lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCC(C1CCN(C(=O)c2cnn(-c3nn4cccc4c(=O)[nH]3)c2C)CC1)C(F)(F)F
InChIKey: OICZIZKFAWMFAI-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 436.44, ALogP 2.96, HBA 6, HBD 1, PSA 88.29, QED 0.68
Compound (SMILES): c1ccc(OCCNC[C@H]2OCCO[C@@H]2c2ccccc2)cc1
InChIKey: ZVHRVSHMCKYIMH-RTBURBONSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Displacement of [3H]Prazosin from human recombinant alpha 1D adrenergic receptor expressed in CHO cells incubated for 30 mins by radioligand competition binding assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 313.4, ALogP 2.81, HBA 4, HBD 1, PSA 39.72, QED 0.8
Compound (SMILES): O=C(CCCCCCn1cc(Nc2ncc(Cl)c(N3CCCCC3)n2)cn1)NO
InChIKey: RJJTZYSKIBYNSU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 using Ulight-CAGAGAIETDKEYYTVKD as substrate measured after 60 mins by LANCE assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 421.93, ALogP 3.52, HBA 8, HBD 3, PSA 108.2, QED 0.31
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cc(C(=O)O)cc(-c2ccccc2)c1)[C@@H](CC)N(O)C=O
InChIKey: FURGAXLPHVAPPJ-DHIUTWEWSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 483.57, ALogP 3.68, HBA 5, HBD 4, PSA 136.04, QED 0.11
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4cccc(NCC5CCOCC5)c4c3)nnc21
InChIKey: WJEUVIUVISQACN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of N-terminal 6-His tagged human recombinant PIM3 using PIM tide (ARKRRRHPSGPPTA) as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 281 nM (pChEMBL 6.550000190734863)
Descriptors: MW 430.51, ALogP 3.61, HBA 8, HBD 1, PSA 76.81, QED 0.53
Compound (SMILES): C1=Cc2ccccc2[C@]2(CC[C@@H](NCC3CCCCC3)CC2)O1
InChIKey: OJYGYOYQVVGKTL-XUTJKUGGSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P97266
Assay: Displacement of [3H]DAMGO from mu opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 311.47, ALogP 5, HBA 2, HBD 1, PSA 21.26, QED 0.85
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cnc(C)o2)c1
InChIKey: AOVHSNAUKQZDQJ-GOSISDBHSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 416.48, ALogP 2.5, HBA 6, HBD 3, PSA 124.77, QED 0.16
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C[C@H]1CC[C@@H](c2ccccc2)CC1)NC(=O)[C@H](Cc1ccccc1)N=[N+]=[N-])C(=O)[C@@]1(C)CO1
InChIKey: CSETXDZLMRQNSX-QVMCWBLBSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of catalytic activity of constitutive proteasome 20s subunit beta2 in human Raji cells incubated for 1 hr by BODIPY(FL)-LU-112 probe based competitive activity based protein profiling assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 678.83, ALogP 5.35, HBA 6, HBD 3, PSA 165.66, QED 0.08
Compound (SMILES): C#CCCN1CCN(c2ccc(Nc3nc(OC4CCN(C(=O)C=C)CC4)c4c(-c5cncc(NC)n5)c[nH]c4n3)cc2)CC1
InChIKey: HDTAJYMSOFSQAY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal His6-tagged JAK3 (781 to end residues) expressed in baculovirus infected Sf21 cells using STK as substrate by HTRF assay
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 606.74, ALogP 3.9, HBA 10, HBD 3, PSA 127.43, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccc(F)cc1)Nc1ccccc1C(=O)O
InChIKey: YSKFGBAYHFLJPZ-JXMROGBWSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: Antagonist activity at human TRPA1 expressed in HEK293 cells assessed as inhibition of CA-induced increase in calcium influx incubated for 10 mins prior to CA addition by Fluo-4-AM dye based fluorescence assayy
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 285.27, ALogP 3.18, HBA 2, HBD 2, PSA 66.4, QED 0.85
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(C)(C)C(=O)O)cc2)n1)[C@@H](CC)N(O)C=O
InChIKey: QLNNFHOKQULRKO-ZJSXRUAMSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 526.63, ALogP 3.74, HBA 6, HBD 4, PSA 148.93, QED 0.09
