lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Oc1cc2c(C(=O)N3CCN(c4ccccc4)CC3)c(C)oc2c2ccccc12
InChIKey: CSJDNGNJPKBBJY-UHFFFAOYSA-N
Target: Serine hydroxymethyltransferase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P34897
Assay: Inhibition of His-tagged human recombinant SHMT2 expressed in Escherichia coli BLR(DE3) assessed as reduction in NADPH level using L-serine, THF and NADP+ incubated for 5 mins by SHMT2-MTHFD coupled reaction based fluorescence assay
Measurement: IC50 = 2880 nM (pChEMBL 5.539999961853027)
Descriptors: MW 428.49, ALogP 4.78, HBA 5, HBD 0, PSA 62.99, QED 0.35
Compound (SMILES): Cc1ccc(-c2cc3ncn(C)c(=O)c3c(NC[C@H]3CCCNC3)n2)cc1
InChIKey: HQXRVTFLFJNGAV-HNNXBMFYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of N-terminal 6His-tagged full length human recombinant SYK expressed in baculovirus using Biotin-AAAEEIYGEI as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 363.47, ALogP 2.72, HBA 6, HBD 2, PSA 71.84, QED 0.75
Compound (SMILES): CC1(C)CC[C@]2(C(=O)NCCCCCCCCCCC(=O)NCC(=O)O)CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)CCCC(=O)O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]2C1
InChIKey: NPEOIYNCLJWYDX-KULYGBLPSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 protease expressed in Escherichia coli using Abz-Ala-Arg-Val-Nle-Tyr(NO2)-Glu-Ala-Nle-NH2 peptide as substrate by FRET assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 811.16, ALogP 9.78, HBA 6, HBD 4, PSA 159.1, QED 0.06
Compound (SMILES): C[C@@H]1CN(c2ccnc3cc(-n4cncn4)ccc23)CC[C@@H]1C(=O)N1CCn2c(nnc2C(F)(F)F)C1
InChIKey: VCAYISBSPJGMOH-WBVHZDCISA-N
Target: 7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNU6
Assay: Inhibition of CYP8B1 in human liver microsomes using 7alpha-hydroxy-4-cholesten-3-one as substrate preincubated followed by substrate addition in presence of NADPH and measured after 45 mins by ESI-MS analysis
Measurement: IC50 = 41.7 nM (pChEMBL 7.380000114440918)
Descriptors: MW 511.51, ALogP 2.93, HBA 9, HBD 0, PSA 97.86, QED 0.42
Compound (SMILES): Oc1c(C(c2ccccn2)N2CCN(Cc3ccccc3)CC2)ccc2cccnc12
InChIKey: YGYWNPWQAYZHAS-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 410.52, ALogP 4.24, HBA 5, HBD 1, PSA 52.49, QED 0.53
Compound (SMILES): CCn1cc(NC(=O)c2ccc3nc(C(O)(c4ccccc4)c4ccccc4)n(CCO)c3c2)cn1
InChIKey: SRMQKDWXEJXKNQ-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of N-terminal 6x-histidine tagged human ACSS2 expressed in insect cells assessed as reduction in pyrophosphate production using CoA and ATP incubated for 30 mins by pyrophosphatase coupled enzymatic assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 481.56, ALogP 3.78, HBA 7, HBD 3, PSA 105.2, QED 0.31
Compound (SMILES): COc1cc2c(NC3CCN(C)CC3)nc(N3CCCN(C)CC3)nc2cc1C#Cc1ccccn1
InChIKey: PHFJFWNEMGAEJQ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of N-terminal GST tagged human recombinant EHMT1 (794 to 1294 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 mins by AMP Glo detection assay
Measurement: IC50 = 3470 nM (pChEMBL 5.460000038146973)
Descriptors: MW 485.64, ALogP 3.08, HBA 8, HBD 1, PSA 69.65, QED 0.57
Compound (SMILES): CC(C)(C)C(=O)Oc1cc(F)ccc1C(=O)CN1C(=O)NC(C)(c2ccc(C#N)cc2)C1=O
InChIKey: RFGIBKFWQVEXNM-UHFFFAOYSA-N
Target: Decaprenylphosphoryl-beta-D-ribose oxidase (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: P9WJF1
Assay: Inhibition of Mycobacterium tuberculosis DprE1 expressed in Escherichia coli BL21(DE3) cells
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 451.45, ALogP 3.3, HBA 6, HBD 1, PSA 116.57, QED 0.32
Compound (SMILES): COC(=O)c1ccc2c(c1)[n+]([O-])c(C)c(C)[n+]2[O-]
InChIKey: WVEMKRQIEQXTKA-UHFFFAOYSA-N
Target: Separin (SINGLE PROTEIN), Homo sapiens
UniProt: Q14674
Assay: Inhibition of epitope-tagged separase (unknown origin) using Rad21-MCA as substrate preincubated for 1 hr followed by substrate addition measured after 3 hrs by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 248.24, ALogP 0.51, HBA 4, HBD 0, PSA 80.18, QED 0.42
Compound (SMILES): Clc1cccc(CN2CCOCC2)c1Cl
InChIKey: UMOUJDYMYCEROQ-UHFFFAOYSA-N
Target: Cytochrome P450 2A13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16696
Assay: Binding affinity to full length recombinant truncated non-catalytic N-terminal transmembrane helix containing C-terminal 4xHis tagged human CYP2A13dH expressed in Escherichia coli by HTS assay
Measurement: Kd = 28500 nM (pChEMBL 4.539999961853027)
Descriptors: MW 246.14, ALogP 2.83, HBA 2, HBD 0, PSA 12.47, QED 0.8
Compound (SMILES): CN(C(=O)Nc1ccc(Cl)cn1)[C@@H]1CCN(C#N)C1
