lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OS(=O)(=O)O)c1cn(C2CC2)c2cc(N3CCNCC3)c(F)cc2c1=O
InChIKey: ZWRBMILGUFADAG-KDOFPFPSSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacillus cereus
UniProt: P14488
Assay: Inhibition of Bacillus cereus beta-lactamase II
Measurement: IC50 = 1.69 nM (pChEMBL 8.770000457763672)
Descriptors: MW 593.59, ALogP -0.35, HBA 10, HBD 4, PSA 182.62, QED 0.26
Compound (SMILES): CCn1nnc(-c2sc(-c3cccnc3)nc2O)n1
InChIKey: DYEGAWKZUMZWSD-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in ethyl 4-methoxy-2-phenylthiazole-5-carboxylate induced Ca2+ efflux preincubated for 5 mins followed by ethyl 4-methoxy-2-phenylthiazole-5-carboxylate addition and measured for 3 mins by FLIPR assay
Measurement: IC50 = 1370 nM (pChEMBL 5.860000133514404)
Descriptors: MW 274.31, ALogP 1.58, HBA 8, HBD 1, PSA 89.61, QED 0.78
Compound (SMILES): CCC(C)COc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: IPTTUGLAFBGALO-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inhibition of BODIPY FL vindoline binding to recombinant human GST-tagged PXR LBD (111 to 434 residues) expressed in baculovirus infected insect cells incubated for 1 mins under shaking condition followed by 60 mins under dark condition by TR-FRET assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 480.61, ALogP 5.57, HBA 7, HBD 1, PSA 87.5, QED 0.43
Compound (SMILES): COC1CCN(c2nccc(Nc3cc4c(cn3)c(C(N)=O)cn4C(C)C)n2)CC1
InChIKey: GBQZWJZYHRNIFT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR T790M/L858R double mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as peptide substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 409.49, ALogP 2.86, HBA 8, HBD 2, PSA 111.19, QED 0.64
Compound (SMILES): O=C(O)c1ccc(C#Cc2ccccc2NS(=O)(=O)c2ccccc2)cc1
InChIKey: RDLIIFRLEDXCGM-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human MDA-MB-231 cells assessed as inhibition of lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 377.42, ALogP 3.59, HBA 3, HBD 2, PSA 83.47, QED 0.68
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)Cc1ccc(F)cc1)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: HCSLUFMFJDDRLP-MYTZRPOQSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human kappa opioid receptor expressed in CHO-K1 cells incubated for 1 hr by 1450 microbeta scintillation counter analysis
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 951.17, ALogP -2.08, HBA 12, HBD 14, PSA 384.58, QED 0.02
Compound (SMILES): Cc1ccc(NC(=O)[C@H]2C[C@H](CN3CCN(C)CC3)C2)cc1Nc1nccc(-c2cccnc2)n1
InChIKey: DSUHCRCPYFLDMP-AQYVVDRMSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of ABL1 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 471.61, ALogP 3.8, HBA 7, HBD 2, PSA 86.28, QED 0.54
Compound (SMILES): CC(C)(O)[C@H]1C[C@H](NC(=O)c2cnc3nc(C4CC4)c(Cl)cc3c2)C1
InChIKey: RYZPVTJHBJPDMD-HDJSIYSDSA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O60760
Assay: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 359.86, ALogP 3.44, HBA 4, HBD 2, PSA 75.11, QED 0.88
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(OCC3CC3)c3ccccc3O)ccc2F)c1
InChIKey: MRQCNDUNWFOAJG-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-p-nitroaniline as substrate assessed as inhibition constant
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 554.54, ALogP 5.96, HBA 6, HBD 3, PSA 102.4, QED 0.22
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccccc3CO)cc2)nc2cnccc12)C(N)=O
InChIKey: NJRSGMXBHJNOAG-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 10 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 437.5, ALogP 4, HBA 6, HBD 3, PSA 124.92, QED 0.4
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccc3c(c2)CCCN3C(=O)c2ccco2)cc1
InChIKey: UWBPPRSRIFBYGK-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Binding affinity to glucocorticoid receptor (unknown origin) by Lanthascreen TR-FRET competition binding assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 412.47, ALogP 3.68, HBA 5, HBD 1, PSA 88.85, QED 0.69
Compound (SMILES): O=C(CCCCc1cn(Cc2ccc3oc(-c4ccc(Cl)cc4)cc(=O)c3c2)nn1)Nc1ccc(F)cc1
InChIKey: TVVGJYYVPGRNCM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B by fluorescence spectrophotometry assay
Measurement: IC50 = 32910 nM (pChEMBL 4.480000019073486)
Descriptors: MW 530.99, ALogP 6.24, HBA 6, HBD 1, PSA 90.02, QED 0.23
Compound (SMILES): CC(=O)O[C@H]1[C@@H](n2ccnc2)C[C@H]2[C@@H]3CC=C4C[C@@H](N5CCCC5)CC[C@]4(C)[C@H]3CC[C@@]21C