Compound (SMILES): Cn1cc(Nc2nccc(N3C[C@H]4CC[C@H](C3)N4C(=O)C3CC3)n2)cn1
InChIKey: NFDUKDPMYWCESJ-HUUCEWRRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human TYK2 using fluorescence labeled peptide as substrate and using 1 mM ATP level by microfluidic based mobility shift assay
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 353.43, ALogP 1.54, HBA 7, HBD 1, PSA 79.18, QED 0.9
Compound (SMILES): Cn1ccc2ccc(N3CCC(C4c5c(F)cccc5-c5cncn54)CC3)cc21
InChIKey: NTZXSJFDPVHDNV-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO in human HeLa cells using tryptophan as substrate measured after 48 hrs in presence of INF gamma microplate reader analysis
Measurement: IC50 = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 386.47, ALogP 5, HBA 4, HBD 0, PSA 25.99, QED 0.48
Compound (SMILES): C=Cc1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc(Cl)s5)ccc4o3)cc2)cc1
InChIKey: URTBUNWGGCXSDH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 572.09, ALogP 6.45, HBA 7, HBD 2, PSA 118.37, QED 0.22
Compound (SMILES): Cc1c(C(=O)N2CC(N3CCC(F)(F)C3)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: LPPQUKFUNMBBJG-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 403.39, ALogP 0.68, HBA 7, HBD 1, PSA 91.53, QED 0.69
Compound (SMILES): COc1ccc2c(n1)CCN(C(C)=O)[C@H]2C(=O)Nc1ccc(OCc2ccccc2OC)cc1
InChIKey: RNCVXSNHCXEILI-RUZDIDTESA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Agonist activity at RORgammaT (unknown origin) expressed in human Jurkat cells co-expressing human IL-17 ROR response element by luciferase reporter gene assay
Measurement: EC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 461.52, ALogP 3.76, HBA 6, HBD 1, PSA 89.99, QED 0.58
Compound (SMILES): CN(Cc1cc2c(=O)[nH]c(N)nc2[nH]1)C(=O)c1cccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c1
InChIKey: PNRJTEIZPOHDEE-AWEZNQCLSA-N
Target: Proton-coupled folate transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NT5
Assay: Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells assessed as antiproliferative activity measured as reduction in cell growth after 96 hrs by Cell-Titer Blue assay
Measurement: IC50 = 747 nM (pChEMBL 6.130000114440918)
Descriptors: MW 470.44, ALogP 0.15, HBA 7, HBD 6, PSA 211.57, QED 0.25
Compound (SMILES): CCC(=O)N(c1ccccc1)C1(C(=O)OC)CCNCC1
InChIKey: HFNFODVRYCEIQL-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins and measured after 1 hr by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 290.36, ALogP 1.72, HBA 4, HBD 1, PSA 58.64, QED 0.86
Compound (SMILES): COC(=O)N[C@H](NC(=O)N1CCC[C@H]1c1nc2ccc(-c3ccc4cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C6CCOCC6)[nH]5)ccc4c3)cc2[nH]1)C1CCOCC1
InChIKey: UGPGGLRZHVFWGS-YKKXUYLKSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1a replicons NS5A infected in human Huh7 cells by luciferase reporter gene assay
Measurement: EC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 862, ALogP 6.54, HBA 10, HBD 5, PSA 205.13, QED 0.1
Compound (SMILES): C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1
InChIKey: GFZNRMYFECIHSP-BVZFJXPGSA-N
Target: Hepatocyte growth factor activator serine protease (SINGLE PROTEIN), Homo sapiens
UniProt: Q04756
Assay: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay
Measurement: Ki = 7984 nM (pChEMBL 5.099999904632568)
Descriptors: MW 584.7, ALogP 4.15, HBA 7, HBD 5, PSA 159.29, QED 0.08
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@H](C)c3cc(F)c(N4CCNCC4)cc3F)sc2n1
InChIKey: DIMLWPCIAHNRFA-LBPRGKRZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 445.54, ALogP 3.41, HBA 6, HBD 3, PSA 83.28, QED 0.56
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(OC)c2F)n1
InChIKey: AYZHKBPOPBLWRT-MRXNPFEDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 460.51, ALogP 2.74, HBA 6, HBD 3, PSA 120.86, QED 0.14
