lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)NC(=O)O[C@@H]1CC[C@H](c2cc(Nc3nccc4nc[nH]c34)n[nH]2)C1
InChIKey: KBDKBXAHCABTNJ-NWDGAFQWSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/Cyclin E1 (unknown origin) assessed as inhibition of substrate peptide phosphorylation using eIF4E-binding protein 1 as peptide substrate incubated for 4 hrs in presence of ATP by Lance Ultra HTRF assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 369.43, ALogP 3.2, HBA 6, HBD 4, PSA 120.61, QED 0.55
Compound (SMILES): CCCCCCCCCC(=O)OC[C@H](CSC[C@@H](N)C(=O)NCCOCCOCCOCCP(=O)(O)O)OC(=O)CCCCCCCCC
InChIKey: JRFLLOZZIWLFBR-FIRIVFDPSA-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 = 1450 nM (pChEMBL 5.840000152587891)
Descriptors: MW 742.95, ALogP 5.13, HBA 11, HBD 4, PSA 192.94, QED 0.04
Compound (SMILES): C=CC(=O)N1CCCC(N2NC(c3cc(C(C)(C)O)n(C)n3)c3c(N)ncnc32)C1
InChIKey: NNJYOOTXCWAFKM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 using biotin as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins in presence of ATP by fluorescence based assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 412.5, ALogP 0.61, HBA 9, HBD 3, PSA 125.43, QED 0.62
Compound (SMILES): C=CC(=O)Nc1ccc2ncc(NC(=O)Nc3ccccc3)nc2c1
InChIKey: KJKCOOWPRZTMQC-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using TK as substrate incubated for 30 min in presence of ATP by TR-FRET assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 333.35, ALogP 3.4, HBA 4, HBD 3, PSA 96.01, QED 0.64
Compound (SMILES): Cc1cc(N2CCN(C(=O)c3ccccc3C)CC2)nc(N(C)C)n1
InChIKey: WSFKAACZXGOARN-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Chaperone activity at GCase N370S GBA mutant in patient derived fibroblast cell using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate assessed as substrate cleavage by measuring concentration required for maximal response incubated for 5 days by fluorescence based assay
Measurement: EC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 339.44, ALogP 2.12, HBA 5, HBD 0, PSA 52.57, QED 0.86
Compound (SMILES): O=c1c2cncn2c2ccccc2n1Cc1ccccn1
InChIKey: XPMUWMNPNZFOHE-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 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 276.3, ALogP 2.09, HBA 5, HBD 0, PSA 52.19, QED 0.56
Compound (SMILES): NCC(=O)NCc1cc2cc(CN3CCOCC3)cc3c(=O)c(C(=O)NCc4ccc(Cl)cc4)cn1c23
InChIKey: GONYIXWMXYEMDC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by automated patch clamp method
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 522.01, ALogP 1.88, HBA 7, HBD 3, PSA 118.17, QED 0.33
Compound (SMILES): Cc1ccc(-c2ccc3c(C)n[nH]c3c2)c2c1[C@H](N(C)C(=O)c1ncccc1C(F)F)CCC2
InChIKey: ZGVMLURVURNUQI-HSZRJFAPSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Binding affinity to his-tagged wild type c-MET (1050 to 1346 residues) (unknown origin) by surface plasmon resonance analysis
Measurement: Kd = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 460.53, ALogP 6.33, HBA 3, HBD 1, PSA 61.88, QED 0.39
Compound (SMILES): COCCN1CCC(c2nnc(-c3nn(C(C)C)c4ccccc34)o2)CC1.O=C(O)C(=O)O
InChIKey: IHXVCXYHHKILAQ-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 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 369.47, ALogP 3.49, HBA 7, HBD 0, PSA 69.21, QED 0.66
Compound (SMILES): O=C(N[C@H]1C[C@@H]1c1ccccc1)[C@@H]1CN(C(=O)C#CC(=O)N2C[C@@H](C(=O)N[C@H]3C[C@@H]3c3ccccc3)[C@H](C(=O)N[C@H]3C[C@@H]3c3ccccc3)C2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: MZUHYVJZHHHYOK-BDJQJBLGSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15399
Assay: Agonist activity at TLR2/TLR1 in human THP-1 cells
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 857.02, ALogP 3.83, HBA 6, HBD 4, PSA 157.02, QED 0.16
Compound (SMILES): Cc1cc(-c2ccnc3ccc(C(N)=O)cc23)cc(-c2cc3n(n2)CCC3)n1
InChIKey: NHPOPKNMQWYZLR-UHFFFAOYSA-N
Target: Transforming growth factor beta-1 proprotein (SINGLE PROTEIN), Homo sapiens
UniProt: P01137
Assay: Inhibition of TGF-beta receptor (unknown origin)
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 369.43, ALogP 3.51, HBA 5, HBD 1, PSA 86.69, QED 0.6
Compound (SMILES): O=c1c2ccccc2nc(-c2cccc(OS(=O)(=O)[O-])c2)n1CCCCCn1c(-c2cccc(OS(=O)(=O)[O-])c2)nc2ccccc2c1=O.[Na+].[Na+]
InChIKey: ICHYXXOOYMWIEJ-UHFFFAOYSA-L
