lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C(=O)c1nc2ccc(-c3cnn(C)c3)cc2[nH]1)[C@@H]1CCN(C#N)C1
InChIKey: ZKPZGHHLNHGFON-CQSZACIVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 349.4, ALogP 1.59, HBA 6, HBD 1, PSA 93.84, QED 0.72
Compound (SMILES): O=C(NCc1cccnn1)c1coc(C2CN(CCc3nc4ccccc4[nH]3)C2)n1
InChIKey: VQLIBSULFJTYGR-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as reduction in Fpn-mediated iron efflux incubated overnight by iron regulatory element -driven beta-lactamase reporter gene assay
Measurement: EC50 = 3860 nM (pChEMBL 5.409999847412109)
Descriptors: MW 403.45, ALogP 1.91, HBA 7, HBD 2, PSA 112.83, QED 0.48
Compound (SMILES): CC(C)c1cc2c(c(O)c1O)[C@@]1(c3nnc(-c4ccc(C#N)cc4)o3)CCCC(C)(C)[C@@H]1CC2
InChIKey: KSTNMHMOTXNCHZ-RBTNQOKQSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 mins by scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 457.57, ALogP 6.2, HBA 6, HBD 2, PSA 103.17, QED 0.45
Compound (SMILES): Cc1noc(C)c1-c1nc2sc3c(c2c(=O)[nH]1)CCN(CC(=O)Nc1ccccc1N)C3
InChIKey: XGOHVFIQCCFBCJ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using biotinylated histone H3 KAc peptide (1 to 21 residues) as substrate by HTRF assay
Measurement: IC50 = 352 nM (pChEMBL 6.449999809265137)
Descriptors: MW 450.52, ALogP 2.84, HBA 8, HBD 3, PSA 130.14, QED 0.41
Compound (SMILES): COc1cc(/C=C/C(=O)NO)ccc1OCCCCN(C)C(=O)c1ccccc1O
InChIKey: ANYFJEUUATYOCN-ZRDIBKRKSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 414.46, ALogP 2.85, HBA 6, HBD 3, PSA 108.33, QED 0.24
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3cc(F)c(N4C[C@@H]5C[C@H]4CN5)cc3F)sc2n1
InChIKey: MSQZTQXBYBQNGY-KBPBESRZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 443.52, ALogP 2.99, HBA 6, HBD 3, PSA 83.28, QED 0.56
Compound (SMILES): CC(C)Sc1nn([C@@H]2O[C@@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: CDIBRSZOZOHBQK-FCCZHNFCSA-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 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 420.47, ALogP -1.25, HBA 12, HBD 4, PSA 188.7, QED 0.41
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(CNc3ncc(C(=O)NO)cn3)c2c(=O)n1-c1ccccc1
InChIKey: WJOMMYWEPXHYNA-IBGZPJMESA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human GST-tagged HDAC2 (1 to 488 residues) expressed in baculovirus infected sf21 cells using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate measured after 1 to 2 hrs by fluorescence assay
Measurement: IC50 = 25480 nM (pChEMBL 4.590000152587891)
Descriptors: MW 563.58, ALogP 3.14, HBA 12, HBD 5, PSA 188.52, QED 0.13
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)c1)[C@@H](CC)N(O)C=O
InChIKey: HMTNCEWNGNAKDX-PZUNEJSGSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 672.69, ALogP 2.1, HBA 9, HBD 7, PSA 248.97, QED 0.03
Compound (SMILES): C=CC(=O)N1CCC[C@@H](n2nc(-c3cn(-c4ccc(C(C)=O)cc4)nn3)c3c(N)ncnc32)C1
InChIKey: CKAJNPCKXKPZBT-QGZVFWFLSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant (unknown origin) by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 457.5, ALogP 2.21, HBA 10, HBD 1, PSA 137.71, QED 0.36
Compound (SMILES): C[C@H]1NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]2CCCN2C1=O
InChIKey: OTUDCPUMJPNZRR-XECWOPBBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]diprenorphine from human DOR expressed in HEK293 cell membranes incubated for 90 mins by liquid scintillation counting
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 501.59, ALogP 1.43, HBA 4, HBD 4, PSA 123.4, QED 0.43
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-n2cc(C)cn2)c1
InChIKey: PNHGGNMGADAUBF-GOSISDBHSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 415.49, ALogP 2.03, HBA 6, HBD 3, PSA 116.56, QED 0.16
Compound (SMILES): O=[N+]([O-])CC(c1ccccc1)c1c(-c2ccccc2)[nH]c2ncccc12
InChIKey: LUCSGVYAUHAHIP-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulatory activity at human CB1R expressed in CHO-K1 cells assessed as increase in CP55940-induced inhibition of forskolin-stimulated cAMP production after 30 mins in presence of CP55940 at EC20 concentration by hit-hunter cAMP assay
