lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1oc2cnccc2c1Nc1ccc2c(c1)CCCC2
InChIKey: ZKFMUMNEAQXGDR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 279.34, ALogP 4.03, HBA 4, HBD 2, PSA 64.08, QED 0.74
Compound (SMILES): C[C@@H](Nc1nc(NC2C3CC4CC(C3)CC2C4)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: IQUHQOIQGCZYCW-FGSOGITGSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 458.53, ALogP 5.4, HBA 6, HBD 2, PSA 75.62, QED 0.6
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: RAQUPWWEGSOPEV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 493.42, ALogP 5.7, HBA 7, HBD 2, PSA 99.41, QED 0.44
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(Cl)n2)n1)C1CC1
InChIKey: GTMXNXATSGQGCH-GHMZBOCLSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant (unknown origin) transfected using lentiviral expression system in human U87MG cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 358.88, ALogP 4.01, HBA 6, HBD 2, PSA 75.62, QED 0.73
Compound (SMILES): CCN(CC)CCOc1cccc(/C=C2\COc3ccccc3C2=O)c1
InChIKey: BTMWXBQNIMYMKU-NBVRZTHBSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 824 nM (pChEMBL 6.079999923706055)
Descriptors: MW 351.45, ALogP 4.07, HBA 4, HBD 0, PSA 38.77, QED 0.71
Compound (SMILES): CC(C)(C#N)CNc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: LWUOICMGVABMMB-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 478.43, ALogP 5.16, HBA 8, HBD 2, PSA 112.3, QED 0.45
Compound (SMILES): O=C(Nc1ccnc(Cl)c1)Nc1cc(C(F)F)ns1
InChIKey: HJJABVPOIGJSFO-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 304.71, ALogP 3.77, HBA 4, HBD 2, PSA 66.91, QED 0.85
Compound (SMILES): CCCNC(=O)NCC1CCc2ccc3ccc(OC)nc3c21
InChIKey: DCMXVAZTUHQTTP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from human 5-HT2C receptor expressed in CHO cell membranes after 60 mins by TopCount scintillation counting method
Measurement: Ki = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 313.4, ALogP 2.98, HBA 3, HBD 2, PSA 63.25, QED 0.89
Compound (SMILES): Cc1cccc(Nc2c(N)oc3cc(C#N)ccc23)c1
InChIKey: LMGAXAXRFXNKFO-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 263.3, ALogP 3.94, HBA 4, HBD 2, PSA 74.98, QED 0.73
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCCN(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: CVRMQFHSOSVJET-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A receptor (unknown origin) by radioligand binding assay
Measurement: Ki = 6059 nM (pChEMBL 5.21999979019165)
Descriptors: MW 538.99, ALogP 7.54, HBA 3, HBD 1, PSA 26.71, QED 0.24
Compound (SMILES): Cc1ccccc1Cn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: IOKZWCBMXXDCIJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.37, ALogP 4.11, HBA 5, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): Nc1oc2c(-c3ccc4c(c3)OCO4)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: ZQULRFIFUUADKZ-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 397.79, ALogP 5.34, HBA 6, HBD 2, PSA 82.54, QED 0.49
Compound (SMILES): O=c1cc(Sc2ccccc2F)[nH]c(=O)n1O
InChIKey: UFNIBOWMYFHXAH-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 254.24, ALogP 1.06, HBA 5, HBD 2, PSA 75.09, QED 0.62
Compound (SMILES): COc1ccc(C[C@@H](NC(=O)C[Se]c2ccc(O)cc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)cc1
InChIKey: MFMOMCUBAFFPQJ-MFVUMRCOSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Displacement of [Ph-Se-acetyl]-LVA from human V1A receptor expressed in CHO cells after 4 hrs by RP-LC-ICPMS analysis
Measurement: Ki = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 1206.23
Compound (SMILES): N#Cc1ccc([C@H](C(=O)NCC(F)(F)C2CC2)N2CCN(C(=O)c3cc(F)ccc3Cl)CC2)cc1
InChIKey: SQVMZLKQHMCEPN-JOCHJYFZSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Mus musculus
UniProt: Q62205
Assay: State-dependent inhibition of mouse NaV1.7 expressed in HEK293 cells by IonWorks Quattro electrophysiology method
