lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccc(N3CCOCC3)cc2)C1
InChIKey: OBGCJFBRMFAJCM-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 300.36, ALogP 0.81, HBA 5, HBD 1, PSA 68.6, QED 0.84
Compound (SMILES): Cc1nn(CCOCCOCCNC(=O)OC(C)(C)C)cc1-c1ccc2cc(CCN3CCC[C@H]3C)ccc2n1
InChIKey: AFOHSYLABSAJBV-HSZRJFAPSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Antagonist activity at human H3 receptor expressed in CHOK1 cells incubated for 10 mins by HTRF assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 551.73, ALogP 4.99, HBA 8, HBD 1, PSA 90.74, QED 0.3
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)N2CCOCC2)c(Sc2ccccc2)cc1Cl
InChIKey: KCHKZYKQHJUTFV-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human carbonic anhydrase 5b expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 412.92, ALogP 2.61, HBA 5, HBD 1, PSA 89.7, QED 0.83
Compound (SMILES): COC(=O)c1ccc(CNC(=O)c2ccc3nc(N)sc3c2)cc1
InChIKey: ZQLODWMGQOHBQR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 341.39, ALogP 2.6, HBA 6, HBD 2, PSA 94.31, QED 0.71
Compound (SMILES): Cc1cc(-c2cc(NS(C)(=O)=O)ccc2Cc2ccccc2)n2cc[nH]c(=O)c12
InChIKey: GZUIXWVKCXTCGT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of SGRG-K(Ac)-GG-K(Ac)-GLG-K(Ac)-GGA-K(Ac)-RHRKVGG-K-Biotin binding to N-terminal His6-tagged BRD4 bromodomain 1 (49 to 170 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by biotin-labeled H4 peptide addition and measured after 10 mins by Alphascreen assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 407.5, ALogP 3.57, HBA 4, HBD 2, PSA 83.44, QED 0.53
Compound (SMILES): Cc1c(C(=O)N2CC(F)(F)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: HLMOLSDAIJEXBO-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 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 334.29, ALogP 0.61, HBA 6, HBD 1, PSA 88.29, QED 0.74
Compound (SMILES): CCOc1ccc(Oc2ccc(-c3cnc(-c4cc(O)c(O)c(Br)c4Br)o3)cc2)cc1
InChIKey: MOHJRHPKFDUKBW-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of SHP1 (unknown origin)
Measurement: IC50 > 36800 nM (pChEMBL 4.434000015258789)
Descriptors: MW 547.2, ALogP 7.14, HBA 6, HBD 2, PSA 84.95, QED 0.25
Compound (SMILES): CN(C)CCCOc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCN(S(C)(=O)=O)CC2)n1
InChIKey: MOLHPKWQCRPJNV-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal p110alpha/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 83 nM (pChEMBL 7.079999923706055)
Descriptors: MW 595.68, ALogP 1.4, HBA 12, HBD 0, PSA 122.05, QED 0.32
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1Cc1cc(-c2ccccc2)no1
InChIKey: NYRYRMYJRLUEEJ-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 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 50.9 nM (pChEMBL 7.289999961853027)
Descriptors: MW 340.36, ALogP 2.69, HBA 5, HBD 0, PSA 80.48, QED 0.73
Compound (SMILES): COc1ccc(-n2nnnc2SCC(=O)Nc2cc(C(C)(C)C)nn2-c2ccccc2)cc1
InChIKey: WRFGNTGMUZETOV-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of recombinant full length human TrkB transfected in CHO cells assessed as inhibition of NGF-stimulated calcium influx by FLIPR assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 463.57, ALogP 3.88, HBA 9, HBD 1, PSA 99.75, QED 0.42
Compound (SMILES): CCc1cc(CN2CCN(C)CC2)cc(NC(=O)c2cccc(C#Cc3cnc4cnc(-c5ccc(N)cc5)cn34)c2C)c1
InChIKey: GLRHZMRFCNDDIZ-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of recombinant human His-tagged TrkC cytoplasmic domain (510 to 825 residues) expressed in baculovirus using tyr 01 as substrate incubated for 1 hr by Z'-Lyte assay