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2ccc(Cl)cc2C(=O)O)c1=O
InChIKey: XVMKABLPIFMWEO-MRXNPFEDSA-N
Target: Dipeptidyl peptidase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86TI2
Assay: Inhibition of recombinant full-length human N-terminal GST-tagged DPP9 expressed in Sf9 insect cells using Gly-Pro-AMC as substrate measured at 60 secs interval for 20 mins by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 430.89, ALogP 1.36, HBA 7, HBD 2, PSA 110.56, QED 0.69
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H]2C[C@@H]2[C@H]1n1cnc2c(NCCc3cccc(F)c3)nc(C#Cc3ccccc3)nc21
InChIKey: MZFRRFIKWVFNDO-IRYUZJHDSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]I-AB-MECA from recombinant mouse A3AR expressed in HEK293 cell membranes measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 264 nM (pChEMBL 6.579999923706055)
Descriptors: MW 469.52, ALogP 2.93, HBA 7, HBD 3, PSA 96.09, QED 0.39
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(-n4ncc5c4CNC5)cc3)sc2n1
InChIKey: MAUCSIJVDXUPIK-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 418.53, ALogP 2.95, HBA 7, HBD 3, PSA 97.86, QED 0.46
Compound (SMILES): CN(CC1CCCCC1)[C@H]1CC[C@]2(CC1)OCCc1ccccc12
InChIKey: FCXSSMKUWDTUIH-GRGXKFILSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from delta opioid receptor in rat membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 565 nM (pChEMBL 6.25)
Descriptors: MW 327.51, ALogP 4.91, HBA 2, HBD 0, PSA 12.47, QED 0.78
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccc(F)cc1
InChIKey: MGFIPRDVFZZANE-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 76000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 368.39, ALogP 4.43, HBA 4, HBD 1, PSA 72.2, QED 0.58
Compound (SMILES): CCOC1Cc2ccccc2[C@]2(CC[C@H](NCC3CCCCC3)CC2)O1
InChIKey: LKSVIRCJQQMHGO-KFWDTITQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P97266
Assay: Displacement of [3H]DAMGO from mu opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 495 nM (pChEMBL 6.300000190734863)
Descriptors: MW 357.54, ALogP 4.93, HBA 3, HBD 1, PSA 30.49, QED 0.81
Compound (SMILES): N#CC(C(=O)NCC(=O)N1CCCC1)c1nc2ccc(-c3ccccc3)cc2s1
InChIKey: BKXXMDCWHCVLJV-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of endothelial lipase in human serum
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 404.5, ALogP 3.31, HBA 5, HBD 1, PSA 86.09, QED 0.71
Compound (SMILES): CNc1cncc(-c2c[nH]c3nc(Nc4ccc(N5CCN(C(C)=O)CC5)cc4)nc(OC4CCOCC4)c23)n1
InChIKey: NHACTKLHFBISNC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal His6-tagged JAK3 (781 to end residues) expressed in baculovirus infected Sf21 cells using STK as substrate by HTRF assay
Measurement: IC50 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 543.63, ALogP 3.43, HBA 10, HBD 3, PSA 133.42, QED 0.32
Compound (SMILES): CN(C)C1(Cc2ccccc2)CCN(c2cc(C(F)(F)F)ccc2CNC(=O)Nc2cccc3[nH]c(=O)ccc23)CC1
InChIKey: JRHYOTTVIVGLGM-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from full length human MOR expressed in chem5 cells incubated for 60 mins by liquid scintillation counter
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 577.65, ALogP 6.01, HBA 4, HBD 3, PSA 80.47, QED 0.25
Compound (SMILES): CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: JVJDWLSGNCORBJ-CZZKCPPWSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 1621.81 nM (pChEMBL 5.789999961853027)
Descriptors: MW 739.92, ALogP 3.98, HBA 8, HBD 6, PSA 186.2, QED 0.11
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cncc(OC)c2)o1
InChIKey: CUCBXONQXHGRSD-OAHLLOKOSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 432.48, ALogP 2.2, HBA 7, HBD 3, PSA 134, QED 0.15
Compound (SMILES): CCN(CCCCCCCCCCOc1ccc(C(C)=O)c(O)c1)Cc1ccccc1
