734863)
Descriptors: MW 507.64, ALogP 3.75, HBA 8, HBD 2, PSA 116.92, QED 0.52
Compound (SMILES): Cc1c(C(=O)N2CCC3(CC2)CC(F)C3)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: CJMIWOKCRBBNHY-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 384.42, ALogP 1.87, HBA 6, HBD 1, PSA 88.29, QED 0.73
Compound (SMILES): Cc1ccccc1NC(=O)N1C(=O)CC1CC(=O)NCC(=O)O
InChIKey: HZLFZIQTWBACFC-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Antagonist activity at alphaVbeta3 in human SK-MEL-24 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 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 319.32, ALogP 0.72, HBA 4, HBD 3, PSA 115.81, QED 0.69
Compound (SMILES): Cn1cnc(-c2nnc3n2CCN(C(=O)c2ccc(/C=C4\Oc5c(C(N)=O)cccc5C4=O)cc2)C3)c1
InChIKey: WUSATWKNDGXYRU-JAIQZWGSSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 495.5, ALogP 2.05, HBA 9, HBD 1, PSA 138.23, QED 0.43
Compound (SMILES): N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H]1CSCc2ccccc2CSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccc(F)cc2)C(=O)NNC(=O)[C@H](Cc2ccc(F)cc2)NC(=O)CNC1=O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: PYJOZFZUINVNAW-FTMHIQFLSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 1 hr by [35S]-GTPgammaS coupling assay
Measurement: EC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 1111.26
Compound (SMILES): O=C(NCc1ncccc1F)c1csc(C2CN(CCc3nc4ccccc4[nH]3)C2)n1
InChIKey: FYBJPPIACCHUAL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 436.52, ALogP 3.13, HBA 6, HBD 2, PSA 86.8, QED 0.46
Compound (SMILES): COc1ccc2c(c1)c(-c1[nH]c(NC(=O)Cc3ccccc3)nc1C)cn2S(=O)(=O)c1ccccc1
InChIKey: RVATUCUFIHFGSE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 500.58, ALogP 4.77, HBA 6, HBD 2, PSA 106.08, QED 0.33
Compound (SMILES): COc1ccc(/C=N/NC(=O)c2nn(-c3ccc(S(N)(=O)=O)cc3)c3nc(C)cc(=O)n23)cc1
InChIKey: VDZKJTZQIBBQIZ-FSJBWODESA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 63.2 nM (pChEMBL 7.199999809265137)
Descriptors: MW 481.49, ALogP 0.61, HBA 10, HBD 2, PSA 163.04, QED 0.3
Compound (SMILES): CCCCc1ccc(OCC(=O)N(CC(=O)Nc2ccnnc2)C(C)C)cc1
InChIKey: ZFUGTCXOROLCPU-UHFFFAOYSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of human caspase-like activity of 20S constitutive proteasome preincubated for 15 mins followed by substrate addition by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.48, ALogP 3.07, HBA 5, HBD 1, PSA 84.42, QED 0.68
Compound (SMILES): O=C(NCc1ncccc1F)c1cnc(CCNCCc2nc3ccccc3[nH]2)o1
InChIKey: IAAKEJBSOKSMGL-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 408.44, ALogP 2.39, HBA 6, HBD 3, PSA 108.73, QED 0.37
Compound (SMILES): COc1cc(S(N)(=O)=O)ccc1-c1noc(-c2ccccc2)n1
InChIKey: SGHGFZFSHPTXEN-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 331.35, ALogP 2.06, HBA 6, HBD 1, PSA 108.31, QED 0.78
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc3[nH]ncc3c2)c2ncc(-c3ccccc3)cc21
InChIKey: XOHKHMXVNYJHEX-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of ACC1 in human HCT116 cells assessed as reduction in [14C]acetate uptake preincubated for 60 mins followed by [14C]acetate addition and measured after 2 hrs by top count scintillation counting method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 395.47, ALogP 5.41, HBA 4, HBD 2, PSA 75.6, QED 0.43
Compound (SMILES): Cc1cc(C)c2c(c1)S(=O)(=O)NC(=O)N2
InChIKey: OLDBDPLNTRFOOO-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 1 hr prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 1637 nM (pChEMBL 5.789999961853027)
Descriptors: MW 226.26, ALogP 1.13, HBA 3, HBD 2, PSA 75.27, QED 0.7
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C(CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(=O)NCC(=O)NCC(=O)N[C@H](C(=O)O)C(C)C
InChIKey: CXMXKOGLTTYFFZ-NYVAKSRESA-N
Target: BTB/POZ domain-containing protein KCTD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96CX2
Assay: Displacement of TAMRA-AAG-SLQLPILHHAYLPSIGGV from recombinant human 6X His-tagged KCTD12 T1 domain (27 to 131 residues) expressed in Escherichia coli BL21 DE3 cells by fluorescence polarization assay