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 583.74, ALogP 5.25, HBA 7, HBD 2, PSA 91.79, QED 0.21
Compound (SMILES): Cc1cc(C)c(CNc2nc(N[C@@H](C)[C@@H](C)O)nc3c2ncn3C(C)C)cn1
InChIKey: PFRMQZGBTCACGO-LSDHHAIUSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 383.5, ALogP 3.21, HBA 8, HBD 3, PSA 100.78, QED 0.58
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(CCOc2ccccc2)C3)n(C)c1=O
InChIKey: SKDISFHJNUKJHY-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX from A2A receptor in rat brain striatum membranes measured after 30 mins by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 355.4, ALogP 0.33, HBA 8, HBD 0, PSA 74.29, QED 0.67
Compound (SMILES): O=C(NO)c1ccc(CN2c3ccccc3C[C@@H]3CCCCC[C@H]32)cc1
InChIKey: FGMWOTOTJBZLHH-AZUAARDMSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4 using fluorogenic HDAC substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 350.46, ALogP 4.32, HBA 3, HBD 2, PSA 52.57, QED 0.64
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2ccc(F)cc2Cl)n(C)c1=O
InChIKey: WOJUZFMWWKKVDV-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 377.81, ALogP 1.64, HBA 7, HBD 0, PSA 65.06, QED 0.68
Compound (SMILES): COc1cc2nn(CC(=O)N3CCN(C)CC3)cc2cc1NC(=O)c1cccc(C(F)(F)F)n1
InChIKey: XWLIUWSVNWAFDJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human liver microsomes CYP1A2 using phenacetin as substrate by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 476.46, ALogP 2.49, HBA 7, HBD 1, PSA 92.59, QED 0.61
Compound (SMILES): CS(=O)(=O)NC1CCN(Cc2cc3nc(-c4cccc5[nH]ncc45)nc(N4CCOCC4)c3s2)C1
InChIKey: FMZIIRAIYJNYCS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 513.65, ALogP 2.19, HBA 9, HBD 2, PSA 116.34, QED 0.4
Compound (SMILES): CNc1cc(Nc2cccn(-c3cccc(F)n3)c2=O)nn2c(C(=O)NC3CC3)cnc12
InChIKey: QXGWTKISSCULND-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in human whole blood assessed as decrease in IFNalpha/IL2-induced STAT phosphorylation preincubated for 1 hr followed by IFNalpha/IL2 stimulation and measured after 15 mins by fluorescence assay
Measurement: Ki = 371 nM (pChEMBL 6.429999828338623)
Descriptors: MW 434.44, ALogP 2.09, HBA 9, HBD 3, PSA 118.24, QED 0.4
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(F)c(-c2ccc(C(=O)O)c(OCC)c2)n1)[C@@H](CC)N(O)C=O
InChIKey: PILJTUKRNXPOTA-XMSQKQJNSA-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 546.6, ALogP 3.61, HBA 7, HBD 4, PSA 158.16, QED 0.08
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O)C(C)C
InChIKey: GMZNLVJBFAAQFP-SFIUMABJSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene assessed as inhibition of NDP-MSH-induced cAMP accumulation up to 10 uM after 6 hrs by beta-galactosidase reporter gene assay
Measurement: Kd = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 718.59, ALogP 0.67, HBA 6, HBD 5, PSA 193.79, QED 0.19
Compound (SMILES): Cc1cc(-c2cc(NS(C)(=O)=O)ccc2Oc2ccccn2)n2cc[nH]c(=O)c12
InChIKey: TWGPDPFDUYJNSJ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of SGRG-K(Ac)-GG-K(Ac)-GLG-K(Ac)-GGA-K(Ac)-RHRKVGG-K-Biotin binding to N-terminal His6-tagged BRD4 bromodomain 1 (49 to 170 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by biotin-labeled H4 peptide addition and measured after 10 mins by Alphascreen assay
Measurement: IC50 = 27.3 nM (pChEMBL 7.559999942779541)
Descriptors: MW 410.46, ALogP 3.16, HBA 6, HBD 2, PSA 105.56, QED 0.53