InChIKey: XRNIVUKXRLMIBN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide incubated for 15 mins as substrate by Ellman's method
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 425.61, ALogP 6.62, HBA 4, HBD 1, PSA 49.77, QED 0.24
Compound (SMILES): CCN1CCN(c2ccc3c(c2)CCN3S(=O)(=O)c2ccccc2)CC1
InChIKey: PRBBGEBXWKOEEQ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]raclopride from human recombinant dopamine D2 long receptor expressed in CHO-K1 cells incubated for 120 mins by scintillation counting analysis
Measurement: Ki = 438 nM (pChEMBL 6.360000133514404)
Descriptors: MW 371.51, ALogP 2.58, HBA 4, HBD 0, PSA 43.86, QED 0.83
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1
InChIKey: SKCJIIRKAVOSJL-SVBPBHIXSA-N
Target: Hepatocyte growth factor activator serine protease (SINGLE PROTEIN), Homo sapiens
UniProt: Q04756
Assay: Inhibition of HGFA catalytic domain (unknown origin) preincubated for 30 mins followed by Boc-QLR-AMC substrate addition and measured for 1 hr by fluorescence assay
Measurement: Ki = 8634 nM (pChEMBL 5.059999942779541)
Descriptors: MW 669.81, ALogP 3.4, HBA 8, HBD 8, PSA 221.19, QED 0.04
Compound (SMILES): COc1cc(NC(=O)N2CCOCC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NC(C)=O)n1
InChIKey: UQWDXRWKSYDDTE-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of recombinant human N-terminal GST-tagged ROS (1883 to 2347 residues) cytoplasmic domain expressed in baculovirus expression system using IRS1 as substrate incubated for 1 hr by mobility shift assay
Measurement: IC50 = 0.73 nM (pChEMBL 9.140000343322754)
Descriptors: MW 511.97, ALogP 4.45, HBA 8, HBD 4, PSA 129.74, QED 0.37
Compound (SMILES): Nc1c(C(=O)NCCc2ccc(N3CCNCC3)cc2)sc2ncc(C(F)F)cc12
InChIKey: OZBJIIOASWVUNL-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 431.51, ALogP 3.2, HBA 6, HBD 3, PSA 83.28, QED 0.56
Compound (SMILES): CCCCCCC(C)(C)c1cc2c(c3c1CCCO3)-c1nn(CC)cc1C(C)(C)O2
InChIKey: BIWZCBFDUJMSGC-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in HEK293 cell membranes assessed as inhibition of forskolin-stimulated cAMP accumulation after 60 mins by HTRF assay
Measurement: IC50 = 25.5 nM (pChEMBL 7.590000152587891)
Descriptors: MW 410.6, ALogP 6.77, HBA 4, HBD 0, PSA 36.28, QED 0.47
Compound (SMILES): Nc1ccc(S(=O)(=O)[N-][N+](=O)[O-])cc1.[Ag+]
InChIKey: BRKMLLKMUBLMKQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 216.2, ALogP 0.52, HBA 5, HBD 1, PSA 117.4, QED 0.45
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCN(C)CC5)cc4)n[nH]c3c2)c1Cl
InChIKey: RBMWCFYMBVLYGJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzyme Kinase Activity Assay: The enzyme reaction substrate Poly(Glu,Tyr) 4:1 was diluted with PBS without potassium ion (10 mM sodium phosphate buffer, 150 mM NaCl, pH7.2-7.4) to 20 μg/mL, 125 μL/well to coat the enzyme plate, and reacted at 37° C. for 12-16 hours. After the liquid was removed from the wells, the plate was washed three times with 200 μL/well of T-PBS (PBS containing 0.1% Tween-20) for 5 minutes each. The enzyme plate was dried in a 37° C. oven for 1-2 hours.50 μL of the ATP solution diluted with the reaction buffer (50 mM HEPES pH 7.4, 50 mM MgCl2, 0.5 mM MnCl2, 0.2 mM Na3VO4, 1 mM DTT) was added into each well at a 5 μM final concentration. The compounds were diluted to the appropriate concentration in DMSO, 1 μL/well or containing the corresponding concentrations of DMSO (negative control wells). The reaction was initiated by addition of each kinase domain recombinant protein diluted with 49 μL of reaction buffer. Two control wells without ATP were set in each experiment. The reaction mixtures were placed on a shaker (100 rpm) to react at 37° C. for 1 hour. The plates were washed with T-PBS for three times. 