InChIKey: NVTIKHFEXJISTN-SNVBAGLBSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 279.73, ALogP 1.75, HBA 4, HBD 1, PSA 72.26, QED 0.84
Compound (SMILES): NC(=O)c1nc(C2CCCCC2)c(-c2ccnc(NC(=O)C3CC3)c2)[nH]1
InChIKey: ORHAEWIQYOTXFO-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin) by ADP-Glo assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 353.43, ALogP 2.97, HBA 4, HBD 3, PSA 113.76, QED 0.77
Compound (SMILES): Cc1c(N2CCN(Cc3ccc(=O)[nH]c3)CC2)c(=O)n(C[C@H](N)c2ccccc2)c(=O)n1Cc1c(F)cccc1C(F)(F)F
InChIKey: NCLUHSXHGBFGGC-SANMLTNESA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity against human GnRH receptor expressed in HEK293 cells co-transfected with pGL4-NFAT promoter AP1-luc assessed as inhibition of 20 nM GnRH-induced NFAT activation pre-incubated for 1 hr before GnRH stimulation and measured after 6 hrs by luciferase reporter gene assay
Measurement: IC50 = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 612.63, ALogP 3.24, HBA 8, HBD 2, PSA 109.36, QED 0.3
Compound (SMILES): COc1cc(F)c(CCCNc2cc(OC(F)(F)F)ccc2-n2cncn2)cc1OC
InChIKey: DUSNTKULOXASFF-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Negative allosteric modulation of rat mGlu7 receptor expressed in HEK cells harboring Ga15 assessed as reduction in L-AP4-induced calcium flux preincubated for 142 secs followed by agonist addition and measured after 120 secs by Fluo-4-AM-dye based fluorescence assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 440.4, ALogP 4.37, HBA 7, HBD 1, PSA 70.43, QED 0.39
Compound (SMILES): O=C(NO)c1cc(CCCCN2c3ccc(Cl)cc3CCc3cc(Cl)ccc32)on1
InChIKey: VDTBXSDZXQXMDR-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length C-terminal His/FLAG tagged human HDAC1 (1 to 482 residues) expressed in baculovirus infected sf9 insect cells using p53 (379 to 382 residues) derived fluorogenic peptide RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and further incubated for 2 hrs by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 446.33, ALogP 5.36, HBA 5, HBD 2, PSA 78.6, QED 0.3
Compound (SMILES): COc1cc(C)nc2sc(C(=O)NCCc3ccc(N4CCNCC4)cc3)c(N)c12
InChIKey: PYROAPFNWWBTDK-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Inhibition of TEV-cleavable hexa-histidine tagged USP28 (1 to 1077 residues) (unknown origin) using ubiquitin-rhodamine 110 as substrate and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 425.56, ALogP 2.58, HBA 7, HBD 3, PSA 92.51, QED 0.56
Compound (SMILES): O=C(NCc1ccc(Cl)s1)c1ccc(NC(=O)c2ccc(-c3nc4cc(Cl)c(Cl)cc4[nH]3)cc2)c(C(=O)O)c1
InChIKey: ISQKUOGLOOSFHU-UHFFFAOYSA-N
Target: Neurotrypsin (SINGLE PROTEIN), Homo sapiens
UniProt: P56730
Assay: Inhibition of human neurotrypsin
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 599.88, ALogP 7.13, HBA 5, HBD 4, PSA 124.18, QED 0.16
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(C)=O)C(C)C)C(C)C)C(=O)N[C@@H](C)C(N)=O
InChIKey: YMSJPSITMHGTIW-QKMPNFGVSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 2559.99
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)C1CCC(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: PCJGZPGTCUMMOT-SVRBNMFFSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Antagonist activity at NSTR1 (unknown origin) assessed as inhibitory constant
Measurement: Ki = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 1672.95
Compound (SMILES): COCCNCCC(=O)Nc1sc2c(c1-c1nc3cc(-n4cnc(C)c4)ccc3s1)CCNC2
InChIKey: FOTLIJUFBWNWHP-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 496.66, ALogP 3.73, HBA 9, HBD 3, PSA 93.1, QED 0.31
Compound (SMILES): CC1CCCc2c(-c3cccc4ccccc34)nc(N)nc21
InChIKey: RKCNBFBFPHJRCB-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Antagonist activity at recombinant human Gi-coupled H3 receptor expressed in HEK293T cells assessed as reduction in histamine-induced inhibition of forskolin-stimulated cAMP accumulation preincubated for 10 to 15 followed by histamine addition for 10 mins and subsequent forskolin-stimulation by Glo-sensor assay
Measurement: IC50 = 2710 nM (pChEMBL 5.570000171661377)
Descriptors: MW 289.38, ALogP 4.32, HBA 3, HBD 1, PSA 51.8, QED 0.73
Compound (SMILES): Cc1c(C(=O)N2CCC(C3(C(F)(F)F)CC3)CC2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: FVTRVWMZWHMNNL-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 435.45, ALogP 2.95, HBA 5, HBD 1, PSA 83.88, QED 0.8
Compound (SMILES): Cc1c(CCC(=O)O)cccc1NC(=O)[C@@H](c1ccc(-c2cncc(Cl)c2)cc1)C1CCCC1
