lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc2c(c1)/C(=N/NC(=O)c1ccc(NC(=O)Nc3ccc(Cl)cc3)cc1)C(=O)N2
InChIKey: CWJWMMHMKSIAGC-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 = 1820 nM (pChEMBL 5.739999771118164)
Descriptors: MW 463.88, ALogP 4.08, HBA 5, HBD 4, PSA 120.92, QED 0.43
Compound (SMILES): CCCC[C@H](N)C(=O)NNc1cccc(C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)OCc2ccccc2)c1
InChIKey: HSUTVEOJRBSEAV-XCZPVHLTSA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Inhibition of human recombinant IRAP expressed in baculovirus infected Sf9 cells using omniMMP fluorogenic substrate incubated for 5 to 10 mins by fluorescence spectrophotometry analysis
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 541.65, ALogP 4.21, HBA 6, HBD 5, PSA 138.34, QED 0.13
Compound (SMILES): Cc1ccc(-c2cc3cccc(C)c3oc2=O)cc1
InChIKey: HPKMVGQGAIWEID-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine receptor A3 expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 16600 nM (pChEMBL 4.78000020980835)
Descriptors: MW 250.3, ALogP 4.08, HBA 2, HBD 0, PSA 30.21, QED 0.61
Compound (SMILES): C=CC(=O)Nc1cc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ccc2N2CCCCC2)ccc1C
InChIKey: ZFRMQNBHXVYHCH-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of cathepsin C in human THP1 cells using H-Gly-Phe-AFC as substrate preincubated for 4 hrs followed by substrate addition and measured after 60 mins
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 556.71, ALogP 5.8, HBA 8, HBD 2, PSA 82.2, QED 0.32
Compound (SMILES): CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: FPYAQRXRBVHTRN-NAVQYVAVSA-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 = 48.98 nM (pChEMBL 7.309999942779541)
Descriptors: MW 845.11, ALogP 1.91, HBA 10, HBD 8, PSA 234.35, QED 0.05
Compound (SMILES): CC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1
InChIKey: BLOFNYQHKSGSGE-MLCQCVOFSA-N
Target: Hepatocyte growth factor activator serine protease (SINGLE PROTEIN), Homo sapiens
UniProt: Q04756
Assay: Inhibition of recombinant HGFA serine protease domain (unknown origin) using Boc-QLR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 661.83, ALogP -0.13, HBA 10, HBD 9, PSA 254.51, QED 0.04
Compound (SMILES): N#Cc1cc(O)cc(OC(=O)N2CCC(C(c3ccccc3)c3ccccc3)CC2)c1
InChIKey: NFAYQCDYTAIPCO-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat FAAH using AAMCA as substrate by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 412.49, ALogP 5.31, HBA 4, HBD 1, PSA 73.56, QED 0.63
Compound (SMILES): OB1OCc2ccc(/N=C/c3ccc(/C=N/c4ccc5c(c4)B(O)OC5)s3)cc21
InChIKey: ZIDJLFURKBSKJY-WDBPGAOMSA-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 = 29700 nM (pChEMBL 4.53000020980835)
Descriptors: MW 402.05
Compound (SMILES): CC(=O)N[C@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O[C@H]3[C@H](O)[C@@H](COS(=O)(=O)O)O[C@@H](OCCCCCCN=[N+]=[N-])[C@@H]3NC(C)=O)O[C@@H]2C(=O)O)O[C@H](COS(=O)(=O)O)[C@@H](O)[C@@H]1O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O
InChIKey: RKNBQDWANIGUBK-YZFKMWOBSA-N
Target: Pleiotrophin (SINGLE PROTEIN), Homo sapiens
UniProt: P21246
Assay: Binding affinity to PTN (unknown origin) by SPR assay
Measurement: Kd = 77.8 nM (pChEMBL 7.110000133514404)
Descriptors: MW 1061.95
Compound (SMILES): O=C1COC2(CCN(CCc3ccccc3)C2)CN1c1ccccc1
InChIKey: XFVLQPBMVRXGBD-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-(+)-pentazocine from human sigma-1 receptor expressed in HEK293 membranes incubated for 120 mins by liquid scintillation counting method
Measurement: Ki = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 336.44, ALogP 2.74, HBA 3, HBD 0, PSA 32.78, QED 0.86
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(O)cc(P(=O)(O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: DHSDRWLAPMLALK-RTBURBONSA-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 525.5, ALogP 2.08, HBA 7, HBD 6, PSA 189.64, QED 0.05
