lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccc(F)c(F)c5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: CWIQIMJDMAGVQL-RJKGWOMYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-diprenorphine from human mu opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 606.71, ALogP 7.09, HBA 5, HBD 1, PSA 54.82, QED 0.22
Compound (SMILES): O=C1c2ccc(O)cc2C(=O)c2c1nnn2-c1cc(F)c(-c2ccccc2F)c(F)c1
InChIKey: JFBJXYCCCLAFEF-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH using dihydroorotate as substrate and CoQ10 as co-substrate preincubated for 30 mins followed by substrate addition by DCIP coupled microplate reader assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 421.33, ALogP 3.83, HBA 6, HBD 1, PSA 85.08, QED 0.47
Compound (SMILES): C/C(=C\COc1ccccc1Cc1c(C)cnn1-c1ccc(C(F)(F)F)cc1)CCC(=O)O
InChIKey: OTMZQLCJJSPSHH-GHRIWEEISA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Transactivation of GAL4-fused human PPARdelta expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 = 11.2 nM (pChEMBL 7.949999809265137)
Descriptors: MW 458.48, ALogP 5.98, HBA 4, HBD 1, PSA 64.35, QED 0.4
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)CNCCN(CC[C@H](N)C(=O)O)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C(=O)N[C@@H](C)C(N)=O
InChIKey: PDHCRHSMSNDZKO-HQWNBOBBSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Inhibition of NTMT1 (unknown origin) pre-incubated for 10 mins before GPKRIA peptide substrate addition by SAHH coupled fluorescence assay
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 1033.21
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(Cc2ccc(C3=CC(=O)C=CC3=O)cc2NS(=O)(=O)c2ccc(Cl)cc2)CC1
InChIKey: PQMPTOIHJKSFJJ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SETD7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WTS6
Assay: Inhibition of SET7 (unknown origin) using biotinylated histone polypeptide as substrate in presence of SAM by AlphaLISA assay
Measurement: IC50 = 90000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 572.08, ALogP 4.28, HBA 7, HBD 1, PSA 113.09, QED 0.51
Compound (SMILES): O=C(C[C@@H](CC1CCCC1)C(=O)N1CC2(CC2)C[C@H]1c1nc(-c2ccc(C(F)(F)F)cc2Cl)no1)NO
InChIKey: OCWYYQISLZIILK-BEFAXECRSA-N
Target: Peptide deformylase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH1
Assay: Inhibition of human PDF expressed in Escherichia coli BL21 pLysS using formyl-Met-Ala-His-Ala peptide as substrate measured after 1 hr by fluorescamine-based fluorescence assay
Measurement: IC50 = 6.47 nM (pChEMBL 8.1899995803833)
Descriptors: MW 540.97, ALogP 5.55, HBA 6, HBD 2, PSA 108.56, QED 0.35
Compound (SMILES): CNC(=O)c1csc([C@H]2C[C@H](NC(=O)[C@@H]3CC(=O)N(C)C(=O)N3)CN2C(=O)c2ccc(-c3nn[nH]n3)cc2)n1
InChIKey: SYFLGRBSBZONAM-OFQRWUPVSA-N
Target: N-alpha-acetyltransferase 50 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZZ1
Assay: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 552.58, ALogP -0.3, HBA 10, HBD 4, PSA 195.27, QED 0.32
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccccc2Cl)cc(OC)c1OC
InChIKey: SSPYAPRDKNCABY-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 502.01, ALogP 4.12, HBA 6, HBD 2, PSA 89.13, QED 0.57
Compound (SMILES): O=C(O)/C=C/c1ccc2nc3n(c(=O)c2c1)-c1ccc(F)cc1C3=O
InChIKey: GKMKNKXSNDAZJT-QHHAFSJGSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin)
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 336.28, ALogP 2.17, HBA 5, HBD 1, PSA 89.26, QED 0.57
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@H]2Cn2ccc(-c3ccc(F)cn3)n2)c1
InChIKey: OMTCPGOATBMMKY-SFHVURJKSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human recombinant OX1R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 30 mins followed by orexin-A stimulation by Fluo4-AM dye based fluorescence analysis
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 431.48, ALogP 3.28, HBA 7, HBD 0, PSA 81.73, QED 0.48
Compound (SMILES): O=C(Nc1ccc(Cl)c(-c2nnc3c(Cl)cccn23)c1)c1ccc(C(F)(F)F)nc1Cl
InChIKey: QDEFGHZHNZXFPG-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Binding affinity to recombinant human Smo receptor assessed as dissociation constant at equilibrium by SPR analysis
Measurement: Kd = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 486.67, ALogP 6.02, HBA 5, HBD 1, PSA 72.18, QED 0.36
