lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(C(=O)O)c2)o1
InChIKey: BRHPGJGDRPZCNS-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 489.53, ALogP 2.89, HBA 7, HBD 4, PSA 158.41, QED 0.1
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(-c4ccccc4Cl)c3)sc2n1
InChIKey: PZZNZEQAYRZGGF-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 506.08, ALogP 4.89, HBA 6, HBD 3, PSA 83.28, QED 0.35
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cccc(P(=O)(O)OC)c2)o1
InChIKey: BEAFZLZVAXIEQV-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 495.47, ALogP 2.25, HBA 7, HBD 4, PSA 158.41, QED 0.08
Compound (SMILES): CCn1ncc(-c2nc3c(N[C@H]4CCN(C(=O)C5CCOCC5)C4)ncnc3n2C)c1C
InChIKey: WFVKABQFHLSPFH-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in anti-IgM-antibody-induced phosphorylation of AKT at Ser473 residue preincubated for 20 mins followed by anti-IgM antibody stimulation and measured after 30 mins by alphascreen assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 438.54, ALogP 1.99, HBA 9, HBD 1, PSA 102.99, QED 0.65
Compound (SMILES): CCCCc1ccc(C(=O)C2CCN(C(=O)c3cc(O)ccc3F)CC2)cc1
InChIKey: NCCCUONVHAETDD-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55,940 to human CB2 receptor expressed in cell membranes after 90 mins by liquid scintillation counting
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 383.46, ALogP 4.61, HBA 3, HBD 1, PSA 57.61, QED 0.74
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cccc(S)c2)c1)[C@@H](CC)N(O)C=O
InChIKey: GIVXBPLHAOSSOJ-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 471.62, ALogP 4.27, HBA 5, HBD 4, PSA 98.74, QED 0.09
Compound (SMILES): O=C(CCCCNC(=S)Nc1ccc2c(c1)C(=O)NC2=O)NO
InChIKey: OUXTXYJFLXSRIU-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK3beta using GSM as substrate incubated for 30 mins by luminescence based assay
Measurement: IC50 = 4110 nM (pChEMBL 5.389999866485596)
Descriptors: MW 336.37, ALogP 0.53, HBA 5, HBD 5, PSA 119.56, QED 0.17
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(-c4ccc(F)cc4)c3)sc2n1
InChIKey: ZYHQFFKCTUOYBG-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 489.62, ALogP 4.38, HBA 6, HBD 3, PSA 83.28, QED 0.37
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cnc(N)nc3C3CC3)c(O)cc2Br)C1=O
InChIKey: LLNCGQQRIWORAU-WCSRMQSCSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with mock Sendai virus and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 477.34, ALogP 3.65, HBA 8, HBD 2, PSA 118.64, QED 0.63
Compound (SMILES): Cc1cc(C)c2c(N)c(C(=O)c3ccc(F)cc3F)sc2n1
InChIKey: IDVZARGAVKYUDU-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 = 3980 nM (pChEMBL 5.400000095367432)
Descriptors: MW 318.35, ALogP 4, HBA 4, HBD 1, PSA 55.98, QED 0.73
Compound (SMILES): Cc1ccc(-c2nn(-c3ccccc3)cc2C(=O)NOCc2ccccc2F)cc1
InChIKey: HVEABAGWWBLXHR-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK in human MCF7 cells
Measurement: IC50 = 15600 nM (pChEMBL 4.809999942779541)
Descriptors: MW 401.44, ALogP 4.85, HBA 4, HBD 1, PSA 56.15, QED 0.47
Compound (SMILES): O=C(O)CSc1nc(Cl)cc(Nc2cccc3c2CCCC3)n1
InChIKey: BPCUCWYWVVQEIW-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Activation of human Gal4-fused RXRgamma LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 349.84, ALogP 3.93, HBA 5, HBD 2, PSA 75.11, QED 0.48
Compound (SMILES): COc1ccc(-n2c(CC#N)nnc2N2C[C@@H]3C[C@]3(c3ccc(F)cc3Cl)C2)cn1
InChIKey: DDPIHYVFODKELW-ZSEKCTLFSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Antagonist activity at human OTR expressed in HEK293 cells assessed as decrease in calcium flux measured after 10 mins in presence of vasopressin by Fluo-4 dye based microplate reader based assay