InChIKey: LUWOXMQWGOWQSN-HHHXNRCGSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of human recombinant FLAG-tagged PTGES expressed in baculovirus infected Hi-5 insect cells using prostaglandin H2 as substrate preincubated for 20 mins followed by substrate addition and incubated for 60 sec by TR-FRET assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 477, ALogP 6.64, HBA 3, HBD 2, PSA 79.29, QED 0.38
Compound (SMILES): N#Cc1cccc(OCCCC(=O)Nc2ncc(C(F)(F)F)s2)c1
InChIKey: KBURQOUKVMBEBU-UHFFFAOYSA-N
Target: Protein Tat (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04608
Assay: Activation of Tat-mediated HIV1 transcription in HEK293- FlpIn-FM cells harboring LTR driven CBR reporter co-expressing CMV driven CBG reporter assessed as LTR-driven gene expression incubated for 48 hr using Chroma-Glo substrate by luciferase dual reporter cellular assay
Measurement: EC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 355.34, ALogP 3.83, HBA 5, HBD 1, PSA 75.01, QED 0.8
Compound (SMILES): Cc1cc(C)c2c(C)c(C(=O)NCc3ccc(S(C)(=O)=O)cc3)sc2n1
InChIKey: HFPOYYXIZZMWTF-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Positive allosteric modulation of Gqi5-fused human M4 AChR assessed as increase in acetylcholine-induced calcium mobilization
Measurement: EC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 388.51, ALogP 3.56, HBA 5, HBD 1, PSA 76.13, QED 0.74
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCCN)NC1=O
InChIKey: QVAUFZIBGIAQDM-HFAJLYCHSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 1086 nM (pChEMBL 5.960000038146973)
Descriptors: MW 2943.58
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC1CCCCC1)NC(=O)[C@H](Cc1ccccc1)N=[N+]=[N-])C(=O)[C@@]1(C)CO1
InChIKey: JPBZTCUYKFBWHX-ICQXYBJGSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of catalytic activity of constitutive proteasome 20s subunit beta5 in human Raji cells incubated for 1 hr by BODIPY(TMR)-NC-005-VS probe based competitive activity based protein profiling assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 658.84, ALogP 5.37, HBA 6, HBD 3, PSA 165.66, QED 0.08
Compound (SMILES): CN1CCOc2c1cnn1c(-c3ccc4cccc(NC5CCC(C)(C)CC5)c4n3)nnc21
InChIKey: VRTGLHNTXQKOQL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of His tagged human recombinant PIM1 using PIM tide (ARKRRRHPSGPPTA) as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 443.56, ALogP 4.55, HBA 8, HBD 1, PSA 80.47, QED 0.5
Compound (SMILES): Cl.Cn1ncc(-c2ccccc2)c1-c1ccc(C(=O)N[C@@H]2CNCC[C@H]2c2cccc(F)c2)s1
InChIKey: AQQMHZWTKXYSOX-IKGOIYPNSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of Akt1 (unknown origin) expressed in Escherichia coli using peptide as substrate incubated for 1 hr by HTRF assay
Measurement: IC50 = 70.4 nM (pChEMBL 7.150000095367432)
Descriptors: MW 460.58, ALogP 4.83, HBA 5, HBD 2, PSA 58.95, QED 0.45
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](Cc2ccccc2)C(=O)N(C)[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)O
InChIKey: GNGZPFKPZMYXMF-MUVJKTISSA-N
Target: Urotensin-2 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P49684
Assay: Agonist activity at urotensin 2 receptor in Sprague-Dawley rat thoracic aortic ring assessed as induction of contraction relative to KCl-induced contraction
Measurement: EC50 = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 1031.27
Compound (SMILES): COc1cc(-c2cnc3cnc(-c4ccc(C(=O)NCCN(C)C)cc4)cn23)ccc1O
InChIKey: XHDCMMUFHWYFOA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: ADP-Glo Kinase Assay: The assay procedure determines the IC50 of each potential FYN kinase inhibitor by measuring the enzyme catalyzed ATP-dependent phosphorylation of the FYN substrate peptide. The ADP-Glo Kinase Assay is specifically designed to quantify kinase activity by measuring the ADP produced in the reaction The reaction buffer comprises 40 mM Tris.HCl (pH 7.5), 20 mM MgCl2, 0.1 mg/ml BSA and 5 microM DTT. Individual compounds within the chemical library were dissolved in DMSO at known concentrations. Briefly, 2.5 microliters of reaction buffer containing 3 picograms of FYN kinase and serial dilutions of each potential FYN kinase inhibitor (9 3-fold dilutions of a 10 micromolar top sample) are placed into each well of a 384 well microtiter plate and incubated at room temperature for 30 minutes. An additional 2.5 microliters of reaction buffer containing 100 picograms of the FYN substrate and 12.5 picomoles of ATP are then added to each well and the reaction carried out for 90 minutes at room temperature.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 431.5, ALogP 3.07, HBA 7, HBD 2, PSA 91.99, QED 0.47