Compound (SMILES): c1cc(NC2=NCCN2)c2cc[nH]c2c1
InChIKey: MFSMQIHVGAPSNQ-UHFFFAOYSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 200.25, ALogP 1.54, HBA 3, HBD 3, PSA 52.21, QED 0.65
Compound (SMILES): CCCCCCCN(CCCCCCC)CC(=O)N(CCc1ccc(S(N)(=O)=O)cc1)Cc1ccccc1
InChIKey: IAFNLMIPUUPYRK-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 946.7 nM (pChEMBL 6.019999980926514)
Descriptors: MW 543.82, ALogP 6.15, HBA 4, HBD 1, PSA 83.71, QED 0.2
Compound (SMILES): O=C(O)c1cnn(-c2nc3cn(Cc4ccc(-c5ccccc5)cc4)nc3c(=O)[nH]2)c1
InChIKey: WXKXBFWBHIRYKG-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of HIF-PHD2 (unknown origin) using FAM-HIF2alpha peptide incubated for 20 to 40 mins by fluorescence polarization assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 412.41, ALogP 2.72, HBA 7, HBD 2, PSA 118.69, QED 0.46
Compound (SMILES): O=C(O)c1cc(-c2ccc(N3CCNCC3)cc2)cc(-n2cc(-c3ccc(C(F)(F)F)cc3)nn2)c1
InChIKey: GSFZEBQEWYYWBC-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of MRS4174 binding to human P2Y14R expressed in CHO cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins at pH 7.4 by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 493.49, ALogP 4.73, HBA 6, HBD 2, PSA 83.28, QED 0.42
Compound (SMILES): CC#CC(CC(=O)O)c1ccc(OCc2ccc3nc(-c4ccc(C)cc4)cn3c2)cc1
InChIKey: XKEINAFABHINCV-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at GPR40 (unknown origin)
Measurement: EC50 = 507 nM (pChEMBL 6.289999961853027)
Descriptors: MW 424.5, ALogP 5.47, HBA 4, HBD 1, PSA 63.83, QED 0.4
Compound (SMILES): CCn1c(=O)c2ccc(-c3c(C)nc4c(OCc5ccc(-c6ccc(F)cc6)cc5)cccn34)cc2n1C.Cl
InChIKey: GOGSALYLGFAFHZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of gamma-secretase in human SK-N-BE cells assessed as decrease in amyloid beta 42 production treated for 6 hrs by ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 506.58, ALogP 6.37, HBA 6, HBD 0, PSA 53.46, QED 0.26
Compound (SMILES): O=S(=O)(NCCCNc1nccc(-n2ccc3cccnc32)n1)c1cccc(C(F)(F)F)c1
InChIKey: LCMBYUOBPFFCDE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of human BRAF V600E mutant by ELISA
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 476.48, ALogP 3.61, HBA 7, HBD 2, PSA 101.8, QED 0.38
Compound (SMILES): CC1(C)SCN(S(=O)(=O)c2ccccc2)[C@@H]1C(=O)NC(CNC(=O)NCc1ccccc1)C(=O)O
InChIKey: XKLHCUGVLCGKKX-MUMRKEEXSA-N
Target: Integrin alpha2/beta1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of human alpha2 beta1 in human platelets assessed as reduction in platelet adhesion to collagen type 1 incubated for 30 mins
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 520.63, ALogP 1.6, HBA 6, HBD 4, PSA 144.91, QED 0.39
Compound (SMILES): COc1cc2c3c(c1OC)-c1cc(N(C)C)ccc1CC3N(C)CC2
InChIKey: HCTOCIWVPDVRFX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-WAY100635 from human 5-HT1A receptor expresssed in stable CHO cell membrane incubated for 90 mins by microbeta counting method
Measurement: Ki = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 338.45, ALogP 3.52, HBA 4, HBD 0, PSA 24.94, QED 0.85
Compound (SMILES): O=C(C1CCN(c2ccc(Cl)c(C(F)(F)F)c2)C1)N1CC2COCC2C1
InChIKey: MYFCONVOQBKWQJ-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human Notum (S81 to T451 residues) Cys330Ser mutant expressed in HEK293S GnTI cells using OPTS as substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 388.82, ALogP 3.29, HBA 3, HBD 0, PSA 32.78, QED 0.78
Compound (SMILES): COc1cc(N2CCOC2=O)ccc1Nc1nc2ccc(-c3ccc(NC(=O)[C@H](C)c4ccc(F)cc4)cc3)cn2n1
InChIKey: SHWCNYPROTZRQA-LJQANCHMSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 566.59, ALogP 5.99, HBA 8, HBD 2, PSA 110.09, QED 0.24
Compound (SMILES): CCOc1cc(Cl)c(C(=O)Nc2nc3ccc(OC4CCN(C)CC4)cc3s2)cc1N1CCOCC1
InChIKey: GOWIGCYUKIGMHY-UHFFFAOYSA-N
Target: Hydroxycarboxylic acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXC0
Assay: Agonist activity at human GPR81 overexpressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP production
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 531.08, ALogP 4.91, HBA 8, HBD 1, PSA 76.16, QED 0.46
Compound (SMILES): CCP(=O)(OC)c1ccc2oc(-c3cccc(Cl)c3F)nc2c1
InChIKey: BODPURINKKUQFC-UHFFFAOYSA-N