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human FXIa using S-2366 as chromogenic substrate preincubated with enzyme for 10 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 = 89000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 704.74, ALogP 4.67, HBA 12, HBD 2, PSA 196.98, QED 0.13
Compound (SMILES): CC(C)=CC[C@H]1C[C@@H]2C[C@@H]3[C@@H](C[C@]4(C)C(C)(C)OC[C@]34C)C(=O)[C@](C(=O)c3ccccc3)(C1=O)C2(C)C
InChIKey: ANMSGGQOWGFCDT-PSBNPPRTSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX-2 (unknown origin)
Measurement: IC50 = 5270 nM (pChEMBL 5.28000020980835)
Descriptors: MW 504.71, ALogP 6.87, HBA 4, HBD 0, PSA 60.44, QED 0.25
Compound (SMILES): c1cnc(N2CCN(CCN3c4ccccc4Sc4ccccc43)CC2)nc1
InChIKey: ULYKLWYODYKRCO-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant LSD1 (unknown origin) expressed in Escherichia coli BL21 (DE3) using H3K4me2 peptide as substrate incubated for 30 mins by fluorescence based microplate reader assay
Measurement: IC50 = 4722 nM (pChEMBL 5.329999923706055)
Descriptors: MW 389.53, ALogP 3.9, HBA 6, HBD 0, PSA 35.5, QED 0.67
Compound (SMILES): C=C(F)C(=O)N1CC[C@H](n2nnc3c(O[C@@H](C)[C@@H]4CCCN4C)nc4c(F)c(-c5ncc(F)c6ccccc56)c(C)cc4c32)C[C@H]1CC#N
InChIKey: WQSXJTGSZYLBRB-KYALDGGBSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant (unknown origin) assessed as inhibition of SOS1 mediated nucleotide exchange incubated for 2 hrs in presence of GppNHp by fluorescence based analysis
Measurement: IC50 <= 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 668.72, ALogP 6.57, HBA 9, HBD 0, PSA 113.06, QED 0.18
Compound (SMILES): O=C(NO)c1ccc(CN2CCN(C(=O)c3c[nH]c4cc(OCc5ccccc5)ccc34)CC2)cc1
InChIKey: XJILHIFYAJQCAV-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using fluorogenic peptide RHKKAc-AMC as substrate by fluorescence-based assay
Measurement: IC50 = 1055 nM (pChEMBL 5.980000019073486)
Descriptors: MW 484.56, ALogP 3.82, HBA 5, HBD 3, PSA 97.9, QED 0.27
Compound (SMILES): CCN/C(=N\S(C)(=O)=O)NCc1cc(-c2ccc(Cl)cc2)n(-c2ccc(Cl)cc2)n1
InChIKey: QTKYBXZVSFBHIT-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 (unknown origin)
Measurement: IC50 = 848 nM (pChEMBL 6.070000171661377)
Descriptors: MW 466.39, ALogP 3.86, HBA 4, HBD 2, PSA 88.38, QED 0.43
Compound (SMILES): COc1cc(/C=C/c2nnc(-c3ccc(Cl)cc3Cl)o2)ccc1O
InChIKey: XIJPSDHGQSTMMS-XVNBXDOJSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin)
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 363.2, ALogP 4.93, HBA 5, HBD 1, PSA 68.38, QED 0.71
Compound (SMILES): Cc1ccc2nc(-c3ccc(NS(=O)(=O)Cc4ccc(C(=O)O)cc4)cc3)sc2c1
InChIKey: YKIOAIJGQJRQSG-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human GAL4-fused RORgamma LBD (262 to 507 residues) transfected in HEK293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 438.53, ALogP 4.91, HBA 5, HBD 2, PSA 96.36, QED 0.45
Compound (SMILES): CNC(=O)[C@@H](NC(=O)c1nn(-c2ccc(Cl)cc2)c(-n2cccc2)c1C)C(C)C
InChIKey: OFUQVXFTLJUYBJ-KRWDZBQOSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]-WIN55212-2 from CB1R in rat brain membranes incubated for 60 mins by radioligand competitive binding assay
Measurement: Ki = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 413.91, ALogP 3.13, HBA 5, HBD 2, PSA 80.95, QED 0.65
Compound (SMILES): O=c1cc(Cn2cc(COc3ccc(F)cc3)nn2)occ1O
InChIKey: VNLGMPPEOPEUEE-UHFFFAOYSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of mushroom tyrosinase
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 317.28, ALogP 1.7, HBA 7, HBD 1, PSA 90.38, QED 0.77
Compound (SMILES): O=C1C(=O)N(C2CCOC2)CCN1Cc1ncc(-c2ccccc2)cn1
InChIKey: IUCNCJOMQSYXPI-UHFFFAOYSA-N
Target: L-amino-acid oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RQ9
Assay: Inhibition of C-terminal 6-His tagged recombinant human IL4I1 (Gln22 to His567 residues) expressed in CHO cells using Phe/Tyr/Trp as substrate assessed as inhibition of H2O2 production measured after 240 mins by Amplex red and horseradish peroxidase based fluorescence assay
Measurement: EC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 352.39, ALogP 1.1, HBA 5, HBD 0, PSA 75.63, QED 0.77
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CN)CSSC[C@@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CNC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: LONNDNYWMXEIQJ-PHIYFGQBSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of human plasmin using Ac-RM(O2)YR-pNA as substrate