Compound (SMILES): COc1cccc(-c2cccc(C(=O)NCNC(=O)[C@H](CC3CCCC3)CN(O)C=O)c2)c1
InChIKey: OMHDETUKGUIRKK-JOCHJYFZSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins using 0.5 nM BMP1 by FRET based assay
Measurement: IC50 < 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 453.54, ALogP 3.21, HBA 5, HBD 3, PSA 107.97, QED 0.21
Compound (SMILES): COc1ccc(Sc2ccc(C(C)N(C)c3ncc4c(N)nc(N)nc4n3)cc2)cc1
InChIKey: JDUGQMYBPCNBEU-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase (SINGLE PROTEIN), Schistosoma mansoni
UniProt: T1VXA1
Assay: Inhibition of recombinant Schistosoma mansoni sirtuin 2 (21 to 322 residues) expressed in Escherichia coli BL21(DE3) cells using ZMAL as substrate after 1 hr in presence of NAD+ by homogeneous fluorescence based analysis
Measurement: IC50 = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 433.54, ALogP 3.94, HBA 9, HBD 2, PSA 116.07, QED 0.47
Compound (SMILES): COc1ncc(-c2ccc3ncnc(NCCN4CCCCC4)c3c2)cc1NS(=O)(=O)C1CC1
InChIKey: KXWGCTJHQGIKQV-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3K alpha (unknown origin) using lipid substrate measured after 40 mins in presence of ATP by Kinase-Glo plus reagent based luminescence assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 482.61, ALogP 3.5, HBA 8, HBD 2, PSA 109.34, QED 0.48
Compound (SMILES): COc1cccc(Cc2c(N)nc(-c3ccccn3)nc2N)c1
InChIKey: AWXDMMPPWOJPOL-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 307.36, ALogP 2.3, HBA 6, HBD 2, PSA 99.94, QED 0.77
Compound (SMILES): O=c1cc(OCCCNCCc2ccccc2)c2ccccc2o1
InChIKey: QYUKAXJTANCXEI-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of acetylcholinesterase in Albino LACA mouse brain homogenates using acetylthiocholine iodide as substrate measured for 2 mins by Ellman's method
Measurement: IC50 = 66950 nM (pChEMBL 4.170000076293945)
Descriptors: MW 323.39, ALogP 3.39, HBA 4, HBD 1, PSA 51.47, QED 0.51
Compound (SMILES): O=C(CCN1CCCCC1)Nc1ccc(-n2cc(-c3cccc(-c4cn(-c5ccc(NC(=O)CCN6CCCCC6)cc5)nn4)c3)nn2)cc1
InChIKey: PLJANQGCTXHSJX-UHFFFAOYSA-N
Target: Telomerase reverse transcriptase (SINGLE PROTEIN), Homo sapiens
UniProt: O14746
Assay: Inhibition of telomerase activity in human A2780 cells incubated for 10 mins by SYBR Green 1 staining based TRAP assay
Measurement: EC50 = 17100 nM (pChEMBL 4.769999980926514)
Descriptors: MW 672.84, ALogP 5.81, HBA 10, HBD 2, PSA 126.1, QED 0.17
Compound (SMILES): N#CCCSc1nn([C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)O2)c2ncnc(N)c12
InChIKey: FGYGLDLTIXKPGI-DJLDLDEBSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 415.46, ALogP -0.72, HBA 12, HBD 3, PSA 192.26, QED 0.38
Compound (SMILES): Cc1[nH]c2ccccc2c1CCNC(=O)CCNCc1cc(Cl)c2cccnc2c1O
InChIKey: GOABROPOBRHMRM-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of recombinant human MMP2 using thiopeptide as substrate preincubated for 30 mins followed by substrate addition and measured every mins for 20 min by colorimetric assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 436.94, ALogP 4.22, HBA 4, HBD 4, PSA 90.04, QED 0.31
Compound (SMILES): O=C(CCCCCn1cc(Nc2ncc(Cl)c(Nc3ccc(Cl)cc3)n2)cn1)NO
InChIKey: MTOQNLGMTJOJOF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 using Ulight-CAGAGAIETDKEYYTVKD as substrate measured after 60 mins by LANCE assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 450.33, ALogP 4.53, HBA 8, HBD 4, PSA 116.99, QED 0.2
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2cc(O)cc(P(=O)(O)O)c2)n1)[C@@H](CC)N(O)C=O.O=C(O)C(F)(F)F
InChIKey: GKYPNZRIUXBBOO-JENXBZAWSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins using 0.5 nM BMP1 by FRET based assay
Measurement: IC50 < 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 536.52, ALogP 1.88, HBA 7, HBD 6, PSA 189.39, QED 0.05
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1S(C)(=O)=O
InChIKey: SYYQNYIBIFOCPS-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of IL-23 induced STAT3 phosphorylation in human KIT225 cells by AlphaLISA assay
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 415.45, ALogP 2.87, HBA 7, HBD 3, PSA 113.08, QED 0.57
Compound (SMILES): COc1ccc(CS(=O)(=O)[C@@H]2C[C@@H](C(=O)N[C@H](C(=O)C(F)(F)C(=O)NCC(F)(F)F)C(C)C)N(C(=O)[C@H](Cc3cccc(Cl)c3)NC(=O)c3ccccn3)C2)cc1
InChIKey: AUCMJTRVVOGXAI-ZRJFKUPHSA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Inhibition of N-terminal 6xHis-SUMO tagged human HTRA1 catalytic PDZ domain (D161 to P480 residues) expressed in Escherichia coli BL21 (DE3) cells using Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by fluorescence method