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 424.87, ALogP 3.31, HBA 7, HBD 0, PSA 79.86, QED 0.62
Compound (SMILES): COc1ccccc1CNC[C@H]1C[C@]1(F)c1ccccc1.Cl
InChIKey: XIYFCBBJYLALPD-CLRXKPRGSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant human 5HT2A receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 285.36, ALogP 3.67, HBA 2, HBD 1, PSA 21.26, QED 0.87
Compound (SMILES): FC(F)(F)c1ccc(/C=N/C2CCN(Cc3ccccc3)CC2)cc1
InChIKey: AXJYQEFCPXMBGY-ZVHZXABRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 using as 7-Methoxycoumarin-4-acetyl-[Asn670, Leu671]-Amyloid beta/A4 precursor protein 770 fragment 667-676-(2,4-dinitrophenyl) Lys-Arg-Arg amide trifluoroacetate salt as substrate incubated for 2 hrs by FRET based florescence assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 346.4, ALogP 4.79, HBA 2, HBD 0, PSA 15.6, QED 0.73
Compound (SMILES): O=C(c1ccccc1)N1CCc2c([nH]c3ccccc23)C1c1ccc(Br)cc1
InChIKey: ZVLRLPQCUOHCMB-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of human ABCG2 expressed in baculovirus infected Sf9 cell membrane assessed as inhibition of vanadate sensitive quercetin-stimulated ATPase activity after 20 mins by colorimetric method
Measurement: IC50 = 863 nM (pChEMBL 6.059999942779541)
Descriptors: MW 431.33, ALogP 5.72, HBA 1, HBD 1, PSA 36.1, QED 0.43
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(Cl)c2)n1)[C@@H](CC)N(O)C=O
InChIKey: NPBCILDTXSXRMM-VEXUSMLFSA-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 634.09, ALogP 2.69, HBA 8, HBD 6, PSA 215.33, QED 0.05
Compound (SMILES): Cc1c(C(=O)N2CC3(CN(CC(F)(F)F)C3)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: XNDXQCKAVJWXGF-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 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 421.38, ALogP 0.84, HBA 7, HBD 1, PSA 91.53, QED 0.68
Compound (SMILES): NC(=O)c1cccc2c1O/C(=C\c1ccc(C(=O)N3CCn4c(nnc4C4CC4)C3)cc1)C2=O
InChIKey: JJCAYWVTBMMQMQ-UNOMPAQXSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 455.47, ALogP 2.53, HBA 7, HBD 1, PSA 120.41, QED 0.6
Compound (SMILES): O=C(NCc1ncccc1F)c1csc(CCN(CCc2nc3ccccc3[nH]2)CCc2nc3ccccc3[nH]2)n1
InChIKey: MHHORLBKGYNPFZ-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 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 568.68, ALogP 4.69, HBA 7, HBD 3, PSA 115.48, QED 0.2
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2cc3c4c(c2)OCc2cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)[C@@H](C)OC)[nH]5)cc(c2-4)OC3)[nH]1)C(C)C
InChIKey: WZEUKUCQPGSKAK-HDGYKJARSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2a JFH1 (L31) infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.01 nM (pChEMBL 11)
Descriptors: MW 810.91, ALogP 5.39, HBA 11, HBD 4, PSA 202.33, QED 0.15
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCc1cn(-c2ccccc2)nn1
InChIKey: GPRREFHLBPUWFY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human N-terminal GST-tagged EGFR kinase domain (696 to end residues) expressed in baculovirus infected sf21 cells using poly(Glu, Tyr) 4:1 as substrate
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 515.94, ALogP 5.45, HBA 8, HBD 2, PSA 106.85, QED 0.26
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](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@@H](C)O)[C@@H](C)O
InChIKey: SZJWBGRSKSWDFV-CJRHXHJGSA-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 = 0.122 nM (pChEMBL 9.90999984741211)