Compound (SMILES): COC(=O)N[C@H](C(=O)N1[C@H](c2ncc(-c3ccc4c(c3)-c3ccc(-c5cnc([C@@H]6C[C@@H]7CCC[C@@H]7N6C(=O)[C@@H](NC(=O)OC)[C@H](C)O)[nH]5)cc3-4)[nH]2)C[C@@H]2CCC[C@@H]21)[C@H](C)O
InChIKey: QHOGHQABGWPWRF-SJCGZLIJSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2a con infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 35.08 nM (pChEMBL 7.460000038146973)
Descriptors: MW 820.95, ALogP 5.21, HBA 10, HBD 6, PSA 215.1, QED 0.11
Compound (SMILES): CCn1c(CCc2ccc(NC(=O)Nc3cccc(C(C)=O)c3)cc2)nc2ccccc21
InChIKey: XOAGHLARLVOCHO-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant human ATP-activated TRKA kinase domain (441 to 796 residues) expressed in baculovirus expression system preincubated with enzyme/ATP mixture for 20 mins followed by TK substrate-biotin addition followed by further incubation for 15 mins in presence of ATP by HTRF assay
Measurement: IC50 = 107.4 nM (pChEMBL 6.96999979019165)
Descriptors: MW 426.52, ALogP 5.69, HBA 4, HBD 2, PSA 76.02, QED 0.37
Compound (SMILES): COCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: HBFALEBDZRZUTP-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 438.96, ALogP 1.47, HBA 6, HBD 2, PSA 132.63, QED 0.62
Compound (SMILES): O=C(NCc1ncccc1F)c1coc(CCNCCc2nc3c(F)cc(F)cc3[nH]2)n1
InChIKey: SUSSRYWHSBXPST-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 444.42, ALogP 2.67, HBA 6, HBD 3, PSA 108.73, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(OP(=O)(Oc2ccc(S(N)(=O)=O)cc2)c2ccccc2)cc1
InChIKey: IADLCVBIHKTGOW-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant carbonic anhydrase 4 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 360.3 nM (pChEMBL 6.440000057220459)
Descriptors: MW 468.45, ALogP 1.96, HBA 7, HBD 2, PSA 155.85, QED 0.5
Compound (SMILES): FC(F)(F)c1ccc2c(c1)C1=NCCCN1C(=S)S2
InChIKey: SRNBQQLYBCYORW-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC3 (1 to 428 residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 302.35, ALogP 3.55, HBA 3, HBD 0, PSA 15.6, QED 0.68
Compound (SMILES): Cc1cc(=O)n2c(C(=O)N/N=C/c3ccc(N4CCN(C)CC4)cc3)nn(-c3ccc(S(N)(=O)=O)cc3)c2n1
InChIKey: KMLUCGSIPFSIST-JVWAILMASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase-9 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 549.62, ALogP 0.35, HBA 11, HBD 2, PSA 160.29, QED 0.26
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCCN3Cc2cccc(Br)c2)n(C)c1=O
InChIKey: ZVQLGURDERQWHN-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]CCPA from rat adenosine A2a receptor
Measurement: Ki = 41000 nM (pChEMBL 4.389999866485596)
Descriptors: MW 418.3, ALogP 2, HBA 7, HBD 0, PSA 65.06, QED 0.64
Compound (SMILES): O=c1[nH]c(N2CCC3(CC2)CN(CCO)c2ccccc23)nc2c1CCCC2
InChIKey: LZWJZQDOBCFTSD-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human PARP1 expressed in Escherichia coli assessed as reduction in auto-PARylation using histone as substrate measured after 45 mins in presence of biotinylated-NAD+ by ELISA
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 380.49, ALogP 2, HBA 5, HBD 2, PSA 72.46, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)n2[nH]c(=O)c3c(F)cccc3c2=O)cc1
InChIKey: MMBIDJYHISXNSU-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 using 4-nitrophenylacetate as substrate by spectrophotometry based esterase assay
Measurement: IC50 = 10.14 nM (pChEMBL 7.989999771118164)
Descriptors: MW 363.33, ALogP 0.16, HBA 6, HBD 2, PSA 132.09, QED 0.67
Compound (SMILES): N#CN1CCC(NC(=O)c2ccnc(N3CCc4ccccc4C3)c2)C1