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](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)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(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)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
InChIKey: NCNNIHNSLHNRQP-BQXNAASMSA-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 = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 3459.99
Compound (SMILES): COc1ccc(C(=O)Cn2c(=O)oc3ccc(F)cc32)cc1OC
InChIKey: URLXIZOBCFWFCE-UHFFFAOYSA-N
Target: Testis-specific chromodomain protein Y 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6F8
Assay: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis
Measurement: Kd = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 331.3, ALogP 2.63, HBA 6, HBD 0, PSA 70.67, QED 0.67
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2cc(F)c(N3CCOCC3)cc2F)C1
InChIKey: DHFPYTPSXLNBKL-LLVKDONJSA-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 336.34, ALogP 1.09, HBA 5, HBD 1, PSA 68.6, QED 0.84
Compound (SMILES): COc1ccc(NC(=O)/C=C/c2sc(N3CCOCC3)nc2-c2ccc([N+](=O)[O-])cc2)cc1
InChIKey: RIIABKPZQNDMFA-ZHACJKMWSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase9 preincubated for 10 mins followed by CO2 solution addition by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 466.52, ALogP 4.22, HBA 8, HBD 1, PSA 106.83, QED 0.32
Compound (SMILES): O=C(NCc1ncccc1F)c1nc(CNCCc2nc3ccccc3[nH]2)cs1
InChIKey: GMSDJDURUBSYSU-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 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 410.48, ALogP 2.82, HBA 6, HBD 3, PSA 95.59, QED 0.39
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(F)c2)c1
InChIKey: UDUXAKYTHXSVSP-HXUWFJFHSA-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 429.49, ALogP 3.34, HBA 4, HBD 3, PSA 98.74, QED 0.16
Compound (SMILES): O=C(O)CO/N=C1\c2ccccc2-c2nc3ccccc3nc21
InChIKey: FYPYRKHDUUOAMZ-CAPFRKAQSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Binding affinity to human partial length JNK3 (V28 to Q422 residues) expressed in HEK293 cells measured after 1 hr by Kinomescan method
Measurement: Kd = 28500 nM (pChEMBL 4.539999961853027)
Descriptors: MW 305.29, ALogP 2.46, HBA 5, HBD 1, PSA 84.67, QED 0.59
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H](CCl)O[C@H]1n1cnc2c(N[C@H]3C[C@H]4CC[C@@H]3C4)ncnc21
InChIKey: PVJGDYDNVNCGBT-XSMNFLGNSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5-N-methyluronamide from human A3A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 379.85, ALogP 1.28, HBA 8, HBD 3, PSA 105.32, QED 0.69
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O)C(C)C
InChIKey: CJLWXPSNKINPJW-SFIUMABJSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q01727
Assay: Full agonist activity at mouse MC1R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 627.14, ALogP 0.72, HBA 6, HBD 5, PSA 193.79, QED 0.22
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CSSCCC(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N2)C(=O)NCC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: JTYYTRAVGLFARZ-KOFKWYMHSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Agonist activity at human oxytocin receptor C47A mutant expressed in HEK293 cells coexpressing Rluc8-tagged Galphaq, N-terminal GFP-tagged Ggamma2 and Gbeta1 protein incubated for 2 mins by Gq protein activation based BRET assay
Measurement: EC50 = 21.7 nM (pChEMBL 7.659999847412109)
Descriptors: MW 2180.63
Compound (SMILES): COC(=O)C(C)(C)S(=O)(=O)c1ccc([C@@H](CO)NC(=O)c2cc3c(Cl)c(Cl)c(C)cc3n2C)cc1
InChIKey: OQWUXXZXANQKOY-QGZVFWFLSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human MDA-MB-468 cells assessed as reduction in [13C3]-serine production incubated for 180 mins by LC/MS/MS analysis