Measurement: IC50 = 0.804 nM (pChEMBL 9.100000381469727)
Descriptors: MW 844.26, ALogP 3.69, HBA 9, HBD 3, PSA 180.94, QED 0.14
Compound (SMILES): N#CN1CC[C@@H](N2CCN(c3cccc(N4CCOCC4)c3)C2=O)C1
InChIKey: RAJVURXVMCCVHL-QGZVFWFLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 341.42, ALogP 1.32, HBA 5, HBD 0, PSA 63.05, QED 0.78
Compound (SMILES): Cc1ccc(NC(=O)C[C@H](CCC(=O)[O-])c2noc(-c3cc(CC(C)C)no3)c2C2CC2)c(Cl)c1.[Na+]
InChIKey: FMRVYGOFADHGAY-LMOVPXPDSA-M
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibition of human GAL4-fused RORgamma LBD transcriptional activity expressed in CHOK1 cells after 2 days by luciferase reporter gene assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 500, ALogP 6.34, HBA 6, HBD 2, PSA 118.46, QED 0.32
Compound (SMILES): CCC(=O)c1ccc(OCCCN2CCN(C3CCCO3)CC2)cc1
InChIKey: RTMBMADCRYKVPG-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]N-alpha-methylhistamine from full length recombinant human H3R expressed in HEK293 cell membranes after 90 mins by beta scintillation counting method
Measurement: Ki = 1392 nM (pChEMBL 5.860000133514404)
Descriptors: MW 346.47, ALogP 2.8, HBA 5, HBD 0, PSA 42.01, QED 0.53
Compound (SMILES): CC[C@@H]1Cc2c(C)cc(-c3ccc(N)cc3)c(O)c2C(=O)O1
InChIKey: IVGGRXBUADBVCK-CYBMUJFWSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAOA using kynuramine as substrate incubated for 10 mins by UPLC-ESI-MS/MS analysis
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 297.35, ALogP 3.44, HBA 4, HBD 2, PSA 72.55, QED 0.66
Compound (SMILES): COc1ccc(OCCN2CCN(C(=O)c3ccccc3OC)CC2)cc1
InChIKey: JOOAJIXGNAIFDC-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3R expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 370.45, ALogP 2.54, HBA 5, HBD 0, PSA 51.24, QED 0.75
Compound (SMILES): CC1(O)CCN(c2cnc3c(C4CCN(C(=O)c5ccc(OC(F)(F)F)cc5)CC4)ncnc3c2)C1
InChIKey: OFHDGXMKRRHYRS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13164
Assay: Inhibition of His-tagged MAP2K5 activated N-terminal GST-tagged recombinant human ERK5 (1 to 398 residues) expressed in Escherichia coli using biotin-Ahx-PPGDYSTTPGGTLFSTTPGGTRI peptide as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 501.51, ALogP 3.9, HBA 7, HBD 1, PSA 91.68, QED 0.58
Compound (SMILES): Nc1ncnc2c1c(SCC1CC1)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@@H]1F
InChIKey: YWJANQKPRBAAER-IEQSHNCZSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Enzyme Assay: The total volume of the ATG7 enzymatic assay is 50 μL and contains 50 mM HEPES Hemisodium (pH 7.5), 0.05% BSA, 0.01% Tween-20, 25 mM NaCl, 5 mM MgCl2, 10 μM ATP, 250 μM GSH, 5 nM ATG3-GST, 5 nM Flag-Gabarap, 100 μM TCEP and 0.15 nM recombinant human His-ATG7 enzyme. The enzymatic reaction mixture, with and without inhibitor, was incubated at 24° C. for 105 min in a 384-well plate before termination with 25 μM of Stop/Detection buffer (0.1M HEPES Hemisodium pH 7.5, 0.05% Tween20, 20 mM EDTA, 410 mM KF, 0.53 nM Europium-Cryptate labeled monoclonal anti-Flag M2 Antibody (CisBio International) and 8.125 μg/ml PHYCOLINK goat anti-GST allophycocyanin (XL-APC) antibody (Prozyme)). After incubation for 2 hours at 24° C., quantification of FRET is performed on the Pherostar (BMG Labtech). Percentage inhibition values at a single concentration or enzyme inhibition (IC50) values are determined from those curves. One skilled in the art will appreciate that the values generated either as percentage inhibition at a single concentration or IC50 values are subject to experimental variation.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 434.48, ALogP -0.27, HBA 11, HBD 3, PSA 168.47, QED 0.49
Compound (SMILES): COc1ccccc1OS(=O)(=O)/C=C/c1cccc(Cl)c1
InChIKey: AGIPYXJTJSDOSL-MDZDMXLPSA-N
Target: Nuclear factor erythroid 2-related factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16236
Assay: Activation of ED-tagged Nrf2 in human U2OS cells co-expressing Keap1 assessed as induction of NRF2 translocation to nucleus after 6 hrs by beta-galactosidase based chemiluminescent assay
Measurement: EC50 = 698 nM (pChEMBL 6.159999847412109)
Descriptors: MW 324.79, ALogP 3.73, HBA 4, HBD 0, PSA 52.6, QED 0.79
Compound (SMILES): C=CC(=O)N1CCC(NC2=C(c3c[nH]c4ccccc34)C(=O)NC2=O)CC1
InChIKey: ORWGBKLEJAMBBV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system in presence of 6 uM ATP by HTRF assay
Measurement: IC50 = 1777 nM (pChEMBL 5.75)
Descriptors: MW 364.41, ALogP 1.3, HBA 4, HBD 3, PSA 94.3, QED 0.56