Target: Utrophin (SINGLE PROTEIN), Homo sapiens
UniProt: P46939
Assay: Modulation of human utrophinA expressed in mouse H2K cells assessed as upregulation of utrophin production after 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 353.72, ALogP 4.86, HBA 4, HBD 0, PSA 52.33, QED 0.63
Compound (SMILES): O=C(N[C@H]1C[C@H](c2nnc(-c3ccccn3)n2-c2ccccc2F)C1)c1ccc(F)cn1
InChIKey: SVDUOSYBBYZAAB-KOMQPUFPSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human TNKS2 (873 to 1162 residues) measured after 20 hrs in presence of NAD+ by fluorescence assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 432.43, ALogP 3.68, HBA 6, HBD 1, PSA 85.59, QED 0.52
Compound (SMILES): O=C(NO)c1ccc(NC(=O)C2(c3ccc(-c4cc[nH]n4)cc3)CCCC2)cc1
InChIKey: KYMSJEYZJABISQ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 pre-incubated for 30 mins before Ac-Leu- Gly-Lys(Ac)-AMC substrate addition and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 390.44, ALogP 3.65, HBA 4, HBD 4, PSA 107.11, QED 0.39
Compound (SMILES): CCCSc1nc(=O)c(CC)c(O)n1-c1ccccc1OC
InChIKey: PIFINVCHWWNGPS-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production
Measurement: EC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 320.41, ALogP 3.01, HBA 6, HBD 1, PSA 64.35, QED 0.65
Compound (SMILES): N[C@@]1(C(=O)O)C[C@]2(CCNC2)C[C@@H]1CCCB(O)O
InChIKey: QZLUPYXYXWEXHN-DLOVCJGASA-N
Target: Arginase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05089
Assay: Inhibition of human arginase1 in presence of DNTB by thio ornithine generation assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 270.14
Compound (SMILES): CN(C)C1CCc2c(cccc2-c2cccc(Cl)c2)C1
InChIKey: ZUXLGQDUZXDSQF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT1A receptor expressed in HEK293T cell membranes incubated for 90 mins by scintillation counting method
Measurement: Ki = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 285.82, ALogP 4.43, HBA 1, HBD 0, PSA 3.24, QED 0.79
Compound (SMILES): Cc1ncn(CC2CC2)c1-c1nnc([C@@H]2C[C@H](N(C)C(=O)c3cccc(C(F)(F)F)c3)CCO2)[nH]1
InChIKey: VCUCMPGZYXJLAL-MOPGFXCFSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 receptor expressed in HEK293 cells assessed as accumulation of inositol phosphate incubated for 1 hr followed by IP1-d2 addition by HTRF assay
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 488.51, ALogP 4.4, HBA 6, HBD 1, PSA 88.93, QED 0.56
Compound (SMILES): O=[N+]([O-])c1cccc(-c2nc3ccc(Br)cc3[nH]2)c1
InChIKey: QRYNOBDMCSLODZ-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of recombinant human MMP2 catalytic domain (Tyr110 to Asp452 residues) expressed in yeast cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 318.13, ALogP 3.9, HBA 3, HBD 1, PSA 71.82, QED 0.58
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(OCc4ccc(-n5cncn5)cc4)cccn23)cn1.Cl
InChIKey: IRTCQYBEAOCPCH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 453.51, ALogP 3.61, HBA 8, HBD 1, PSA 99.23, QED 0.4
Compound (SMILES): Cl.Clc1cncc(OC[C@@H]2CC[C@H]3C[C@H]3N2)c1
InChIKey: QXXGSDLLTDKYFE-WIQREMAASA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 31.3 nM (pChEMBL 7.5)
Descriptors: MW 238.72, ALogP 2.25, HBA 3, HBD 1, PSA 34.15, QED 0.88
Compound (SMILES): COc1cc(C[C@H]2CN3C(=O)[C@@]4(O[C@H]4c4ccccc4)[C@H](c4cc(OC)c5c(c4)OCO5)[C@H]3CN2C(C)=O)cc2c1OCO2
InChIKey: IKMTWSYMQMGXCQ-HGSJAIJISA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp mediated multidrug resistance in human SW620/AD300 cells assessed as potentiation of doxorubicin-induced antiproliferative activity by measuring doxorubicin IC50 at 2.5 uM after 48 hrs by MTT assay (Rvb = 4.9 microM)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 600.62, ALogP 3.44, HBA 9, HBD 0, PSA 108.53, QED 0.39
Compound (SMILES): CCP(=O)(OC)c1ccc2oc(-c3ccc4ccncc4c3)nc2c1
InChIKey: QXTKUTPKHLSAKT-UHFFFAOYSA-N
Target: Utrophin (SINGLE PROTEIN), Homo sapiens
UniProt: P46939
Assay: Modulation of human utrophinA expressed in mouse H2K cells assessed as upregulation of utrophin production after 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 332 nM (pChEMBL 6.480000019073486)
Descriptors: MW 352.33, ALogP 4.61, HBA 5, HBD 0, PSA 65.22, QED 0.5
Compound (SMILES): O=C(Nc1ccc(Cl)c(-c2nnc3c(Cl)cccn23)c1)c1ccc(C(F)(F)F)cc1F