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 3290.81
Compound (SMILES): CN1CCC(Nc2ccc(C(=O)Nc3cc(-c4cccc5ncn(C)c45)[nH]n3)cc2)CC1
InChIKey: JVIZPNZQKXJCIO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3-ITD mutant preincubated with enzyme for 20 mins followed by [gamma-33P]ATP addition and measured after 120 mins by filter binding method
Measurement: IC50 = 213.3 nM (pChEMBL 6.670000076293945)
Descriptors: MW 429.53, ALogP 3.72, HBA 6, HBD 3, PSA 90.87, QED 0.45
Compound (SMILES): COc1cc(F)c(/C=C/c2ccc(C(=O)NO)cc2)cc1OC
InChIKey: NZGLVXVWLBYILW-VMPITWQZSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin)
Measurement: IC50 = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 317.32, ALogP 3.13, HBA 4, HBD 2, PSA 67.79, QED 0.5
Compound (SMILES): CS(=O)(=O)c1cccc(C(=O)NC[C@@H]2CCCN2C(=O)C[C@H](N)[C@H]2CCc3cc(F)c(F)cc32)c1
InChIKey: MRWOAUNXINHSAL-LTMIRXACSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human DPP-4 expressed in human Caco-2 cells using H-Gly-Pro-AMC as substrate measured for 30 mins by microplate reader analysis
Measurement: IC50 = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 505.59, ALogP 2.54, HBA 5, HBD 2, PSA 109.57, QED 0.6
Compound (SMILES): N[C@@H](Cc1c[nH]cn1)C(=O)NCc1ccc(SC(F)(F)F)cc1
InChIKey: CYTLJLLFGURITO-LBPRGKRZSA-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 = 28160 nM (pChEMBL 4.550000190734863)
Descriptors: MW 344.36, ALogP 2.21, HBA 4, HBD 3, PSA 83.8, QED 0.7
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(C(=O)c2ccc(Nc3nccc(-c4ccc(F)cc4OCc4ccccc4)n3)cc2)CC1
InChIKey: ZTPJRXHTKPICNY-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using as PDKtide substrate incubated for 1 hr in presence of ATP by ADP-glo luminescent assay
Measurement: IC50 = 85.5 nM (pChEMBL 7.070000171661377)
Descriptors: MW 583.66, ALogP 6.3, HBA 7, HBD 1, PSA 96.89, QED 0.27
Compound (SMILES): CN1C(=O)CN(Cc2ccc(C(=O)NO)cc2)C(=O)C1Cc1ccccc1
InChIKey: OTYSFTPFJQVCGV-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 16.7 nM (pChEMBL 7.78000020980835)
Descriptors: MW 367.4, ALogP 1.22, HBA 4, HBD 2, PSA 89.95, QED 0.61
Compound (SMILES): CC1(C)CC(C(=O)Nc2cc(C(=O)Nc3cnccc3-c3ccccc3)ccn2)C1
InChIKey: GKMDVMDXNKYJRV-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 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 400.48, ALogP 4.77, HBA 4, HBD 2, PSA 83.98, QED 0.65
Compound (SMILES): CC(C)(C)[C@H](CC(=O)O)Nc1nc(-c2c[nH]c3ncc(Cl)cc23)ncc1F
InChIKey: XKMRUVINQUKSEC-ZDUSSCGKSA-N
Target: Polymerase basic protein 2 (SINGLE PROTEIN), Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
UniProt: P03428
Assay: Binding affinity to full length Influenza A virus PB2 cap-binding domain assessed as dissociation constant incubated for 60 mins by fluorescence polarization assay
Measurement: Kd = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 391.83, ALogP 4.11, HBA 5, HBD 3, PSA 103.79, QED 0.6
Compound (SMILES): COc1cccc(-c2noc(CNC(=O)C3C(C)=C3c3ccccc3)n2)c1
InChIKey: IINVNSHMTBHTQU-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 = 39320 nM (pChEMBL 4.409999847412109)
Descriptors: MW 361.4, ALogP 3.46, HBA 5, HBD 1, PSA 77.25, QED 0.73
Compound (SMILES): CC(C)CN(c1ccc(C(=O)O)c(O)c1)S(=O)(=O)c1ccc(Oc2ccccc2)cc1
InChIKey: JHTQTAIFWLPTNR-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 = 5766 nM (pChEMBL 5.239999771118164)
Descriptors: MW 441.51, ALogP 4.73, HBA 5, HBD 2, PSA 104.14, QED 0.52
Compound (SMILES): CCCCCCCCCCCC(=O)OC[C@H](CSC[C@@H](N)C(=O)NCCOCCOCCP(=O)(O)O)OC(=O)CCCCCCCCCCC
InChIKey: YHZYFWSFEIMQJX-CZNDPXEESA-N
Target: Toll-like receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60603
Assay: Agonist activity at human TLR2 transfected in HEK293 cells
Measurement: EC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 755.01, ALogP 6.67, HBA 10, HBD 4, PSA 183.71, QED 0.03
Compound (SMILES): CC(C)CC(=O)c1ccc(CCCN2C(=O)CC[C@@H]2CC[C@@H](O)Cc2cccc(C(F)(F)F)c2)s1
InChIKey: SHPLALYCOYXIBQ-FCHUYYIVSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Agonist activity at human EP4 receptor expressed in CHO cells co-transfected with CRE-beta-lactamase reporter gene assessed as increase in intracellular cAMP measured after 3 hrs by TR FRET based assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 509.63, ALogP 6.3, HBA 4, HBD 1, PSA 57.61, QED 0.34