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 504.94, ALogP 4.01, HBA 4, HBD 1, PSA 76.44, QED 0.62
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(Cc3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: VRAACNQPRYXGQE-OYUWMTPXSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: A5Z252
Assay: Inhibition of Influenza A virus A/Anhui/1/2005(H5N1) neuraminidase N1 H274Y mutant using fluorogenic MUNANA as substrate preincubated for 10 mins followed by substrate addition measured after 40 to 60 mins by fluorescence-based assay
Measurement: IC50 = 915.67 nM (pChEMBL 6.039999961853027)
Descriptors: MW 464.61, ALogP 4.23, HBA 4, HBD 3, PSA 87.66, QED 0.46
Compound (SMILES): Cn1nc(C(N)=O)c2c1-c1nc(Nc3ccc(N4CCOCC4)cn3)ncc1CC2
InChIKey: IGFRKWYWGSYHGA-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 406.45, ALogP 1.05, HBA 9, HBD 2, PSA 124.08, QED 0.66
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cc2)n(CCCC)c1=O
InChIKey: VYOHUSOIZGQDAX-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 679.84, ALogP 2.8, HBA 11, HBD 2, PSA 163.55, QED 0.18
Compound (SMILES): Cc1[nH]c(=O)c(C(N)=O)cc1-c1ccncc1
InChIKey: SWKVSFPUHCMFJY-UHFFFAOYSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Inhibition of human full length N-terminal GST-tagged Aurora B (1 to 344 end residues)/His-tagged INCENP (803 to 918 end residues) expressed in baculovirus expression system using fluorescence-labeled FL-Peptide 21 as substrate after 60 mins in presence of ATP by fluorescence assay based Cheng-Prusoff equation analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 229.24, ALogP 0.84, HBA 3, HBD 2, PSA 88.84, QED 0.8
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccc(Br)cc3)[se]2)cc1
InChIKey: RIVXATBATHBBHV-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 3098 nM (pChEMBL 5.510000228881836)
Descriptors: MW 442.2
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCN(C(=O)C4COC4)CC3)n2c1)S(C)(=O)=O
InChIKey: VOTCYCXUADIEDK-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 518.04, ALogP 2.34, HBA 7, HBD 0, PSA 87.46, QED 0.5
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(C)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: XVOPWUWRTVGXCT-ZXYZSCNASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells after 3 mins by cAMP assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 642.76, ALogP 1.55, HBA 6, HBD 7, PSA 203.96, QED 0.09
Compound (SMILES): CCN(Cc1nc2c(N)nc3cc(-c4ccccc4)ccc3c2[nH]1)C(C)=O
InChIKey: NIOGKLGRFWVTGS-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin) expressed in HEK-Blue cells
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 359.43, ALogP 3.73, HBA 4, HBD 2, PSA 87.9, QED 0.58
Compound (SMILES): CC(C)(C)S(=O)(=O)c1ccc2nccc(Nc3n[nH]c4ncc(F)cc34)c2c1
InChIKey: PMBRUJZGSHBGAZ-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 by Qpatch clamp assay
Measurement: IC50 = 12140 nM (pChEMBL 4.920000076293945)
Descriptors: MW 399.45, ALogP 3.96, HBA 6, HBD 2, PSA 100.63, QED 0.54
Compound (SMILES): COCC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(N(C)S(C)(=O)=O)cn23)CC1
InChIKey: DCAMMTAPONDXMO-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 506.03, ALogP 2.34, HBA 7, HBD 0, PSA 87.46, QED 0.49
Compound (SMILES): CCOC(=O)CN1C(=O)C(=NNC(=O)c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: PFBMKJHLXRKXJY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 430.44, ALogP 0.38, HBA 7, HBD 2, PSA 148.23, QED 0.5
Compound (SMILES): N#Cc1[nH]nnc1-c1ccnc(-c2cn(CCc3cccc4ccccc34)cn2)c1
InChIKey: SZQNWLSVYUSLQI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 uM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen Streptavidin-coated Donor beads, and AlphaScreen Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 ug/ml beads.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 391.44, ALogP 4, HBA 6, HBD 1, PSA 96.07, QED 0.49