InChIKey: GPFFVTDRKDVTRS-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 347.42, ALogP 1.93, HBA 5, HBD 1, PSA 72.26, QED 0.86
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)O
InChIKey: UDCBKDXOJWQLIW-ADUILBNFSA-N
Target: Disabled homolog 2-interacting protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWQ8
Assay: Binding affinity to human Dab2 DH domain (33 to 191 residues) expressed in Escherichia coli BL21 (DE3) RIL cells in phosphate buffer by ITC assay
Measurement: Kd = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 1995.08
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)/C(Cc2ccc(O)c(Br)c2)=N/O)cc1
InChIKey: FRCCNEXCBPNWQH-RCCKNPSSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 expressed in Escherichia coli GOLD BL21 (DE3) by stopped-flow CO2 hydration assay
Measurement: Ki = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 456.32, ALogP 1.53, HBA 6, HBD 4, PSA 142.08, QED 0.28
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](N)CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: MFKLABRPOAGSME-DXGDDUEYSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 962.08, ALogP -2.14, HBA 13, HBD 14, PSA 403.26, QED 0.02
Compound (SMILES): CC1(C)COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@H]1COCCN21
InChIKey: PMJQDXRPCAZOAR-AWEZNQCLSA-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 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 382.47, ALogP 1.5, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Cc1nc2sc(C(=O)NC[C@@H](C)c3ccc(N4CC5CCC(C4)N5)c(F)c3)c(N)c2cc1F
InChIKey: HPKDXUMDAFPRKD-UWTIGNOOSA-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 471.58, ALogP 3.94, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): CC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F
InChIKey: PJMRFVQJHKBEOL-OCBLZGDUSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 760.94, ALogP 2.72, HBA 8, HBD 6, PSA 212.14, QED 0.12
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC
InChIKey: QYURRUOYMLPRIT-RKTHYPFQSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 3772.31
Compound (SMILES): O=C(NCCO)[C@@]12C[C@@H]1[C@@H](n1cnc3c(N[C@H]4C[C@H]5CC[C@@H]4C5)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: AWXOZEOHMQXOAJ-NQNJJODYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]2-[p-(2-carboxyethyl)phenylethylamino]-5-N-ethylcarboxamidoadenosine from human A2A adenosine receptor expressed in HEK293 cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 462.94, ALogP 0.47, HBA 9, HBD 5, PSA 145.42, QED 0.39
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)Nc2ccc(/N=C3\C(=O)N(Cc4cccc(F)c4)c4ccccc43)cc2)cc1
InChIKey: JGTCHDMKFMGUFH-ZXPTYKNPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped flow CO2 hydration assay
Measurement: Ki = 54.5 nM (pChEMBL 7.260000228881836)
Descriptors: MW 543.58, ALogP 4.78, HBA 5, HBD 3, PSA 133.96, QED 0.32
Compound (SMILES): O=C(NO)c1ccc(Cn2c(=O)n(CCc3ccccc3)c(=O)c3ccc(F)cc32)cc1
InChIKey: YMUAAICTDYRNRC-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human full-length recombinant HDAC8 expressed in baculovirus infected Sf9 insect cells using fluorogenic peptide RHKAcKAc as substrate after 2 hrs
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 433.44, ALogP 2.71, HBA 6, HBD 2, PSA 93.33, QED 0.36
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-OAHLLOKOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at C-terminal RLuc8-fused D2 long receptor (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): CC(=O)N1CCN(c2ccc(CN3[C@@H](C)CC[C@H](c4ccccc4)S3(=O)=O)c(F)c2)CC1