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 343.39, ALogP 4.64, HBA 3, HBD 1, PSA 71.82, QED 0.42
Compound (SMILES): Cc1nc2sc(C(=O)NCCc3ccc(N4CCNCC4)c(Cl)c3)c(N)c2cc1F
InChIKey: KKEQKWAYCQDJFA-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 447.97, ALogP 3.36, HBA 6, HBD 3, PSA 83.28, QED 0.56
Compound (SMILES): CCc1nc(N)nc(N)c1C#CCc1cc(OC)c(OC)c(-c2ccncc2)c1
InChIKey: GCDLAOPKRFVDHQ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition of TMP/methicillin-resistant Staphylococcus aureus recombinant DHFR F98Y mutant expressed in Escherichia coli BL21 (DE3) cells assessed as oxidation of NADPH pre-incubated for 5 mins followed by dihydrofolate substrate addition
Measurement: Ki = 12.13 nM (pChEMBL 7.920000076293945)
Descriptors: MW 389.46, ALogP 2.88, HBA 7, HBD 2, PSA 109.17, QED 0.65
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: PLUOMRKSSTXRGM-HSGJTTTCSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in absence of albumin by CRE luciferase reporter gene assay
Measurement: EC50 = 0.012 nM (pChEMBL 10.920000076293945)
Descriptors: MW 3638.09
Compound (SMILES): COc1ncc(-c2cc(OCCCCCCCC(=O)NO)c3ncnc(C)c3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: WSPUWFLFRIFQSS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human PI3Kalpha using PIP2 as substrate incubated for 1 hr by kinase-glo assay
Measurement: IC50 = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 615.66, ALogP 5.31, HBA 9, HBD 3, PSA 152.63, QED 0.1
Compound (SMILES): O=C(NC1=NN(c2ccc(Cl)c(Cl)c2)CC1)c1ccncn1
InChIKey: XRIAOJJBTZBDDN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Displacement of Myr-GQQPGKVLGDQRRPSL(K-TAMRA)G-amide from N-terminal-truncated human c-ABL D382N mutant (46 to 534 residues) after 30 mins by fluorescence polarization binding assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 336.18, ALogP 2.74, HBA 5, HBD 1, PSA 70.48, QED 0.92
Compound (SMILES): Cc1ncc(CNC(=O)c2cc(-c3ccc(N4CCN(C(C)C)CC4)nc3)cc3c2cnn3C(C)C)c(=O)[nH]1
InChIKey: PPVPMTIDZNDEEK-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92800
Assay: Inhibition of EZH1 histone methyltransferase activity of EZH1/EED/SUZ12/RBBP4/AEBP2 protein complex (unknown origin) using histone H3 peptide as substrate (21 to 44 residues) in presence of [3H]-S-adenosylmethionine after 2 hrs by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.66, ALogP 3.53, HBA 8, HBD 2, PSA 112.04, QED 0.38
Compound (SMILES): C[C@@H]1CN(c2ccccc2)CCN1C(=O)Oc1cccc(N2CCS(=O)(=O)CC2)c1
InChIKey: IEDPCBGAOHTUKR-GOSISDBHSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat recombinant His/GST-tagged FAAH expressed in Escherichia coli cells using AAMCA as substrate incubated for 15 mins followed by substrate addition and measured after every 20 mins for 4 hrs by fluorescence based assay
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 429.54, ALogP 2.63, HBA 6, HBD 0, PSA 70.16, QED 0.75
Compound (SMILES): CCOP(=O)(CC)NCCNc1nonc1/C(=N/O)Nc1cccc(Br)c1
InChIKey: XRFHAZHGTKNHJB-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant N-terminal His-tagged human IDO1 expressed in Escherichia coli assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate
Measurement: IC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 461.26, ALogP 3.33, HBA 8, HBD 4, PSA 133.9, QED 0.1
Compound (SMILES): COc1cc(-c2cc(=O)n(C(C)(C)C)[s+]2[O-])cc(OC)c1OC
InChIKey: MBBUZUPIQLIKFO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 339.41, ALogP 3.02, HBA 6, HBD 0, PSA 72.75, QED 0.8
Compound (SMILES): COc1ccc(F)c(-c2ccc3c(n2)CC[C@H]3Oc2cccc([C@H](C3CC3)[C@H](C)C(=O)O)c2)c1
InChIKey: VQDHDZKTXGXQFV-GENHPLMOSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Positive allosteric modulation of recombinant human GPR40 expressed in HEK293 cells assessed as increase in [3H]-myo-inositol phosphate accumulation measured after 60 mins in absence of human serum by microbeta counting method
Measurement: EC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 461.53, ALogP 6.18, HBA 4, HBD 1, PSA 68.65, QED 0.43
Compound (SMILES): Cc1c(C(=O)N2CCC(c3nc(C(F)(F)F)cs3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: OAHKZXGGRIOJFK-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 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 477.47, ALogP 3.01, HBA 8, HBD 1, PSA 101.18, QED 0.49