Compound (SMILES): CCCCCCCCCCCC(=O)OC[C@H](CSC[C@@H](N)C(=O)NCCCP(=O)(O)O)OC(=O)CCCCCCCCCCC
InChIKey: OFHIDHOBIKLOEQ-LOYHVIPDSA-N
Target: Toll-like receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60603
Assay: Agonist activity at human TLR2 transfected in HEK293 cells
Measurement: EC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 680.93, ALogP 7.03, HBA 8, HBD 4, PSA 165.25, QED 0.03
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(C(=O)c2cnc(Nc3ncc(F)c(-c4ccc5scnc5c4)n3)nc2)CC1
InChIKey: GOLYKWMUWHYJCR-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of hexa His-tagged DYRK2 (72 to 479 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as substrate phosphorylation using 4E-BP1 as substrate in presence of [gamma33-P]ATP incubated for 2 hrs by scintillation counter analysis
Measurement: IC50 = 535 nM (pChEMBL 6.269999980926514)
Descriptors: MW 536.59, ALogP 4.12, HBA 10, HBD 1, PSA 126.33, QED 0.41
Compound (SMILES): O=c1[nH]n2c(=O)c3ccccc3nc2/c1=C/c1ccccc1F
InChIKey: QBEFEKVWQFUNGO-XFXZXTDPSA-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 30 secs by ELISA
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 307.28, ALogP 1.22, HBA 4, HBD 1, PSA 67.23, QED 0.57
Compound (SMILES): N#Cc1ccc(-c2cs/c(=N\C(=O)c3cccs3)n2-c2ccccc2)cc1
InChIKey: PNEVVVKCYKJTGO-LNVKXUELSA-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 387.49, ALogP 4.88, HBA 5, HBD 0, PSA 58.15, QED 0.5
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCN(C)Cc1cccc(O)c1
InChIKey: OHBHEABPPWROKD-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 408.54, ALogP 5.25, HBA 5, HBD 1, PSA 54.7, QED 0.33
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(CCF)CC3)o2)c2ccccc21
InChIKey: LCUDWPDAGINEBW-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 = 1814 nM (pChEMBL 5.739999771118164)
Descriptors: MW 357.43, ALogP 3.82, HBA 6, HBD 0, PSA 59.98, QED 0.69
Compound (SMILES): CC(Br)C(=O)Nc1cccc(-c2ncnc3[nH]ccc23)c1
InChIKey: ZOOBGGMBNZCDLL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) incubated for 45 mins by LC-MS/MS analysis
Measurement: IC50 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 345.2, ALogP 3.35, HBA 3, HBD 2, PSA 70.67, QED 0.72
Compound (SMILES): O=C(c1ccccc1-c1ccncn1)N1CCC(O)(Cc2ccccn2)CC1
InChIKey: BRKNQBGATQGRTM-UHFFFAOYSA-N
Target: Cholesterol 24-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6A2
Assay: Inhibition of full length N-terminal his6-tagged human CH24H (28 to 494 residues) expressed in Escherichia coli DH5alpha using [14C] cholesterol as substrate preincubated for 15 mins followed by substrate addition and measured after 5 min in presence of beta-NADPH
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 374.44, ALogP 2.75, HBA 5, HBD 1, PSA 79.21, QED 0.76
Compound (SMILES): CN(C)Cc1cn(Cc2cc(F)cc(OC3CCN(C(=O)c4ccc(O[C@H]5CCNC5)c(C5CCCCC5)c4)CC3)c2)nn1.Cl.Cl
InChIKey: JYROQQLCTCTCDS-ARIINYJRSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)/N-terminal biotinylated human BCL9 HD2 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 604.77, ALogP 5, HBA 8, HBD 1, PSA 84.75, QED 0.35
Compound (SMILES): CCNS(=O)(=O)c1ccc(OC)cc1C1(O)CCN(Cc2cccc(Oc3ccccc3OC)c2)CC1
InChIKey: LQVDZKAJZHWQQE-UHFFFAOYSA-N
Target: C-C chemokine receptor type 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P51685
Assay: Inhibition of CCR8 mutant (unknown origin)
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 526.66, ALogP 4.28, HBA 7, HBD 2, PSA 97.33, QED 0.41
Compound (SMILES): Cc1cc(NC(=O)CN2CCC3(CCCN(Cc4ccc(F)c(F)c4)C3)C2)ccc1F
InChIKey: WLNCDWOGRLAGPA-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 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 431.5, ALogP 4.34, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@H](CSC[C@@H](COC(=O)CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)C(=O)NCCOCCOCCOCCP(=O)(O)O
InChIKey: PLDQLNIGVWUTJN-CDKYPKJRSA-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 1037.48
Compound (SMILES): CC(C)N(CCNC(=O)c1ccc(Nc2nccc(-c3ccc(F)cc3OCc3ccccc3)n2)cc1)C(C)C
InChIKey: FJXYQEIZYBJVSF-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using as PDKtide substrate incubated for 1 hr in presence of ATP by ADP-glo luminescent assay
Measurement: IC50 = 59.6 nM (pChEMBL 7.21999979019165)
Descriptors: MW 541.67, ALogP 6.45, HBA 6, HBD 2, PSA 79.38, QED 0.21
