lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(F)c3)cs1)CCCCC2
InChIKey: XZSZHBDACAQPPG-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 436.56, ALogP 5.67, HBA 7, HBD 1, PSA 60.56, QED 0.41
Compound (SMILES): Cc1cn(-c2ccc(-c3csc(Nc4c5c(nn4C)CCC5)n3)cc2F)cn1
InChIKey: XWWVQEYJLIHQAH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 394.48, ALogP 4.41, HBA 7, HBD 1, PSA 60.56, QED 0.56
Compound (SMILES): Cc1cn(-c2ccc(-c3csc(Nc4c5c(nn4C(C)(C)C)CCCC5)n3)cc2F)cn1
InChIKey: HQZXJMBWRQVDEC-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 450.59, ALogP 6.02, HBA 7, HBD 1, PSA 60.56, QED 0.41
Compound (SMILES): COc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCCN3c2cccc(F)c2)ccn1
InChIKey: CYQUZTVMTBZINH-FAQVEIGNSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase (unknown origin) assessed as decrease in amyloid beta-42 secretion by cell based AlphaLisa assay
Measurement: EC50 = 0.0103 nM (pChEMBL 10.989999771118164)
Descriptors: MW 449.53, ALogP 3.69, HBA 8, HBD 1, PSA 71.34, QED 0.64
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(F)c3)cs1)CCCCC2
InChIKey: XZSZHBDACAQPPG-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 436.56, ALogP 5.67, HBA 7, HBD 1, PSA 60.56, QED 0.41
Compound (SMILES): Cc1cn(-c2ccc(-c3csc(Nc4c5c(nn4C)CCC5)n3)cc2F)cn1
InChIKey: XWWVQEYJLIHQAH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 394.48, ALogP 4.41, HBA 7, HBD 1, PSA 60.56, QED 0.56
Compound (SMILES): Cc1cn(-c2ccc(-c3csc(Nc4c5c(nn4C(C)(C)C)CCCC5)n3)cc2F)cn1
InChIKey: HQZXJMBWRQVDEC-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Modulation of gamma-secretase in human SH-SY5Y cells overexpressing wild-type human APP751 assessed as inhibition of Abeta42 level after 24 hrs by ELISA
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 450.59, ALogP 6.02, HBA 7, HBD 1, PSA 60.56, QED 0.41
Compound (SMILES): O=C(NNS(=O)(=O)c1ccccc1F)c1cc(F)cc(-c2ccccn2)c1
InChIKey: QLXULUNLCRKWRD-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92993
Assay: Inhibition of KAT5 (unknown origin)
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 389.38, ALogP 2.65, HBA 4, HBD 2, PSA 88.16, QED 0.66
Compound (SMILES): C=CC(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2CCN(c2cc(O)cc4ccccc24)C3)CC1
InChIKey: GQSSXKRUKAMOQS-QFIPXVFZSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIAPaCa2 cells assessed as reduction in ERK phosphorylation measured after 3 hrs by Western blot analysis
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 528.66, ALogP 3.21, HBA 8, HBD 1, PSA 85.27, QED 0.49
Compound (SMILES): C[C@H](Nc1ccc(C#N)n(C)c1=O)c1cc2cc(Cl)c(OCC3CC3)cc2[nH]c1=O
InChIKey: MWYSDNPPAIJPJV-LBPRGKRZSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant in human HCT116 cells assessed as reduction in 2-HG levels after 24 hrs by RapidFire high-throughput mass spectrometry assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 424.89, ALogP 3.71, HBA 6, HBD 2, PSA 99.91, QED 0.63
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)N3CCC(N4CCOCC4)CC3)nc3cnc4[nH]ccc4c32)CC1
InChIKey: JDRBWHJXQOIQSD-XUTJKUGGSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 489.62, ALogP 3.42, HBA 7, HBD 1, PSA 103.07, QED 0.59
Compound (SMILES): Cc1nc(C)c(C(=O)NCc2ccccc2)s1
InChIKey: FXFUXZVNPRJEHK-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as decrease in CP55940-induced beta-arrestin recruitment pretreated with non-selective cannabinoid receptor agonist CP55940 for 30 mins and measured after 20 mins by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 246.34, ALogP 2.69, HBA 3, HBD 1, PSA 41.99, QED 0.9