Compound (SMILES): C[C@@H](Cc1ccsc1)NC(=O)NC[C@H](Cc1ccc2ccccc2c1)N(C)C
InChIKey: JRTJIFATICCDPS-JTSKRJEESA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Inhibition of mu opioid receptor (unknown origin) expressed in HEK293 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation preincubated for 30 mins followed by forskolin-stimulation and measured after 60 mins
Measurement: EC50 = 52.41 nM (pChEMBL 7.28000020980835)
Descriptors: MW 395.57, ALogP 4.3, HBA 3, HBD 2, PSA 44.37, QED 0.6
Compound (SMILES): CCOc1ccc(-c2ccc(CCCc3nn(-c4cccc(C(F)(F)F)c4)c(=O)n3-c3ccccc3F)cc2)cc1CC(=O)O
InChIKey: WKHTTYBFGIINHV-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Antagonist activity at recombinant human PPARalpha assessed as inhibition of GW7647-induced receptor activation after overnight incubation by cell-based luciferase reporter gene assay
Measurement: IC50 = 678 nM (pChEMBL 6.170000076293945)
Descriptors: MW 619.62, ALogP 7.05, HBA 6, HBD 1, PSA 86.35, QED 0.16
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(C(=O)n2cc(-c3ccc(OC(F)(F)F)cc3)nn2)C(Cc2ccccc2)C1
InChIKey: CQGMWUWJVBKTRM-UHFFFAOYSA-N
Target: Diacylglycerol lipase-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4D2
Assay: Inhibition human DAGLalpha expressed in HEK293T cell membrane fractions using DAG as substrate preincubated for 30 mins followed by ABP HT01 probe addition measured after 30 mins in presence of probe by gel-based ABPP competition assay
Measurement: IC50 = 0.5012 nM (pChEMBL 9.300000190734863)
Descriptors: MW 531.54, ALogP 4.98, HBA 7, HBD 0, PSA 89.79, QED 0.47
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-UWELNFAVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z′-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen Biochemical Kinase Profiling Service. The Z′-LYTE biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores one at each end that make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophore on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CCCCCCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: KUSKRNBCFWEDGT-DSCYDBDCSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human NPY Y4 receptor expressed in HEK293 cells co-expressing CRE-Luc gene assessed as inhibition of forskolin stimulated luciferase activity after 4.5 hrs by luminescence assay
Measurement: EC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 1590.9
Compound (SMILES): C[C@@H](CN1CCC2(CC1)C(=O)NC[C@H]2c1ccc(F)cc1)NC(=O)c1ccc(F)cc1
InChIKey: ZRRZCDIHCHFDRR-KKSFZXQISA-N
Target: Phospholipase D1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13393
Assay: Inhibition of PLD1 in human Calu1 cells
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 427.5, ALogP 3.08, HBA 3, HBD 2, PSA 61.44, QED 0.77
Compound (SMILES): Cc1cc(-c2ccc(O)cc2)c(O)c2c1C[C@@H](C)OC2=O
InChIKey: HUHHYEFPQAXAFB-SNVBAGLBSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB using kynuramine as substrate incubated for 10 mins by UPLC-ESI-MS/MS analysis
Measurement: IC50 = 38900 nM (pChEMBL 4.409999847412109)
Descriptors: MW 284.31, ALogP 3.17, HBA 4, HBD 2, PSA 66.76, QED 0.79
Compound (SMILES): O=C(/C=C/c1ccccc1F)c1ccc2ccccc2c1O
InChIKey: QTZDJNALMODSAW-ZRDIBKRKSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 expressed in supersomes using 7-ethoxyresorufin as substrate after 15 mins in presence of NADP+ by EROD assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 292.31, ALogP 4.58, HBA 2, HBD 1, PSA 37.3, QED 0.57
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1CCC[C@@H]1C(N)=O)C(C)C
InChIKey: BBMXUZDQYHSAJB-CBPXPLCBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene assessed as inhibition of NDP-MSH-induced cAMP accumulation up to 10 uM after 6 hrs by beta-galactosidase reporter gene assay
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 684.58, ALogP -0.3, HBA 6, HBD 7, PSA 212.6, QED 0.06
Compound (SMILES): COc1ccc(-c2ccc3ncnc(-c4cccc(C(=O)N5CCN(C)CC5)c4)c3c2)cn1