Descriptors: MW 3878.35
Compound (SMILES): O=C1Oc2ccccc2C12CCN(c1nc3c(c(=O)[nH]1)CCCC3)CC2
InChIKey: XGTNOTWEBRRAKO-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 351.41, ALogP 2.11, HBA 5, HBD 1, PSA 75.29, QED 0.63
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(Cc5ccc(OCCOCCOC)cc5)CC4)cc3)[nH]c2c1=O
InChIKey: GJCIASZFDKSPKP-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from recombinant human A1 adenosine receptor expressed in CHO cell membranes measured after 90 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 1010 nM (pChEMBL 6)
Descriptors: MW 626.74, ALogP 2.04, HBA 10, HBD 2, PSA 151.85, QED 0.2
Compound (SMILES): NC(=O)c1ccc(OCCCN2C[C@H]3CCC[C@H]3C2)cc1
InChIKey: MRNMYWNBLVJWKG-GASCZTMLSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Inverse agonist activity at human Histamine H3 receptor
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 288.39, ALogP 2.29, HBA 3, HBD 1, PSA 55.56, QED 0.82
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)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)N1CCC[C@H]1C(=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: PUUYZGUJCFFWLL-OMQKSHNASA-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 = 0.154 nM (pChEMBL 9.8100004196167)
Descriptors: MW 3789.3
Compound (SMILES): CN1CCN(c2ccc(CCNC(=O)c3sc4nc(Cl)ccc4c3N)cc2)CC1
InChIKey: BKYXQYOKUBCGOW-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 429.98, ALogP 3.26, HBA 6, HBD 2, PSA 74.49, QED 0.61
Compound (SMILES): COc1ccc(OCCN2CCN(C(=O)c3cc4ccncc4[nH]3)CC2)cc1
InChIKey: PQDYOEMOWGGFPI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2R expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 120 mins by beta-galactosidase based PathHunter assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 380.45, ALogP 2.41, HBA 5, HBD 1, PSA 70.69, QED 0.71
Compound (SMILES): FC(F)(F)c1ccc(-c2cn(Cc3ccc(-c4cn[nH]c4)cc3)nn2)cc1
InChIKey: HUBIPQNHRKHYAE-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: Inhibition of EphB4 (unknown origin) after 1 hrs by ADP-Glo luminescence assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 369.35, ALogP 4.4, HBA 4, HBD 1, PSA 59.39, QED 0.58
Compound (SMILES): O=c1cc(NCCCN2CCN(c3nccc4ccc(F)cc34)CC2)c2c(o1)CCSC2
InChIKey: ZFSYWNWTEZXQAZ-UHFFFAOYSA-N
Target: DNA gyrase subunit A (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0AES4
Assay: Inhibition of Escherichia coli ATCC 25922 DNA gyrase A assessed as reduction in enzyme-mediated supercoiling of relaxed pBR322 DNA by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 454.57, ALogP 3.74, HBA 7, HBD 1, PSA 61.61, QED 0.57
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(Br)o2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: CYJUFMHEEQFJAT-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 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 459.3, ALogP 4, HBA 5, HBD 2, PSA 94.22, QED 0.6
Compound (SMILES): COc1nc2ccc(C(O)(c3cnc(C)n3C)c3cnc(C)n3C)cc2c(Cl)c1CN1CCC(C(F)(F)F)CC1
InChIKey: BCOLIFXOHYTQLJ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-DNA binding domain-fused human full length RORgammat LBD expressed in pGL4.31 transfected HEK293T cells assessed as inhibition of RORGgammat driven transcriptional activity after 24 hrs by dual-luciferase reporter gene assay
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 577.05, ALogP 5.04, HBA 8, HBD 1, PSA 81.23, QED 0.35
Compound (SMILES): Oc1ccccc1C1CC(c2ccccc2)=NN1c1nc(-c2cccc(Br)c2)cs1