InChIKey: KZPNCXIHDYJAKC-JWLDDNKLSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase (unknown origin)
Measurement: IC50 = 4897.79 nM (pChEMBL 5.309999942779541)
Descriptors: MW 451.66, ALogP 5.39, HBA 5, HBD 0, PSA 47.36, QED 0.46
Compound (SMILES): O=C(c1ccc(-c2n[nH]c3ncc(Cc4cc(F)ccc4F)cc23)cc1)N1CCCC(O)C1
InChIKey: BLVOTEXWHIOGMU-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) using TK as substrate in presence of ATP incubated for 30 mins by HTRF KinEASE assay
Measurement: IC50 = 571 nM (pChEMBL 6.239999771118164)
Descriptors: MW 448.47, ALogP 4.09, HBA 4, HBD 2, PSA 82.11, QED 0.49
Compound (SMILES): CC(C)(C)[Si](F)(c1ccc(C(=O)NCC(NC(=O)CC(C(=O)O)N2CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC2)C(=O)N[C@H](CCCCNC(=O)CCC(=O)NCCC[C@@H](NC(=O)CC[C@H](NC(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)O)C(=O)O)C(=O)O)cc1)C(C)(C)C
InChIKey: WKOSSKVSDDUZIM-CZLSFGLKSA-N
Target: Glutamate carboxypeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04609
Assay: Inhibition of recombinant PSMA (unknown origin)
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 1457.6
Compound (SMILES): CCc1c(-c2cncc(C#N)c2)cnc(N)c1-c1ccc(O)cc1
InChIKey: ZINOFMOWAMSGQS-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using ubiquitin-Rho as substrate incubated for 1 hrs
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 316.36, ALogP 3.53, HBA 5, HBD 2, PSA 95.82, QED 0.77
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]c(=O)[nH]c3c2)Cn2nnnc2N1C
InChIKey: IGVZGUCRPHIRLR-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of N-terminal GST-fused human wild type LRRK2 using fluorescein-labeled LRRKtide as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by TR-FRET assay
Measurement: IC50 > 8600 nM (pChEMBL 5.065999984741211)
Descriptors: MW 326.32, ALogP 0.21, HBA 7, HBD 3, PSA 124.59, QED 0.62
Compound (SMILES): CCCCCCCP(=O)(C(C)C)C(C)C
InChIKey: TXGFWTAHDCIQST-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Agonist activity at human TRMP8 expressed in HEK293 cells by fluorometric imaging plate reader analysis
Measurement: EC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 232.35, ALogP 5.14, HBA 1, HBD 0, PSA 17.07, QED 0.42
Compound (SMILES): CN1C(=S)N(c2ccccc2)C(=O)/C1=C\c1ccc(N(C)CCO)cc1O
InChIKey: YJTQKBGERFHCOI-SFQUDFHCSA-N
Target: NADPH oxidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPH5
Assay: Inhibition of human NOX4 assessed as reduction in ROS production using lucigenin as substrate in presence of NADPH by chemiluminescence based microplate reader analysis
Measurement: IC50 = 5140 nM (pChEMBL 5.289999961853027)
Descriptors: MW 383.47, ALogP 2.43, HBA 5, HBD 2, PSA 67.25, QED 0.61
Compound (SMILES): O=C(Nc1cnccc1N1CCC(F)(F)CC1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: GRYSKXCHMRRJMC-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay
Measurement: IC50 = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 401.42, ALogP 3.31, HBA 5, HBD 2, PSA 87.22, QED 0.8
Compound (SMILES): CC(C)CN(c1ccc(C(=O)O)c(O)c1)S(=O)(=O)c1ccc(Br)cc1
InChIKey: WWKYHKSRRKGJMV-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 16980 nM (pChEMBL 4.769999980926514)
Descriptors: MW 428.3, ALogP 3.7, HBA 4, HBD 2, PSA 94.91, QED 0.73
Compound (SMILES): CCCCCn1c(C)c(Br)c(C(=O)c2cccc3ccccc23)c1C
InChIKey: OJCIPDIKAMTTAD-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Binding affinity to rat CB1 receptor
Measurement: EC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 398.34, ALogP 6.44, HBA 2, HBD 0, PSA 22, QED 0.35
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNc2nc(-c3ccccc3)c(-c3ccccc3)o2)cc1
InChIKey: SVGDDLZPOUNBAG-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 by fluorescence based assay method
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 460.54, ALogP 6.46, HBA 5, HBD 3, PSA 93.18, QED 0.24
Compound (SMILES): CC(=O)N1CCC(O)(Cn2cnc3cc(Cl)ccc3c2=O)CC1
InChIKey: SAEBNEGULYBVDG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-AMC as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 335.79, ALogP 1.42, HBA 5, HBD 1, PSA 75.43, QED 0.9
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2Cl)CCC1(O)c1cccc(O)c1
InChIKey: VZKYGOFDBBGOOF-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H] DAMGO from mouse MOR expressed in CHO cell membrane incubated for 90 mins by scintillation method
Measurement: Ki = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(ccn2-c2cc(C)nc(N)n2)cn1