InChIKey: OIJYSJZSPNJQBW-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of recombinant PI3Kbeta (unknown origin) using phosphatidyl inositol as substrate after 30 to 60 mins in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 4150 nM (pChEMBL 5.380000114440918)
Descriptors: MW 439.52, ALogP 3.76, HBA 6, HBD 0, PSA 71.45, QED 0.48
Compound (SMILES): Cc1cc(C(F)(F)F)c2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(F)c3)sc2n1.Cl
InChIKey: CUPGRVNIMYRNBP-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 < 200 nM (pChEMBL 6.698999881744385)
Descriptors: MW 481.52, ALogP 3.73, HBA 6, HBD 3, PSA 83.28, QED 0.48
Compound (SMILES): COc1ccc(C(=O)Cn2c(=O)oc3ccccc32)cc1OC
InChIKey: MYLHWEZWWUETMM-UHFFFAOYSA-N
Target: Chromodomain Y-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N8U2
Assay: Binding affinity to recombinant human N-terminal GST-tagged CDYL2 (1 to 70 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 313.31, ALogP 2.49, HBA 6, HBD 0, PSA 70.67, QED 0.68
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccc(C(N)=O)cc1OC
InChIKey: PENFDVUMLLDOTA-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human whole blood assessed as decrease in IFNalpha-induced STAT5 phosphorylation preincubated for 1 hr followed by stimulation with IFN-alpha for 15 mins by fluorescence analysis
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 410.41, ALogP 2.57, HBA 7, HBD 4, PSA 131.26, QED 0.47
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CCCCC[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: SDXFRAOZSUERSZ-DFWPTFNMSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Agonist activity at human NPY Y4 receptor expressed in HEK293 cells co-expressing CRE-Luc gene assessed as inhibition of forskolin stimulated luciferase activity after 4.5 hrs by luminescence assay
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 1520.8
Compound (SMILES): O/N=C(/CCCN1CCCN(c2ccccn2)CC1)c1ccc(F)cc1
InChIKey: DXUQNBORIUMGPM-NMWGTECJSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement [3H]-DTG from sigma 2 receptor (unknown origin) expressed in HEK cell membranes
Measurement: Ki = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 356.44, ALogP 3.39, HBA 5, HBD 1, PSA 51.96, QED 0.49
Compound (SMILES): O=C(c1cn(-c2nn3cccc3c(=O)[nH]2)nn1)N1CCN(C2CC2)CC1
InChIKey: UTKYDYGEQIBYKQ-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 354.37, ALogP -0.48, HBA 8, HBD 1, PSA 104.42, QED 0.68
Compound (SMILES): Cc1cccc(-c2nc(C)c(COc3ccc(OCC(=O)O)c(F)c3)s2)c1
InChIKey: AFJXEHIRHUBJKQ-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in CHO cells by Fluo 4-AM dye based FLIPR assay
Measurement: EC50 = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 387.43, ALogP 4.61, HBA 5, HBD 1, PSA 68.65, QED 0.64
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(I)c(Nc3ccccc3P(C)(C)=O)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: BPGJJKMCXBBEBI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type GST-tagged human EGFR cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using Poly G:T (4:1) as substrate after 30 mins by Z-LYTE assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 663.5, ALogP 4.95, HBA 9, HBD 3, PSA 111.72, QED 0.14
Compound (SMILES): CC(=O)N1N=C(c2cccc(OS(N)(=O)=O)c2)CC1c1ccccc1
InChIKey: KHSKUDXMSRHVHU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 39.4 nM (pChEMBL 7.409999847412109)
Descriptors: MW 359.41, ALogP 1.97, HBA 5, HBD 1, PSA 102.06, QED 0.9
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)Nc1ccc(-c2ccncc2)s1
InChIKey: RWTUJQYVLQBWRL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Allosteric modulator activity at human CB1 receptor expressed in HEK293 cell membranes assessed as suppression of 100 nM CP55,940-induced [35S]GTPgammaS binding incubated for 60 mins by scintillation counting method
Measurement: IC50 = 263 nM (pChEMBL 6.579999923706055)
Descriptors: MW 329.81, ALogP 5.11, HBA 3, HBD 2, PSA 54.02, QED 0.7
Compound (SMILES): COc1ccc(N(C)Cc2cc(=O)c(O)co2)cc1
InChIKey: YWBSEKVNARDIKJ-UHFFFAOYSA-N
Target: Polymerase acidic protein (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03433