InChIKey: BJKRPBZRGHLHLQ-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP-8 using Mca-PLGL-Dpa-AR-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured for 5 mins by fluorescence assay
Measurement: IC50 = 86500 nM (pChEMBL 4.059999942779541)
Descriptors: MW 476.4, ALogP 6.63, HBA 5, HBD 1, PSA 48.72, QED 0.36
Compound (SMILES): Cn1c(CCc2ccc(NC(=O)Nc3cccc(Cl)c3)cc2)nc2ccccc21
InChIKey: CCGPKQXZPRBYGU-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 = 163.4 nM (pChEMBL 6.789999961853027)
Descriptors: MW 404.9, ALogP 5.66, HBA 3, HBD 2, PSA 58.95, QED 0.45
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(C4CCNCC4)c(F)c3)sc2n1
InChIKey: YKMONAJQGXMGGG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). 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 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). 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 412.53, ALogP 3.77, HBA 5, HBD 3, PSA 80.04, QED 0.6
Compound (SMILES): CCN(CC)CCNc1nc(/C=C/c2ccc(C(C)C)cc2)nc2ccc(F)cc12
InChIKey: DZVYKLXBTBFEFR-NTEUORMPSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 D835Y (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 406.55, ALogP 5.82, HBA 4, HBD 1, PSA 41.05, QED 0.49
Compound (SMILES): C[C@@H]1C[C@H]2C(=O)OC[C@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)Nc3ccc(Cl)cc3)C(=O)N3CCC[C@H]3C(=O)N3CCCC[C@H]3C(=O)N[C@@H](C)C(=O)N2C1
InChIKey: SWYQMNGIOBPETQ-CSGPBTBZSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Activation of Staphylococcus aureus ClpP using BODIPY-FL-casein as substrate incubated for 30 mins by Enz-Check protease assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 778.31, ALogP 2.23, HBA 8, HBD 4, PSA 186.56, QED 0.32
Compound (SMILES): O=C1CCc2cc(N3CC[C@](O)(C(=O)NCc4ccc(F)c(Cl)c4F)C3=O)ccc2N1
InChIKey: XUXUWHAAFGOLQN-NRFANRHFSA-N
Target: Methionine aminopeptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53582
Assay: Inhibition of N-terminal MetAP1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.84, ALogP 2.29, HBA 4, HBD 3, PSA 98.74, QED 0.49
Compound (SMILES): CCCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChIKey: KJGHYDVBLIXARQ-KNXBSLHKSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 477.54, ALogP 3.48, HBA 8, HBD 2, PSA 111.72, QED 0.6
Compound (SMILES): CCCCN(c1nc2cc(CNC(=O)NC)ccc2o1)[C@H](C)c1ccc(-c2ccccc2-c2nnn[nH]2)cc1
InChIKey: KFWLXBQVZWESCT-LJQANCHMSA-N
Target: Chemerin-like receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99788
Assay: Agonist activity at chemR23 expressed in human CAL1 cells assessed as increase in intracellular calcium ion concentration
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 524.63, ALogP 5.47, HBA 7, HBD 3, PSA 124.86, QED 0.22
Compound (SMILES): C[C@H]1[C@H]2Cc3ccc(O)cc3[C@]1(C)CCN2CCC(=O)NCC(c1ccccc1)c1ccccc1
InChIKey: LUJZXARUKQUEFU-JOHVVKFNSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human DOR expressed in CHO cells
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 468.64, ALogP 5.25, HBA 3, HBD 2, PSA 52.57, QED 0.5
Compound (SMILES): O=CN(O)C[C@@H](CC1CCCC1)C(=O)NCNC(=O)c1cccc(-c2ccccc2)c1
InChIKey: VNEGSKMNJTWROA-JOCHJYFZSA-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 423.51, ALogP 3.2, HBA 4, HBD 3, PSA 98.74, QED 0.24
Compound (SMILES): O=C(NC1CCC(=Cc2cccc(Oc3ccc(C(F)(F)F)cn3)c2)CC1)c1cncnc1
InChIKey: YMHMMIRRHFVEGM-YBEGLDIGSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 454.45, ALogP 5.44, HBA 5, HBD 1, PSA 77, QED 0.56
Compound (SMILES): N=C(N)NCCCC[C@H](N)C(=O)NCCCC[C@H](N)C(=O)N[C@@H](CCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: KROMCBSZKAWFOP-SXYSDOLCSA-N