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CCCC5)c(OC)c4)nn32)CC1
InChIKey: WDZZTNVBOLILQA-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 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 507.64, ALogP 4.11, HBA 7, HBD 2, PSA 111.71, QED 0.55
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)CCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CSCc1ccccc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(N)=O)C(C)C
InChIKey: XUMGVGFCIDQIMX-GKUUNLLTSA-N
Target: Histone-lysine N-methyltransferase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q03164
Assay: Competitive binding affinity to full length wild type MLL (unknown origin)
Measurement: Kd = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 1963.22
Compound (SMILES): CNCCNCc1cccc(-c2nc(NC3CCOCC3)c(C)c(-c3c(C)nn(C)c3C)n2)c1
InChIKey: GETDLVBESQDEJK-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of human CARM1 (140 to 480 residues) incubated for 15 mins measured after 60 min by AlphaLISA assay
Measurement: IC50 = 0.65 nM (pChEMBL 9.1899995803833)
Descriptors: MW 463.63, ALogP 3.37, HBA 8, HBD 3, PSA 88.92, QED 0.42
Compound (SMILES): CC#CCOc1ccc2cc(C(O)(c3ccc(Cl)cc3)c3cccnc3)oc2c1
InChIKey: ZSELVLWOAHFVSR-UHFFFAOYSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human JEG-3 cells using Androst-4-ene-3,17-dione [1beta-3H] as substrate incubated for 1 hrs by scintillation counting analysis
Measurement: IC50 = 1.05 nM (pChEMBL 8.979999542236328)
Descriptors: MW 403.87, ALogP 5.17, HBA 4, HBD 1, PSA 55.49, QED 0.47
Compound (SMILES): COCCc1nc2c(N)nc3ccccc3c2n1CCCCN(CCCN1CCOCC1)Cc1cccc(OC(C)(C)C(=O)OC)c1
InChIKey: URWCJXUFUIUVIE-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 transfected in HEK293 cells assessed as induction of SEAP production incubated overnight by SEAP reporter gene based assay
Measurement: EC50 = 87.7 nM (pChEMBL 7.059999942779541)
Descriptors: MW 646.83, ALogP 4.69, HBA 11, HBD 1, PSA 117.2, QED 0.13
Compound (SMILES): Cc1cccc2c1n1cncc1c(=O)n2Cc1cccnc1
InChIKey: HSXSMQSDLMVYCV-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 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 290.33, ALogP 2.4, HBA 5, HBD 0, PSA 52.19, QED 0.57
Compound (SMILES): O=C(O)CCc1cccc(NC(=O)c2ccccc2NC(=O)c2ccc(-c3ccoc3)cc2)c1
InChIKey: QXOKDJBSGAIVGL-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR in human HeLa cells incubated for 24 hrs by Dual-Glo luciferase assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 454.48, ALogP 5.47, HBA 4, HBD 3, PSA 108.64, QED 0.33
Compound (SMILES): COc1cc(NC(=O)c2nnn(-c3cc(OC)ccc3OC)c2C)cc(C(C)(C)C)c1
InChIKey: HBCQQFOBPKEVPA-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 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 424.5, ALogP 4.15, HBA 7, HBD 1, PSA 87.5, QED 0.64
Compound (SMILES): Cc1cc(CN(C)c2ccc(OCc3c(-c4c(Cl)cccc4Cl)noc3C3CC3)nc2C(F)(F)F)ccc1C(=O)O
InChIKey: JDFLHOZFGITPCJ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR (unknown origin) by FRET assay
Measurement: EC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 606.43, ALogP 8.16, HBA 6, HBD 1, PSA 88.69, QED 0.21
Compound (SMILES): Clc1ccc(COc2ccc(OCCOCCNC3CCCCC3)cc2)cc1
InChIKey: RKTLOUYERGLRCM-UHFFFAOYSA-N
Target: Forkhead box protein M1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q08050
Assay: Binding affinity to recombinant FOXM1 DBD (222 to 360 residues) (unknown origin) by SPR analysis
Measurement: Kd = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 403.95, ALogP 5.24, HBA 4, HBD 1, PSA 39.72, QED 0.52
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2ccnc(Nc3ccc(N4CCC(CCc5ccc(/C=C/CC(=O)NO)cc5)CC4)cc3)n2)cc1
InChIKey: HCBAGPOEIWZQBJ-NSCUHMNNSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 626.78, ALogP 6.02, HBA 8, HBD 4, PSA 136.55, QED 0.11
Compound (SMILES): Cc1ccc(-c2noc(-c3cccc(OCC4CCN(Cc5ccco5)CC4)c3)n2)cn1
InChIKey: LDLLUDZHMHZSLM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using ATC and BTC iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by DTNB reagent based assay
Measurement: IC50 = 2530 nM (pChEMBL 5.599999904632568)
Descriptors: MW 430.51, ALogP 4.99, HBA 7, HBD 0, PSA 77.42, QED 0.41
Compound (SMILES): COc1ccc(C2CC(c3c(O)c4ccccc4oc3=O)=NN2c2ccccc2)cc1OC
InChIKey: QZUWGDSAAXXRKW-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) assessed as inhibition constant