Assay: Inhibition of 8-histidine tagged influenza virus H1N1 N-terminal PA endonuclease expressed in Escherichia coli BL21 cells using single-stranded 5'-FAM fluorophore/3'-TAMRA quencher)-labeled 17-mer ssDNA-oligomer substrate measured over 45 mins by FRET analysis
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 261.28, ALogP 1.99, HBA 5, HBD 1, PSA 62.91, QED 0.91
Compound (SMILES): Cc1c(F)c(Nc2ccc(-c3cn(C)cn3)cn2)cc2c1ncn2CC1CC1
InChIKey: INGJMHPGMVUEKY-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P47869
Assay: Binding affinity to GABA-A alpha2 (unknown origin)
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 376.44, ALogP 4.43, HBA 6, HBD 1, PSA 60.56, QED 0.56
Compound (SMILES): FC(F)(F)c1cccc(OCc2cc(OC[C@@H]3CCCN3)no2)c1.O=C(O)C(F)(F)F
InChIKey: ABLMURDFYSLYGK-YDALLXLXSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from rat brain sigma2 receptor by PDSP assay
Measurement: Ki = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 342.32, ALogP 3.4, HBA 5, HBD 1, PSA 56.52, QED 0.87
Compound (SMILES): O=c1oc2ccccc2c2nn(S(=O)(=O)c3ccc(F)cc3)cc12
InChIKey: DECSOBNHXQFDQD-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 67920 nM (pChEMBL 4.170000076293945)
Descriptors: MW 344.32, ALogP 2.52, HBA 6, HBD 0, PSA 82.17, QED 0.52
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2c(OS(=O)(=O)F)cccc21)C1CCCCC1
InChIKey: YVERFLKIJOIKPE-HXGJMTJLSA-N
Target: Baculoviral IAP repeat-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13489
Assay: Inhibition of N-terminal 6x-His-tagged recombinant human cIAP2-BIR3 (244 to 349 residues) expressed in Escherichia coli incubated for 2 hrs without 6 hrs pre-incubation with enzyme by biotinylated AVPI peptide based DELFIA
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 552.67, ALogP 2.05, HBA 7, HBD 3, PSA 133.91, QED 0.4
Compound (SMILES): Cc1c(C(=O)N(C)Cc2ccc3ncccc3c2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: PXHCVRXRZRCFGY-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 414.47, ALogP 2.57, HBA 6, HBD 1, PSA 96.77, QED 0.55
Compound (SMILES): Cc1ccccc1N(C)CCN(C)C(=O)CSCc1c(C)noc1C
InChIKey: ZCOBDPFVEWNCAY-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 18400 nM (pChEMBL 4.739999771118164)
Descriptors: MW 361.51, ALogP 3.43, HBA 5, HBD 0, PSA 49.58, QED 0.72
Compound (SMILES): NC(=O)c1cnc2ccc(-c3cccnc3)cc2c1SC1CCCC1
InChIKey: NLZAONPHATZEGO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in Chk1 phosphorylation at Ser-345 residue after 60 mins in presence of 4-nitroquinoline-1-oxide by Hoechst 33258 staining based plate reader analysis
Measurement: IC50 > 23000 nM (pChEMBL 4.638000011444092)
Descriptors: MW 349.46, ALogP 4.43, HBA 4, HBD 1, PSA 68.87, QED 0.76
Compound (SMILES): C[C@H]1C[C@@H](N)C2(CCN(c3nc(N)c(Sc4cccnc4C(F)(F)F)c(=O)n3C)CC2)C1
InChIKey: YASURKJIUFJZHZ-GXTWGEPZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 468.55, ALogP 3.27, HBA 8, HBD 2, PSA 103.06, QED 0.71
Compound (SMILES): CC(C)=CCc1ccc(/C=C/C(=O)O)cc1NC(=O)CCc1ccc(F)cc1
InChIKey: LMUONPDACJHQEA-RIYZIHGNSA-N
Target: Aldo-keto reductase family 1 member C2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52895
Assay: Inhibition of recombinant human AKR1C2 expressed in Escherichia coli BL21 (D3) using S-tetralol as substrate in presence of NADP+ by UV-spectrophotometric method
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 381.45, ALogP 5, HBA 2, HBD 2, PSA 66.4, QED 0.5
Compound (SMILES): N#CC(C(=O)NCC(=O)NC1CC1)c1nc2ccc(-c3cccc(C(=O)N4CCCCC4)c3)cc2s1
InChIKey: YZHXHJDSIMLGFY-UHFFFAOYSA-N
Target: Hepatic triacylglycerol lipase (SINGLE PROTEIN), Homo sapiens
UniProt: P11150
Assay: Inhibition of hepatic lipase (unknown origin)
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 501.61, ALogP 3.59, HBA 6, HBD 2, PSA 115.19, QED 0.51
Compound (SMILES): COc1ccc2c([nH]c3nc(C)nc(-c4ccnc5ccccc45)c32)c1-c1c(C)noc1C
InChIKey: FOABSIKDDZSLTQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain 2 (unknown origin)
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 435.49, ALogP 5.92, HBA 6, HBD 1, PSA 89.72, QED 0.37
Compound (SMILES): CC(=O)c1ccc(NC(=O)N2CCN(c3ccnc(Nc4ccc(N5CCOCC5)cc4)n3)CC2)cc1