Target: Neuropilin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14786
Assay: Inhibition of human biotinylated VEGF-A165 binding to recombinant human NRP1 receptor after 2 hrs by chemiluminescence analysis
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 669.83, ALogP -3.76, HBA 10, HBD 13, PSA 346.77, QED 0.03
Compound (SMILES): O=C(/C=C(\O)C(=O)O)/C=C/c1ccc(NC(=O)c2ccc3ccccc3c2)cc1
InChIKey: ZSFVWJGOTUAOPM-DWVIGKKNSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 2084 nM (pChEMBL 5.679999828338623)
Descriptors: MW 387.39, ALogP 4.2, HBA 4, HBD 3, PSA 103.7, QED 0.43
Compound (SMILES): O=C1N[C@H](c2cncc(C#Cc3ccnc(F)c3)c2)[C@@H](c2ccc(F)cc2)O1
InChIKey: CDOCIDGSLALRDQ-WOJBJXKFSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Agonist activity at human mGluR5A transfected in HEK293 cells assessed as induction of calcium release by FLIPR assay
Measurement: EC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 377.35, ALogP 3.68, HBA 4, HBD 1, PSA 64.11, QED 0.55
Compound (SMILES): Cc1ccccc1C(=O)N1C(=O)C[C@H]1C(=O)O
InChIKey: RSPIDHXLVXDISW-VIFPVBQESA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Binding affinity to alpha5beta1 integrin receptor (unknown origin) incubated fro 30 mins by competitive solid-phase binding assay
Measurement: IC50 = 59.3 nM (pChEMBL 7.230000019073486)
Descriptors: MW 233.22, ALogP 0.82, HBA 3, HBD 1, PSA 74.68, QED 0.61
Compound (SMILES): CC(C)Nc1nc(Nc2ccccc2)nc(-c2ccccc2Cl)n1
InChIKey: XTUJYUYJEDAYCK-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 339.83, ALogP 4.76, HBA 5, HBD 2, PSA 62.73, QED 0.7
Compound (SMILES): CC(=O)NCCNCc1cc(C)c(OCc2cccc(-c3cccc(COc4cc(OCc5cncc(C#N)c5)c(CNCCNC(C)=O)cc4C)c3C)c2C)cc1OCc1cncc(C#N)c1
InChIKey: RNCINFJGGSQEHN-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD1 stably expressed in human Jurkat T cells co-expressing NFAT-induced luciferase/human PDL1 stably expressed in CHOK1 cells co-expressing aAPC protein-protein interaction assessed as increase in NFAT signaling measured after 6 hrs by bio-glo luciferase reporter gene assay
Measurement: EC50 = 763 nM (pChEMBL 6.119999885559082)
Descriptors: MW 915.11, ALogP 7.89, HBA 12, HBD 4, PSA 192.54, QED 0.05
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](C)NC1=O
InChIKey: ZDSIXCUNSXFSMQ-LBCAYJJCSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of human fibronectin binding to human integrin alpha5beta1 receptor after 1 hr by solid-phase binding assay
Measurement: IC50 = 38.4 nM (pChEMBL 7.420000076293945)
Descriptors: MW 925.06, ALogP -2.93, HBA 11, HBD 11, PSA 343.52, QED 0.06
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(c2)Oc2ccc4cc(-c5cnc([C@@H]6CCCN6C[C@@H](NC(=O)OC)C6CCOCC6)[nH]5)ccc4c2[C@H]3C)[nH]1)C1CCOCC1
InChIKey: XYYNLRWFHZDVKB-PWCZPXJNSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2b assessed as decrease in viral replication
Measurement: EC50 = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 901.08, ALogP 7.98, HBA 11, HBD 4, PSA 185.26, QED 0.1
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4cccnc34)n2)c(OC)cc1NCCN(C)C
InChIKey: MATQRKXWDVRHDA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR (696-end residues) expressed in baculovirus expression system using Srctide as substrate by fluorescence assay
Measurement: IC50 = 77000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 486.58, ALogP 3.88, HBA 9, HBD 3, PSA 109.23, QED 0.29
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCN(C)CC4)cc3)c2C)cc(F)c1C(N)=O