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 541.45, ALogP 3.98, HBA 7, HBD 2, PSA 114.7, QED 0.44
Compound (SMILES): CCN(CC)CC.CCN(CC)CC.CCN(CC)CC.CO[C@@H]1O[C@@H](COP(=O)(O)O)[C@H](O)[C@@H](OP(=O)(O)O)[C@@H]1OP(=O)(O)O
InChIKey: GYHBPYVCJCPILA-HIDONCAJSA-N
Target: Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29994
Assay: Partial agonist activity at rat IP3R1 expressed in HEK cells assessed as increase in calcium release in cytosol by measuring fluorescence signal by Mag-Fluo4 dye based assay
Measurement: EC50 = 87700 nM (pChEMBL 4.059999942779541)
Descriptors: MW 434.12, ALogP -2.22, HBA 9, HBD 7, PSA 238.97, QED 0.2
Compound (SMILES): CCc1cc(NC(=O)c2ccc3c(c2)C[C@H](N(C)c2cncnc2)C3)cc(-n2cnc(C)c2)c1
InChIKey: SBGAHKXLTGCPRN-XMMPIXPASA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged human TrkA expressed in baculovirus expression system using Tyr1 peptide as substrate after 1.5 hrs by FRET-based Z-LYTE assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 452.56, ALogP 4.39, HBA 6, HBD 1, PSA 75.94, QED 0.47
Compound (SMILES): Cc1nc2sc(C(=O)NC[C@H](C)c3ccc(N4CC5CCC(C4)N5)c(F)c3)c(N)c2cc1F
InChIKey: HPKDXUMDAFPRKD-JQRITLKVSA-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): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(P(=O)(O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccc(-n2cccc2)cc1.N.N
InChIKey: VXNZNRAYRPHMNT-ZAMYOOMVSA-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 722.73, ALogP 4.95, HBA 9, HBD 4, PSA 189.64, QED 0.03
Compound (SMILES): Cc1c(C(=O)N2CCC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: DXDJOOZOYDRUIQ-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 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 298.31, ALogP 0.36, HBA 6, HBD 1, PSA 88.29, QED 0.74
Compound (SMILES): CC1OC2(CCN(CCc3ccccc3)CC2)CN(c2ccccc2)C1=O
InChIKey: RSVBTLSIVBWMNF-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHOK1 cells assessed as stimulation of cAMP accumulation incubated for 45 mins by HTRF assay
Measurement: EC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 364.49, ALogP 3.52, HBA 3, HBD 0, PSA 32.78, QED 0.83
Compound (SMILES): COC(=O)C1=C(CN2CC(F)(F)C[C@H]2C(=O)O)NC(c2nccs2)=N[C@@]1(C)c1ccc(F)cc1
InChIKey: ZUNJWALIUFZGCH-BTYIYWSLSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using substrate preincubated for 10 mins followed by NADPH addition measured after 30 mins by LC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 494.5, ALogP 2.77, HBA 8, HBD 2, PSA 104.12, QED 0.6
Compound (SMILES): N#Cc1ncnn1C(=O)c1cc(=O)[nH]c2ccccc12
InChIKey: XXKVMXDKVFFSCX-UHFFFAOYSA-N
Target: DNA dC->dU-editing enzyme APOBEC-3A (SINGLE PROTEIN), Homo sapiens
UniProt: P31941
Assay: Inhibition of recombinant APOBEC3A (unknown origin) expressed in HEK293 cells assessed as reduction in cytosine deaminase activity using 5'-6-FAM and 3'-TAMRA quench molecule tagged cytosine-containing single-stranded DNA substrate incubated for 2 hrs by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 265.23, ALogP 0.68, HBA 6, HBD 1, PSA 104.43, QED 0.7
Compound (SMILES): Nc1cc(C(F)F)c2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)cc3)sc2n1
InChIKey: SRTMEUZKKHKITG-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 446.53, ALogP 2.78, HBA 7, HBD 4, PSA 109.3, QED 0.46
Compound (SMILES): Nc1ncc(C(=O)C(F)(F)F)c(N2CC[C@H]2c2nn3ccc(Cl)c3c(=O)n2-c2ccccc2)n1
InChIKey: JBPFTIQLGQPNCK-AWEZNQCLSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full length human p110beta/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate measured after 80 mins by transcreener fluorescence polarization assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 489.85, ALogP 3.21, HBA 9, HBD 1, PSA 111.41, QED 0.44
Compound (SMILES): COc1ccc(Cl)cc1NCC1C(c2ccc(S(N)(=O)=O)cc2)C1(C)C