Compound (SMILES): CC(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: HDWCWNNKLHTKJH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.37, ALogP 4.36, HBA 5, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): CN(CCCCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1)c1ccccc1
InChIKey: BDQAHKHKPTXCHB-ZBJSNUHESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 8610 nM (pChEMBL 5.070000171661377)
Descriptors: MW 413.52, ALogP 5.64, HBA 4, HBD 0, PSA 38.77, QED 0.35
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(N)=O)CC3
InChIKey: AIOFAAQPUFNQBS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from human 5-HT2C receptor expressed in CHO cell membranes after 60 mins by TopCount scintillation counting method
Measurement: Ki = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 270.33, ALogP 2.55, HBA 2, HBD 2, PSA 64.35, QED 0.9
Compound (SMILES): CC[C@H](Nc1nc(N[C@@H](CC)C(F)(F)F)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: QTQWJQDDICMREO-UWVGGRQHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 476.35, ALogP 5.46, HBA 6, HBD 2, PSA 75.62, QED 0.52
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@H](c2cccc(S(=O)(=O)NCCOCCOCCOCCNC(=O)CCC(CCC(=O)NCCOCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)(CCC(=O)NCCOCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)NCc3ccc(-c4ccc(Cl)cc4)cc3)c2)C1
InChIKey: FHVQDQLSYHSUKS-GBDQAQDBSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P48764
Assay: Cell-based activity under Prompt Conditions: Cell-based activity under Prompt Conditions. Rat or human NHE3-mediated Na+-dependent H+ antiport was measured using a modification of the pH sensitive dye method originally reported by Paradiso (PNAS USA. 81:7436-7440, 1984). Opossum kidney (OK) cells were obtained from the ATCC and propagated per their instructions. The rat NHE3 gene (GenBank M85300) or the human NHE3 gene (GenBank NM_004174.1) was introduced into OK cells via electroporation, and cells were seeded into 96 well plates and grown overnight. Medium was aspirated from the wells, cells were washed twice with NaCl-HEPES buffer (100 mM NaCl, 50 mM HEPES, 10 mM glucose, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4), then incubated for 30 min at room temperature with NH4Cl-HEPES buffer (20 mM NH4Cl, 80 mM NaCl, 50 mM HEPES, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4) containing 5 μM bis(acetoxymethyl) 3,3′-(3′,6′-bis(acetoxymethoxy)-5-((acetoxymethoxy)carbonyl)-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-2′,7′-diyl)dipropanoate (BCECF-AM).Cells were washed twice with Ammonium free, Na+-free HEPES (100 mM choline, 50 mM HEPES, 10 mM glucose, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4) and incubated in the same buffer for 10 minutes at room temperature to lower intracellular pH. NHE3-mediated recovery of neutral intracellular pH was initiated by addition of Na-HEPES buffer containing 0.4 μM ethyl isopropyl amiloride (EIPA, a selective antagonist of NHE-1 activity that does not inhibit NHE3) and 0-30 μM test compound, or a pharmaceutically acceptable salt thereof, and monitoring the pH sensitive changes in BCECF fluorescence (λex 505 nm, λem, 538 nm) normalized to the pH insensitive BCECF fluorescence (λex 439 nm, λem, 538 nm). Initial rates were plotted as the average 2 or more replicates, and pIC50 values were estimated using GraphPad Prism.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 2033.42
Compound (SMILES): O=C1[C@@H]2[C@H](C(=O)N1CCCCN1CCN(c3cccc4ccsc34)CC1)[C@H]1C=C[C@@H]2C1
InChIKey: MBWYSJMSOMZNFK-KNGAYFSHSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 435.59, ALogP 3.61, HBA 5, HBD 0, PSA 43.86, QED 0.4