InChIKey: NFYSXTZFDGPIHU-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Binding affinity to recombinant human Smo receptor assessed as dissociation constant at equilibrium by SPR analysis
Measurement: Kd = 13600 nM (pChEMBL 4.869999885559082)
Descriptors: MW 469.23, ALogP 6.11, HBA 4, HBD 1, PSA 59.29, QED 0.37
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cn(C)c3c(=O)[nH]ccc23)cc2c1cnn2Cc1ccc(F)cc1
InChIKey: PLMHLVJNEUKQRJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of APC-labeled biotinylated-avidin from Euphorium-chelated recombinant human BRD4 bromodomain 1 expressed in Escherichia coli preincubated for 15 mins followed by APC-labeled biotinylated-avidin addition and measured after 1 hr under dark condition by TR-FRET assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 479.54, ALogP 3.83, HBA 6, HBD 2, PSA 101.78, QED 0.39
Compound (SMILES): O=S(=O)(CCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1)NCC1CC1
InChIKey: KJKYKKMSXZVPCW-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 60 mins by fluorescence based assay
Measurement: IC50 = 312 nM (pChEMBL 6.510000228881836)
Descriptors: MW 477.32, ALogP 1.96, HBA 8, HBD 4, PSA 141.74, QED 0.19
Compound (SMILES): N#Cc1cnc2cc(OC[C@@H](O)CO)c(NC(=O)CC3CSSC3)cc2c1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
InChIKey: UVWRRZRGHPHHLL-QHCPKHFHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) in presence of radiolabelled gammaATP by radioisotope filter binding assay
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 655.17, ALogP 6.29, HBA 10, HBD 4, PSA 136.73, QED 0.13
Compound (SMILES): CC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(Br)cc1)C(=O)N[C@H](C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(N)=O)C1CCCC1
InChIKey: ZFCISWNBGCJTCX-OPGKZIRUSA-O
Target: Chromobox protein homolog 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O95503
Assay: Inhibition of CBX6 (unknown origin) assessed as inhibition of CBX4 disruption by competitive FP assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 944.95, ALogP 1.03, HBA 9, HBD 9, PSA 275.22, QED 0.05
Compound (SMILES): COc1ccc(-c2cc(=O)c3c(OC)c([C@H]4O[C@H](C(=O)N[C@H](C)C(F)(F)F)[C@@H](O)[C@H](O)[C@H]4O)c(OC)cc3o2)cc1OC
InChIKey: YATALNCQFFCOMZ-LXIVEFDESA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of Glycogen synthase kinase-3 beta in human SH-SY5Y cells after 2 hrs by ELISA
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 613.54, ALogP 2.08, HBA 11, HBD 4, PSA 166.15, QED 0.29
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2nc3ccccc3[nH]2)cc(OC)c1OC
InChIKey: SQHCFKSEFLRQSH-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 464.57, ALogP 3.9, HBA 6, HBD 2, PSA 88.71, QED 0.55
Compound (SMILES): CC(C(N)=O)N1CCOc2cc(OCc3ccccc3F)ccc2C1
InChIKey: LATOVHLPFLETOV-UHFFFAOYSA-N
Target: Sodium channel protein type 3 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY46
Assay: Inhibition of Nav1.3 (unknown origin) expressed in HEK293 cells assessed as inhibition of sodium current incubated for 3 to 3.5 mins by electrophysiology assay
Measurement: IC50 > 63095.73 nM (pChEMBL 4.199999809265137)
Descriptors: MW 344.39, ALogP 2.47, HBA 4, HBD 1, PSA 64.79, QED 0.9
Compound (SMILES): Cc1ccc(S(=O)(=Nc2ccc(F)cc2)NC(=O)Nc2c3c(cc4c2CCC4)CCC3)cc1
InChIKey: JGYIIJYXVNGZCA-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS-primed human THP1 cells assessed as reduction in IL-1beta level preincubated for 1 hr followed by addition of ATP and nigericin further incubated for 1 hrs and measured post ATP addition 1 hr by ELISA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 463.58, ALogP 6.01, HBA 3, HBD 2, PSA 70.56, QED 0.5
Compound (SMILES): CCP(=O)(OC)c1ccc2oc(-c3cccc(F)c3)nc2c1
InChIKey: RQCCPTZSXFJZEW-UHFFFAOYSA-N
Target: Utrophin (SINGLE PROTEIN), Homo sapiens
UniProt: P46939
Assay: Modulation of human utrophinA expressed in mouse H2K cells assessed as upregulation of utrophin production after 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 823 nM (pChEMBL 6.079999923706055)
Descriptors: MW 319.27, ALogP 4.2, HBA 4, HBD 0, PSA 52.33, QED 0.68
Compound (SMILES): Cc1nc2cc(C(=O)NC3CN(c4cc(Cl)ncc4Cl)C3)ccc2s1
InChIKey: WVJPUSNNBCYZQQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of human muscarinic M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 393.3, ALogP 3.93, HBA 5, HBD 1, PSA 58.12, QED 0.69
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCN3c2ccc(C(F)(F)F)cc2)ncn1
InChIKey: ZARAJXPSYXIZAY-CWPLJXCYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 470.5, ALogP 3.87, HBA 8, HBD 1, PSA 75, QED 0.62
Compound (SMILES): Cc1sc2ncnc(SCC(=O)N3CC(=O)N(C)C3)c2c1Cl
InChIKey: UESWSZOPRMZQLA-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human His6-tagged NOTUM (81 to 451 residues) Cys330Ser mutant transfected in HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 356.86, ALogP 2, HBA 6, HBD 0, PSA 66.4, QED 0.62
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(NC(=O)/C=C/c3ccc(Oc4cccc(-c5ccccn5)c4)nc3)cc1)CC2
InChIKey: AJGWAABNSFMUOW-RVDMUPIBSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of Pgp-mediated DOX resistance in human SW620/AD300 cells assessed as potentiation of DOX-induced cytotoxicity by measuring DOX IC50 at 1 uM incubated for 48 hrs by SRB assay (Rvb = 33.39 +/- 7.08 uM)
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 612.73, ALogP 7.21, HBA 7, HBD 1, PSA 85.81, QED 0.16
Compound (SMILES): C/C(=C\c1ccccc1)[C@@H]1C[C@H]1N
InChIKey: RQFOXSGEDMXTCU-MJEUXHFXSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant N-terminal His-tagged LSD1 (unknown origin) expressed in Escherichia coli expression system using ART-K(Me1)-QTARKSTGGKAPRKQLAGGK(Biotin) as substrate incubated for 60 mins by TR-FRET assay
Measurement: IC50 = 898 nM (pChEMBL 6.050000190734863)
Descriptors: MW 173.26, ALogP 2.44, HBA 1, HBD 1, PSA 26.02, QED 0.73
Compound (SMILES): COc1ccc(C(=O)N[C@@H](Cc2ccccc2)[C@H](O)CN(C[C@H](C)O)S(=O)(=O)c2ccc([N+](=O)[O-])cc2)c(O)c1
InChIKey: UVIHVECSWOMFKT-ZNCVFPSASA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of HIV-1 protease expressed in Escherichia coli using Arg-Glu(EDANS)-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys(DABCYL)-Arg as substrate preincubated for 20 to 30 mins followed by substrate addition by FRET based assay
Measurement: IC50 = 504.9 nM (pChEMBL 6.300000190734863)
Descriptors: MW 573.62, ALogP 2.08, HBA 9, HBD 4, PSA 179.54, QED 0.18
Compound (SMILES): COc1cc2cc[n+]3c(c2cc1OC)[C@](C)(O)c1ccc(OC)c(OC)c1C3.O=C([O-])C(F)(F)F
InChIKey: VWQAAJKQNJEIPW-VZYDHVRKSA-M
Target: Liver carboxylesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23141
Assay: Inhibition of human CE1 using D-luciferin methyl ester as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 382.44, ALogP 2.78, HBA 5, HBD 1, PSA 61.03, QED 0.7
Compound (SMILES): N=C(N)Nc1ccc(CNC(=O)[C@@H](NC(=O)c2ccc(OC3CCCCC3)cc2)c2ccc(OCc3ccccc3)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: FDRAVTRHGBWKEK-WAQYZQTGSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus serotype 2 NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Nle-Lys-Arg-Arg-Ser-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition and measured for 15 mins by FRET assay
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 605.74, ALogP 6.07, HBA 5, HBD 5, PSA 138.56, QED 0.1
Compound (SMILES): CN1CCCc2cc(CCNC(=O)C(=O)Nc3ccc4c(c3)OCO4)ccc21
InChIKey: UTYLBKPZVZEDLJ-UHFFFAOYSA-N
Target: Falcipain 2 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9N6S8
Assay: Inhibition of recombinant Plasmodium falciparum falcipain-2 expressed in bacterial expression system using ZFR-AMC as substrate measured for 30 mins by fluorimetric assay
Measurement: IC50 = 14710 nM (pChEMBL 4.829999923706055)
Descriptors: MW 381.43, ALogP 2.1, HBA 5, HBD 2, PSA 79.9, QED 0.79
Compound (SMILES): CCOC(=O)c1cnc2ccc(-c3cc(Cl)cc(Cl)c3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: YAMOZEAMATUUOE-UKIBZPOASA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human DYRK1A transfected in HEK293T cells co-transfected with Renilla plasmid, pGL3-NFAT and NFATc1 assessed as derepression of NFAT-dependent luciferase activity measured after 48 hrs by luciferase assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 501.46, ALogP 6.31, HBA 6, HBD 1, PSA 67.35, QED 0.38
Compound (SMILES): Cc1cc(-n2nnc3c2C(=O)c2ccccc2C3=O)ccc1F