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4ccccc4)C3)cc2oc1=O.Cl
InChIKey: GHBXHJUNRCOQBQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Binding affinity to recombinant human MAO-B expressed in Pichia pastoris assessed as inhibition constant using benzylamine as substrate by Michaelis-Menten equation based horseradish peroxidase coupled spectrophotometric analysis
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 377.48, ALogP 4.7, HBA 4, HBD 0, PSA 42.68, QED 0.6
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)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](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)N[C@@H](CCC(N)=O)C(=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(C)C)[C@@H](C)O
InChIKey: BCZBXBPPQPLALA-ZXXUFNDKSA-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 = 0.193 nM (pChEMBL 9.710000038146973)
Descriptors: MW 3989.54
Compound (SMILES): O=C(CN1CCN(c2ccc(Cl)cn2)CC1)Nc1cncnc1
InChIKey: ZZGIOJNVAOUXRN-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 332.8, ALogP 1.29, HBA 6, HBD 1, PSA 74.25, QED 0.91
Compound (SMILES): Cc1cccc(C#CC=C2CCN(C(=O)c3cccc(F)c3)CC2)n1
InChIKey: MDIBBZYMQUDVAP-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Displacement of [3H]MPEP from human mGlu5 receptor expressed in CHO-TREx cell membranes after 60 mins by liquid scintillation spectrometric analysis
Measurement: Ki = 15.8 nM (pChEMBL 7.800000190734863)
Descriptors: MW 334.39, ALogP 3.74, HBA 2, HBD 0, PSA 33.2, QED 0.74
Compound (SMILES): C=Cc1ccc(S(=O)(=O)Nc2ccc(-c3nc4ccccc4o3)cc2)cc1
InChIKey: VLVDVVWLCJDPGT-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 91000 nM (pChEMBL 4.039999961853027)
Descriptors: MW 376.44, ALogP 4.94, HBA 4, HBD 1, PSA 72.2, QED 0.54
Compound (SMILES): Nc1ncc(N2CCN(c3ccc(Cl)cc3)CC2)c(N)n1
InChIKey: WIVLWIBQXXJWKL-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Leishmania major
UniProt: P07382
Assay: TBD: TBD
Measurement: IC50 = 7.59 nM (pChEMBL 8.119999885559082)
Descriptors: MW 304.79, ALogP 1.62, HBA 6, HBD 2, PSA 84.3, QED 0.88
Compound (SMILES): NC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SCCc1ccccc1
InChIKey: YEZJTTVQWKXURB-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human carbonic anhydrase 5b expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 370.88, ALogP 2.42, HBA 4, HBD 2, PSA 103.25, QED 0.76
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(C(=O)Nc2ccccc2N)cc1)B1O[C@@H]2[C@@H]3C[C@H](C[C@]2(C)O1)C3(C)C
InChIKey: CADXOGZMLIVVAM-HGHHWUKJSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) pre-incubated for 5 mins before fluorogenic substrate Boc-Lys (acetyl)-AMC or Boc-Lys (triflouroacetyl)-AMC addition and measured after 30 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 650.63
Compound (SMILES): NS(=O)(=O)c1ccc2c(c1)S(=O)(=O)NC2=O
InChIKey: CRSHTYPFKXPVRE-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated for 15 mins by measured for 10 to 100 secs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 64.8 nM (pChEMBL 7.190000057220459)
Descriptors: MW 262.27, ALogP -1.23, HBA 5, HBD 2, PSA 123.4, QED 0.66
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2O[C@H](c3ccccc3)O[C@H]21
InChIKey: BCGDNNLMSKVHGV-TVTGSROBSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7R transfected in human 1321N1 cells assessed as inhibition of Bz-ATP-induced calcium influx