Compound (SMILES): COc1ccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: NSCFCNLNWUYORR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 414.39, ALogP 4, HBA 6, HBD 1, PSA 81.51, QED 0.52
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)c(C#N)c1
InChIKey: VFQWDEDHEXEJLC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 334.34, ALogP 2.72, HBA 6, HBD 1, PSA 101.03, QED 0.77
Compound (SMILES): Nc1sc2c(-c3ccccc3)cccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: GTMRSQDLGFFXES-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 368.86, ALogP 6.69, HBA 3, HBD 2, PSA 38.05, QED 0.42
Compound (SMILES): CC(=O)Nc1ccc(-c2ccnc(Nc3cccc(OCCCCCCCC(=O)NO)c3)n2)cc1.Cl
InChIKey: IEBSBPYXJSVQNG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Arg-His-Lys-Lys(Ac) as substrate preincubated with enzyme followed by substrate addition for 2 hrs and measured for 1.5 hrs at 15 mins time interval by fluorescence assay
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 477.57, ALogP 5.07, HBA 7, HBD 4, PSA 125.47, QED 0.15
Compound (SMILES): CCOc1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: BBIILYRHGSEGLE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 134.1 nM (pChEMBL 6.869999885559082)
Descriptors: MW 351.38, ALogP 2.08, HBA 5, HBD 4, PSA 130.75, QED 0.61
Compound (SMILES): Cn1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3CC3)c2=O)cn1
InChIKey: KQWQMWPUWTWEIR-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 443.53, ALogP 1.19, HBA 8, HBD 1, PSA 107.99, QED 0.59
Compound (SMILES): O=C(CCCCCN1CCC(c2noc3cc(F)ccc23)CC1)c1cc2c3c(c1)CCN3C(=O)CC2
InChIKey: ICTOAQCFEMKCKY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 34.7 nM (pChEMBL 7.460000038146973)
Descriptors: MW 489.59, ALogP 5.42, HBA 5, HBD 0, PSA 66.65, QED 0.31
Compound (SMILES): FC(F)c1csc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: GVVHKJZVVILBHY-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 424.37, ALogP 4.35, HBA 7, HBD 2, PSA 75.62, QED 0.67
Compound (SMILES): COc1ccccc1-n1nc([C@H]2C[C@@H](C)O[C@@H](C)C2)cc1-c1ccc(Cl)cc1
InChIKey: ZSYIDVKYMLIJDL-VQFNDLOPSA-N
Target: Voltage-dependent N-type calcium channel subunit alpha-1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q00975
Assay: Inhibition of low frequency stimulation-induced Cav2.2 (unknown origin) expressed in HEK293 cells at -80 mV holding membrane potential by automated patch clamp assay
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 396.92, ALogP 5.87, HBA 4, HBD 0, PSA 36.28, QED 0.55
Compound (SMILES): O=C1c2ccccc2C(=Cc2cccc(O)c2)c2ccccc21
InChIKey: KGQNBZACENOOOR-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition of R1881-induced full length AR transcriptional activity in human LNCAP cells harboring AR2PB-eGFP construct after 72 hrs by fluorescence assay
Measurement: IC50 = 316.2 nM (pChEMBL 6.5)
Descriptors: MW 298.34, ALogP 4.53, HBA 2, HBD 1, PSA 37.3, QED 0.56
Compound (SMILES): CNC(=O)c1cccc2cc(Oc3ccnc(NC(=O)c4ccc(N5CCN(CCO)CC5)cc4)c3)ccc12
InChIKey: AISWQGLURAAAKE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant FGFR2 (unknown origin) incubated for 60 mins by ELISA analysis
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 525.61, ALogP 3.75, HBA 7, HBD 3, PSA 107.03, QED 0.32
Compound (SMILES): Nc1oc2cnccc2c1Nc1cccc(C(F)(F)F)c1
InChIKey: PTSDVYRCPPHQHX-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 293.25, ALogP 4.17, HBA 4, HBD 2, PSA 64.08, QED 0.74
Compound (SMILES): C[C@H]1Cc2ccc(-c3ncnc4[nH]ccc34)cc2[C@@H]1NC#N
InChIKey: FOOVWQSSBRMHTG-ZUZCIYMTSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 JH1 domain using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 603 nM (pChEMBL 6.21999979019165)
Descriptors: MW 289.34, ALogP 2.93, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)cc1)c1cc(Br)cc(Br)c1
InChIKey: MWCTYQOZTHGGAI-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 520.27, ALogP 7.22, HBA 4, HBD 1, PSA 41.99, QED 0.31