Measurement: Ki = 3.26 nM (pChEMBL 8.489999771118164)
Descriptors: MW 442.47, ALogP 4.87, HBA 7, HBD 1, PSA 84.5, QED 0.44
Compound (SMILES): O=C(O)c1ccc(C#Cc2ccccc2NS(=O)(=O)c2ccc3ccccc3c2)cn1
InChIKey: ZUDDUZPKZJWUSI-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 428.47, ALogP 4.13, HBA 4, HBD 2, PSA 96.36, QED 0.48
Compound (SMILES): CC/C(C)=N/Oc1ccc(C(=O)/C=C/c2ccccc2)cc1
InChIKey: JTNZASXKBYGHTA-IFIIVODNSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using benzylamine as substrate
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 293.37, ALogP 4.75, HBA 3, HBD 0, PSA 38.66, QED 0.33
Compound (SMILES): Cc1noc(C)c1-c1ccc2[nH]c(=O)cc(NCc3ccccc3Br)c2c1
InChIKey: MKWIDJDPCGKCEW-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain 1/2 (unknown origin) assessed as dissociation constant by DiscoveRx BROMOscan assay
Measurement: Kd = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 424.3, ALogP 5.17, HBA 4, HBD 2, PSA 70.92, QED 0.47
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@H]2C1
InChIKey: MUKMJPGPFMWVJK-POLFCZAWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of human USP7 using human N-terminal GST-tagged UBA52 as substrate preincubated for 10 mins followed by substrate addition measured after 45 mins by coomassie brilliant blue staining-based SDS-PAGE analysis
Measurement: IC50 = 33300 nM (pChEMBL 4.480000019073486)
Descriptors: MW 470.74, ALogP 7.48, HBA 2, HBD 2, PSA 57.53, QED 0.41
Compound (SMILES): CNC(=O)NC(=N)NCCCCCCCCN1CCCCCOc2ccccc2CNC(=N)NC1=O
InChIKey: CRSFLNOEDGZOJB-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of human AMCase using 4-methylumbelliferyl-beta-D-N,N',N''-triacetylchitotriose as substrate assessed as substrate hydrolysis by measuring inhibition constant preincubated with compound for 20 mins and measured immediately after substrate addition by fluorescence based assay
Measurement: Ki = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 502.66, ALogP 3.08, HBA 5, HBD 7, PSA 154.46, QED 0.16
Compound (SMILES): Cc1cc(N2CCN(C(=O)c3ccc(Cl)cc3)CC2)nc(N2CCCC2)n1
InChIKey: WCDCNLWPXUMDRB-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Chaperone activity at GCase N370S GBA mutant in patient derived fibroblast cell using 4-methylumbelliferyl-beta-D-glucopyranoside as substrate assessed as substrate cleavage by measuring concentration required for maximal response incubated for 5 days by fluorescence based assay
Measurement: EC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 385.9, ALogP 3, HBA 5, HBD 0, PSA 52.57, QED 0.81
Compound (SMILES): O=C(O)c1ccc(-c2nn(C(=O)c3c(Cl)cccc3C3(C(F)(F)F)CC3)c3cccnc23)c(F)c1
InChIKey: NZGCUSAQKOXNPX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibition of human GAL4-fused RORgammat LBD transfected in Escherichia coli BL21(DE3) cell measured after 16 hrs by HTRF assay
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 503.84, ALogP 5.87, HBA 5, HBD 1, PSA 85.08, QED 0.35
Compound (SMILES): COc1cnc(-c2ccccn2)nc1CC(C)C
InChIKey: LVVMRLLYLMFZJU-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Agonist activity at human recombinant TRPM8
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 243.31, ALogP 2.75, HBA 4, HBD 0, PSA 47.9, QED 0.83
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2F)CCC1(O)c1cccc(O)c1
InChIKey: GQWCSKCBLAGZJA-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 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 386.47, ALogP 2.37, HBA 4, HBD 2, PSA 64.01, QED 0.83
Compound (SMILES): N#Cc1c(-c2ccc(Br)cc2)nc2cnccc2c1NCC(N)=O
InChIKey: AVFUUQONLDOKTI-UHFFFAOYSA-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 = 7450 nM (pChEMBL 5.130000114440918)
Descriptors: MW 382.22, ALogP 2.83, HBA 5, HBD 2, PSA 104.69, QED 0.72
Compound (SMILES): C=CC(=O)N1CCCCCCCCCn2cc(c3ccccc32)-c2ccnc(n2)Nc2cccc1c2
InChIKey: JGSRURALHADGHE-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR d746-750/T790M/C797S triple mutant (unknown origin)
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 479.63, ALogP 7.11, HBA 5, HBD 1, PSA 63.05, QED 0.3
Compound (SMILES): Cc1ccc2c(=O)[nH]c(-c3ccc([C@](C)(O)CCO)cc3)cn12
InChIKey: SSRCPYMXFHISQW-GOSISDBHSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of TNKS1 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 312.37, ALogP 2.19, HBA 4, HBD 3, PSA 77.73, QED 0.69