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 595.29, ALogP 1.13, HBA 14, HBD 5, PSA 257.13, QED 0.22
Compound (SMILES): CCCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: WSLYGKKLLXKPSY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from recombinant human 5HT2C receptor expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 479.06, ALogP 6.53, HBA 3, HBD 1, PSA 41.57, QED 0.3
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4cccc(C(F)(F)F)n4)cc3)c(C(N)=O)c2N)C1
InChIKey: LNMYMSAHQVYVMW-CQSZACIVSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of full-length recombinant human C-terminal His-tagged SRC cytoplasmic domain expressed in baculovirus expression system using FAM-Srctide peptide as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 = 14400 nM (pChEMBL 4.840000152587891)
Descriptors: MW 471.44, ALogP 3.56, HBA 8, HBD 2, PSA 136.08, QED 0.54
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2oc(-c3ccccc3)nc2c1
InChIKey: SYIKRSKRVUVZON-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coli DH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured rhodanese refolding by measuring rhodanese enzyme activity after 45 mins by Fe(SCN)3 dye based spectrometric analysis
Measurement: IC50 = 89000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 380.43, ALogP 4.3, HBA 5, HBD 1, PSA 81.43, QED 0.56
Compound (SMILES): Cn1ncc(Cl)c1-c1cc(C(=O)N[C@@H]2CNCC[C@H]2c2ccc(F)c(F)c2)oc1Cl.O=C(O)[C@H](O)[C@@H](O)C(=O)O
InChIKey: PWVOEHRYNRDIPZ-TULPLBIPSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Inhibition of human Akt2 by mobile shift assay
Measurement: IC50 < 0.64 nM (pChEMBL 9.194000244140625)
Descriptors: MW 455.29, ALogP 4.14, HBA 5, HBD 2, PSA 72.09, QED 0.62
Compound (SMILES): NCC1(c2cccc(-c3ccnc4[nH]nc(C(F)(F)F)c34)c2)CCOCC1
InChIKey: JTJAWKUSBMOQSN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 376.38, ALogP 3.65, HBA 4, HBD 2, PSA 76.82, QED 0.73
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2cc1NC(=O)CC1CCSS1
InChIKey: QCVAULIYZATFDX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Binding affinity to human partial length EGFR L747-T751del/Sins mutant expressed in bacterial expression system by KinomeScan assay
Measurement: Kd = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 609.15, ALogP 8.1, HBA 8, HBD 2, PSA 96.27, QED 0.17
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)Cc1ccc(/N=N/c2ccc(N(C)C)cc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: PUHQWQPHJZSPFH-BGDZGSFMSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 1041.27
Compound (SMILES): CC(C)=CCc1ccc(/C=C/C(=O)O)cc1OC(=O)CCc1ccccc1
InChIKey: ZDAFNOSGSMUQEY-GXDHUFHOSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of AKR1C3 in human HL60 cells assessed as potentiation of etoposide-induced cytotoxicity by measuring etoposide IC50 after 24 to 72 hrs by MTS assay (Rvb = 1.16 uM)
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 364.44, ALogP 4.83, HBA 3, HBD 1, PSA 63.6, QED 0.32
Compound (SMILES): NC(=O)c1ccc(Cc2ccccc2)cc1-c1cccc(CCC(=O)O)c1
InChIKey: UHEGDWIZAOPGIY-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human Cav3.2 expressed in CHO cells by patch clamp assay
Measurement: IC50 > 33300 nM (pChEMBL 4.478000164031982)
Descriptors: MW 359.43, ALogP 4.06, HBA 2, HBD 2, PSA 80.39, QED 0.67
Compound (SMILES): Cc1cc(C(=O)NC(C)(C)C)cc(C#Cc2ccc3c4c(oc3c2)C(C)(C)c2cc(NS(C)(=O)=O)ccc2C4=O)n1