InChIKey: ZOUWFECDLDOKNV-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of C-terminal nanoluciferase-fused ALK2 (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition by NanoBRET assay
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 434.52, ALogP 3.72, HBA 5, HBD 1, PSA 71.69, QED 0.66
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CO)NC1=O)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N2
InChIKey: STJCUZOTQPIXIR-JWKNPDOPSA-N
Target: Kallikrein-14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0G3
Assay: Inhibition of recombinant human KLK14 expressed in Spodoptera frugiperda Sf9 cells using Boc-QAR-MCA as susbtrate measured every 60 secs for 10 mins by fluorescence based assay
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 1672.87
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)NCCCCCn1cc(C(=O)c2cccc3ccccc23)c2ccccc21
InChIKey: XOXIGOYEWHFRCB-GORMCOKISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]HS-665 from KOR in guinea pig brain membranes after 60 mins by liquid scintillation analysis
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 852.01, ALogP 4.05, HBA 9, HBD 7, PSA 213.75, QED 0.04
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CCC(=O)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: VQPWOMHPWMPGET-JTEMBWBYSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: Inhibition of HIV1 gp41-induced cell-cell fusion between viral envelope expressing human HL2/3 cells to CD4/CCR5 receptor expressing TZM-bl cells at 2:1 ratio of hCS6ERE to compound incubated for 6 hrs by luciferase reporter gene assay
Measurement: EC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 3013.46
Compound (SMILES): Cc1nc2sc(C(=O)NCCc3cc(F)c(N4CC5CCC(C4)N5)cc3F)c(N)c2cc1F
InChIKey: WYIFELZJFYXBGL-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). 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 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). 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 475.54, ALogP 3.52, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): NS(=O)(=O)NCc1nnc(C(=O)c2nc3ccc(-c4ccc5c(c4)C(=O)NC5)cc3s2)o1
InChIKey: MAHUWMXSXAPPEC-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 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 470.49, ALogP 1.11, HBA 9, HBD 3, PSA 170.17, QED 0.35
Compound (SMILES): CC[C@H]1c2ccc(O)cc2OC[C@@]1(C)N
InChIKey: GJTGEGKNBHSUEU-CMPLNLGQSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-Pentazocine from human recombinant sigma2 receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 207.27, ALogP 2, HBA 3, HBD 2, PSA 55.48, QED 0.74
Compound (SMILES): Cc1ccc(-c2cnc3ccn(CC(=O)N(C)C)c3c2)s1
InChIKey: QLVPQOVZXHEIDR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 299.4, ALogP 3.16, HBA 4, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): C[C@]1(c2cc(NC(=O)c3ccc(Cl)cn3)cc(F)c2F)N=C(N)S[C@@]2(CO)C[C@H]21
InChIKey: SYUXGKTZZPXWFX-GDIGMMSISA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 < 2 nM (pChEMBL 8.699000358581543)
Descriptors: MW 438.89, ALogP 3.29, HBA 6, HBD 3, PSA 100.6, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)C(CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(=O)NCC(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O
InChIKey: ACILESWMMGLQMP-BHICQDQESA-N
Target: BTB/POZ domain-containing protein KCTD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96CX2
Assay: Displacement of TAMRA-AAG-SLQLPILHHAYLPSIGGV from recombinant human 6X His-tagged KCTD12 T1 domain (27 to 131 residues) expressed in Escherichia coli BL21 DE3 cells by fluorescence polarization assay