InChIKey: WLCIIQPUMOJJOF-MHECFPHRSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at GAL4-fused human RORb expressed in HEK293 cells assessed as activation of basal transcriptional activity by dual-glo luciferase reporter gene assay
Measurement: EC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 459.59, ALogP 3.55, HBA 4, HBD 0, PSA 60.93, QED 0.7
Compound (SMILES): CN(C)C(=O)c1ccc(N(CC2CCCCC2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: ZBCASIFBVICMSH-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDHK1 (unknown origin) by radiometric biochemical kinase assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 396.49, ALogP 4.03, HBA 4, HBD 2, PSA 81.08, QED 0.8
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(C(=O)O)c2O)o1)[C@@H](CC)N(O)C=O
InChIKey: MZINFLMNYYWSDH-YLJYHZDGSA-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 533.58, ALogP 3.38, HBA 8, HBD 5, PSA 178.64, QED 0.07
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc2c(Oc3ccc(Cl)c(C(F)(F)F)c3)nccc2c1
InChIKey: TWPBQQCOMOTZRM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in HEK293 cells after 45 mins by scintillation counting analysis
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.82, ALogP 4.39, HBA 5, HBD 1, PSA 85.36, QED 0.64
Compound (SMILES): COCCN1CCN(c2ccc(CCNC(=O)c3sc4nc(C)ccc4c3N)cc2)CC1
InChIKey: COFBVZDSYGLJJE-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 453.61, ALogP 2.93, HBA 7, HBD 2, PSA 83.72, QED 0.55
Compound (SMILES): COc1ccccc1N1CCN(CCCn2nnnc2C(c2ccccc2)c2ccccc2)CC1
InChIKey: HVOHLUNNYMNOQY-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of [3H]-5-norepinephrine reuptake in human NET expressed in HEK293 cells by liquid scintillation counting method
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 468.61, ALogP 4.07, HBA 7, HBD 0, PSA 59.31, QED 0.37
Compound (SMILES): C=C=C[C@H]1CC[C@H](c2cc(=O)c3ccc4ccccc4c3o2)CC1
InChIKey: MEXPNMGWMKCEES-JCNLHEQBSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 using 7-ethoxyresorufin as substrate after 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 36.4 nM (pChEMBL 7.440000057220459)
Descriptors: MW 316.4, ALogP 5.56, HBA 2, HBD 0, PSA 30.21, QED 0.46
Compound (SMILES): CC1(C)CCC(CN2CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NCCCCCC(=O)NO)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)=C(c2ccc(Cl)cc2)C1
InChIKey: WKZSQFCCBXZCQS-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of FAM-Bid peptide binding to Bcl2 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 899.47, ALogP 8.3, HBA 12, HBD 5, PSA 212.13, QED 0.03
Compound (SMILES): COc1ccccc1OCCNCC[C@@H]1CO[C@H](C(c2ccccc2)c2ccccc2)O1.O=C(O)C(=O)O
InChIKey: JLDHKWRQWBBSLH-VFFVIGNKSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Displacement of [3H] prazosin from human cloned adrenoceptor alpha 1D expressed in CHO cell membrane incubated for 30 mins by liquid scintillation counter
Measurement: Ki = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 433.55, ALogP 4.63, HBA 5, HBD 1, PSA 48.95, QED 0.45
Compound (SMILES): Cl.N=C(N)c1ccc(C2Cc3ccccc3B(O)O2)cc1OCc1cccnc1
InChIKey: KRVQMQVYRRLIIY-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human C-terminal 6-His-tagged KLKB1 (G20-A638 residues) expressed in mouse NS0 cells using PFR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 373.22