InChIKey: DCGOHGQJHJXBGW-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of TRKB (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 569.68, ALogP 5.31, HBA 6, HBD 2, PSA 118.37, QED 0.32
Compound (SMILES): Cc1c(-c2cccc(S(=O)(=O)N(C)C)c2)c2cc(C(=O)O)ccc2n1C/C(F)=C/CN.Cl
InChIKey: PWSRWJMEGVKWES-WPTDRQDKSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of LOXL2 in human IMR90 cells 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 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 445.52, ALogP 3.38, HBA 5, HBD 2, PSA 105.63, QED 0.58
Compound (SMILES): NCc1ncc(S(=O)(=O)c2ccc3ccccc3c2)s1
InChIKey: VXKXYVIOPMTDAL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAOA expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate measured after 1 hr by MAO-glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 304.4, ALogP 2.59, HBA 5, HBD 1, PSA 73.05, QED 0.81
Compound (SMILES): O=C(Nc1ccnnc1)c1cc(N2CCOCC2)ccc1OCc1ccccc1
InChIKey: ABAQMTMQQSSUGL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of parkinson's patient-derived LRRK2 G2019S mutant
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 390.44, ALogP 3.14, HBA 6, HBD 1, PSA 76.58, QED 0.7
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4cc(F)ccc4F)cc3F)ccnc2cc1OCCCN1CCCC(C)C1
InChIKey: UFFFDUINWKEBCZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 615.67, ALogP 6.75, HBA 7, HBD 1, PSA 89.99, QED 0.19
Compound (SMILES): C[C@@]12CN(c3ccccc3)c3ccccc3[C@@H]1CCN2
InChIKey: OHCPINQLTJGNRS-FUHWJXTLSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from human recombinant dopamine D1 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 264.37, ALogP 3.67, HBA 2, HBD 1, PSA 15.27, QED 0.85
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCCCNC(=O)CCCCCN1/C(=C/C=C/C=C/C2=[N+](CCCCS(=O)(=O)[O-])c3ccccc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: GCOJNVSSODRPBC-LZUDCTEISA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Binding affinity to human neurotensin receptor 1 stably expressed in CHO cells incubated for 60 mins in presence of NT (8 to 13) without compound washout by Hoechst H33342 staining confocal microscopy analysis
Measurement: Kd = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 1598.02
Compound (SMILES): Cl.NCC1C(c2ccccc2)C1(F)F
InChIKey: SIMBDBWJNGBXGP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant human 5HT2A receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 3679 nM (pChEMBL 5.429999828338623)
Descriptors: MW 183.2, ALogP 1.99, HBA 1, HBD 1, PSA 26.02, QED 0.75
Compound (SMILES): S=C1Sc2cc(Br)ccc2C2=NCCCN12
InChIKey: CMXWNQQNLFMQSM-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 313.25, ALogP 3.29, HBA 3, HBD 0, PSA 15.6, QED 0.68
Compound (SMILES): Cn1cc(-c2cc(S(C)(=O)=O)cc(S(=O)(=O)c3cnc(CN)s3)c2)cn1
InChIKey: AFJUDDQTSKTAGP-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate measured after 1 hr by MAO-glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 412.52, ALogP 1.24, HBA 9, HBD 1, PSA 125.01, QED 0.67
Compound (SMILES): Cc1cc(N2CC(c3n[nH]c(=S)o3)CC2=O)c(Cl)c(C)c1S(N)(=O)=O
InChIKey: QAUFHDKPIPYJNO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 402.88, ALogP 2.17, HBA 6, HBD 2, PSA 122.29, QED 0.76
Compound (SMILES): COc1ccc2c(c1)CCN(CCC(F)Cc1ccccc1)CC2
InChIKey: UORHUEYQEKFSIE-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) by cAMP assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 327.44, ALogP 4.07, HBA 2, HBD 0, PSA 12.47, QED 0.79