Compound (SMILES): Cc1c(C(=O)N2CCC[C@@H](C(F)(F)F)C2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: RMTFKVQQWWDVDP-LLVKDONJSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 395.39, ALogP 2.17, HBA 5, HBD 1, PSA 83.88, QED 0.84
Compound (SMILES): CS(=O)(=O)c1ccc(-c2ccc(CNS(=O)(=O)c3cc4cc(Cl)ccc4[nH]3)cc2)cc1
InChIKey: BZCMUSNKWOWWJI-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Negative allosteric modulation of human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP55940 induced beta arrestin recruitment preincubated for 30 mins followed by addition of CP55940 for 90 mins by chemiluminescence assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 474.99, ALogP 4.37, HBA 4, HBD 2, PSA 96.1, QED 0.43
Compound (SMILES): Cn1cncc1[C@@](O)(COc1ccc(C#N)cc1-c1ccc(OC(F)(F)F)cc1)c1ccc(C#N)cc1
InChIKey: HEUVRFNVTLGKMZ-AREMUKBSSA-N
Target: Protein farnesyltransferase (PROTEIN COMPLEX), Bos taurus
UniProt: P29702
Assay: Scintillation proximity assay (SPA)
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 504.47, ALogP 5.04, HBA 7, HBD 1, PSA 104.09, QED 0.38
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(NC(=O)[C@H](C(C)C)N(C)C)cc3n2)cc1Cl
InChIKey: SSDNXOWYURZRGT-NRFANRHFSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 96.1 nM (pChEMBL 7.019999980926514)
Descriptors: MW 430.94, ALogP 4.2, HBA 6, HBD 1, PSA 68.1, QED 0.61
Compound (SMILES): Fc1ccc(-c2cc(Nc3ccncc3)c3cc[nH]c3n2)cc1F
InChIKey: YBZAHHNJSRROLU-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 322.32, ALogP 4.65, HBA 3, HBD 2, PSA 53.6, QED 0.58
Compound (SMILES): O=Cc1c(OCc2cn(CCCOc3ccc4ccc(=O)oc4c3)nn2)ccc2ccccc12
InChIKey: NARJOJGQAMSQMD-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 455.47, ALogP 4.4, HBA 8, HBD 0, PSA 96.45, QED 0.18
Compound (SMILES): Cc1cc(NC(=O)c2cccc(S(F)(F)(F)(F)F)c2)cc(-n2ccn3nc(-c4cccnc4)cc23)c1
InChIKey: MOONEVNPHKFNGV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor Tie-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35590
Assay: Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000703a TIE1
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 519.5, ALogP 7.41, HBA 5, HBD 1, PSA 64.22, QED 0.25
Compound (SMILES): CCn1c(C(O)(c2ccccc2)c2ccccc2)nc2ccc(C(=O)Nc3ccn(CC(C)C)n3)cc21
InChIKey: UGZIGIJMULWDEE-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of N-terminal 6x-histidine tagged human ACSS2 expressed in insect cells assessed as reduction in pyrophosphate production using CoA and ATP incubated for 30 mins by pyrophosphatase coupled enzymatic assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 493.61, ALogP 5.45, HBA 6, HBD 2, PSA 84.97, QED 0.3
Compound (SMILES): Cc1ccc(Cn2cc(CCC(=O)Nc3nnc(CCCCc4nnc(NC(=O)Cc5ccccc5)s4)s3)nn2)c(C)c1
InChIKey: UEYZNLMORAVFHM-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Binding affinity to human GLS1 expressed in Escherichia coli strain BL21 (DE3)pLysS by SPR assay
Measurement: Kd = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 615.79, ALogP 4.96, HBA 11, HBD 2, PSA 140.47, QED 0.17
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(B(O)O)cc4C[C@@H](CCCCCCCCC[S+]([O-])CCCC(F)(F)C(F)(F)F)[C@H]3[C@@H]1CC[C@@H]2O
InChIKey: FIAYIYKWRBIBQG-GDWZZRAASA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluoromone ligand from recombinant ER-alpha (unknown origin) by LanthaScreen TR-FRET assay
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 634.6
Compound (SMILES): C[C@@]1(CO)C[C@@H](O)C[C@@]2(C)[C@@H]3CC[C@](C)(C(=O)O)C=C3CC[C@H]12
InChIKey: QCXVGHMPEJDENF-WGBOWRHLSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human factor Xa using Z-D-Arg-Gly-Arg-pNA.2HCl as substrate preincubated for 15 mins followed by substrate addition by UV absorption analysis
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 322.44, ALogP 2.98, HBA 3, HBD 3, PSA 77.76, QED 0.68
Compound (SMILES): CC(=O)Nc1sc2c(c1-c1nc3cc(N(C)C)ccc3s1)CCNC2
InChIKey: PGVMKMBJXYVZBY-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 372.52, ALogP 3.69, HBA 6, HBD 2, PSA 57.26, QED 0.74
Compound (SMILES): N[C@H]1CC[C@H](CCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1
InChIKey: OSFYUOBMIMRRQJ-SHTZXODSSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human Gi/o-coupled D2R expressed in HEK293T cells assessed as inhibition of isoproterenol-induced cAMP accumulation preincubated for 15 mins followed by isoproterenol-stimulation and measured by Glosensor-based luminescence assay
Measurement: EC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 356.34, ALogP 4.02, HBA 3, HBD 1, PSA 32.5, QED 0.88
Compound (SMILES): COc1cccc(CNc2nc(Nc3cccc(S(N)(=O)=O)c3)nc3cc(OC)c(OC)cc23)c1