Measurement: IC50 = 4820 nM (pChEMBL 5.320000171661377)
Descriptors: MW 1979.32
Compound (SMILES): Cc1c(C(=O)N2CCN(CC3CCC3)[C@H](C)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: IUEQYINPISPONW-CQSZACIVSA-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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 409.49, ALogP 1.46, HBA 7, HBD 1, PSA 91.53, QED 0.7
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2ccccc2)c1
InChIKey: SCUKDJAKLMTQPY-OAQYLSRUSA-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 411.5, ALogP 3.2, HBA 4, HBD 3, PSA 98.74, QED 0.16
Compound (SMILES): O=C(CCCCCCn1cc(Nc2ncc(Cl)c(Nc3ccc(Cl)cc3)n2)cn1)NO
InChIKey: QZZCBJMHOODNJW-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 = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 464.36, ALogP 4.92, HBA 8, HBD 4, PSA 116.99, QED 0.18
Compound (SMILES): O=C(CC(=O)Nc1ccc2c(c1)B(O)OC2)Nc1ccc2c(c1)B(O)OC2
InChIKey: IXTVZIHDEVZCRN-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human carbonic anhydrase 4 assessed as reduction in CO2 hydration preincubated for 15 mins to 2 hrs by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 6276 nM (pChEMBL 5.199999809265137)
Descriptors: MW 365.95
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc(CN5CCNCC5)ccn4)[nH]c3c2)n1
InChIKey: FQLDODIEEKFQOP-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of recombinant full length human C-terminal GST-tagged IKKepsilon expressed in baculovirus expression system using biotin-labelled Ahx-GDEDFSSFAEPG peptide as substrate preincubated with enzyme for 15 mins followed by substrate addition and further incubated for 30 mins in presence of 10 uM of ATP by TR-FRET assay
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 390.45, ALogP 2.47, HBA 8, HBD 3, PSA 107.79, QED 0.48
Compound (SMILES): O=C(c1ccccn1)N1CCC(C(=O)N2N=CCC2c2ccccc2)CC1
InChIKey: CWBLKBNCFMSXMO-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIP1 in human U937 cells assessed as reduction in TNFalpha/QVD-Oph-induced necroptosis measured after 24 hrs by cell titer-glo luminescent cell viability assay
Measurement: IC50 = 316 nM (pChEMBL 6.5)
Descriptors: MW 362.43, ALogP 2.89, HBA 4, HBD 0, PSA 65.87, QED 0.84
Compound (SMILES): COc1cc(Nc2ccnc3cc(C#N)ccc23)cc(OC)c1OC
InChIKey: BLWQIEISIMYCHD-UHFFFAOYSA-N
Target: Atypical kinase COQ8A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI60
Assay: Binding affinity to biotinylated full length human ADCK3 expressed in Escherichia coli incubated for 1.5 hrs by fluorescent tracer dependent TR-FRET based competitive ligand binding displacement assay
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 335.36, ALogP 3.88, HBA 6, HBD 1, PSA 76.4, QED 0.76
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C[C@@H](C)Oc1ccccc1
InChIKey: PUGXENIKUPHCAF-CYBMUJFWSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of CLK1 (unknown origin) by TR-FRET assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 374.45, ALogP 3.43, HBA 7, HBD 2, PSA 104.87, QED 0.55
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@H](C)c3ccc(N4CC5CCC(C4)N5)c(C#N)c3)sc2n1
InChIKey: NSXWVLYZUZRLNB-YCMKEVRSSA-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 460.61, ALogP 3.53, HBA 7, HBD 3, PSA 107.07, QED 0.54
Compound (SMILES): CNC(=O)NC1CCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)CC1
InChIKey: NHLSOFMOYDDMIY-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 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 505.65, ALogP 3.57, HBA 7, HBD 3, PSA 98.41, QED 0.38