InChIKey: GRSNWUGFAXKMQP-SFHVURJKSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 321.38, ALogP 2.22, HBA 6, HBD 2, PSA 89.85, QED 0.71
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(N)=O)c2C#N)cc1
InChIKey: KIWBVAQAICXQKZ-KRWDZBQOSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 10 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 3240 nM (pChEMBL 5.489999771118164)
Descriptors: MW 436.52, ALogP 4.9, HBA 5, HBD 1, PSA 101.89, QED 0.44
Compound (SMILES): Cc1noc2c1-c1ccccc1C(c1ccc(Cl)cc1)=NC2C(N)=O
InChIKey: OXAOKSYHGBRQPM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD1 in human MV4-11 cells assessed as reduction of MYC RNA expression after 4 hrs by PCR analysis
Measurement: EC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 351.79, ALogP 3.68, HBA 4, HBD 1, PSA 81.48, QED 0.76
Compound (SMILES): O=C(c1cccs1)c1sc(N(c2ccccc2)c2ccccc2)nc1-c1ccc([N+](=O)[O-])cc1
InChIKey: NYIWDONCIPTYBI-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX-2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by ELISA
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 483.57, ALogP 7.48, HBA 7, HBD 0, PSA 76.34, QED 0.14
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CBr)[C@@H]1CCC2=O
InChIKey: ZWWRBZHWUQWCAY-BGJMDTOESA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 1399.59 nM (pChEMBL 5.849999904632568)
Descriptors: MW 365.31, ALogP 4.46, HBA 2, HBD 0, PSA 34.14, QED 0.64
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(N4CCOC[C@H]4C)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: BYYFORUHJRHMMU-MRVPVSSYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 469.35, ALogP 4.42, HBA 6, HBD 3, PSA 107.55, QED 0.52
Compound (SMILES): C[C@@]12CC[C@@H]3[C@@](CC[C@H]4[C@@]3(C)CCC[C@@]4(C)C(=O)OCCN3CCNCC3)(CC1=O)C2
InChIKey: QDNFHEBSODTWQH-DCWXTMKTSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) by DAS-ELISA
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 430.63, ALogP 3.81, HBA 5, HBD 1, PSA 58.64, QED 0.69
Compound (SMILES): CCCn1ncc2ccc(N(Cc3ccc(F)cc3)C(=O)NCCCn3cncc3C)cc21
InChIKey: BUETXBMLMXGHAV-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis
Measurement: IC50 = 62.4 nM (pChEMBL 7.210000038146973)
Descriptors: MW 448.55, ALogP 4.9, HBA 5, HBD 1, PSA 67.98, QED 0.37
Compound (SMILES): N[C@@H](CCNC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
InChIKey: VSMPMKXRMDRUSC-JTQLQIEISA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP-4 (unknown origin)
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 436.36, ALogP 2.2, HBA 5, HBD 2, PSA 89.07, QED 0.56
Compound (SMILES): COc1ccc(Nc2ccnc3c2ccn3-c2ccc(C)c(C)c2)cc1Cl
InChIKey: CZZRCHAIYWGHDK-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant PI5P4Kalpha (unknown origin) expressed in Escherichia coli BL21(DE3) by ADP-Glo reagent based assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 377.88, ALogP 6.05, HBA 4, HBD 1, PSA 39.08, QED 0.47
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(O)c(F)c3)c(N)c2c1C
InChIKey: GOWAKXRORUSYKE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulator activity at human M4 receptor expressed in CHO cells co-expressing Gqi5 in presence of EC20 concentration of acetylcholine by calcium mobilization assay
Measurement: EC50 = 59.1 nM (pChEMBL 7.230000019073486)
Descriptors: MW 346.39, ALogP 2.67, HBA 6, HBD 3, PSA 101.13, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(N)=O
InChIKey: KVBYOLYKARPVJR-BWJWTDLKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human kappa opioid receptor expressed in CHO-K1 cells incubated for 1 hr by 1450 microbeta scintillation counter analysis
Measurement: Ki = 23003 nM (pChEMBL 4.639999866485596)
Descriptors: MW 570.7, ALogP -3.91, HBA 8, HBD 12, PSA 323.3, QED 0.04
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(C)=O)[C@@H](C)O)CCC/C=C\CCC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N(c2ccc3ccccc3c2)[C@@H](C)C(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: RZNVRPFTVXTCDL-KBLPGWQZSA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Binding affinity to human beta catenin assessed as dissociation constant
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 1601.96
Compound (SMILES): CCCNc1cnc2ccc(-c3cccc(O)c3)nn12
InChIKey: IGGYXWVZIKKADS-UHFFFAOYSA-N
Target: Calcium-dependent protein kinase 1 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: P62344