InChIKey: ROCMXAPLOMGRPK-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH using dihydroorotate as substrate and CoQ10 as co-substrate preincubated for 30 mins followed by substrate addition by DCIP coupled microplate reader assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 307.28, ALogP 2.49, HBA 5, HBD 0, PSA 64.85, QED 0.54
Compound (SMILES): CCN(c1cc(/C=C/c2ccc(S(=O)(=O)N3CCOCC3)cc2)cc(C(=O)NCc2c3c(c(C)[nH]c2=O)CCCC3)c1C)C1CCOCC1
InChIKey: JCZLQOLTQBSZDA-MDZDMXLPSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of wild type EZH2 (unknown origin) by AlphaLISA assay
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 688.89, ALogP 5, HBA 7, HBD 2, PSA 121.04, QED 0.29
Compound (SMILES): COCCCn1cc(-c2cnc(N)c(OC(C)c3cc(F)ccc3Cl)c2)cn1
InChIKey: GJMOWPNLZOPPJD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 404.87, ALogP 4.5, HBA 6, HBD 1, PSA 75.19, QED 0.56
Compound (SMILES): Cc1ccc(OC[C@@H]2C[C@H]3C[C@H]3N2C)cn1
InChIKey: IPCBFNXNVLCHMF-GMXVVIOVSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 218.3, ALogP 1.86, HBA 3, HBD 0, PSA 25.36, QED 0.77
Compound (SMILES): Nc1ncnc2c1c(Oc1cccc(Cl)c1)nn2[C@H]1C[C@H](F)C1
InChIKey: TXHXVNJDQPMZHD-MGCOHNPYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition Assay: Certain of the compounds prepared as described above were assayed to determine their IC50 for inhibition of T. gondii CDPK1 (tgCDPK1). At least three independent replicates of the assay were conducted for each compound tested.
Measurement: IC50 = 41.1 nM (pChEMBL 7.389999866485596)
Descriptors: MW 333.75, ALogP 3.53, HBA 6, HBD 1, PSA 78.85, QED 0.79
Compound (SMILES): OC1CCN(c2cc(-c3cccc(-c4cnc5ccc(N6CCC[C@@H]6c6cccc(F)c6)nn45)n3)ccn2)CC1
InChIKey: BLGCSOKKBWHJMB-HHHXNRCGSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Binding affinity to human partial length TRKA expressed in mammalian expression system by kinomescan method
Measurement: Kd = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 535.63, ALogP 5.3, HBA 8, HBD 1, PSA 82.68, QED 0.33
Compound (SMILES): Cc1c[nH]c(C)c1C(=O)O
InChIKey: XBPJVSRTTKVMEN-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human Notum (S81 to T451 residues) Cys330Ser mutant expressed in HEK293S GnTI cells using OPTS as substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 139.15, ALogP 1.33, HBA 1, HBD 2, PSA 53.09, QED 0.62
Compound (SMILES): CNC(=O)COc1cc2cc(Nc3nc(NCc4cccc(S(=O)(=O)F)c4)ncc3Cl)cc(OC)c2n(C)c1=O
InChIKey: VNVCMPVIJOIVJD-UHFFFAOYSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition FITC-labeled BCoR peptide binding to wild type human BCL6 BTB domain (5 to 129 residues) expressed in baculovirus infected Sf9 cells after 30 mins by TR-FRET assay
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 591.02, ALogP 3.13, HBA 11, HBD 3, PSA 153.54, QED 0.23
Compound (SMILES): Nc1ccc(-c2cncc3ccc(OC4CCNCC4)cc23)cc1
InChIKey: GDHNVSGPIIDEFR-UHFFFAOYSA-N
Target: Protein kinase C zeta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q05513
Assay: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method
Measurement: IC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 319.41, ALogP 3.61, HBA 4, HBD 2, PSA 60.17, QED 0.72
Compound (SMILES): CC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)[C@@]1(C)CO1
InChIKey: YPRSGAQWKNXYOF-DNHJLFCISA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of LMP2 in human 20S immunoproteasome using Ac-PAL-AMC as substrate after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 341.86 nM (pChEMBL 6.46999979019165)
Descriptors: MW 548.64, ALogP 0.93, HBA 6, HBD 3, PSA 137.21, QED 0.34
Compound (SMILES): Cc1ccc(CNc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)cc1
InChIKey: JKQOOYGCFGIDQC-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of recombinant human full-length N-terminal His-tagged CDK6/cyclinD3 expressed in baculovirus infected Sf9 insect cells using histone H1 as substrate measured after 60 mins by ADP-glo assay
Measurement: IC50 = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 423.95, ALogP 3.94, HBA 7, HBD 2, PSA 69.21, QED 0.62
Compound (SMILES): COc1cc2cc(NC(=O)C3CCN(Cc4ccccc4)CC3)c(=O)oc2cc1OC
InChIKey: KBDRPSKQRUYQSJ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholineiodide as substrate measured for every 30 sec for 5 mins by Ellman's method