InChIKey: VHEYXIOPTOLEIM-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged human FLT3 cytoplasmic domain (564 to 993 residues) expressed in baculovirus expression system musing FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr in presence of ATP by mobility shift assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 501.59, ALogP 3.61, HBA 8, HBD 2, PSA 102.93, QED 0.49
Compound (SMILES): O=C(O)/C=C/c1ccc(-c2cccc(CO)c2)c(NC(=O)CCc2ccccc2)c1
InChIKey: ZQXXQPSOYQDECN-SDNWHVSQSA-N
Target: Aldo-keto reductase family 1 member C2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52895
Assay: Inhibition of recombinant human AKR1C2 expressed in Escherichia coli BL21 (D3) using S-tetralol as substrate in presence of NADP+ by UV-spectrophotometric method
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 401.46, ALogP 4.52, HBA 3, HBD 3, PSA 86.63, QED 0.48
Compound (SMILES): COc1ccccc1Cc1cc(C)nn(CC(=O)Nc2ccc(C#N)cc2)c1=O
InChIKey: LOGQKDBAHABNGM-UHFFFAOYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Biased agonist activity at human FPR1 expressed in FlpIn-CHO cells assessed as intracellular calcium mobilization by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 388.43, ALogP 2.66, HBA 6, HBD 1, PSA 97.01, QED 0.7
Compound (SMILES): O=S(=O)(c1ccc(N2CC(CN3CCC(C4(C5CCCC5)NCCc5ccccc54)CC3)C2)cc1)C1CCC1
InChIKey: IKIGKYBUAHEXDC-UHFFFAOYSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Inhibition of FAM-probe binding to Menin (unknown origin) after 60 mins by fluorescence polarization competitive binding assay
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 547.81, ALogP 5.39, HBA 5, HBD 1, PSA 52.65, QED 0.5
Compound (SMILES): Nc1nc2ccc(S(=O)(=O)Cc3ccc(Cl)c(Cl)c3)cc2s1
InChIKey: FEWIACLEPXGFDG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 373.29, ALogP 4.16, HBA 5, HBD 1, PSA 73.05, QED 0.75
Compound (SMILES): O=CN(O)C[C@@H](CC1CCCC1)C(=O)NCNC(=O)c1ccc(-c2ccccc2)o1
InChIKey: VQWFQBPLTXSGQV-GOSISDBHSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 413.47, ALogP 2.79, HBA 5, HBD 3, PSA 111.88, QED 0.24
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N(C)C)cc3)[nH]c2c1=O
InChIKey: RMYAPIOEGJPQDL-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]MSX-2 from recombinant human A2A adenosine receptor expressed in CHO cell membranes measured after 30 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 52.7 nM (pChEMBL 7.28000020980835)
Descriptors: MW 377.43, ALogP 0.74, HBA 6, HBD 2, PSA 120.92, QED 0.68
Compound (SMILES): Cc1c(-c2cccc(S(=O)(=O)N(C)C)c2)c2ncccc2n1C/C(F)=C/CN.Cl
InChIKey: KLWZKAGUIGUVAY-LFMIJCLESA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P33072
Assay: Inhibition of LOX in bovine aorta using putrescine as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every 2.5 mins for 30 mins by Amplex-Red oxidation assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 402.5, ALogP 3.07, HBA 5, HBD 1, PSA 81.22, QED 0.69
Compound (SMILES): O=C(c1cncc(N2CC3CC(C2)N3)c1)N1CCCc2ccccc21
InChIKey: XMYWPQXQUQJAEN-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Displacement of [125I]alpha-bungarotoxin from alpha7nAChR in rat hippocampus membrane
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 334.42, ALogP 2.23, HBA 4, HBD 1, PSA 48.47, QED 0.91
Compound (SMILES): COc1ncc(N2CCc3ncnc(-c4ccnc(N[C@H]5CC[C@H](O)CC5)c4)c3C2)cc1C
InChIKey: RXKIAMVXRIBVOB-KESTWPANSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha using phosphatidyl inositol as substrate after 3 hrs by Kinase-Glo Plus reagent-based luminescence assay
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 446.56, ALogP 3.53, HBA 8, HBD 2, PSA 96.29, QED 0.61
Compound (SMILES): Cc1cc2c(cc1CCC(=O)O)nc(Nc1ccc(C(C)C)cc1)n2[C@@H]1C[C@H](C)CC(C)(C)C1