Assay: Inhibition of Plasmodium falciparum CDPK1
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 268.32, ALogP 2.92, HBA 5, HBD 2, PSA 62.45, QED 0.76
Compound (SMILES): O=C(Nc1nc2ccccc2[nH]1)C1CC1c1ccccc1
InChIKey: XSIZKMVNFSTJAG-UHFFFAOYSA-N
Target: Lysophosphatidic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBW0
Assay: Inhibition of LPA2 receptor (unknown origin)
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 277.33, ALogP 3.31, HBA 2, HBD 2, PSA 57.78, QED 0.77
Compound (SMILES): Cc1nc(Nc2nc(=O)c3ccccc3[nH]2)nc2ccc(N3CCOCC3)cc12
InChIKey: RHLXJCVXIPYTGM-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Binding affinity to STAT3 (unknown origin) by SPR analysis
Measurement: Kd = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 388.43, ALogP 2.75, HBA 7, HBD 2, PSA 96.03, QED 0.56
Compound (SMILES): CCOC(=O)c1ccc(NC(=S)NC(=O)Cc2c(C)n(C(=O)c3ccc(Cl)cc3)c3ccc(OC)cc23)cc1
InChIKey: CNWMVFFPTJIZQZ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX-2 colorimetric enzyme immunoassay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 564.06, ALogP 5.53, HBA 7, HBD 2, PSA 98.66, QED 0.23
Compound (SMILES): CCOc1ccc(F)c(N2CCC(Oc3ccc(N4C[C@H](OCCCOC)C[C@@H]4CC(=O)O)cc3)CC2)c1
InChIKey: VZXNHQJRGRHQLM-ATIYNZHBSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of PPARgamma (unknown origin)
Measurement: EC50 > 47000 nM (pChEMBL 4.328000068664551)
Descriptors: MW 530.64, ALogP 4.75, HBA 7, HBD 1, PSA 80.7, QED 0.37
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3cc(OC)c(C)c(OC)c3)nn21
InChIKey: ZEIZIRVZVXALHM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal His-tagged recombinant human BTK (393 to 659 residues) expressed in baculovirus infected Sf9 cells using Biotin-AVLESEEELYSSARQ-NH2 as substrate preincubated for 1 hrs followed by substrate addition in presence of ATP at Km concentration and measured after 1 hrs by TR-FRET assay
Measurement: IC50 = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 461.52, ALogP 3.5, HBA 7, HBD 3, PSA 120.5, QED 0.46
Compound (SMILES): CN1CCC2(CC1)c1ccccc1N(Cc1ccc(C(=O)NO)cc1)C2c1ccccc1
InChIKey: GHSNRQJQGJQKRS-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using ZMAL (Z-(Ac)Lys-AMC) as fluorogenic substrate incubated for 120 mins by microplate reader assay
Measurement: IC50 = 4290 nM (pChEMBL 5.369999885559082)
Descriptors: MW 427.55, ALogP 4.53, HBA 4, HBD 2, PSA 55.81, QED 0.47
Compound (SMILES): O=C(Nc1cnccc1-c1cccc(F)c1F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: NUQDMQZYZIYAFS-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin) assessed as decrease in tau phosphorylation by high content cell based assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 394.38, ALogP 4.02, HBA 4, HBD 2, PSA 83.98, QED 0.68
Compound (SMILES): CCCC[C@H](NC(=O)c1[nH]c2c(c1CC)C(=O)CC(C)(C)C2)C(=O)Nc1ccccc1
InChIKey: LTXNDWHATSHPKB-SFHVURJKSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of N-terminal GST-tagged human recombinant G9a (785 to 1210 residues) expressed in baculovirus infected Sf9 cells incubated for 1 hr by AlphaLISA analysis
Measurement: IC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 423.56, ALogP 4.66, HBA 3, HBD 3, PSA 91.06, QED 0.58
Compound (SMILES): Clc1cc(Cl)cc(Nc2nc(-c3nc(-c4ccccc4Cl)cs3)cs2)c1
InChIKey: OULVZVSWNBPRDB-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 6.636 nM (pChEMBL 8.180000305175781)
Descriptors: MW 438.79, ALogP 7.64, HBA 5, HBD 1, PSA 37.81, QED 0.36
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1O)c1cccs1
InChIKey: HFJFEYAKDAKSFT-GQCTYLIASA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of mushroom tyrosinase using L-tyrosine as substrate assessed as diphenolase activity incubated for 20 mins by microplate reader analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 246.29, ALogP 3.06, HBA 4, HBD 2, PSA 57.53, QED 0.65
Compound (SMILES): C=CC(=O)Nc1cccc(Cn2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)c1
InChIKey: QNECGPNPZHRUNN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) incubated for 40 mins in the presence of ATP by scintillation based radiometric protein kinase assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 462.51, ALogP 5.04, HBA 7, HBD 2, PSA 107.95, QED 0.33
Compound (SMILES): O=c1c2cncn2c2c(Cl)cccc2n1Cc1cccnc1
InChIKey: BRFUYNWSKXSYOM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P31644
Assay: Displacement of flumazenil from alpha5 GABAA receptor (unknown origin)