InChIKey: LWWDCTBUJUEFDE-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.92, ALogP 3.85, HBA 4, HBD 2, PSA 81.42, QED 0.78
Compound (SMILES): CCCCCCC(Sc1nc2ccc(NCc3ccc4ccccc4c3)cc2s1)C(=O)O
InChIKey: NSUMQLGBRFQKCQ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Partial agonist activity at Gal4-fused PPARdelta LBD (unknown origin) expressed in HEK293T cells after 14 to 16 hrs by dual-Glo luciferase assay
Measurement: EC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 464.66, ALogP 7.58, HBA 5, HBD 2, PSA 62.22, QED 0.18
Compound (SMILES): COc1ccc(C(/C=C\CN2CCCC(C(=O)O)C2)(Cc2ccccc2)c2ccc(OC)cc2)cc1
InChIKey: ODWRKVSHVHKBSL-GXHLCREISA-N
Target: GABA transporter 3 (SINGLE PROTEIN), Mus musculus
UniProt: P31649
Assay: Inhibition of mouse GAT2 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 10 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 30199.52 nM (pChEMBL 4.519999980926514)
Descriptors: MW 485.62, ALogP 5.59, HBA 4, HBD 1, PSA 59, QED 0.38
Compound (SMILES): CC(C)C[C@H](NC(=O)OC1CCN(S(=O)(=O)c2ccc(Cl)cc2)CC1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1.O=C(O)C(F)(F)F
InChIKey: BYBDMHBXAJKOQB-DKIIUIKKSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human N-terminal met-His6-tagged matriptase catalytic domain (Gly596 to Val855 residues) expressed in Escherichia coli using Boc-QAR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 706.29, ALogP 3.87, HBA 9, HBD 5, PSA 196.67, QED 0.07
Compound (SMILES): CC(Oc1cc(-c2cnn(C3CCNCC3)c2)cnc1N)c1cc(F)ccc1Cl
InChIKey: VRPBEXXAJILOFI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human recombinant N-terminal hexahistidine tagged JAK2 JH1 catalytic domain (835 to 1132 residues) expressed in baculovirus infected Sf9 cells using Tyr6 peptide as substrate incubated for 30 secs under shaking condition measured after 1 hr by Z'-LYTE assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 415.9, ALogP 4.38, HBA 6, HBD 2, PSA 77.99, QED 0.65
Compound (SMILES): C=CC(=O)NCc1ccc(-n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)cc1
InChIKey: GXIHBWCRCZNSHX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 454.49, ALogP 3.52, HBA 7, HBD 3, PSA 131.83, QED 0.35
Compound (SMILES): CC(C)[C@H]1CC[C@@H](N2CCC(n3cc(CN4CCCC4)c4ccccc43)CC2)CC1
InChIKey: NGKDULCWDLWYAO-QUPDYRNUSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human DOP expressed in CHO cell membrane incubated for 60 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 407.65, ALogP 6.09, HBA 3, HBD 0, PSA 11.41, QED 0.59
Compound (SMILES): C=CC(=O)N1CCC[C@@H]1Cn1/c(=N/C(=O)c2ccc(C(F)F)s2)[nH]c2cc(CN[C@@H](C)C(C)(C)C)ccc21
InChIKey: NXTKFBGDLDPFLB-PKOBYXMFSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of ITK in anti-CD3/CD28 beads-stimulated human Jurkat cells assessed as reduction in Plcgamma1 phosphorylation incubated for 2 hrs followed by stimulation with anti-CD3/CD28 beads by Western blot analysis
Measurement: EC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 543.68, ALogP 5.41, HBA 5, HBD 2, PSA 82.49, QED 0.37
Compound (SMILES): N#Cc1ccc(-c2ccc(C(=O)c3cc(=O)n(O)c(=O)[nH]3)cc2)cc1
InChIKey: FHEIBFFRHYMBMZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV1 integrase strand transfer activity using 5'-biotinylated oligonucleotide as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 333.3, ALogP 1.54, HBA 6, HBD 2, PSA 115.95, QED 0.56
Compound (SMILES): N#CC(C(=O)NCC(=O)NC1CC1)c1nc2ccc(-c3ccc4c(c3)CNC4=O)cc2s1
InChIKey: PPOFQLCKXICRRP-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of endothelial lipase in human serum
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 445.5, ALogP 2.21, HBA 6, HBD 3, PSA 123.98, QED 0.54
Compound (SMILES): CCC(C#N)C1(O)CCN(C(=O)c2cnn(-c3nn4cccc4c(=O)[nH]3)c2C)CC1