100 μL/well of the primary antibody PY99 dilution was added, and reacted on a shaker (100 rpm) at 37° C. for 0.5 hour. The plates were washed with T-PBS for three times. 100 μL/well of the secondary anti-horseradish peroxidase-labeled goat anti-mouse IgG dilution was added, and reacted on a shaker at 37° C. for 0.5 hour. The plates were washed with T-PBS for three times. 100 μL/well of 2 mg/mL OPD developing solution (diluted with 0.1M citric acid-sodium citrate buffer containing 0.03% H2O2 (pH=5.4)), and reacted in dark for 1-10 minutes at 25° C. (Ultrasound is needed in OPD dissolution, and the developing solution should be prepared on the site). The reaction was quenched with 50 μL/well of 2M H2SO4, and read out at 490 nm using a tunable microplate microplate reader SPECTRA MAX 190.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 540.45, ALogP 5.56, HBA 6, HBD 2, PSA 82.72, QED 0.33
Compound (SMILES): Nc1ccc(-c2nc(N3CCOCC3)nc3c2C[C@@H]2COCCN32)cn1
InChIKey: BZNSXRRFSXPCLY-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of alexa fluor 647-labeled kinase tracer 314 binding to recombinant human N-terminal GST-fused mTOR (1360 to 2549 residues) expressed in baculovirus expression system by TR-FRET assay
Measurement: Ki = 1279 nM (pChEMBL 5.889999866485596)
Descriptors: MW 354.41, ALogP 0.72, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): N#CCC(=O)Nc1nc(-c2ccc(Cl)c(Cl)c2)cs1
InChIKey: UVZNRMKUEHJMJX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 312.18, ALogP 3.97, HBA 4, HBD 1, PSA 65.78, QED 0.93
Compound (SMILES): CC(=O)N1N=C(c2ccccc2)CC1c1cccc(OS(N)(=O)=O)c1
InChIKey: HLCALJKAJDSHLZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 359.41, ALogP 1.97, HBA 5, HBD 1, PSA 102.06, QED 0.9
Compound (SMILES): Cc1cc(-c2cnc3ccc(N[C@@H](C)c4ccc(F)cc4F)nn23)[nH]n1
InChIKey: SMKJDFHRUWJNRS-NSHDSACASA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human ALK expressed in HEK293 cells assessed as reduction in ALK autophosphorylation at Tyr1604 residue incubated for 60 mins by sandwich ELISA
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 354.36, ALogP 3.88, HBA 5, HBD 2, PSA 70.9, QED 0.58
Compound (SMILES): CCS(=O)(=O)c1ccc([C@@H](NC(C)=O)C(=O)Nc2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)cc1
InChIKey: HJJYGXDBXQAVQG-QGZVFWFLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of tritiated 2-(4-(ethylsulfonyl)phenyl)-N-(4-(2-(methoxymethyl)phenyl)thiophen-2-yl)acetamide from human N-(HN)6-GST-TCS-RORC LBD (258 to 518 residues) incubated for 16 hrs by scintillation proximity competition binding assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 526.46, ALogP 3.61, HBA 5, HBD 3, PSA 112.57, QED 0.48
Compound (SMILES): COc1cccc(OC)c1OCCNC[C@H]1OCCO[C@@H]1c1ccccc1
InChIKey: FIDRRYSVIRIHOV-WOJBJXKFSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Displacement of [3H]Prazosin from human recombinant alpha 1D adrenergic receptor expressed in CHO cells incubated for 30 mins by radioligand competition binding assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 373.45, ALogP 2.83, HBA 6, HBD 1, PSA 58.18, QED 0.68
Compound (SMILES): C=CCC(C#N)C1CCN(C(=O)c2cnn(-c3nn4cccc4c(=O)[nH]3)c2C)CC1
InChIKey: QGMPLAPJBZATBS-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 405.46, ALogP 2.08, HBA 7, HBD 1, PSA 112.08, QED 0.65
Compound (SMILES): C[C@@H]1CN(S(=O)(=O)c2cc(NC(=O)CN3C(=O)CNC3=O)ccc2Cl)C[C@@H]1C
InChIKey: QKIHHGPTFWWAHI-PHIMTYICSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647-labeled ligand from BRD4 BD1 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 428.9, ALogP 1.11, HBA 5, HBD 2, PSA 115.89, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)OC)C(=O)N1CCC[C@H]1c1ncc(-c2cc3c4c(c2)OCc2cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)[C@@H](C)CC)[nH]5)cc(c2-4)OC3)[nH]1