Measurement: Ki = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 310.74, ALogP 2.75, HBA 5, HBD 0, PSA 52.19, QED 0.57
Compound (SMILES): CC1(CCCCCC(=O)NCCOCCOCCOCCOc2ccnc3c(S(=O)(=O)Nc4ccccc4C#Cc4ccc(C(=O)O)nc4)cccc23)C(/C=C/C=C/C=C2\N(CCCS(=O)(=O)O)c3ccc(S(=O)(=O)O)cc3C2(C)C)=[N+](CCCS(=O)(=O)[O-])c2ccc(S(=O)(=O)O)cc21
InChIKey: CRTKUBQOJOGREB-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human MDA-MB-231 cells assessed as inhibition of lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 1461.7
Compound (SMILES): Clc1ccc(-c2c(-n3ccnc3)c(-c3ccc(Br)cc3)nn2-c2ccc(Cl)c(Cl)c2)cc1
InChIKey: KXIOGQRSFMIHRF-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease using DabcylKTSAVLQSGFRKME-Edans amide as substrate by FRET assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 544.67, ALogP 8.11, HBA 4, HBD 0, PSA 35.64, QED 0.23
Compound (SMILES): COC1=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@@]2(C)CCC1=O
InChIKey: JYMVNNNTLDUEBG-PFIYWFKMSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 7194.49 nM (pChEMBL 5.139999866485596)
Descriptors: MW 316.44, ALogP 4.06, HBA 3, HBD 0, PSA 43.37, QED 0.73
Compound (SMILES): NS(=O)(=O)CCN[C@H]1CS(=O)(=O)C[C@@H]1S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: TZYOKZXGKCLYKY-RYUDHWBXSA-N
Target: Nuclear factor erythroid 2-related factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16236
Assay: Activation of Nrf2 in human IMR-32-ARE-Luc cells by Bright-Glo luciferase assay
Measurement: EC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 451.38, ALogP -0.19, HBA 7, HBD 2, PSA 140.47, QED 0.61
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccccc4)cs3)c(OCCC3CCNCC3)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: NAGHVWWLSLYLFS-UHFFFAOYSA-M
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Inhibition of HIS-tagged recombinant Leishmania infantum TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 545.78, ALogP 4.66, HBA 7, HBD 2, PSA 81.87, QED 0.19
Compound (SMILES): CN1Cc2c(ncnc2N2CCC(CNS(N)(=O)=O)CC2)NC1=O.Cl
InChIKey: XMNKODRXOIESSH-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22413
Assay: Inhibition of ENPP1 (unknown origin)
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 355.42, ALogP -0.54, HBA 6, HBD 3, PSA 133.55, QED 0.66
Compound (SMILES): Clc1ccc2c(c1)c1cc(Cl)ccc1n2CCCCN1CCOCC1
InChIKey: NXEVXQUJSINAEF-UHFFFAOYSA-N
Target: Plasma membrane ATPase 1 (SINGLE PROTEIN), Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
UniProt: P05030
Assay: Inhibition of Saccharomyces cerevisiae H+ ATPase pma1 isoform assessed as ATP hydrolysis incubated for 30 mins by colorimetric method
Measurement: IC50 = 24900 nM (pChEMBL 4.599999904632568)
Descriptors: MW 377.32, ALogP 5.21, HBA 3, HBD 0, PSA 17.4, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(=N)N)C1c2ccccc2-c2ccccc21)C(=O)N[C@@H](CCSC)C(=O)O
InChIKey: KWNDZEBBZWNYCL-CPMBYVPVSA-N
Target: Substance-P receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14600
Assay: Inhibition of [125I]BHSP binding to neurokinin receptor 1 in rat brain synaptosomes
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 1326.59
Compound (SMILES): CN(C)C(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCOCCOCCF
InChIKey: JXNRAAQRFHINGN-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3beta (unknown origin)
Measurement: IC50 = 426 nM (pChEMBL 6.369999885559082)
Descriptors: MW 466.54, ALogP 2.64, HBA 8, HBD 1, PSA 102.88, QED 0.45
Compound (SMILES): O=C(N[C@H]1CCNC1=O)c1cnc2nc(C3CC3)ccc2c1
InChIKey: DMOPHVMVVUKTFV-ZDUSSCGKSA-N
Target: Hematopoietic prostaglandin D synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O60760
Assay: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 296.33, ALogP 1.13, HBA 4, HBD 2, PSA 83.98, QED 0.89
Compound (SMILES): N[C@H](Cc1cccc(F)c1)NC(=O)c1ccc(-c2ccncc2)cc1
InChIKey: QVRPQJUVEIYKGC-IBGZPJMESA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of human ROCK1
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 335.38, ALogP 3.15, HBA 3, HBD 2, PSA 68.01, QED 0.7
Compound (SMILES): O=C(C#Cc1ccccc1)NCc1nc(-c2ccc(C(F)(F)F)cc2)no1
InChIKey: KSABZAUCRGTZGL-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease expressed in Escherichia coli BL21 (DE3) using MDA-AVLQSGFR-Lys(Dnp)-Lys-NH2 as substrate incubated for 10 mins by FRET analysis
Measurement: IC50 = 46870 nM (pChEMBL 4.329999923706055)
Descriptors: MW 371.32, ALogP 3.42, HBA 4, HBD 1, PSA 68.02, QED 0.72