Measurement: IC50 = 223 nM (pChEMBL 6.650000095367432)
Descriptors: MW 422.48, ALogP 3.66, HBA 6, HBD 1, PSA 81.01, QED 0.61
Compound (SMILES): Fc1ccc(C2CCCCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4cnnc(Cl)c4)C5)nc32)c(F)c1F
InChIKey: GUQVVVPFTFBSKS-XYQMTRTISA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 503.96, ALogP 4.78, HBA 7, HBD 1, PSA 71.76, QED 0.52
Compound (SMILES): C[C@H]1CCCOc2nn(C)cc2C(=O)Nc2cccc(n2)-c2nncn21
InChIKey: JNTRRDGKMKNYAI-NSHDSACASA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of human ASK1 using myelin basic protein substrate preincubated for 20 mins before [33P]-ATP addition and measured after 2 hrs by filter-binding method
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 353.39, ALogP 2.06, HBA 8, HBD 1, PSA 99.75, QED 0.66
Compound (SMILES): O=c1n(Cc2nc3ncccc3n2CCCCO)c2cnccc2n1C1CC1
InChIKey: QUVNSJRASRRCGV-UHFFFAOYSA-N
Target: Fusion glycoprotein F0 (SINGLE PROTEIN), human respiratory syncytial virus
UniProt: Q89535
Assay: Inhibition of GFP-fused RSV 224 fusion protein infected in human HeLa cells assessed as reduction in viral replication after 3 days by laser microscopic analysis
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 378.44, ALogP 2.1, HBA 8, HBD 1, PSA 90.76, QED 0.5
Compound (SMILES): COC1CCC(=O)c2c(O)c(-c3cc(O)c4c(c3O)C(=O)CCC4OC)cc(O)c21
InChIKey: LPKDHIORBUNKFZ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTP1B expressed in Escherichia coli BL21 (DE3) cells using PNPP as substate preincubated for 5 mins followed by substrate additon and measured after 15 mins
Measurement: IC50 = 10900 nM (pChEMBL 4.960000038146973)
Descriptors: MW 414.41, ALogP 3.5, HBA 8, HBD 4, PSA 133.52, QED 0.56
Compound (SMILES): CC(C)(C)c1cc(CN(C(=O)c2cccc(C(F)(F)F)c2)c2ccc(C(=O)NO)cc2)cc(C(C)(C)C)c1
InChIKey: YODBHMPKJJAHAO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of C-terminal His-tagged and N-terminal GST-tagged full length human HDAC3 expressed in baculovirus expression system co-expressed with human NCOR2 using FAM-RHKK(Ac)-NH2 substrate incubated for 3 hrs by EMSA method
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 526.6, ALogP 7.27, HBA 3, HBD 2, PSA 69.64, QED 0.27
Compound (SMILES): CCOC(=O)C1=C(N)Oc2cc(O)ccc2C1c1ccc(OCCN2CCCCC2)cc1
InChIKey: VEGWPNQJDLCZQJ-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluorescent estrogen ligand from recombinant human full length untagged ERalpha expressed in baculovirus infected insect cells incubated in dark for 2 hrs by Beacon single-tube fluorescent polarization assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 438.52, ALogP 3.51, HBA 7, HBD 2, PSA 94.25, QED 0.64
Compound (SMILES): c1nc(N2CCOCC2)c2cc[nH]c2n1
InChIKey: GIAZHSRKWYDANE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 (780 to end residues) expressed in baculovirus infected Sf9 cells using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 204.23, ALogP 0.79, HBA 4, HBD 1, PSA 54.04, QED 0.75
Compound (SMILES): COc1cccc(C2CCCN2Cc2ccc(Oc3ccc(C(=O)NO)cc3F)cc2)c1
InChIKey: PNXYJJOCUIMQBK-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opiod receptor expressed in CHO cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 2154 nM (pChEMBL 5.670000076293945)
Descriptors: MW 436.48, ALogP 5.08, HBA 5, HBD 2, PSA 71.03, QED 0.4
Compound (SMILES): CON(C)C(=O)[C@H]1CC=C(CCC=C(C)C)C[C@@H]1c1ccccc1
InChIKey: QVUOHKMJFICORO-VQTJNVASSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 327.47, ALogP 4.87, HBA 2, HBD 0, PSA 29.54, QED 0.55
Compound (SMILES): Cc1c(C(=O)NC(CN(C)C)c2ccccc2)cnn1-c1ccc(F)cc1
InChIKey: CUPIIQDCZZWMQY-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 366.44, ALogP 3.35, HBA 4, HBD 1, PSA 50.16, QED 0.73
Compound (SMILES): COc1ccc(OCC2c3ccc(OC)cc3CC(=O)N2CC(F)(F)F)cc1
InChIKey: LDUKHYCYDUJTJQ-UHFFFAOYSA-N
Target: Ionotropic glutamate receptor NMDA 1/2D (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q62645
Assay: Positive allosteric modulation of recombinant rat GluN1a/GluN2D receptor expressed in Xenopus laevis oocytes assessed as increase in glycine/L-glutamate-induced channel current by two-electrode voltage clamp method
Measurement: EC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 395.38, ALogP 3.77, HBA 4, HBD 0, PSA 48, QED 0.75