InChIKey: HYLMTEUPACFZBJ-BIKBBBLQSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A L31M mutant in HCV genotype 2a JFH1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 822.96, ALogP 6.79, HBA 10, HBD 4, PSA 193.1, QED 0.12
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCc2ccc(C(=O)O)cc2)C[C@H](NCc2ccc(N(CC)CC)cc2)[C@H]1NC(C)=O
InChIKey: DQAAOMURCXVKGJ-OJDZSJEKSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of influenza A virus (A/Anhui/1/2005(H5N1)) Neuraminidase N1 H274Y mutant in using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 578.75, ALogP 4.41, HBA 6, HBD 4, PSA 120, QED 0.25
Compound (SMILES): Cl.Fc1ccccc1OCc1cc(OC[C@@H]2CCCN2)no1
InChIKey: PXHVNZHGXQZQHV-MERQFXBCSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Displacement of [3H]-WIN35428 from human DAT expressed in HEK293 cells measured after 30 mins
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 292.31, ALogP 2.52, HBA 5, HBD 1, PSA 56.52, QED 0.89
Compound (SMILES): NS(=O)(=O)NCc1nnc(C(=O)c2nc3cc(F)c(-c4ccc(C(=O)N5CCOCC5)c(F)c4)cc3s2)o1
InChIKey: KBNKBFXGKWROGE-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of EL in human HT1080 cells using D31-POPC-HDL as substrate incubated for 2 hrs in presence of human serum by LC/MS analysis
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 564.55, ALogP 1.62, HBA 10, HBD 2, PSA 170.61, QED 0.32
Compound (SMILES): CC1(C)CC(NC(=O)c2ccc(Nc3ncc(F)c(Nc4ccc(C(=O)Nc5ccccc5Cl)cc4)n3)cc2)CC(C)(C)N1[O]
InChIKey: SLYMRFHIVVKAEL-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A phosphorylation at Thr288 residue in human HeLa cells after 12 hrs by ELISA
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 631.13, ALogP 7.11, HBA 7, HBD 4, PSA 131.18, QED 0.16
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(NS(=O)(=O)c2cccnc2)c2cn[nH]c2c1
InChIKey: OFYNYVHMYAQAHK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human His-tagged JAK2 expressed in baculovirus using biotin-synthetic peptide as substrate after 20 mins by HTRF assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 412.45, ALogP 3.83, HBA 5, HBD 3, PSA 107.97, QED 0.46
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cc(COCC)cc(S(N)(=O)=O)c2)n1)[C@@H](CC)N(O)C=O
InChIKey: DLMIHDLAJGAHHF-RCZVLFRGSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 577.7, ALogP 2.56, HBA 8, HBD 4, PSA 181.02, QED 0.07
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccnc(-c2ccccc2)n1
InChIKey: ABHWJOXUPLKNJM-QGZVFWFLSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 413.48, ALogP 1.99, HBA 6, HBD 3, PSA 124.52, QED 0.16
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C(F)(F)F)cc2)C(=O)CN(Cc2c(F)c(F)c(F)c(F)c2F)S(=O)(=O)c2ccc(F)cc2)cc1
InChIKey: XDQSFVRYGKGMFJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 expressed in SF9 baculoviral system using FAM-labeled acetylated peptide as substrate by EMSA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 705.56, ALogP 6.08, HBA 5, HBD 2, PSA 107.02, QED 0.07
Compound (SMILES): C=CC(=O)Nc1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)ncc1-c1ccc(OC)nc1
InChIKey: WAEYWKWSXPSJHE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human His-tagged FGFR1 (308 to 731 residues) expressed in baculovirus expression system using tyrosine-4 peptide as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 536.64, ALogP 4.91, HBA 9, HBD 3, PSA 107.54, QED 0.26
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cncc(-c2ccc(P(=O)(O)O)c(OCC)c2)n1)[C@@H](CC)N(O)C=O
InChIKey: YOPWKNLEPGIXMZ-WIYYLYMNSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 565.56, ALogP 1.97, HBA 8, HBD 5, PSA 191.28, QED 0.05