Compound (SMILES): C[C@H](NC[C@@H](c1cccnc1)N(C(=O)C(Cl)Cl)c1ccc(-c2ccccc2)cc1)c1ccccc1
InChIKey: UZPPNWVDUAIPFK-IDISGSTGSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 Main protease
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 504.46, ALogP 6.98, HBA 3, HBD 1, PSA 45.23, QED 0.25
Compound (SMILES): c1cc(CNCCCNC2CCCCC2)cc(CNCCCNC2CCCCC2)c1
InChIKey: NYXFLBKAKUKQHI-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Binding affinity to CXCR4 (unknown origin) expressed in CHO cells incubated for 40 mins by competitive binding assay method
Measurement: IC50 = 155.5 nM (pChEMBL 6.809999942779541)
Descriptors: MW 414.68, ALogP 4.49, HBA 4, HBD 4, PSA 48.12, QED 0.34
Compound (SMILES): Cc1cccc(CN2CCc3c(c(=O)n(Cc4ccc(C(F)(F)F)cc4)c(=O)n3CCCN)C2)c1
InChIKey: LNJXVMWNCHOCHA-UHFFFAOYSA-N
Target: ATP-dependent Clp protease proteolytic subunit, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16740
Assay: Agonist activity at human recombinant CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay
Measurement: EC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 486.54, ALogP 3.29, HBA 6, HBD 1, PSA 73.26, QED 0.56
Compound (SMILES): O=C(CCl)Nc1cccc(Oc2cc(NCc3cc(C(F)(F)F)cc(C(F)(F)F)c3)ncn2)c1
InChIKey: SYFIOVQEHUOPSD-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O14733
Assay: Inhibition of human recombinant full-length MEK7 using JNK1 as substrate incubated for 30 mins followed by ATP addition measured after 1 hr by ADP Glo luminescent assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 504.82, ALogP 6.1, HBA 5, HBD 2, PSA 76.14, QED 0.3
Compound (SMILES): CCC[S+]([O-])Nc1ccc(F)c(Cc2c[nH]c3nc(N)n(C)c(=O)c23)c1F
InChIKey: KVHNOFJXGOWHOE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant (unknown origin) by ELISA based assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 395.44, ALogP 2.2, HBA 6, HBD 3, PSA 111.79, QED 0.55
Compound (SMILES): COc1ccc2occ(CCc3nc4cc(C)ccc4n3-c3ccccc3)c(=O)c2c1
InChIKey: QQYAIRFCYUWSPI-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 410.47, ALogP 5.23, HBA 5, HBD 0, PSA 57.26, QED 0.4
Compound (SMILES): O=C(NCCCNC1CCCCC1)c1ccc(C(=O)NCCCNC2CCCCC2)cc1
InChIKey: LWJFGKSEPZQLHS-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Binding affinity to CXCR4 (unknown origin) expressed in CHO cells incubated for 40 mins by competitive binding assay method
Measurement: IC50 = 1697.7 nM (pChEMBL 5.769999980926514)
Descriptors: MW 442.65, ALogP 3.77, HBA 4, HBD 4, PSA 82.26, QED 0.37
Compound (SMILES): Clc1cnc2n1CCCc1nnc([C@H]3CC[C@H](Oc4ccccn4)CC3)n1-2
InChIKey: CXXPPSRYQJMDLL-HDJSIYSDSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1A receptor expressed in human 1321N1 cells assessed as Ca2+ mobilization incubated for 15 mins by FLIPR calcium 5 assay
Measurement: IC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 384.87, ALogP 3.56, HBA 7, HBD 0, PSA 70.65, QED 0.69
Compound (SMILES): CCCCCCCCCCNC(=O)OC[C@H](CSC[C@@H](N)C(=O)NCCOCCOCCOCCP(=O)(O)O)OC(=O)NCCCCCCCCCC
InChIKey: AAEMYQBTFDDLIX-CZNDPXEESA-N
Target: Toll-like receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60603
Assay: Agonist activity at human TLR2 transfected in HEK293 cells relative to control
Measurement: EC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 801.04, ALogP 5.49, HBA 11, HBD 6, PSA 217, QED 0.03
Compound (SMILES): O=C(Cc1ccc(C(F)(F)F)cc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: NESIORPNFVEQNP-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16798
Assay: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 364.37, ALogP 3.3, HBA 3, HBD 1, PSA 43.78, QED 0.91
Compound (SMILES): CCCCCCCCCCCCCCCc1cc(-c2cn([C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3N)nn2)ccc1C(=O)O
InChIKey: CBHOHJQIXUMOHW-URYJJRPLSA-N
Target: Heparanase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y251
Assay: Inhibition of Heparanase-1 (unknown origin) by HTRF method
Measurement: IC50 = 21500 nM (pChEMBL 4.670000076293945)
Descriptors: MW 574.72, ALogP 4.31, HBA 9, HBD 5, PSA 181.02, QED 0.16
Compound (SMILES): CCCOCCCCCCCCCC[C@@H]1OC[C@@H](N)[C@@H]1O
InChIKey: YZTVWYPNKDHRGS-IKGGRYGDSA-N
Target: Sphingosine kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYA1
Assay: Inhibition of SphK1 (unknown origin) using ATP as substrate preincubated for 40 mins followed by substrate addition and measured after 5 mins by spectrophotometric analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 301.47, ALogP 3.01, HBA 4, HBD 2, PSA 64.71, QED 0.51