Compound (SMILES): FC(F)(F)c1ccccc1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: IQXPWKHDTIHLLB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 452.36, ALogP 5.01, HBA 5, HBD 1, PSA 72.28, QED 0.43
Compound (SMILES): OC[C@@H]1CCC[C@@H](c2ccc(O)cc2)CC1
InChIKey: TYZPZHWTUNATHL-VXGBXAGGSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at full length ERalpha (unknown origin) after 24 hrs by ERE-driven luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 220.31, ALogP 3.05, HBA 2, HBD 2, PSA 40.46, QED 0.75
Compound (SMILES): CNc1ncc(C(=O)OCc2ccc(C)cc2)c2nc(-c3ccco3)nn12
InChIKey: LZDJWNMSPWMOSJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 363.38, ALogP 3.09, HBA 8, HBD 1, PSA 94.55, QED 0.54
Compound (SMILES): Oc1ccc(-c2c[se]cc2-c2ccc(OCCN3CCCCC3)cc2)cc1
InChIKey: FCAXEWIYGYWTJP-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Antagonist activity at ERbeta (unknown origin) expressed in HEK293T cells assessed as inhibition of 17beta-estradiol stimulated transcriptional activity after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 451 nM (pChEMBL 6.349999904632568)
Descriptors: MW 426.42
Compound (SMILES): COc1nc(-c2ccnc(NC(=O)C3CC3)c2)sc1C(=O)NCCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: XYSJVXMQSXKJCN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human full length N-terminal GST-tagged GSK-3beta expressed in Sf9 insect cells using prephosphorylated polypeptide as substrate after 30 mins by kinase-Glo reagent based luminescence assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 556.69, ALogP 5.22, HBA 8, HBD 3, PSA 118.13, QED 0.23
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O
InChIKey: ICCWQBANNIZSDH-ILMFCTMOSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 4213.78
Compound (SMILES): COc1cc(-c2nc(NCc3ccc(C(=O)NO)cc3)cc3c2[nH]c2ccccc23)cc(OC)c1OC
InChIKey: XVLFDROZMUKWLL-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 498.54, ALogP 5.14, HBA 7, HBD 4, PSA 117.73, QED 0.17
Compound (SMILES): Cl.Nc1sc2ccc(Cl)cc2c1Nc1cccc(C(F)(F)F)c1
InChIKey: MPKUZCPHJRROBQ-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 342.77, ALogP 5.9, HBA 3, HBD 2, PSA 38.05, QED 0.61
Compound (SMILES): CCN1CCN(C2CCN(C(=O)COc3ccc(-c4ccccc4F)cc3)CC2)CC1
InChIKey: SGLADPJLVFJEPA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using acetylthiocholine iodide as substrate measured over 60 secs by Ellman assay
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 425.55, ALogP 3.5, HBA 4, HBD 0, PSA 36.02, QED 0.71
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cncc(Cl)n3)n2)CC1
InChIKey: MEWHAARPVJKYDP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.88, ALogP 4.96, HBA 7, HBD 2, PSA 88.51, QED 0.61
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: RQRJJSVAJSUINU-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 448.36, ALogP 4.17, HBA 8, HBD 2, PSA 112.3, QED 0.56
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cncc(C(F)(F)F)n3)n2)c1
InChIKey: CUSSJQLSJJSNTA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 487.38, ALogP 5.36, HBA 7, HBD 2, PSA 88.51, QED 0.47
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CCN)C(=O)N1CCC[C@@H]1C(=O)N[C@@H]1CCc2c(F)cccc21
InChIKey: NWJPNEPAUOWBDK-NUDXDXSLSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 76.9 nM (pChEMBL 7.110000133514404)
Descriptors: MW 433.53, ALogP 0.36, HBA 5, HBD 4, PSA 116.56, QED 0.47
Compound (SMILES): CCCCc1ccccc1NCc1ccc(C(=O)Nc2nc(CC(=O)O)cs2)s1
InChIKey: YSRCIJVCLXAWIY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 429.57, ALogP 5.04, HBA 6, HBD 3, PSA 91.32, QED 0.42
Compound (SMILES): CC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(N4CCCCS4(=O)=O)cn23)CC1
InChIKey: OZOIQAKTOSCMAO-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 502.04, ALogP 3.25, HBA 6, HBD 0, PSA 78.23, QED 0.55