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl)c1cccnc1
InChIKey: QTEMPVGNCZGUQZ-JTQLQIEISA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 8394 nM (pChEMBL 5.079999923706055)
Descriptors: MW 412.9, ALogP 4.3, HBA 6, HBD 2, PSA 83.98, QED 0.63
Compound (SMILES): CCCN1C[C@H]2N(C(=O)[C@H]3CC[C@H](C(=O)O)CC3)CC[C@@]2(S(=O)(=O)c2ccc(F)cc2)c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc21
InChIKey: BTJFMVNGAMYMNQ-IBBOJXSKSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Activity at LXRbeta (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 696.66, ALogP 6.51, HBA 5, HBD 1, PSA 94.99, QED 0.26
Compound (SMILES): CS(=O)(=O)c1cccc(S(=O)(=O)c2ccc(CN)s2)c1
InChIKey: XTTIHPZLEXNANF-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Sus scrofa
UniProt: P45845
Assay: LOX Enzyme Activity Assay : LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 331.44, ALogP 1.44, HBA 6, HBD 1, PSA 94.3, QED 0.91
Compound (SMILES): O=C(O)CSc1nc(Cl)cc(Nc2ccc(Cl)c3c2CCC3)n1
InChIKey: MCBRWQUTXJYWCL-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human Gal4-fused PPARdelta LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 370.26, ALogP 4.19, HBA 5, HBD 2, PSA 75.11, QED 0.47
Compound (SMILES): O=S(=O)(Nc1ccc2oc(-c3ccccc3)nc2c1)c1cccc(O)c1
InChIKey: YHIKLLSOXYXUBM-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 58000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 366.4, ALogP 4, HBA 5, HBD 2, PSA 92.43, QED 0.57
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccc(O)cc1
InChIKey: MCFVAJQSSWIGSN-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 366.4, ALogP 4, HBA 5, HBD 2, PSA 92.43, QED 0.57
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc2n1C
InChIKey: DCHQNZAIUFIFEB-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CDK2 (1 to 298 residues)/cyclin A2 (1 to 432 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay
Measurement: IC50 > 3333 nM (pChEMBL 5.4770002365112305)
Descriptors: MW 478.55, ALogP 3.68, HBA 8, HBD 1, PSA 75, QED 0.45
Compound (SMILES): Cc1cccc(S(=O)(=O)[C@@]23CCN(C(=O)[C@H]4CC[C@H](C(=O)O)CC4)[C@@H]2CCc2cc(C(F)(C(F)(F)F)C(F)(F)F)ccc23)c1
InChIKey: UCLOLQONKUCIPI-FGXABTBTSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Activity at LXRalpha (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 649.63, ALogP 6.39, HBA 4, HBD 1, PSA 91.75, QED 0.38
Compound (SMILES): O=C(O)c1ccc(Nc2nc(-c3cccc(Br)c3)cs2)cc1
InChIKey: BQIQIDNGQSNUJD-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of recombinant human GST-tagged CK2alpha V73A mutant in presence of ATP by radiometric kinase assay
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 375.25, ALogP 5.01, HBA 4, HBD 2, PSA 62.22, QED 0.67
Compound (SMILES): CC[C@@H]1CN2CC[C@]3(Nc4cccc(-c5ccccc5)c4C3=O)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: VCRVOVUTAHEQNK-RHLYTPARSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [125I]-IBNtxA from mouse mu opioid receptor-1 expressed in CHO cell membranes incubated for 90 mins
Measurement: Ki = 0.91 nM (pChEMBL 9.039999961853027)
Descriptors: MW 460.57, ALogP 4.52, HBA 6, HBD 1, PSA 67.87, QED 0.4
Compound (SMILES): O=C(Nc1cnc(Oc2ccc(F)cc2)nc1)N1CCc2ncccc2[C@@H]1c1ccc(F)cc1
InChIKey: VKQBTIMLSDGNLG-QHCPKHFHSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 459.46, ALogP 5.12, HBA 5, HBD 1, PSA 80.24, QED 0.46
Compound (SMILES): Cn1cc(Nc2nccc(N3C[C@H]4CC[C@H](C3)N4C(=O)[C@@H]3CC3(F)F)n2)cn1
InChIKey: BUWBRTXGQRBBHG-MCIONIFRSA-N