Compound (SMILES): Cc1nc(C(C)(C)C)sc1C(=O)NC12CC3CC(CC(C3)C1)C2
InChIKey: KZPAMVWVULWRAC-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal Flag epitope tagged CB2 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 = 3981 nM (pChEMBL 5.400000095367432)
Descriptors: MW 332.51, ALogP 4.45, HBA 3, HBD 1, PSA 41.99, QED 0.87
Compound (SMILES): CCCN1CCN(c2cccc3c2CCN3S(=O)(=O)c2ccccc2)CC1
InChIKey: VEMOQUROGJYIHS-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 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 385.53, ALogP 2.97, HBA 4, HBD 0, PSA 43.86, QED 0.79
Compound (SMILES): N#CN1CC[C@@H](NC(=O)N2CCC(c3ccccn3)C2)C1
InChIKey: OZVKDRROSKNCJC-ZGTCLIOFSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 285.35, ALogP 1.14, HBA 4, HBD 1, PSA 72.26, QED 0.83
Compound (SMILES): CC(C)C[C@H](N[C@@H](c1ccc(-c2ccccc2)cc1)C(F)(F)F)C(=O)NC1(C#N)CC1
InChIKey: VVENSUKHMNEUHS-SFTDATJTSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain assessed as inhibitor constant using Z-Phe-Arg-7-amido-4-methylcoumarin as substrate preincubated for 2 mins followed by susbtrate addition by fluorescence based analysis
Measurement: Ki = 2488.48 nM (pChEMBL 5.599999904632568)
Descriptors: MW 429.49, ALogP 5.13, HBA 3, HBD 2, PSA 64.92, QED 0.61
Compound (SMILES): Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1COc1ccc2c(c1)OC[C@H]2CC(=O)O
InChIKey: YBBZJHLFUPKHJD-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of GAL4-fused human PPARgamma LBD expressed in HEK293 cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.45, ALogP 5.67, HBA 5, HBD 1, PSA 68.65, QED 0.53
Compound (SMILES): COCCS(=O)(=O)Nc1cc(-c2cc3c(c(OC[C@H]4CN(C5COC5)CCO4)c2)COC3)cnc1OC
InChIKey: ZWPJBXLFZFLGMV-OAQYLSRUSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 535.62, ALogP 1.65, HBA 10, HBD 1, PSA 117.68, QED 0.46
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(O)cc(OCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: WSUGCVXJWUXTPE-NHCUHLMSSA-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 489.57, ALogP 3.68, HBA 7, HBD 4, PSA 141.34, QED 0.1
Compound (SMILES): Cn1ccnc1CN1CCC2(CC1)C(=O)N(c1ccc(-c3ccccc3)cc1)C(=O)N2c1ncccn1
InChIKey: XFDLXPQRAGQNLN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of KDM4A (unknown origin) using H3 K9Me3 (1 to 15 residues) as substrate
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 493.57, ALogP 3.89, HBA 7, HBD 0, PSA 87.46, QED 0.39
Compound (SMILES): O=C(O)C1CCN(c2nn(C(=O)c3c(Cl)cccc3C(F)(F)F)c3cccc(F)c23)CC1
InChIKey: DEUVSXRRKCXTAG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Biological Assay: The compounds of the invention inhibit RORgammaT activity. Activation of RORgammaT activity can be measured using, e.g., biochemical TR-FRET assay. In such an assay, interaction of cofactor-derived peptides with human RORgammaT-Ligand Binding Domain (LBD) can be measured. The TR-FRET technique is a sensitive biochemical proximity assay that will give information concerning the interaction of a ligand with the LBD, in the presence of cofactor-derived peptides (Zhou et al., Methods 25:54-61, 2001).To identify novel antagonists of RORgammaT, an assay was developed which employs the interaction of RORgammaT with its co-activator peptide SRC1_2. This peptide mimics the recruitment of co-activators to RORgammaT through its interaction with the LXXLL (SEQ ID NO:1) (e.g., NR box) motifs (Xie et al., J. Immunol. 175: 3800-09, 2005; Kurebayashi et al., Biochem. Biophys. Res. Commun. 