Compound (SMILES): CC(Nc1nc(NC(C)C(F)(F)F)nc(-c2cncc(Cl)n2)n1)C(F)(F)F
InChIKey: QETWKMKQNIKDLH-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 415.73, ALogP 3.71, HBA 7, HBD 2, PSA 88.51, QED 0.72
Compound (SMILES): CNC(=O)c1cccc2cc(Oc3ccnc(NC(=O)c4ccc(N5C[C@@H](C)N[C@@H](C)C5)cc4)c3)ccc12
InChIKey: CHZKEAYTNKCUEF-BGYRXZFFSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 in presence of ATP by mobility shift assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 509.61, ALogP 4.83, HBA 6, HBD 3, PSA 95.59, QED 0.34
Compound (SMILES): CC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(S(C)(=O)=O)cn23)CC1
InChIKey: KQPJVIFJOKBGDJ-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 446.96, ALogP 2.72, HBA 6, HBD 0, PSA 74.99, QED 0.62
Compound (SMILES): COc1cc([C@H]2[C@H](C(=O)O)[C@H](c3ccc(O)c(OC)c3)[C@H]2C(=O)Oc2cccc3ccccc23)ccc1O
InChIKey: ULSDOUSGHGOKSJ-LJWNLINESA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: High Throughput Fluorescence Displacement Assay : FABP5 was purified and delipidated as described previously (Kaczocha, M. et al. 2012). FABP5 (30 μg), NBD-stearate (1 μM), and a competitor test compound were incubated in 30 mM Tris-HCl, 100 mM NaCl buffer (pH 7.6). Competitors included arachidonic acid, BMS309403, 48 test compounds from ChemDiv library, Compound 26 and Compound 49. The initial assay was run with buffer (30 mM Tris-HCl buffer), negative controls (buffer and NBD-stearate), positive controls (buffer, NBD-stearate, FABP5), and experimental wells with a variable test compound added (arachidonic acid or one of the 48 test compounds) at 10 μM. Test compounds that produced high inhibition and proved statistically significant were then added to the fluorescent assay at 10 μM and tested in triplicate to verify their success. The most effective test compound and BMS309403 were measured in increasing concentrations (0.01-50 μM), as were the Compound 26 and γ-truxillic acid 1-naphthyl ester, which were discovered following the test. The fluorescent assays were tested in the wells of Microtest 96-well Assay Plates, Optilux (BD Biosciences, Franklin Lakes, N.J.) and loss of fluorescence intensity was measured with a FLUOstar OPTIMA spectrofluorometer set to excitation and emission wavelengths of 460 nm and 544 nm, respectively. For the most effective test compounds, IC50 values were calculated with GraphPad Prism. GraphPad Prism was also used to determine the Ki of these select competitors from the equation Ki=IC50/(1+([NBD-stearate]/Kd)).
Measurement: Ki = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 514.53, ALogP 5.07, HBA 7, HBD 3, PSA 122.52, QED 0.23
Compound (SMILES): O=C(O)CC1COc2cc(OCCCOc3cccc(Cl)c3)ccc21
InChIKey: KNTFJPOCGUBOIF-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human GAL4 fused PPARalpha-LBD expressed in human HepG2 cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 362.81, ALogP 4.14, HBA 4, HBD 1, PSA 64.99, QED 0.71
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)CCC(=O)NCCCC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)O)NC1=O
InChIKey: ZYTMKKYSSNUDMO-DUYILPCASA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 1699.94
Compound (SMILES): O=S(=O)(Nc1ncns1)c1ccc(OCc2ccc(OC(F)(F)F)c(Cl)c2)cc1
InChIKey: XOYPCMZEMYSCQC-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human NaV1.7
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 465.86, ALogP 4.47, HBA 7, HBD 1, PSA 90.41, QED 0.55
Compound (SMILES): O=C(O)c1ccnc(-n2nc(Cc3ccccc3)cc2O)c1
InChIKey: GAAWGDKZMZYRLG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in Escherichia coli using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 295.3, ALogP 2.26, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): CC(O)(c1ccc(S(=O)(=O)C2SC(N3CCCCC3)=NC2C(F)(F)F)cc1)C(F)(F)F