Target: JAK2/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1/JAK2 signaling pathway in human CD3 +ve cells of whole blood assessed as reduction in IL-6 induced STAT3 phosphorylation preincubated for 45 mins followed by IL-6 addition and measured measured after 15 mins by FACS assay
Measurement: IC50 = 641 nM (pChEMBL 6.190000057220459)
Descriptors: MW 389.41, ALogP 1.79, HBA 7, HBD 1, PSA 79.18, QED 0.86
Compound (SMILES): O=C(NNS(=O)(=O)c1ccccc1F)c1cc(F)cc(-c2ccccn2)c1
InChIKey: QLXULUNLCRKWRD-UHFFFAOYSA-N
Target: Histone acetyltransferase KAT7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95251
Assay: Inhibition of KAT7 (unknown origin)
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 389.38, ALogP 2.65, HBA 4, HBD 2, PSA 88.16, QED 0.66
Compound (SMILES): C[C@H](Nc1ccc(C#N)n(C)c1=O)c1cc2cc(Cl)c(OCC3CC3)cc2[nH]c1=O
InChIKey: MWYSDNPPAIJPJV-LBPRGKRZSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Biochemical Assay: Please see paper.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 424.89, ALogP 3.71, HBA 6, HBD 2, PSA 99.91, QED 0.63
Compound (SMILES): N#CC[C@H]1CC[C@H](n2c(CC(=O)N3CCC(N4CCOCC4)CC3)nc3cnc4[nH]ccc4c32)CC1
InChIKey: JDRBWHJXQOIQSD-XUTJKUGGSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 489.62, ALogP 3.42, HBA 7, HBD 1, PSA 103.07, QED 0.59
Compound (SMILES): Cc1c(C)c2ccc(OCC3CCCN(Cc4ccccc4)C3)cc2oc1=O.Cl
InChIKey: GHBXHJUNRCOQBQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE by spectrophotometric Ellman's method
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 377.48, ALogP 4.7, HBA 4, HBD 0, PSA 42.68, QED 0.6
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)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](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)N[C@@H](CCC(N)=O)C(=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(C)C)[C@@H](C)O
InChIKey: BCZBXBPPQPLALA-ZXXUFNDKSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P32214
Assay: Displacement of [125I]-labeled rat amylin from rat amylin receptor expressed in BHK tkts13 cell membranes co-expressing RAMP3 incubated for 120 mins by scintillation proximity assay
Measurement: IC50 = 0.091 nM (pChEMBL 10.039999961853027)
Descriptors: MW 3989.54
Compound (SMILES): C=Cc1ccc(S(=O)(=O)Nc2ccc(-c3nc4ccccc4o3)cc2)cc1
InChIKey: VLVDVVWLCJDPGT-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 376.44, ALogP 4.94, HBA 4, HBD 1, PSA 72.2, QED 0.54
Compound (SMILES): NC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SCCc1ccccc1
InChIKey: YEZJTTVQWKXURB-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human carbonic anhydrase 6 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 370.88, ALogP 2.42, HBA 4, HBD 2, PSA 103.25, QED 0.76
Compound (SMILES): N#CN1CCC[C@@H](n2nc(-c3ccc(Oc4cccc(C(F)(F)F)n4)cc3)c(C(N)=O)c2N)C1
InChIKey: LNMYMSAHQVYVMW-CQSZACIVSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR cytoplasmic domain expressed in baculovirus expression system using FITC-C6-KKAEEEEYFELVAKK-NH2 as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by TR-FRET Lanthascreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 471.44, ALogP 3.56, HBA 8, HBD 2, PSA 136.08, QED 0.54
Compound (SMILES): COc1ccccc1S(=O)(=O)Nc1ccc2oc(-c3ccccc3)nc2c1
InChIKey: SYIKRSKRVUVZON-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 85000 nM (pChEMBL 4.070000171661377)
Descriptors: MW 380.43, ALogP 4.3, HBA 5, HBD 1, PSA 81.43, QED 0.56
Compound (SMILES): Cn1ncc(Cl)c1-c1cc(C(=O)N[C@@H]2CNCC[C@H]2c2ccc(F)c(F)c2)oc1Cl.O=C(O)[C@H](O)[C@@H](O)C(=O)O