InChIKey: BHJVJIFGPZMTNN-YADARESESA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Biochemical Assay: The biochemical reactions were performed at 32° C. in 384-well plates using a reaction volume of 41 μL and the following assay buffer conditions: 50 mM Tris pH 7.5, 100 mM NaCl, 20 mM MgCl2, 0.05% BSA, 0.01% Brij, 1 μM NADPH, and 250 μM α-KG. The IDH1 R132H enzyme was used in a final concentration of 1.5 nM. Test compounds were used in a concentration range between 0.002 and 10 μM. The final DMSO concentration was 2.4%.The reaction was incubated for 30 minutes, then 40 μL of detection mix (0.75 μg/ml Luciferase, 0.02 U/ml Oxidoreductase, 4 μg/mL FMN, 2 μL/ml decanal/ethanol, 50 mM Tris pH 7.5, 0.5% Glycerin, 0.01% Tween-20, 0.05% BSA) was added. Luminescence was measured on a luminescent reader (10 seconds measuring time, 1 second integration period, 30% sensitivity). The decrease in luminescence is proportional to mIDH1 activity.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 461.65, ALogP 7.62, HBA 4, HBD 2, PSA 67.15, QED 0.38
Compound (SMILES): CC(C)COc1ncc(-c2cn(C)c3cc(C(=O)NS(C)(=O)=O)ccc23)cc1C#N
InChIKey: NSCWVFCGCPIMTE-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells after 600 secs at -50 mV holding potential by ion works barracuda population patch clamp method
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 426.5, ALogP 2.84, HBA 7, HBD 1, PSA 114.08, QED 0.65
Compound (SMILES): COC1CCC(C[C@H](NC(=O)[C@H](Cc2ccccc2)N=[N+]=[N-])C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]2(C)CO2)CC1
InChIKey: DCZBCXUZOSJEJQ-FQLCGHSNSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of catalytic activity of immunoproteasome 20s subunit beta5 in human Raji cells incubated for 1 hr by BODIPY(TMR)-NC-005-VS probe based competitive activity based protein profiling assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 674.84, ALogP 4.6, HBA 7, HBD 3, PSA 174.89, QED 0.09
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)ccc1F)Nc1ccc(Oc2ncnc3cc(OCCCN4CCOCC4)c4c(c23)OCCO4)cc1Cl
InChIKey: FYTRUYUAAMASJP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Test of Small Molecule Compounds for Inhibiting the Activity of VEGFR-2 Kinase: 1. Dilution of the compound: a total of 12 concentrations were obtained using a 4-fold gradient dilution from the highest concentration of 10000 nM (the maximum final concentration of the drug used in this experiment is 10000 nM, and the minimum final concentration is 0.002384 nM),2. 2.5 μl of the gradient-diluted compounds was taken with a transfer pipette to a 384-well plate,3. Addition of enzyme: 5 μl of 2×VEGFR-2 kinase was taken with a transfer pipette to the corresponding reaction well of the 384-well plate, which was mixed and pre-reacted at room temperature for 30 min,4. 2.5 μl of 4× substrate/ATP Mix was taken with a transfer pipette to the corresponding reaction well of the 384-well plate,5. Negative control: 2.5 μl/well 4× substrate/ATP Mix and 7.5 μl 1× Kinase Assay Buffer were added to the wells of the 384-well plate,Positive control: 2.5 μl/well 4× substrate/ATP Mix, 2.5 μl/well 1× Kinase Assay Buffer containing 4% DMSO, and 5 μl/well 2×VEGFR-2 solution were added to the 384-well plate. The final concentration of DMSO in the reaction system is 4%,6. The mixture was mixed well and then centrifuged and reacted at room temperature in dark for 60 min,7. Termination of the enzymatic reaction: 5 μl of 4× Stop solution was taken with a transfer pipette to the wells of the 384-well plate, mixed and then centrifuged, and reacted at room temperature for 5 min,8. Development of the reaction: 5 μl of 4× Detection Mix was taken with a transfer pipette to the wells of the 384-well plate for color development, and the mixture was mixed and then centrifuged and reacted at room temperature for 60 min,9. The 384-well plate was placed into the Envision plate reader and the signal was detected using the appropriate program,10. Analysis and processing of the raw data:The drug concentrations and the corresponding inhibition rates were input into GraphPad Prism5 for calculation, and the inhibition rate of the compound was calculated as follows: inhibition rate (%)=[1−(experimental well reading value−negative control well reading value)/(positive control well reading value−negative control well reading value)]×100%. Processing with GraphPad Prism5 software yielded the corresponding IC50 value (the concentration of the compound at which 50% of the highest inhibition of the enzyme is achieved).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 678.04, ALogP 6.75, HBA 9, HBD 2, PSA 116.3, QED 0.15