InChIKey: XTYDNXBVXBEVMY-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 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 409.45, ALogP 1.03, HBA 8, HBD 2, PSA 132.31, QED 0.66
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)C(=O)Nc1cccc2ccccc12
InChIKey: MLLRFAQZDIFLTH-CPCREDONSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteosome beta 5 purified from human HCT116 cells using Suc-LLVY-AMC as substrate incubated for 30 to 120 mins by fluorimetry
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 644.81, ALogP 5.75, HBA 6, HBD 4, PSA 142.7, QED 0.15
Compound (SMILES): COc1cc(NCc2cc3cc(Cl)c(OC[C@@H]4CCCN4C)cc3[nH]c2=O)ccc1C#N
InChIKey: AUSQEMWCDVUKEF-IBGZPJMESA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 452.94, ALogP 4.15, HBA 6, HBD 2, PSA 90.38, QED 0.56
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2cc(-c3ccccc3)no2)C1
InChIKey: ZAPPZFCYJDQNFP-GFCCVEGCSA-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 282.3, ALogP 1.63, HBA 5, HBD 1, PSA 82.16, QED 0.87
Compound (SMILES): CCOc1cc(C(=O)N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(S(C)(=O)=O)c1ccccc1C(=O)N2C
InChIKey: HTFNVAVTYILUCF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin)
Measurement: Kd = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 648.79, ALogP 3.16, HBA 10, HBD 1, PSA 131.52, QED 0.41
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCn4cc(CCCCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: PQKXOUMEBXDAAB-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 833.89, ALogP 8.69, HBA 13, HBD 0, PSA 154.35, QED 0.06
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: DKTHXDHZNKFNNS-PLUWKHBFSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 896.08, ALogP -0.47, HBA 10, HBD 8, PSA 241.24, QED 0.14
Compound (SMILES): Cc1ccc(CCCOC(=O)N(c2ccccc2)C2CN3CCC2CC3)cc1F
InChIKey: QCKCTTSCZBLBGX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 396.51, ALogP 4.8, HBA 3, HBD 0, PSA 32.78, QED 0.66
Compound (SMILES): Cn1cncc1-c1c[nH]c2ccc(I)cc12
InChIKey: UZRMRNOPEVQTSO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H] LSD from human recombinant 5-HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 407 nM (pChEMBL 6.389999866485596)
Descriptors: MW 323.14, ALogP 3.17, HBA 2, HBD 1, PSA 33.61, QED 0.69
Compound (SMILES): Cc1c(C(=O)N2CCCN(CC(F)(F)F)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: PGFLMHQSZSGEOJ-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 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 423.4, ALogP 1.23, HBA 7, HBD 1, PSA 91.53, QED 0.68
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC(=O)O)cc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: ZURXEANTGKYQTD-BHIFYINESA-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 662.65, ALogP 1.69, HBA 10, HBD 7, PSA 262.11, QED 0.03
Compound (SMILES): C=CC(=O)Nc1ccc(CNc2cc(Nc3cnn(CCO)c3)ncn2)cc1
InChIKey: AQIJEZOKLLGFTD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and further incubated for 30 mins and subsequently measured after 1 hr by HTRF assay
Measurement: IC50 = 1240 nM (pChEMBL 5.909999847412109)
Descriptors: MW 379.42, ALogP 2.15, HBA 8, HBD 4, PSA 116.99, QED 0.42
Compound (SMILES): Cl.Cl.N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCCCNc1c2c(nc3cc(Cl)ccc13)CCCC2
InChIKey: XKCDJNBSUKXBGX-IKXQUJFKSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62600
Assay: Inhibition of nNOS in Wistar rat cortical homogenates incubated for 30 mins
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 476.02, ALogP 4.74, HBA 4, HBD 4, PSA 95.83, QED 0.28
Compound (SMILES): Cc1nn(-c2ccccn2)c2c1C(c1ccccc1Cl)C1=C(N2)c2ccccc2C1=O
InChIKey: ZUWTUMOFLHZZRE-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: PUBCHEM_BIOASSAY: qHTS for Inhibitors of Tau Fibril Formation, Thioflavin T Binding. (Class of assay: confirmatory) [Related pubchem assays: 596 ]