InChIKey: PWVOEHRYNRDIPZ-TULPLBIPSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of human Akt1 expressed in Escherichia coli using STK Substrate 2-biotin as substrate incubated for 1 hr by HTRF assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 455.29, ALogP 4.14, HBA 5, HBD 2, PSA 72.09, QED 0.62
Compound (SMILES): CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2cc1NC(=O)CC1CCSS1
InChIKey: QCVAULIYZATFDX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Binding affinity to human partial length EGFR L747-E749del/A750P mutant expressed in bacterial expression system by KinomeScan assay
Measurement: Kd = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 609.15, ALogP 8.1, HBA 8, HBD 2, PSA 96.27, QED 0.17
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCCNC(=O)Cc1ccc(/N=N/c2ccc(N(C)C)cc2)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: PUHQWQPHJZSPFH-BGDZGSFMSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of recombinant human SIRT3 (118 to 399 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 1041.27
Compound (SMILES): CC(C)=CCc1ccc(/C=C/C(=O)O)cc1OC(=O)CCc1ccccc1
InChIKey: ZDAFNOSGSMUQEY-GXDHUFHOSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of AKR1C3 in human KG1a cells assessed as potentiation of etoposide-induced cytotoxicity by measuring etoposide IC50 cotreated at 72 hrs by MTS assay (Rvb = 6.70 uM)
Measurement: IC50 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 364.44, ALogP 4.83, HBA 3, HBD 1, PSA 63.6, QED 0.32
Compound (SMILES): NC(=O)c1ccc(Cc2ccccc2)cc1-c1cccc(CCC(=O)O)c1
InChIKey: UHEGDWIZAOPGIY-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of human Cav1.2 expressed in CHO cells by patch clamp assay
Measurement: IC50 > 33300 nM (pChEMBL 4.478000164031982)
Descriptors: MW 359.43, ALogP 4.06, HBA 2, HBD 2, PSA 80.39, QED 0.67
Compound (SMILES): Cc1cc(C(=O)NC(C)(C)C)cc(C#Cc2ccc3c4c(oc3c2)C(C)(C)c2cc(NS(C)(=O)=O)ccc2C4=O)n1
InChIKey: DCGOHGQJHJXBGW-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin)
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 569.68, ALogP 5.31, HBA 6, HBD 2, PSA 118.37, QED 0.32
Compound (SMILES): Cc1c(-c2cccc(S(=O)(=O)N(C)C)c2)c2cc(C(=O)O)ccc2n1C/C(F)=C/CN.Cl
InChIKey: PWSRWJMEGVKWES-WPTDRQDKSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Mus musculus
UniProt: P58022
Assay: Inhibition of recombinant mouse C-terminal His-tagged LOLX2 (26-776 residues) expressed in mouse myeloma cells 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 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 445.52, ALogP 3.38, HBA 5, HBD 2, PSA 105.63, QED 0.58
Compound (SMILES): NCc1ncc(S(=O)(=O)c2ccc3ccccc3c2)s1
InChIKey: VXKXYVIOPMTDAL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate measured after 1 hr by MAO-glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 304.4, ALogP 2.59, HBA 5, HBD 1, PSA 73.05, QED 0.81
Compound (SMILES): O=C(Nc1ccnnc1)c1cc(N2CCOCC2)ccc1OCc1ccccc1
InChIKey: ABAQMTMQQSSUGL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant 6His-Tev-tagged LRRK2 (1326 to 2527) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-RLGRDKYKTLRQIRQGNTKQR-OH as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 390.44, ALogP 3.14, HBA 6, HBD 1, PSA 76.58, QED 0.7
Compound (SMILES): C[C@@]12CN(c3ccccc3)c3ccccc3[C@@H]1CCN2