315: 919-27, 2004; Jin et al., Mol. Endocrinology 24:923-29, 2010). The RORγ-Ligand Binding Domain TR-FRET Assay was run according to the following protocol.HIS-tagged RORγ-LBD protein was expressed in SF9 cells using a baculovirus expression system. The RORγ-LBD protein was purified by glutathione sepharose chromatography. Separately, SF9 cells not expressing any recombinant protein were lysed and the lysate was added to the purified RORγ-LBD at 0.25 μl lysate (from 10,000 SF9 cells)/nM purified protein. The mixture was then diluted in assay buffer (50 mM Tris pH 7.0, 50 mM KCl, 1 mM EDTA, 0.1 mM DTT) to obtain RORγ-LBD final concentration of 3 nM in 384-well assay plate.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 469.82, ALogP 4.84, HBA 5, HBD 1, PSA 75.43, QED 0.56
Compound (SMILES): Cc1ccc2[nH]c(CNCCCc3ccncc3)cc(=O)c2c1
InChIKey: PALPPRFQCFXPCD-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand binding assay (DRD2)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 307.4, ALogP 2.95, HBA 3, HBD 2, PSA 57.78, QED 0.69
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC(=O)O)cc(C(=O)O)c2O)o1)[C@@H](CC)N(O)C=O
InChIKey: MVGYSELXXWZWIN-VQIMIIECSA-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 563.56, ALogP 2.44, HBA 9, HBD 6, PSA 215.94, QED 0.05
Compound (SMILES): O=C1NCCc2c1cccc2-c1ccccc1
InChIKey: LZDKSVWIIDLVQF-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of human PARP10 catalytic domain assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 223.28, ALogP 2.64, HBA 1, HBD 1, PSA 29.1, QED 0.79
Compound (SMILES): COc1cccc(NC(=O)Nc2ccc(C(=O)N/N=C3\C(=O)Nc4ccc(Cl)cc43)cc2)c1
InChIKey: DGDHQRAXJZJONL-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of PDGFR-beta (unknown origin) by ELISA
Measurement: IC50 = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 463.88, ALogP 4.08, HBA 5, HBD 4, PSA 120.92, QED 0.43
Compound (SMILES): COc1ccc(CN2CCC(CCC(=O)c3cc(Cl)c(N)cc3OC)CC2)cc1O
InChIKey: YWZXQPUTUAXEKS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13639
Assay: Partial agonist activity at human HA-tagged 5HT4 receptor expressed in COS7 cells assessed as induction of cAMP production measured after 10 mins by HTRF assay
Measurement: EC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 432.95, ALogP 4.52, HBA 6, HBD 2, PSA 85.02, QED 0.47
Compound (SMILES): CC(=O)N(C)C1CCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)C1
InChIKey: OONZXAFGOJTJGL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 490.63, ALogP 3.73, HBA 7, HBD 1, PSA 77.59, QED 0.46
Compound (SMILES): Cn1cc(-c2cc(C(=O)N3CC[C@@H]4CN(C#N)C[C@@H]43)ccc2F)cn1
InChIKey: KWDLHMCDAUEXPE-DYVFJYSZSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Kinetic Assay: USP30 biochemical fluorescence intensity IC50 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
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 339.37, ALogP 1.85, HBA 5, HBD 0, PSA 65.16, QED 0.78
Compound (SMILES): c1ccc(OCCNC[C@H]2OCCO[C@H]2c2ccccc2)cc1
InChIKey: ZVHRVSHMCKYIMH-MOPGFXCFSA-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): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(P(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: FVXAELMESLNQIY-FQLXRVMXSA-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 785.78, ALogP 5.86, HBA 15, HBD 3, PSA 227.7, QED 0.02
Compound (SMILES): C[C@@H](Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)C(=O)N1CC[C@H](F)C1