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccccc4)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: NWYMNUYUDBBQTQ-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in ERK phosphorylation incubated for 6 hrs by MSD assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 471.99, ALogP 5.71, HBA 4, HBD 1, PSA 66.81, QED 0.39
Compound (SMILES): Cn1c(=O)c2cc(S(N)(=O)=O)ccc2n(C)c1=O
InChIKey: SPVAPRPWSANMJL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) preincubated for 10 mins followed by ATP addition and measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 17490 nM (pChEMBL 4.760000228881836)
Descriptors: MW 269.28, ALogP -1.12, HBA 6, HBD 1, PSA 104.16, QED 0.71
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4ccccc4)c(C)s3)cs2)cc(OC)c1
InChIKey: KRDRSHGJSDNOHL-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 = 64.8 nM (pChEMBL 7.190000057220459)
Descriptors: MW 409.54, ALogP 6, HBA 7, HBD 1, PSA 56.27, QED 0.42
Compound (SMILES): Cc1nnc(/N=C2\NC(=O)/C(=C/c3ccc(O)cc3)S2)s1
InChIKey: GYTFZLNMJZCJLE-POHAHGRESA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 318.38, ALogP 2.44, HBA 7, HBD 2, PSA 87.47, QED 0.83
Compound (SMILES): COCCc1nc2c(N)nc3ccccc3c2n1CCCN(Cc1cccc(CC(=O)OC)c1)C(=O)CN1CCN(C)CC1
InChIKey: LKRPXKGFSKFBQC-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 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 601.75, ALogP 2.74, HBA 10, HBD 1, PSA 119.05, QED 0.23
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccc(F)cc3OC)cc2)nc2cnccc12)C(N)=O
InChIKey: VDPQATJURMCMDU-OAQYLSRUSA-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 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 455.49, ALogP 4.66, HBA 6, HBD 2, PSA 113.92, QED 0.42
Compound (SMILES): CC(C)n1nc(-c2nnc(CC3CCN(C4CCC4)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: JBVWUUUWTXYKGV-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 = 255 nM (pChEMBL 6.590000152587891)
Descriptors: MW 379.51, ALogP 4.47, HBA 6, HBD 0, PSA 59.98, QED 0.65
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](NC(=O)CCCCCCCCCCCCCCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)[C@@H](C)O)C(=O)NCCc1cccc(O)c1
InChIKey: FDMXXQQBWCZJMY-KLGRSVOBSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of recombinant HIV1 Protease
Measurement: IC50 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 881.13, ALogP 4.08, HBA 9, HBD 9, PSA 266.35, QED 0.05
Compound (SMILES): CCNC(=S)N1N=C(c2ccc(C)cc2)CC1c1ccc(F)cc1
InChIKey: UHPVHHKFRWNELW-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A by spectrofluorimetric analysis
Measurement: Ki = 0.1 nM (pChEMBL 10)
Descriptors: MW 341.46, ALogP 4.18, HBA 2, HBD 1, PSA 27.63, QED 0.85
Compound (SMILES): Cc1c(-c2ccccc2)cccc1-c1nc2cc(CNCCO)c(OCCN3CCOCC3)cc2o1
InChIKey: VSLGIPZHVMRWRE-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 <= 10 nM (pChEMBL 8)
Descriptors: MW 487.6, ALogP 4.26, HBA 7, HBD 2, PSA 79.99, QED 0.32
Compound (SMILES): O=C(/C=C/c1ccc(N2CC(=O)N3C(Cc4c([nH]c5ccccc45)C3c3ccc4c(c3)OCO4)C2=O)cc1)NO
InChIKey: DOKZSZOGYUKABQ-KPKJPENVSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5 (unknown origin)
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 536.54, ALogP 3.3, HBA 6, HBD 3, PSA 124.2, QED 0.21
Compound (SMILES): CNCC1Cc2cc(F)cc(-c3c(Cl)cccc3Cl)c2O1
InChIKey: KYLAEKGVXSXQOG-UHFFFAOYSA-N
Target: Aquaporin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29972
Assay: Inhibition of human AQP1 water channel expressed in CHO cells incubated for 10 mins by FLIPR Tetra assay
Measurement: IC50 = 29400 nM (pChEMBL 4.53000020980835)
Descriptors: MW 326.2, ALogP 4.32, HBA 2, HBD 1, PSA 21.26, QED 0.91
Compound (SMILES): COCCc1nc2c(N)nc3ccccc3c2n1CCCCN(CCN(C)C)Cc1cccc(OCC(=O)OC(C)(C)C)c1
InChIKey: IEBWFDPUIMCTDL-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 transfected in HEK293 cells assessed as induction of SEAP production incubated overnight by SEAP reporter gene based assay
Measurement: EC50 = 56.4 nM (pChEMBL 7.25)
Descriptors: MW 604.8, ALogP 4.92, HBA 10, HBD 1, PSA 107.97, QED 0.14
Compound (SMILES): CN(C(=O)c1c(-c2ccc(F)cc2)nc2ncccn12)c1ccc(Cl)cc1
InChIKey: MYMDDQXDKXNMIX-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at human TGR5 transfected in CHO cells assessed as increase in cAMP production