InChIKey: VOVYSWVSPMEQRI-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: O54735
Assay: Inhibition of rat lung PDE5 using [3H]cGMP as substrate measured after 10 mins by scintillation counting method
Measurement: IC50 = 443 nM (pChEMBL 6.349999904632568)
Descriptors: MW 495.56, ALogP 3.66, HBA 9, HBD 3, PSA 137.69, QED 0.32
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCn3cc(CCCC(=O)NCCCCC(NC(=O)CCCc4cn(CCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCC(=O)N[C@H]5CSSC[C@@H]6NC(=O)[C@H](C)NC(=O)[C@@H]7CCCN7C(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@H](CO)NC(=O)[C@H](CSSC[C@@H](C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]7CCCN7C(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC6=O)NC5=O)nn4)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(N)=O)nn3)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: IEDFIQCVIQRLBV-ABLAXWMQSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Inhibition of human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of ACh-evoked currents by two-electrode voltage clamp assay
Measurement: IC50 = 353.6 nM (pChEMBL 6.449999809265137)
Descriptors: MW 5363.2
Compound (SMILES): COc1ccc(N2C(=O)c3cccnc3C2Nc2ccc(OC)c(OC)c2)cc1
InChIKey: MFQOJYNMMHHTET-UHFFFAOYSA-N
Target: Serine hydroxymethyltransferase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P34897
Assay: Inhibition of His-tagged human recombinant SHMT2 expressed in Escherichia coli BLR(DE3) assessed as reduction in NADPH level using L-serine, THF and NADP+ incubated for 5 mins by SHMT2-MTHFD coupled reaction based fluorescence assay
Measurement: IC50 = 2950 nM (pChEMBL 5.53000020980835)
Descriptors: MW 391.43, ALogP 3.88, HBA 6, HBD 1, PSA 72.92, QED 0.69
Compound (SMILES): Nc1nc(-c2ccccn2)nc(N)c1Cc1ccc(F)cc1
InChIKey: JRECLTNSIRZAIQ-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 295.32, ALogP 2.43, HBA 5, HBD 2, PSA 90.71, QED 0.77
Compound (SMILES): Cc1c(C(=O)N2CCC(F)(F)C2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: KZMHWOWAEOKOEU-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 348.31, ALogP 1, HBA 6, HBD 1, PSA 88.29, QED 0.75
Compound (SMILES): O=C(NCC(F)(F)F)c1cc(-c2cnn3cc(-c4ccc5ccoc5c4)cnc23)cs1
InChIKey: FQTQQQOXDGYLJS-UHFFFAOYSA-N
Target: MAP/microtubule affinity-regulating kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27448
Assay: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 442.42, ALogP 5.16, HBA 6, HBD 1, PSA 72.43, QED 0.42
Compound (SMILES): Cc1cc(C)cc(-c2nc3sc4c(c3c(=O)[nH]2)CCC4)c1
InChIKey: XCGOXYHNDJQVNY-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of GST-tagged BRD4 bromodomain (unknown origin) using biotinylated histone H4KAc peptide (1 to 21 residues) as substrate by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 296.39, ALogP 3.76, HBA 3, HBD 1, PSA 45.75, QED 0.74
Compound (SMILES): Cc1c(C(=O)Nc2nc(C3CCC3)c(N3CCN(C)CC3)s2)cnn1Cc1ccc(F)cc1.Cl.Cl
InChIKey: VXZYLZYWYXAAHK-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Inhibition of human TRPV4 expressed in HEK293 cells assessed as reduction in Ca2+ influx incubated for 30 mins by Fluo4-AM dye based
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 468.6, ALogP 4.11, HBA 7, HBD 1, PSA 66.29, QED 0.59
Compound (SMILES): CS(=O)(=O)CCn1c(CN2C(=O)C3(CC3)c3ccncc32)cc2ccccc21
InChIKey: KHHLCYXJSGSSBR-UHFFFAOYSA-N
Target: Protein M2-1 (SINGLE PROTEIN), Human respiratory syncytial virus A (strain A2)
UniProt: P04545
Assay: Viral Cytopathic Effect (CPE) Assay: To measure anti-RSV activity of compounds, 96-well plates are seeded with 6×103 cells per well in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS). Cells are infected the next day with sufficient RSV Long strain (ATCC) to produce an approximately 80-90% cytopathic effect after 6 days, in the presence of serial half-log diluted compound in a total volume of 200 μA per well. The viability of cells is assessed after 6 days using Cell Counting kit-8 (Dojindo Molecular Technologies). The absorbance at 450 nm and referenced at 630 nm is measured to determine 50% effective concentration (EC50)The compounds of the present invention were tested for their anti-RSV activity, and the activation as described herein. The Examples were tested in the above assay and found to have EC50 of about 0.0001 μM to about 10 μM. Particular compound of formula (I) were found to have EC50 of about 0.0001 μM to about 1 μM. Further particular compound of formula (I) were found to have EC50 of about 0.0001 μM to about 0.1 μM.