Measurement: IC50 = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 1938.31
Compound (SMILES): CCCCCCN1C(=O)C2C3c4ccccc4C(c4ccccc43)C2C1=O
InChIKey: QETAQJKVCACISO-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant cannabinoid CB2 receptor expressed in HEK293 cell membranes incubated for 90 mins by Cheng-Prusoff equation analysis
Measurement: Ki = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 359.47, ALogP 4.46, HBA 2, HBD 0, PSA 37.38, QED 0.58
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccccc2C(F)(F)F)CC1
InChIKey: VMSLPQBRZIOWEV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 1128 nM (pChEMBL 5.949999809265137)
Descriptors: MW 481.56, ALogP 6.2, HBA 3, HBD 0, PSA 26.79, QED 0.36
Compound (SMILES): CC(=O)OC[C@](C)(OC(C)=O)[C@@H]1C[C@@H]2[C@@H](O)c3c(cc(-c4cccnc4)oc3=O)O[C@@]2(C)[C@H](OC(C)=O)C1
InChIKey: NIGGKHQHUNJNPM-YBEFSANESA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75908
Assay: Inhibition of SOAT2 (unknown origin)
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 529.54, ALogP 2.73, HBA 11, HBD 1, PSA 151.46, QED 0.43
Compound (SMILES): NS(=O)(=O)CC(=O)NCCSc1nonc1/C(=N/O)Nc1cccc(Cl)c1
InChIKey: ONYXYPAXVUWGTM-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition IDO1 in LPS/IFN-gamma stimulated human whole blood assessed as reduction in tryptophan/kynurenine level preincubated for 15 mins followed by LPS/IFN-gamma stimulation measured after 20 hrs by LC-MS/MS analysis
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 434.89, ALogP 0.47, HBA 9, HBD 4, PSA 172.8, QED 0.11
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCN[C@H](CO)C4)cc3)sc2n1
InChIKey: VYSSWPBTCCCHHZ-INIZCTEOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 425.56, ALogP 1.93, HBA 7, HBD 4, PSA 103.51, QED 0.48
Compound (SMILES): COc1cc(Nc2ccnc3ccc(C#N)cc23)cc(OC)c1OC
InChIKey: AHESYZXOYPHUOT-UHFFFAOYSA-N
Target: Atypical kinase COQ8A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI60
Assay: Binding affinity to biotinylated full length human ADCK3 expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 335.36, ALogP 3.88, HBA 6, HBD 1, PSA 76.4, QED 0.76
Compound (SMILES): CN(CCCN1CCN(c2nccc3ccccc23)CC1)c1cc(=O)oc2ccccc12
InChIKey: ZLGQQPDCDMXOMS-UHFFFAOYSA-N
Target: DNA topoisomerase 4 subunit A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0C1U9
Assay: Inhibition of Staphylococcus aureus ATCC 29213 DNA topoisomerase 4 subunit ParC assessed as reduction in decatenation of kinetoplast DNA incubated for 30 mins by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 428.54, ALogP 3.99, HBA 6, HBD 0, PSA 52.82, QED 0.43
Compound (SMILES): Cc1c(-c2cnc3ccccc3c2)ccc2c1CCNC2=O
InChIKey: XZSLEAXPZQWQSC-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 13803.84 nM (pChEMBL 4.860000133514404)
Descriptors: MW 288.35, ALogP 3.5, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): COc1ccc(-n2c(CO[C@H]3CCOC3)nnc2N2C[C@@H]3C[C@]3(c3ccc(F)cc3Cl)C2)cn1
InChIKey: PQVZXGGQYNPGOA-RGUAHJAXSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Antagonist activity at human OTR expressed in HEK293 cells assessed as decrease in calcium flux measured after 10 mins in presence of vasopressin by Fluo-4 dye based microplate reader based assay
Measurement: IC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 485.95, ALogP 3.55, HBA 8, HBD 0, PSA 74.53, QED 0.51
Compound (SMILES): O=C(O)[C@H]1[C@H](Cn2nnc3ccccc3c2=O)CC[C@@H]1C(=O)c1ccc(OCCC2CCOCC2)cc1
InChIKey: ZGBAPSHWPBXEKN-OPHFCASCSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Selectivity interaction (Lead profiling screen (Eurofins, enzymes, transporters, GPCRs, ion chanels)) EUB0000728a MMP13
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 505.57, ALogP 3.6, HBA 8, HBD 1, PSA 120.61, QED 0.44
Compound (SMILES): O=C(NCc1ncccc1F)c1cnc(C2CN(CCc3nc4cc(F)ccc4[nH]3)C2)o1
InChIKey: FFTGCUMQTXCDIH-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHI9