Measurement: EC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 380.81, ALogP 4.47, HBA 4, HBD 0, PSA 50.5, QED 0.53
Compound (SMILES): CCc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(OCC3CCOCC3)c(CN)c2)cc1
InChIKey: FKIVGSPFNRLCSY-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of BODIPY from APC-labelled human RORgammat LBD incubated for 15 mins by by LANCE detection analysis
Measurement: IC50 = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 460.64, ALogP 4.36, HBA 5, HBD 1, PSA 81.86, QED 0.57
Compound (SMILES): COc1ccc2nc(C(=O)OCc3ccc(C(F)(F)F)cc3)sc2c1
InChIKey: IZVJAUOCKLZVQR-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Displacement of [11C]PBB3 in human brain tau incubated for 30 mins by radioligand binding assay
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 367.35, ALogP 4.68, HBA 5, HBD 0, PSA 48.42, QED 0.63
Compound (SMILES): CC(C)=CCc1ccc(O)c([C@@]2(O)c3c(O)cc(C)cc3C(=O)C2(C)C)c1O
InChIKey: JIIKZACQDAPJRU-QHCPKHFHSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35610
Assay: Inhibition of human SOAT1 expressed in mouse AC29 cells
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 382.46, ALogP 4.08, HBA 5, HBD 4, PSA 97.99, QED 0.6
Compound (SMILES): Cc1c(O)c(O)c(C=O)c2c1C1(CC2)c2ccccc2-c2ccccc21
InChIKey: HHHPSUSUQCIPOI-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 342.39, ALogP 4.48, HBA 3, HBD 2, PSA 57.53, QED 0.51
Compound (SMILES): CCCCCCCCCCCCCCOc1ccccc1NC(=O)c1c(C(=O)O)cc(Cl)c(Cl)c1Cl
InChIKey: AMDWYOJEFOKNMO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin)
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 556.96, ALogP 9.68, HBA 3, HBD 2, PSA 75.63, QED 0.15
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3C3CCC3)cc2)cc1
InChIKey: IADQVLCQLDGDGX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human GAL4-fused RORgamma LBD (262 to 507 residues) transfected in HEK293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 487.63, ALogP 5.71, HBA 5, HBD 1, PSA 81.06, QED 0.36
Compound (SMILES): NCn1c(-c2nonc2N)nc2cnccc21
InChIKey: FAWUVVKQRJHKOZ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of DYRK1A (unknown origin)
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 231.22, ALogP -0.02, HBA 8, HBD 2, PSA 121.67, QED 0.63
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN(CC[C@H](N)C(=O)O)S(=O)(=O)c2ccc(Cl)c(C(F)(F)F)c2)[C@@H](O)[C@H]1O
InChIKey: IFHQILVPHPORTO-BPAMBQHCSA-N
Target: tRNA (cytosine(38)-C(5))-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: O14717
Assay: Displacement of FTAD from full-length human DNMT2 expressed in bacteria incubated for 10 mins by MST assay
Measurement: Kd = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 609.97, ALogP 0.19, HBA 12, HBD 5, PSA 220.01, QED 0.22
Compound (SMILES): O=C1Nc2ccc(NC(=O)C(NC(=O)c3cccn(Cc4ccc(F)c(F)c4)c3=O)c3ccccc3)cc2/C1=C/c1cnc[nH]1
InChIKey: XCPMMIISBZJPHR-MYYYXRDXSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDK1 (unknown origin)
Measurement: IC50 = 416 nM (pChEMBL 6.380000114440918)
Descriptors: MW 606.59, ALogP 4.5, HBA 6, HBD 4, PSA 137.98, QED 0.19
Compound (SMILES): CCCCC(NC(=O)c1[nH]c2c(c1C)C(=O)CC(C)(C)C2)C(=O)Nc1ccccc1
InChIKey: LPSQWMJVEOJPJL-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin)
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 409.53, ALogP 4.41, HBA 3, HBD 3, PSA 91.06, QED 0.63
Compound (SMILES): CC1(C)CN(C(N)=O)c2ccc(F)c(F)c2N1Cc1ccc(COc2ccc(CO)cc2)cc1
InChIKey: JCOIRZMTHVXDKJ-UHFFFAOYSA-N
Target: AMP deaminase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01433
Assay: Inhibition of recombinant human AMPD2 using AMP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by spectrophotometric analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 467.52, ALogP 4.72, HBA 4, HBD 2, PSA 79.03, QED 0.55
Compound (SMILES): COc1ccc(Nc2nncc(-n3c(C)nc4ccccc43)n2)cc1
InChIKey: DDYCFKPDEOLUNU-UHFFFAOYSA-N
Target: Polycomb complex protein BMI-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35226
Assay: Inhibition of BMI1 (unknown origin) by ELISA assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 332.37, ALogP 3.27, HBA 7, HBD 1, PSA 77.75, QED 0.62
Compound (SMILES): N[C@@H]1CC[C@@]2(CN=C(N3CCc4ccccc4[C@@H]3c3ccc(F)cc3)O2)C1
InChIKey: SLQDPMUDTLRKND-CBQOVEMMSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 365.45, ALogP 3.41, HBA 4, HBD 1, PSA 50.85, QED 0.84