InChIKey: AADZRZOWFKIFTL-UHFFFAOYSA-N
Target: Glycine receptor alpha-3/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins in presence of GlyRs inhibitor strychnine by FLIPR assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 490.49, ALogP 4.08, HBA 6, HBD 1, PSA 69.97, QED 0.65
Compound (SMILES): CO[C@@H]1O[C@H](CNCCCCCCCCCNc2c3c(nc4ccccc24)CCCC3)[C@H]2OC(C)(C)O[C@@H]12
InChIKey: UQDYDWLHFFFFGT-PYYPWFDZSA-N
Target: Cholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: Q03311
Assay: Inhibition of mouse serum BuChE
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 525.73, ALogP 5.74, HBA 7, HBD 2, PSA 73.87, QED 0.3
Compound (SMILES): N#CN[C@@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 844 nM (pChEMBL 6.070000171661377)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CCOc1ccccc1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: LAHJCVJYCGEQRW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JMJD3 (1043 to end residues) expressed in baculovirus infected Sf9 cells using H3K27me3-biotin labelled peptide as substrate measured after 20 mins by AlphaScreen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 428.42, ALogP 4.39, HBA 6, HBD 1, PSA 81.51, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc(C(F)F)cc2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: ZDFIRHIJKVNVDY-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of recombinant human Nav1.7 expressed in HEK293 cells at -70 mV holding potential by patch clamp electrophysiology method
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 422.43, ALogP 4.14, HBA 4, HBD 1, PSA 68.17, QED 0.67
Compound (SMILES): O=C(NCc1ccc(OC(F)(F)F)c(Cl)c1)c1ccc(S(=O)(=O)Nc2nccs2)c(F)c1
InChIKey: ZUXRUQOEFBOTGF-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human NaV1.5
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 509.89, ALogP 4.57, HBA 6, HBD 2, PSA 97.39, QED 0.45
Compound (SMILES): N#CC1(c2cc(Nc3nc(NCC(F)(F)F)nc(-c4cccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: BNHMYSZGOLVPEX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 480.38, ALogP 4.62, HBA 8, HBD 2, PSA 112.3, QED 0.49
Compound (SMILES): FC(F)(F)c1cccc(-c2nc(NCC3CC3(F)F)nc(NCC3CC3(F)F)n2)n1
InChIKey: XHKYLNZMSNXADF-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 436.34, ALogP 4.09, HBA 6, HBD 2, PSA 75.62, QED 0.64
Compound (SMILES): Clc1cccc(Cn2cnc(-c3cc(-c4nn[nH]n4)ccn3)c2)c1Cl
InChIKey: COHJFYQXZDDDSL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 372.22, ALogP 3.48, HBA 6, HBD 1, PSA 85.17, QED 0.59
Compound (SMILES): Cc1ccc(-n2c(C(=O)c3sc(N4CCOCC4)nc3-c3ccccc3)cnc2N)cc1
InChIKey: CIFGRYLZBIIHOR-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at recombinant human A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 445.55, ALogP 3.95, HBA 8, HBD 1, PSA 86.27, QED 0.47
Compound (SMILES): CC(=O)n1nc(C)c(-c2ccc(Cl)c(Cl)c2)c1N
InChIKey: HJXDCOSNNVYHCY-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 284.15, ALogP 3.41, HBA 4, HBD 1, PSA 60.91, QED 0.87
Compound (SMILES): O=C(O)c1ccc2ccc(C(=O)c3ccc(C(F)(F)F)cc3)c-2cc1
InChIKey: AIHVJYFGVPIWAT-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using mephenytoin as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 344.29, ALogP 4.74, HBA 2, HBD 1, PSA 54.37, QED 0.7
Compound (SMILES): Nc1cccc(C(OCCN2CCCCC2)c2cc3nccc(C(=O)O)c3s2)c1
InChIKey: FTKYSFLMVOPKTH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Irreversible inhibition of KDM5A ARID/PhD1 domain deletion mutant (1 to 739 residues) (unknown origin) using 100 uM alpha-KG by succinate-glo demethylase assay
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 411.53, ALogP 4.17, HBA 6, HBD 2, PSA 88.68, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O
InChIKey: YIDIBSNLMUVHEC-YOGANYHLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 4182.77