InChIKey: HOQGZKUBNCAZBE-MNOVXSKESA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14123
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE1C (2 to 634 residues) expressed in baculovirus infected Sf9 cells using 3H-cGMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 362.41, ALogP 1.61, HBA 6, HBD 2, PSA 95.91, QED 0.86
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: XWUPZLVRPOPXNL-IUHBMISASA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of [125I]-labeled rat amylin from human amylin receptor expressed in BHK570 cell membranes co-expressing RAMP3 incubated for 120 mins by scintillation proximity assay
Measurement: IC50 = 0.077 nM (pChEMBL 10.109999656677246)
Descriptors: MW 3519.02
Compound (SMILES): CCN1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(C)cc3)cc2)CC1.Cl.Cl
InChIKey: LNTHOAIOHNFYBD-JYOLQUMFSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to GST-tagged ERRgamma LBD (unknown origin) using fluorescein-conjugated coactivator PGC-1alpha incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 440.63, ALogP 5.87, HBA 3, HBD 1, PSA 26.71, QED 0.44
Compound (SMILES): CCOC(=O)[C@@H](C)N[P@@](=O)(CC/C=C(\C)CO)Oc1ccccc1
InChIKey: YGSLLMNEAQXTQJ-TUMROOAMSA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA
Measurement: EC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 355.37, ALogP 3.13, HBA 5, HBD 2, PSA 84.86, QED 0.38
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: HXZBCIBTOVQQKQ-YGOBJZQWSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.08 nM (pChEMBL 10.100000381469727)
Descriptors: MW 4138.64
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3CCc2ccncc2)n(C)c1=O
InChIKey: CHDFWMROKFLVMQ-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 340.39, ALogP 0.28, HBA 8, HBD 0, PSA 77.95, QED 0.68
Compound (SMILES): CC(C)(C)C#Cc1cc(N(CC(=O)N2CCOCC2)C(=O)[C@H]2CC[C@H](C)CC2)c(C(=O)O)s1
InChIKey: CJMUCUZDSIJPFR-IYARVYRRSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1a NS5B M423T mutant
Measurement: EC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 474.62, ALogP 3.86, HBA 5, HBD 1, PSA 87.15, QED 0.66
Compound (SMILES): S=C(NNc1c2c(nc3ccccc13)CCCC2)Nc1ccccc1
InChIKey: ACCSWVGAMRADDI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate pre-incubated for 20 mins before substrate addition and measured for 180 secs by spectrophotometry based Ellman's method
Measurement: IC50 = 748 nM (pChEMBL 6.130000114440918)
Descriptors: MW 348.48, ALogP 4.43, HBA 3, HBD 3, PSA 48.98, QED 0.48
Compound (SMILES): CCc1ccccc1C(=O)Nc1n[nH]c2c(C)c(F)c(C3C(C#N)=C(C)N(C)C(C)=C3C#N)cc12
InChIKey: OZFFKOSQNBBYCA-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 2843.81 nM (pChEMBL 5.550000190734863)
Descriptors: MW 468.54, ALogP 5.45, HBA 5, HBD 2, PSA 108.6, QED 0.53
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cc(OCC)cc(S(=O)(=O)O)c2)c1)[C@@H](CC)N(O)C=O
InChIKey: DZYZONWMNGRQTN-JWQCQUIFSA-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 563.67, ALogP 3.63, HBA 7, HBD 4, PSA 162.34, QED 0.06
Compound (SMILES): CCC1(CC)c2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C4CCOCC4)[nH]3)cc2Oc2cc3ccc(-c4cnc([C@@H]5CCCN5C[C@@H](NC(=O)OC)C5CCOCC5)[nH]4)cc3cc21
InChIKey: RDPYORRNCUPPGH-RPJSXHHRSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A Y93H mutant in HCV genotype 1a assessed as decrease in viral replication
Measurement: EC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 943.16, ALogP 8.93, HBA 11, HBD 4, PSA 185.26, QED 0.09