Compound (SMILES): CCCC[C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)[C@@H](C)O
InChIKey: AJFDPFJFPPPGKD-DNBONZEVSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Inverse agonist activity at SNAP-tagged human GHSR expressed in HEK293T cells assessed as reduction in inositol phosphate production after 30 mins by HTRF assay
Measurement: EC50 = 6633 nM (pChEMBL 5.179999828338623)
Descriptors: MW 817.99, ALogP -0.47, HBA 9, HBD 11, PSA 303.74, QED 0.04
Compound (SMILES): COC(=O)c1cccc(-n2cc(O)c(=O)cc2C)c1
InChIKey: IBQKAUNVXUGTAX-UHFFFAOYSA-N
Target: Polymerase acidic protein (SINGLE PROTEIN), Influenza A virus (A/Puerto Rico/8/1934(H1N1))
UniProt: P03433
Assay: Inhibition of 8-histidine tagged influenza virus H1N1 N-terminal PA endonuclease expressed in Escherichia coli BL21 cells using single-stranded 5'-FAM fluorophore/3'-TAMRA quencher)-labeled 17-mer ssDNA-oligomer substrate measured over 45 mins by FRET analysis
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 259.26, ALogP 1.64, HBA 5, HBD 1, PSA 68.53, QED 0.83
Compound (SMILES): CCOc1ccc(N(CC)CC)cc1-n1c(C=C(C)C)c(C(=O)N2CCN[C@H](C)C2)cc(-c2nc(-c3ccc(Cl)cc3)cs2)c1=O
InChIKey: OXVBVWOBSRAYJW-XMMPIXPASA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) using alpha-KG after 105 mins by NADPH depletion assay
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 660.28, ALogP 7.38, HBA 8, HBD 1, PSA 79.7, QED 0.19
Compound (SMILES): Cc1noc(C)c1CSCC(=O)N1C[C@@H](C)N(c2ccccc2)[C@@H](C)C1
InChIKey: MSVPDQQKVQBLHA-GASCZTMLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Activity of Compounds in PSA Luciferase Assay: The biological activity of analogs 5-16, 18, 20, 26, JJ-450, and the resolved enantiomers JJ-450A and J-450B was determined and compared to HTS hit 1 (IC50 7.3 μM) and MDV3100 (IC50 1.1 μM) using the Dual-Glo luciferase system (Promega, WI, USA) in C4-2-PSA-rl cells, which were generated by transfection with PSA6.1-luc and pRL-TK followed by stable selection using G418 and puromycin. C4-2-PSA-rl stable cells were cultured in RPMI 1640 medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, 10 mg/mL puromycin, and 50 mg/mL G418. C4-2-PSA-rl cells were seeded in 24-well plates such that they reached 75-80% cell monolayer density after 24 h. C4-2-PSA-rl cells were then treated for 24 h with 0, 0.2, 0.8, 3.2, 12.8, or 25 μM of each compound dissolved in DMSO (0.8% DMSO/well) in the presence of 1 nM synthetic androgen R1881, with each experimental condition in triplicate. The cells were also treated in parallel with 12.8 μM compound 1 and 12.8 μM MDV3100 as positive controls. Each compound was tested in at least two independent experiments. Luciferase activity was assayed using the Dual-Luciferase® Reporter Assay System (Promega) using LMax II Microplate Reader (Molecular Devices). The luciferase assay results were acquired using SoftMax Pro5.45 software (Molecular Devices) and analyzed using GraphPad Prism. PSA6.1-luc activity was normalized to the Renilla luciferase activity. Relative luciferase activity was calculated as the quotient of androgen-induced PSA-firefly/Renilla luciferase activity. Since PSA promoter activity correlates to AR transcriptional activity, inhibition of AR will result in decreased PSA-luciferase activity. IC50 values were calculated using GraphPad Prism and data represent the mean and SD of 2-6 independent experiments.
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 373.52, ALogP 3.65, HBA 5, HBD 0, PSA 49.58, QED 0.8
Compound (SMILES): CN1CCN(c2ccc(Nc3cc(NCc4cccc(NC#N)c4)ncn3)cc2)CC1
InChIKey: CGGWUIFZDGYPFM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and further incubated for 30 mins and subsequently measured after 1 hr by HTRF assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 414.52, ALogP 3.48, HBA 8, HBD 3, PSA 92.14, QED 0.4
Compound (SMILES): Cc1cc(-c2cnc(N)c(-c3ccc4c(c3)CCNC4=O)c2)ncc1S(=O)(=O)NC1CC1
InChIKey: FGFPLDKODKMIRV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 449.54, ALogP 2.43, HBA 6, HBD 3, PSA 127.07, QED 0.55