Compound (SMILES): CC(=O)N1CCN(Cc2cnc(NC(=O)/C(=N/N3CCCC3)c3ccc(S(=O)(=O)C4CC4)cc3)s2)CC1
InChIKey: NDSGMBBHSCYMQL-WEMUOSSPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 544.7, ALogP 2.18, HBA 9, HBD 1, PSA 115.28, QED 0.51
Compound (SMILES): Cc1nc[nH]c1-c1nnc([C@H]2CCC[C@@H](N(C)C(=O)c3cccc(C(F)(F)F)c3)C2)[nH]1
InChIKey: SURIPAFCVGJTMM-XJKSGUPXSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 receptor expressed in HEK293 cells assessed as accumulation of inositol phosphate incubated for 1 hr followed by IP1-d2 addition by HTRF assay
Measurement: EC50 < 120 nM (pChEMBL 6.921000003814697)
Descriptors: MW 432.45, ALogP 4.32, HBA 4, HBD 2, PSA 90.56, QED 0.64
Compound (SMILES): O=C(CN1[C@@H]2CCC[C@H]1C[C@H](NC(=O)c1ccc3c(c1)OCO3)C2)Nc1ccc(Cl)cc1
InChIKey: SBZMQCURHLRERG-OWZKRDHZSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 455.94, ALogP 3.82, HBA 5, HBD 2, PSA 79.9, QED 0.72
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)[C@H]2C)cc1
InChIKey: UYZMRCLCECMQPF-YLJYHZDGSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 = 7790 nM (pChEMBL 5.110000133514404)
Descriptors: MW 539.73, ALogP 5.95, HBA 8, HBD 2, PSA 100.36, QED 0.27
Compound (SMILES): O=C(NN1CCCCC1)c1cn(-c2ccc(Cl)cc2Cl)c(-c2ccc(C#Cc3ccc(C(F)(F)F)cc3)s2)c1CNS(=O)(=O)N1CCCC1
InChIKey: GJYXFYBGIQWHJU-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at cannabinoid CB1 receptor (unknown origin)
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 750.7, ALogP 7.49, HBA 6, HBD 2, PSA 86.68, QED 0.18
Compound (SMILES): COc1cccc(-c2ccc(COC3CN(C#N)C3)cc2)c1OC
InChIKey: QEKMEHDUPXUYDM-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 324.38, ALogP 3.05, HBA 5, HBD 0, PSA 54.72, QED 0.76
Compound (SMILES): N=c1oc2c(O)cccc2cc1C(=O)Nc1ccc(F)cc1
InChIKey: QCQCGUXVKSMDJY-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of recombinant AKR1C4 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 298.27, ALogP 3.01, HBA 4, HBD 3, PSA 86.32, QED 0.68
Compound (SMILES): O=c1ccc(-c2cc(C(F)(F)F)c3nn(C4CCNCC4)cc3c2)c2n1CCC2
InChIKey: ZUDHZCGRRSHVGC-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human PBMC assessed as inhibition of DOTAP-ssRNA40 induced TNFalpha production preincubated for 30 mins followed by ssRNA40 addition measured after 20 hrs by HTRF assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 402.42, ALogP 3.75, HBA 5, HBD 1, PSA 51.85, QED 0.71
Compound (SMILES): C=CC(=O)N1CCC(Oc2cccc3[nH]c(-c4n[nH]c5cc(C(F)F)ccc45)cc23)C1
InChIKey: LBCGVXHTXJMXAA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 1339 nM (pChEMBL 5.869999885559082)
Descriptors: MW 422.44, ALogP 4.81, HBA 3, HBD 2, PSA 74.01, QED 0.45
Compound (SMILES): CC(C)[C@@H](NC(=O)c1cc(C(F)(F)F)ccc1F)C(=O)N1CCC2(CC1)C(=O)N(C)C(=O)N2c1ccccc1
InChIKey: TXPSXZIHPCEXFF-OAQYLSRUSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 548.54, ALogP 4.06, HBA 4, HBD 1, PSA 90.03, QED 0.45
Compound (SMILES): O=c1c2ccc(OCCN3CCCC3)cc2oc2cc(OCCN3CCCC3)cc(O)c12
InChIKey: MIYYUTVRKWENFL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine as substrate by Ellman's method
Measurement: IC50 = 3699 nM (pChEMBL 5.429999828338623)
Descriptors: MW 438.52, ALogP 3.6, HBA 7, HBD 1, PSA 75.38, QED 0.54
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(C)(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: KJGPTLRDVLLNKQ-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 663.54, ALogP 4.81, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(C(C)(C)O)o3)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: JZWYAKQKQPTWNS-JTQLQIEISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to recombinant human RORgammat transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 660.5, ALogP 5.2, HBA 9, HBD 2, PSA 138.52, QED 0.33
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1C[C@]12CCN(C)C2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: FHNMOTPPVMNTJS-BWQBABIRSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 517.67, ALogP 5.06, HBA 6, HBD 2, PSA 100.21, QED 0.33
Compound (SMILES): CCCCCc1cc(OC)cc(OCCCCCCCCCCC(=O)NCC2CC2)c1
InChIKey: BWBKHGUAKRTYDZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 431.66, ALogP 6.84, HBA 3, HBD 1, PSA 47.56, QED 0.24