Compound (SMILES): Nc1cc(CNC(=O)[C@@H]2CCCN2C(=O)[C@H](N)Cc2ccccc2)ccn1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: GEJSXHIYLBBIKS-LWPKXAGOSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Bos taurus
UniProt: P00760
Assay: Binding affinity to bovine beta-trypsin in phosphate/HEPES/Tricine/Tris buffer by ITC method
Measurement: Kd = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 367.45, ALogP 0.84, HBA 5, HBD 3, PSA 114.34, QED 0.7
Compound (SMILES): Cl.Cl.N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCCCCCNc1c2c(nc3cc(Cl)ccc13)CCCC2
InChIKey: URGIIUXIZICBQS-ASMAMLKCSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62600
Assay: Inhibition of nNOS in Wistar rat cortical homogenates incubated for 30 mins
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 504.08, ALogP 5.52, HBA 4, HBD 4, PSA 95.83, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)CC(C)CN(Cc2ccc(C(=O)O)o2)C3=O)cc(C)c1Cl
InChIKey: BXCVCPISNXGTQU-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 677.63, ALogP 8.18, HBA 7, HBD 1, PSA 102.73, QED 0.16
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccccc2)C(=O)CN(Cc2c(F)c(F)c(F)c(F)c2F)S(=O)(=O)c2ccc(F)cc2)cc1
InChIKey: RRXUMIHVJXZUFJ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 3 hrs by electrophoretic mobility shift assay
Measurement: IC50 = 90.6 nM (pChEMBL 7.039999961853027)
Descriptors: MW 637.56, ALogP 5.06, HBA 5, HBD 2, PSA 107.02, QED 0.08
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)N[C@@H](C(=O)O)C(C)C)C[C@H](NCc2ccc(N3CCCC3)cc2)[C@H]1NC(C)=O
InChIKey: HHWOPYJJCIJJQS-KUXCXQDQSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of influenza A virus (A/Anhui/1/2005(H5N1)) Neuraminidase N1 H274Y mutant in using 4-MUNANA as substrate preincubated for 10 mins followed by substrate addition and measured after 40 mins by fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 542.72, ALogP 3.38, HBA 6, HBD 4, PSA 120, QED 0.3
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](Cc2ccccc2)N=[N+]=[N-])C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]2(C)CO2)cc1
InChIKey: FNYVHRVKMVFVPO-ICQXYBJGSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of catalytic activity of constitutive proteasome 20s subunit beta2 in human Raji cells incubated for 1 hr by BODIPY(FL)-LU-112 probe based competitive activity based protein profiling assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 668.8, ALogP 4.26, HBA 7, HBD 3, PSA 174.89, QED 0.08
Compound (SMILES): OCc1cccn2c(C3(c4ccc(Cl)cc4)CC3)nnc12
InChIKey: QHHUTGUKHPGDBA-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of recombinant human 11beta-HSD1 expressed in HEK293 cell microsomes using [3H]cortisone as substrate after 4 hrs by homogeneous immuno-radiometric scintillation proximity assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 299.76, ALogP 2.95, HBA 4, HBD 1, PSA 50.42, QED 0.81
Compound (SMILES): CC(C)Nc1nc(Nc2cccc(F)c2)nc(-c2nc(C(F)(F)F)cs2)n1
InChIKey: HUUVMRRBTGPHRV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant in human U87MG cells assessed as reduction in 2-HG levels after 48 hrs by celltiter glo reagent-based assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 398.39, ALogP 4.72, HBA 7, HBD 2, PSA 75.62, QED 0.61
Compound (SMILES): O=C(NCC(=O)N1CCC(Cc2nc(C3CC3)no2)CC1)c1ccccc1
InChIKey: KEAGXERJQJPUCK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Binding affinity to His-tagged human LDHA in absence of NAD+ by isothermal titration calorimetry
Measurement: Kd = 43200 nM (pChEMBL 4.369999885559082)
Descriptors: MW 368.44, ALogP 2.16, HBA 5, HBD 1, PSA 88.33, QED 0.84
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccc(-c3cnc4nccn4c3)cc2F)C1
InChIKey: RPBBEGTXSLMRET-CQSZACIVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 350.36, ALogP 1.82, HBA 6, HBD 1, PSA 86.32, QED 0.73
Compound (SMILES): CC1CCCc2c(-c3ccccc3)nc(N)nc21