Compound (SMILES): N#C/C(=C\c1cn(-c2ccccn2)c2ccccc12)C(=O)O
InChIKey: PBSMJFLWDXXGJH-FMIVXFBMSA-N
Target: Monocarboxylate transporter 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P53987
Assay: Inhibition of MCT1 in rat Brain-like endothelial cells incubated for 15 mins in presence of [14C]lactic acid by scintillation counter assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 289.29, ALogP 3.02, HBA 4, HBD 1, PSA 78.91, QED 0.59
Compound (SMILES): CCCCCNc1nc(N)nc(C)c1CCCN(Cc1ccc(CC(=O)OC)cc1)C(=O)CN1CCCCC1
InChIKey: UMECBZLEILSIMU-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 by reporter cell based assay
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 538.74, ALogP 4.13, HBA 8, HBD 2, PSA 113.68, QED 0.26
Compound (SMILES): CCCC[C@@H](C)[C@H]1CC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](C)C(=O)N[C@H]([C@@H](C)CC)C(=O)O1
InChIKey: VEELKRGSLCNVAR-SUPLHOOBSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35610
Assay: Inhibition of SOAT1 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrs
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 487.64, ALogP 2.89, HBA 5, HBD 3, PSA 113.6, QED 0.49
Compound (SMILES): CC(C)(C)Nc1nc(Nc2ccc(CC(=O)O)cc2)nc2[nH]cnc12
InChIKey: MWWIFXXTISLVDZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) using biotinylated EDPDYEWPSA as substrate incubated for 30 mins in presence of 33P-ATP by Scintillation Proximity Assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 340.39, ALogP 2.93, HBA 6, HBD 4, PSA 115.82, QED 0.56
Compound (SMILES): O=[N+]([O-])C1=Cc2cccc(I)c2OC1C(F)(F)F
InChIKey: OINSXVBMFZOPDW-UHFFFAOYSA-N
Target: P2Y purinoceptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15077
Assay: Antagonist activity at human P2Y6R expressed in human 1321N1 cells assessed as inhibition of UDP-induced calcium mobilization by FLIPR assay
Measurement: IC50 = 4090 nM (pChEMBL 5.389999866485596)
Descriptors: MW 371.05, ALogP 3.23, HBA 3, HBD 0, PSA 52.37, QED 0.43
Compound (SMILES): Cc1ccc2[nH]ncc2c1-c1cccc(C(=O)N2CCC(O)(Cn3cnn4cccc4c3=O)CC2)c1
InChIKey: LCXSKDLJIHYQMU-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using ubiquitin-Rh110 as substrate incubated for 23 to 45 mins by fluorescence based assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 482.54, ALogP 3.02, HBA 7, HBD 2, PSA 108.52, QED 0.41
Compound (SMILES): Cc1ccc(CN2CC=C(/C=C/c3ccc4c(Cl)cc(Cl)c(O)c4n3)CC2)cc1.Cl
InChIKey: WCZWFCCKAXUEFV-UHDJGPCESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 425.36, ALogP 6.4, HBA 3, HBD 1, PSA 36.36, QED 0.53
Compound (SMILES): N=C(N)NCCC[C@@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)c1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC1CCCCC1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: RNCVCRVWDGZPTQ-FJFXRYBISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human kappa opioid receptor expressed in CHO-K1 cells incubated for 1 hr by 1450 microbeta scintillation counter analysis
Measurement: Ki = 0.59 nM (pChEMBL 9.229999542236328)
Descriptors: MW 1035.31
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(CO)c3)cc2)nc2cnccc12)C(N)=O
InChIKey: HVLNHRNIHXMFSR-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 10 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 284 nM (pChEMBL 6.550000190734863)
Descriptors: MW 437.5, ALogP 4, HBA 6, HBD 3, PSA 124.92, QED 0.4
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccc(Cl)c4)n3)cc2C(F)(F)F)CC1
InChIKey: CSIMBPGKVWPGTE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Inhibition of Mycobacterium tuberculosis recombinant PknB (1 to 331 residues) expressed in Escherichia coli BL21-Rosetta cells using GarA and ATP as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 1 hr by ATP-competitive biochemical assay
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 447.89, ALogP 5.31, HBA 5, HBD 1, PSA 44.29, QED 0.59
Compound (SMILES): NC(=O)c1nn(CCO)cc1NC(=O)c1ccc2cnc(NC3CCCCC3N)nn12.O=C(O)C(F)(F)F
InChIKey: FDJPZKGPXRXNAA-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of human GST-tagged IRAK4 incubated for 30 mins in presence of ATP by fluorescent polarization assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 427.47, ALogP -0.05, HBA 10, HBD 5, PSA 178.48, QED 0.35
Compound (SMILES): CC(O)(CCCc1ccccc1Cl)c1cc(C(=O)N2Cc3ccccc3C2)ccc1O