InChIKey: OHCPINQLTJGNRS-FUHWJXTLSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: Displacement of [3H]-CGP12177 from human recombinant adrenergic Beta3 receptor expressed in Flp-In HEK cells after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 264.37, ALogP 3.67, HBA 2, HBD 1, PSA 15.27, QED 0.85
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)NC(=O)NCCCCNC(=O)CCCCCN1/C(=C/C=C/C=C/C2=[N+](CCCCS(=O)(=O)[O-])c3ccccc3C2(C)C)C(C)(C)c2cc(S(=O)(=O)O)ccc21)C(=O)N[C@@H](CC(C)C)C(=O)O.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: GCOJNVSSODRPBC-LZUDCTEISA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Binding affinity to human neurotensin receptor 1 stably expressed in CHO cells incubated for 75 mins in presence of NT (8 to 13) followed by compound washout with HBSS-BSA by Hoechst H33342 staining based confocal microscopy analysis
Measurement: Kd = 3.802 nM (pChEMBL 8.420000076293945)
Descriptors: MW 1598.02
Compound (SMILES): S=C1Sc2cc(Br)ccc2C2=NCCCN12
InChIKey: CMXWNQQNLFMQSM-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human C-terminal His-tagged N-terminal GST-tagged HDAC7 (518 to end residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 313.25, ALogP 3.29, HBA 3, HBD 0, PSA 15.6, QED 0.68
Compound (SMILES): Cn1cc(-c2cc(S(C)(=O)=O)cc(S(=O)(=O)c3cnc(CN)s3)c2)cn1
InChIKey: AFJUDDQTSKTAGP-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Sus scrofa
UniProt: P00371
Assay: Inhibition of porcine kidney DAO measured after 1 hrs by ROS-glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 412.52, ALogP 1.24, HBA 9, HBD 1, PSA 125.01, QED 0.67
Compound (SMILES): Cc1cc(N2CC(c3n[nH]c(=S)o3)CC2=O)c(Cl)c(C)c1S(N)(=O)=O
InChIKey: QAUFHDKPIPYJNO-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 402.88, ALogP 2.17, HBA 6, HBD 2, PSA 122.29, QED 0.76
Compound (SMILES): COc1ccc2c(c1)CCN(CCC(F)Cc1ccccc1)CC2
InChIKey: UORHUEYQEKFSIE-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at -80 mV holding potential by automated patch clamp electrophysiology assay
Measurement: IC50 = 553 nM (pChEMBL 6.260000228881836)
Descriptors: MW 327.44, ALogP 4.07, HBA 2, HBD 0, PSA 12.47, QED 0.79
Compound (SMILES): CS(=O)(=O)c1cccc(S(=O)(=O)c2ccc(CN)s2)c1
InChIKey: XTTIHPZLEXNANF-UHFFFAOYSA-N
Target: Arachidonate 12-lipoxygenase (SINGLE PROTEIN), Sus scrofa
UniProt: P16469
Assay: LOX Enzyme Activity Assay: LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls:0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix:Volume Reagent 1 x plate 2 x plate Final ConcnAssay Buffer  2 ml    3 ml 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM20 mM Amplex Red 10 μl   15 μl 100 μM1000 U/ml HRP 10 μl   15 μl   35 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader:Excitation wavelength: 545 nmEmission wavelength: 585 nmHRP Counter Assay Protocol
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 331.44, ALogP 1.44, HBA 6, HBD 1, PSA 94.3, QED 0.91
Compound (SMILES): O=S(=O)(Nc1ccc2oc(-c3ccccc3)nc2c1)c1cccc(O)c1
InChIKey: YHIKLLSOXYXUBM-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 = 76000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 366.4, ALogP 4, HBA 5, HBD 2, PSA 92.43, QED 0.57
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccc(O)cc1
InChIKey: MCFVAJQSSWIGSN-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human HSP60 expressed in Escherichia coli Rosetta 2(DE3)/human HSP10 expressed in Escherichia coli Rosetta 2(DE3) pLysS cells assessed as reduction in HSP60/HSP10-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 366.4, ALogP 4, HBA 5, HBD 2, PSA 92.43, QED 0.57