InChIKey: KBWMQRHXUDLDNF-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at recombinant human Gs-coupled H2 receptor expressed in HEK293T cells assessed as inhibition of forskolin-stimulated cAMP accumulation preincubated for 10 to 15 followed by forskolin-stimulation by Glo-sensor assay
Measurement: EC50 = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 239.32, ALogP 3.17, HBA 3, HBD 1, PSA 51.8, QED 0.83
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1ccc(OS(=O)(=O)O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1cccc2ccccc12)C(N)=O
InChIKey: IUSFSIDKWAJIKQ-CGOQMMCRSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Agonist activity at human CCK1R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay
Measurement: EC50 = 0.1622 nM (pChEMBL 9.789999961853027)
Descriptors: MW 1873.15
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1c(C)ccnc1C
InChIKey: QQSGVLILNAWGIU-FPNNDXFKSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 765.82, ALogP 4.02, HBA 11, HBD 5, PSA 243.77, QED 0.04
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN3Cc2cccc(Br)c2)n(C)c1=O
InChIKey: CRNMGLPHBFEMDH-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB603 from recombinant human adenosine A2b receptor expressed in HEK293 cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 390.24, ALogP 1.22, HBA 7, HBD 0, PSA 65.06, QED 0.66
Compound (SMILES): Cc1c(C(=O)N2CCC(OCC(F)(F)F)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: ASYGPIQTBPKWOH-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 424.38, ALogP 1.7, HBA 7, HBD 1, PSA 97.52, QED 0.69
Compound (SMILES): Cc1ncnc2c1ccn2[C@@H]1C[C@H](Oc2cc(C(F)F)c(F)c3c2CNCC3)[C@@H](O)[C@H]1O
InChIKey: HBGHQRGHFNTSDP-DJABAAGCSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 in human A427 cells assessed as reduction in sDMA level incubated for 72 hrs by liquid scintillation analysis
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 448.45, ALogP 2.58, HBA 7, HBD 3, PSA 92.43, QED 0.57
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cc(OC)cc(OC)c2)o1
InChIKey: NTADQKUJASWQIZ-MRXNPFEDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 461.52, ALogP 2.81, HBA 7, HBD 3, PSA 130.34, QED 0.13
Compound (SMILES): O=C(Nc1ccc(OC(F)F)nc1)NC1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: LTNOPYMLPTUXSM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]astemizole from human ERG measured after 60 mins by scintillation counting
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 625.47, ALogP 6.58, HBA 8, HBD 2, PSA 110.09, QED 0.21
Compound (SMILES): NS(=O)(=O)c1ccc(-n2ncc(NCc3ccccc3)c(Cl)c2=O)cc1
InChIKey: OUJUAIANBYBSLD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic CA 2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 390.85, ALogP 2.15, HBA 6, HBD 2, PSA 107.08, QED 0.69
Compound (SMILES): Nc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: USBWTMHHGYJVJX-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 253.7 nM (pChEMBL 6.599999904632568)
Descriptors: MW 318.34, ALogP 1.71, HBA 7, HBD 2, PSA 104.23, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nc(C3CC3)no2)cc1
InChIKey: QRGXANRYPQYSJU-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to human recombinant CA1 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 27.4 nM (pChEMBL 7.559999942779541)
Descriptors: MW 265.29, ALogP 1.26, HBA 5, HBD 1, PSA 99.08, QED 0.9
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn(C)c3C(=O)NOC(C)(C)C)cc2)[nH]n1
InChIKey: BMQWIMXUMVEYAP-WOJBJXKFSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of recombinant human CYP2C8 expressed in Escherichia coli using luciferin-ME as substrate by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 506.61, ALogP 4.21, HBA 7, HBD 3, PSA 131, QED 0.33