InChIKey: GGIGZLLYBIOCGK-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Binding affinity to N-terminal 6His tagged human HSP90alpha (1 to 223 residues) expressed in Escherichia coli BL21 (DE3) cells incubated for 24 hrs by fluorescence polarization assay
Measurement: IC50 = 279 nM (pChEMBL 6.550000190734863)
Descriptors: MW 435.95, ALogP 5.43, HBA 3, HBD 2, PSA 60.77, QED 0.54
Compound (SMILES): CC1=CC[C@@]2(C)CC[C@@](O)(C(C)C)[C@@H]2C(OC(=O)c2ccc(O)cc2)C1
InChIKey: CYSHNJQMYORNJI-LMSKBGPXSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 358.48, ALogP 4.46, HBA 4, HBD 2, PSA 66.76, QED 0.62
Compound (SMILES): O=C(O)c1ccc(N(C2CCCC2)S(=O)(=O)c2ccc3ccccc3c2)cc1O
InChIKey: DJNCDDPHSXBDHZ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 24749 nM (pChEMBL 4.610000133514404)
Descriptors: MW 411.48, ALogP 4.38, HBA 4, HBD 2, PSA 94.91, QED 0.65
Compound (SMILES): N[C@H](Cc1c[nH]cn1)C(=O)NCc1ccc(SC(F)(F)F)cc1
InChIKey: CYTLJLLFGURITO-GFCCVEGCSA-N
Target: Neurolysin, mitochondrial (SINGLE PROTEIN), Rattus norvegicus
UniProt: P42676
Assay: Activation of recombinant rat Neurolysin using QFS as substrate incubated for 10 mins
Measurement: EC50 = 16100 nM (pChEMBL 4.789999961853027)
Descriptors: MW 344.36, ALogP 2.21, HBA 4, HBD 3, PSA 83.8, QED 0.7
Compound (SMILES): COCCCN1CCC(NC(=O)c2nn(C(C)C)c3ccccc23)CC1.O=C(O)C(=O)O
InChIKey: DKIOXWPVYPUNRY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13639
Assay: Partial agonist activity at human 5HT4E receptor expressed in CHO cells assessed as cAMP accumulation incubated for 4 hrs by luciferase reporter gene luminescence assay
Measurement: EC50 = 291 nM (pChEMBL 6.539999961853027)
Descriptors: MW 358.49, ALogP 2.85, HBA 5, HBD 1, PSA 59.39, QED 0.77
Compound (SMILES): Cn1cc2c(Cl)c(-c3n[nH]c4nc(N5C[C@@H]6[C@H](C5)[C@@]6(CN)c5ccccc5)cnc34)ccc2n1
InChIKey: NMMDXGOWSVAAHM-FLJMWOENSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 using IRS1 peptide and DiFMUP as substrate incubated for 30 mins followed by DiFMUP addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 470.97, ALogP 3.52, HBA 7, HBD 2, PSA 101.54, QED 0.42
Compound (SMILES): COc1ccccc1COCc1c(C=O)c(O)c(O)c(C)c1-c1ccccc1
InChIKey: NYSXTYGWMMTSDQ-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition of androgen receptor in human LNCaP cells assessed as inhibition of AR transcription activity by dual-luciferase reporter assays
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 378.42, ALogP 4.61, HBA 5, HBD 2, PSA 75.99, QED 0.46
Compound (SMILES): O=c1c2ccc(Cl)cc2ncn1CC1(O)CCN(CCCc2ccccc2)CC1
InChIKey: QKTRIYQZSKPDRE-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using Ub-AMC as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.93, ALogP 3.51, HBA 5, HBD 1, PSA 58.36, QED 0.67
Compound (SMILES): COC(=O)c1c(Sc2c(O)cc(OC)c(C(=O)c3c(O)cc(C)cc3O)c2C(=O)OC)c(O)cc(OC)c1C(=O)c1c(O)cccc1O
InChIKey: RSGQPLWRQKZZEB-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of Amyloid beta (1 to 42) (unknown origin) aggregation incubated for 24 hrs by ThioflavinT-dye based fluorescence analysis
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 680.64, ALogP 4.43, HBA 15, HBD 6, PSA 226.58, QED 0.1
Compound (SMILES): Cc1cncn1CCCNC(=O)N(Cc1ccc(F)cc1)c1ccc2cnn(C)c2c1
InChIKey: VEKHXGWQUKKGBE-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of human glutaminyl cyclase using L-glutamine-7-amido-4-methylcoumarin as substrate incubated for 10 mins in presence of pyroglutamyl peptidase by fluorometry analysis
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 420.49, ALogP 4.02, HBA 5, HBD 1, PSA 67.98, QED 0.46
Compound (SMILES): Nc1c(C(=O)Nc2cccc(Cl)c2)nnn1Cc1ccc(CN2CCOCC2)cc1
InChIKey: PUNHTNLSRWJCPR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG potassium channel by Q-patch clamp assay
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 426.91, ALogP 2.65, HBA 7, HBD 2, PSA 98.3, QED 0.63
Compound (SMILES): COc1ccc2nc(-c3ccc(N4CCCCCCC4)cc3)sc2c1
InChIKey: JOSKQIGLWUFDPM-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binding affinity to amyloid beta (1 to 40) (unknown origin) aggregates assessed as dissociation constant
Measurement: Kd = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 352.5, ALogP 5.74, HBA 4, HBD 0, PSA 25.36, QED 0.6
Compound (SMILES): c1ccc(COC2CCN(Cc3cn4ccccc4n3)CC2)nc1
InChIKey: VUGZNXOHTNGPHN-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 322.41, ALogP 2.91, HBA 5, HBD 0, PSA 42.66, QED 0.72