Measurement: EC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 395.48, ALogP 2.66, HBA 5, HBD 0, PSA 72.27, QED 0.67
Compound (SMILES): CC(C)(C)c1ccc(-c2nnn([C@@H](Cc3ccccc3)C(=O)NO)c2C#CC2CC2)cc1
InChIKey: LERROIJXRINUAL-QHCPKHFHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using fluorophore-conjugated substrate by fluorescence assay
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 428.54, ALogP 4.29, HBA 5, HBD 2, PSA 80.04, QED 0.36
Compound (SMILES): Fc1ccc(Cn2ccc3c(N4CCC(N5CCCCC5)CC4)ncnc32)cc1
InChIKey: JYDMOJYANAKRDD-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]N-alpha-methylhistamine from human histamine H3 receptor expressed in HEK-293 cells incubated for 90 mins by radioligand displacement assay based Cheng-Prusoff equation analysis
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 393.51, ALogP 4.07, HBA 5, HBD 0, PSA 37.19, QED 0.67
Compound (SMILES): COc1cnc(C(=O)Nc2ccnc([C@]34CN(c5ncc(F)cn5)C[C@H]3CSC(N)=N4)c2)cn1
InChIKey: IIMOLGKMCNSOEC-QKVFXAPYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 (1 to 460 residues) expressed in HEK293 cells after 16 to 24 hrs by FRET assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 481.52, ALogP 1.45, HBA 11, HBD 2, PSA 144.4, QED 0.55
Compound (SMILES): Nc1ncc(/C=C/c2cc(/C=C3\Sc4ncccc4C3=O)c(Br)cc2O)cn1
InChIKey: RKQXCLCQPXJOQM-XELDAMHRSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of recombinant His6-SUMO tagged human CGAS expressed in Escherichia coli BL21/pLys cells incubated for 20 mins by Kinase Glo chemiluminescence assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 453.32, ALogP 4.42, HBA 7, HBD 2, PSA 101.99, QED 0.57
Compound (SMILES): CN(C)CCOc1ccc2c3c(c(=O)oc2c1)CN(C(=O)c1ccc(C(=O)O)cc1)CC3
InChIKey: QSABLWKAFNXKQN-UHFFFAOYSA-N
Target: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P13995
Assay: Inhibition of recombinant MTHFD2 (unknown origin) using THF as substrate incubated for 30 mins in presence of NAD
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 436.46, ALogP 2.63, HBA 6, HBD 1, PSA 100.29, QED 0.59
Compound (SMILES): Nc1ncnc2c1c(SC(F)F)nn2[C@H]1C[C@H](O)[C@@H](COS(N)(=O)=O)O1
InChIKey: IRHPRJHUUCEIBI-KVQBGUIXSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Enzyme Assay: The total volume of the ATG7 enzymatic assay is 50 μL and contains 50 mM HEPES Hemisodium (pH 7.5), 0.05% BSA, 0.01% Tween-20, 25 mM NaCl, 5 mM MgCl2, 10 μM ATP, 250 μM GSH, 5 nM ATG3-GST, 5 nM Flag-Gabarap, 100 μM TCEP and 0.15 nM recombinant human His-ATG7 enzyme. The enzymatic reaction mixture, with and without inhibitor, was incubated at 24° C. for 105 min in a 384-well plate before termination with 25 μM of Stop/Detection buffer (0.1M HEPES Hemisodium pH 7.5, 0.05% Tween20, 20 mM EDTA, 410 mM KF, 0.53 nM Europium-Cryptate labeled monoclonal anti-Flag M2 Antibody (CisBio International) and 8.125 μg/ml PHYCOLINK goat anti-GST allophycocyanin (XL-APC) antibody (Prozyme)). After incubation for 2 hours at 24° C., quantification of FRET is performed on the Pherostar (BMG Labtech). Percentage inhibition values at a single concentration or enzyme inhibition (IC50) values are determined from those curves. One skilled in the art will appreciate that the values generated either as percentage inhibition at a single concentration or IC50 values are subject to experimental variation.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 412.4, ALogP -0.41, HBA 11, HBD 3, PSA 168.47, QED 0.53
Compound (SMILES): CCn1c2ccc(C)cc2c2cc(-c3nc4c(C)c(C(=O)O)ccc4n3CCOC)ccc21
InChIKey: FHXIZAPGGULPIK-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Test for Antagonism: 4 μl of a cAMP-d2/cell suspension (625000 cells/ml) were added to a test plate containing the substance solutions already initially introduced (0.05 μl; 100% DMSO, concentration range from 0.8 nM-16.5 μM). After a 20-minute preincubation at room temperature (RT), 2 μl of a 3xPGD2 solution (6 nM, in PBS-IBMX) were added and incubated in the presence of the agonist for a further 30 min at RT (volume: ¿6 μl). Subsequently, the reaction was stopped by addition of 2 μl of lysis buffer and incubated for a further 20 min at RT before the actual measurement (volume: ¿8 μl).
Measurement: IC50 = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 441.53, ALogP 5.79, HBA 5, HBD 1, PSA 69.28, QED 0.36