Measurement: Potency = 12589.3 nM (pChEMBL 4.900000095367432)
Descriptors: MW 424.89, ALogP 5.39, HBA 5, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): CNCc1ccc(-c2cc(-c3nc(-c4ccc(S(=O)(=O)C(C)C)cc4)cnc3N)on2)cc1Cl
InChIKey: WEOFJQBDUVLXHQ-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length ATM (unknown origin) using DPSVEPPLSQETFSDKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis
Measurement: Ki = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 498.01, ALogP 4.6, HBA 8, HBD 2, PSA 124, QED 0.38
Compound (SMILES): CC(C)N1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(Br)cc3)cc2)CC1.Cl.Cl
InChIKey: KQOSLTWWFIOWBQ-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 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 519.53, ALogP 6.71, HBA 3, HBD 1, PSA 26.71, QED 0.34
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccccc2F)CC1
InChIKey: KUWVCFQZKSJXPD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5HT2AR expressed in CHO-K1 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 524 nM (pChEMBL 6.28000020980835)
Descriptors: MW 431.56, ALogP 5.32, HBA 3, HBD 0, PSA 26.79, QED 0.45
Compound (SMILES): COc1ccccc1CNCC1CC1(F)c1cc(F)ccc1OC.Cl
InChIKey: BIRIRFXEYPAVNI-UHFFFAOYSA-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 = 30.9 nM (pChEMBL 7.510000228881836)
Descriptors: MW 333.38, ALogP 3.82, HBA 3, HBD 1, PSA 30.49, QED 0.84
Compound (SMILES): COc1cc(Cl)cc(-c2cc(=O)c3ccc4ccccc4c3o2)c1
InChIKey: YDFWKDMNPCFIBE-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 using 7-ethoxyresorufin as substrate in presence of glucose-6-phosphate, glucose-6-phosphate dehydrogenase and NADPH-generating system incubated for 50 mins by fluorometry
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 336.77, ALogP 5.28, HBA 3, HBD 0, PSA 39.44, QED 0.47
Compound (SMILES): Cc1nc(N)ncc1COc1cc(/C=C2\SC(=O)N(C)C2=O)c(Br)c(F)c1O
InChIKey: RRRSWNRWNOFEFL-WCIBSUBMSA-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 469.29, ALogP 3.22, HBA 8, HBD 2, PSA 118.64, QED 0.66
Compound (SMILES): Cc1cc(Oc2ccccn2)ccc1-c1c(C)ncc2nccn12
InChIKey: WTAQXBIUGFOXSY-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant C-terminal RLuc8-fused human D1 receptor expressed in HEK29T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 15 mins in presence of coelenterazine H by BRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 316.36, ALogP 4.2, HBA 5, HBD 0, PSA 52.31, QED 0.57
Compound (SMILES): COc1nn(C)cc1Nc1ncc(F)c(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: OEONIHQPMGEGIL-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 507.57, ALogP 2.82, HBA 9, HBD 3, PSA 116.23, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCC3)C2=O)cc1
InChIKey: KZSVRJBEJFDDMB-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Inhibition of human carbonic anhydrase 3 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 380.43, ALogP 0.53, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): COc1ccc(CCN(C(=O)OC2C[C@H]3CC[C@H](C2)N3C)c2ccccc2)cc1OC
InChIKey: RMBYJNZDODDRNO-NHCUHLMSSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 424.54, ALogP 4.51, HBA 5, HBD 0, PSA 51.24, QED 0.65
Compound (SMILES): COc1ccc(F)c([C@H]2CC[C@H](COc3cccc([C@H](C4CC4)C(C)(C)C(=O)O)c3)CC2)c1
InChIKey: OVDXPEDIWITCEX-DGUDUIIESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human GPR40 expressed in CHOK1 cells assessed as induction of Galphaq-mediated IP1 accumulation after 90 mins HTRF assay
Measurement: EC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 454.58, ALogP 6.79, HBA 3, HBD 1, PSA 55.76, QED 0.45
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(Oc5ccccc5)nn34)cc2s1
InChIKey: VXDZHVOUKUBMKJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 co-expressed with human P450 reductase and human b5 reductase assessed as reduction in 7-Hydroxyquinoline production using 7-benzyloxyquinoline as substrate and NADPH incubated for 15 mins by fluorimetry
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 548.65, ALogP 4.13, HBA 11, HBD 2, PSA 118.8, QED 0.29
Compound (SMILES): C[C@H]1COCCN1c1nc(-c2ccc(N)nc2)nc2c1C[C@H]1COCCN21
InChIKey: FFFOZOQSDJISHN-JSGCOSHPSA-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 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 368.44, ALogP 1.11, HBA 8, HBD 1, PSA 89.63, QED 0.84
Compound (SMILES): Nc1ccc2ccc(CC[C@H]3C[C@@H](n4ccc5c(N)ncnc54)[C@H](O)[C@@H]3O)cc2n1
InChIKey: IUBFXROFEOCTGQ-GVXRKXQCSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 404.47, ALogP 2.06, HBA 8, HBD 4, PSA 136.1, QED 0.41
Compound (SMILES): CC(C)CC(NC(=O)c1ccc(-c2ccc(S(C)(=O)=O)cc2)cc1)C(=O)N(C)N(C)C#N
InChIKey: XHBRHGRXSUUCGR-UHFFFAOYSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human liver cathepsin L
Measurement: Ki = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 456.57, ALogP 2.69, HBA 6, HBD 1, PSA 110.58, QED 0.37
Compound (SMILES): Cc1c(C(=O)N2CC3CCC(C2)C3(O)C(F)(F)F)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: RAKBPNXTYOBFAT-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 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 436.39, ALogP 1.29, HBA 7, HBD 2, PSA 108.52, QED 0.63
Compound (SMILES): Nc1cc(C(F)(F)F)c(-c2nc(N3CCOCC3)nc(N3CCN(C(=O)c4cc(Cc5n[nH]c(=O)c6ccccc56)ccc4F)CC3)n2)cn1
InChIKey: QEEHFLKQODURKT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human PARP1 using histone as substrate after 1 hr in presence of biotinylated NAD+ by ELISA
Measurement: IC50 = 9.55 nM (pChEMBL 8.020000457763672)
Descriptors: MW 690.66, ALogP 3.3, HBA 11, HBD 2, PSA 159.35, QED 0.25
Compound (SMILES): C=CC(=O)Nc1cc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ccc2N2CCN(C)CC2)ccc1C
InChIKey: NLNKYGYNCGYYSC-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of cathepsin C in human THP1 cells using H-Gly-Phe-AFC as substrate preincubated for 4 hrs followed by substrate addition and measured after 60 mins
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 571.73, ALogP 4.56, HBA 9, HBD 2, PSA 85.44, QED 0.36
Compound (SMILES): NCc1ccc(S(=O)(=O)c2cc(C(F)(F)F)cc(S(=O)(=O)N3CCCC3)c2)s1
InChIKey: MXAUHQFRBMWDEY-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 454.52, ALogP 2.84, HBA 6, HBD 1, PSA 97.54, QED 0.75
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)n2[nH]c(=O)c3ccc(C(=O)O)cc3c2=O)cc1
InChIKey: SZPQUXUZTPEXGX-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 389.35, ALogP -0.28, HBA 7, HBD 3, PSA 169.39, QED 0.55
Compound (SMILES): N#Cc1cccc(OC(=O)N2CCN(C(c3ccc(F)cc3)c3ccc(F)cc3)CC2)c1
InChIKey: FXMFZVNEZQXTHI-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat FAAH using AAMCA as substrate by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 433.46, ALogP 4.74, HBA 4, HBD 0, PSA 56.57, QED 0.6
Compound (SMILES): Cn1cncc1-c1cn(Cc2ccc(C(=O)NO)cc2)c2ccccc12
InChIKey: ANMZNMDSWZJYNP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of dye-labeled tracer binding to HDAC6 (unknown origin) transfected in human HeLa cells measured after 2 hrs by nano-luciferase reporter gene-based BRET assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 346.39, ALogP 3.21, HBA 5, HBD 2, PSA 72.08, QED 0.44
Compound (SMILES): CC[C@@H]1C(=O)N(C)c2cnc(Nc3cc(F)c(C(=O)NC4CCOCC4)cc3OCCO)nc2N1C(C)C
InChIKey: IJDPNONZYDDAHT-HXUWFJFHSA-N
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of recombinant human GST-tagged PLK3 (58 to 340 residues) expressed in baculovirus expression system using ser/thr 16 as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 974.33 nM (pChEMBL 6.010000228881836)
Descriptors: MW 530.6, ALogP 2.61, HBA 9, HBD 3, PSA 129.15, QED 0.45