Assay: Inhibition of ferroportin in mouse J774 cells assessed as reduction in binding of hepcidin to ferroportin pre-incubated for 15 mins before TMR-hepcidin addition and further incubated for 2 hrs by fluorescence based hepcidin internalization assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 438.44, ALogP 2.8, HBA 6, HBD 2, PSA 99.94, QED 0.46
Compound (SMILES): CN(CCCSc1nnc(-c2ccccc2)n1C)CC1CC1c1cc(F)ccc1OCCF.Cl
InChIKey: YGLJFTGMBJXSPI-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D4 receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 977.2 nM (pChEMBL 6.010000228881836)
Descriptors: MW 472.61, ALogP 5.19, HBA 6, HBD 0, PSA 43.18, QED 0.27
Compound (SMILES): Cn1c(C(=O)NC2(c3ccc([C@@H](O)c4cccnc4)cc3)COC2)cc2c(Cl)c(Cl)ccc21
InChIKey: YBVGWRRPMBSVHG-HSZRJFAPSA-N
Target: Malate dehydrogenase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: P40925
Assay: Inhibition of recombinant human MDH1 expressed in Escherichia coli using malate as substrate incubated for 30 mins followed by substrate addition
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 482.37, ALogP 4.62, HBA 5, HBD 2, PSA 76.38, QED 0.44
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(OS(=O)(=O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N(C)[C@H](CC(=O)O)C(=O)N(C)[C@@H](Cc1cccc2ccccc12)C(N)=O
InChIKey: BMZYXLWLLWZVBA-PPAHWLEZSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Agonist activity at human CCK2R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay
Measurement: EC50 = 151.36 nM (pChEMBL 6.820000171661377)
Descriptors: MW 1901.21
Compound (SMILES): COc1ccc(CCN(C(=O)OC2CN3CCC2CC3)c2ccccc2)cc1
InChIKey: KHJKTXKHUACAIJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 380.49, ALogP 3.98, HBA 4, HBD 0, PSA 42.01, QED 0.76
Compound (SMILES): CN[C@@H]1CN(c2cc(F)c(CCNC(=O)c3sc4nc(C)ccc4c3N)cc2F)C[C@@H]1F
InChIKey: SQZSNZZALOBTRY-DLBZAZTESA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 463.53, ALogP 3.18, HBA 6, HBD 3, PSA 83.28, QED 0.52
Compound (SMILES): COc1ccc(N(Cc2cccc(F)c2)NC(=O)NCCCN2CCN(c3ccccc3OC)CC2)cc1
InChIKey: LJZKZXJPHHZDQF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H] Spiperone from human D4.4 receptor expressed in CHO cells by competitive radioligand binding assay
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 521.64, ALogP 4.28, HBA 6, HBD 2, PSA 69.31, QED 0.29
Compound (SMILES): CCN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2cc(Cl)ccc21
InChIKey: AWODLBDOTQJIQR-HKWRFOASSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 51.2 nM (pChEMBL 7.289999961853027)
Descriptors: MW 378.84, ALogP 2.17, HBA 5, HBD 2, PSA 104.86, QED 0.8
Compound (SMILES): CC(C)(COc1ccc(-c2ccc(-c3nc4cc(Cl)ccc4[nH]3)cn2)cn1)C(=O)O
InChIKey: VIESBBSLVITZSP-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: Ki = 8140 nM (pChEMBL 5.090000152587891)
Descriptors: MW 422.87, ALogP 4.83, HBA 5, HBD 2, PSA 100.99, QED 0.46
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cccc(C(=O)NC)c2)o1
InChIKey: RXFXUTDMWSSFCJ-GOSISDBHSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 458.52, ALogP 2.15, HBA 6, HBD 4, PSA 140.98, QED 0.12
Compound (SMILES): Cl.Cl.OCCC/C(=C(\c1ccc(Br)cc1)c1ccc(N2CCNCC2)cc1)c1ccccc1
InChIKey: KSOHJXHZMVIUAY-ZNKLZGLFSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) using fluorescein-conjugated coactivator PGC-1alpha incubated for 1 hr by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 477.45, ALogP 5.59, HBA 3, HBD 2, PSA 35.5, QED 0.44
Compound (SMILES): COCC(=O)NC1CCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)CC1
InChIKey: RCYSKZYQEULPIS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 520.66, ALogP 3.4, HBA 8, HBD 2, PSA 95.61, QED 0.39
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: MDJAIWTXSMIKIR-OOGSTSQOSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.057 nM (pChEMBL 10.239999771118164)
Descriptors: MW 3820.27
Compound (SMILES): Nc1nc(NC(=O)Nc2ccccc2)nn1-c1ccc(S(N)(=O)=O)cc1
InChIKey: MDFYLPAPFMHRAH-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase-12 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 373.4, ALogP 1.14, HBA 7, HBD 4, PSA 158.02, QED 0.54