CEP-1347   Click here for help

GtoPdb Ligand ID: 8173

Synonyms: CEP 1347 | CEP1347 | KT-7515 | KT7515 [5]
Compound class: Synthetic organic
Comment: CEP-1347 is a semi-synthetic analogue of the natural alkaloid K-252a [5]. CEP-1347 was originally identified as a pan-mixed lineage kinase (MLK) family inhibitor [8]. In this setting it inhibits downstream c-jun N-terminal kinase (JNK) activation and has neuroprotective activity [1-2,7].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 145.32
Molecular weight 615.19
XLogP 7.52
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCSCc1ccc2c(c1)c1c3C(=O)NCc3c3c4c1n2C1CC(C(O1)(n4c1c3cc(cc1)CSCC)C)(O)C(=O)OC
Isomeric SMILES CCSCc1ccc2c(c1)c1c3C(=O)NCc3c3c4c1n2[C@H]1C[C@]([C@](O1)(n4c1c3cc(cc1)CSCC)C)(O)C(=O)OC
InChI InChI=1S/C33H33N3O5S2/c1-5-42-15-17-7-9-22-19(11-17)26-27-21(14-34-30(27)37)25-20-12-18(16-43-6-2)8-10-23(20)36-29(25)28(26)35(22)24-13-33(39,31(38)40-4)32(36,3)41-24/h7-12,24,39H,5-6,13-16H2,1-4H3,(H,34,37)/t24-,32+,33+/m1/s1
InChI Key SCMLRESZJCKCTC-KMYQRJGFSA-N
References
1. Apostol BL, Simmons DA, Zuccato C, Illes K, Pallos J, Casale M, Conforti P, Ramos C, Roarke M, Kathuria S et al.. (2008)
CEP-1347 reduces mutant huntingtin-associated neurotoxicity and restores BDNF levels in R6/2 mice.
Mol Cell Neurosci, 39 (1): 8-20. [PMID:18602275]
2. Conforti P, Ramos C, Apostol BL, Simmons DA, Nguyen HP, Riess O, Thompson LM, Zuccato C, Cattaneo E. (2008)
Blood level of brain-derived neurotrophic factor mRNA is progressively reduced in rodent models of Huntington's disease: restoration by the neuroprotective compound CEP-1347.
Mol Cell Neurosci, 39 (1): 1-7. [PMID:18571429]
3. Goodfellow VS, Loweth CJ, Ravula SB, Wiemann T, Nguyen T, Xu Y, Todd DE, Sheppard D, Pollack S, Polesskaya O et al.. (2013)
Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3.
J Med Chem, 56 (20): 8032-48. [PMID:24044867]
4. Harris CA, Deshmukh M, Tsui-Pierchala B, Maroney AC, Johnson Jr EM. (2002)
Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons.
J Neurosci, 22 (1): 103-13. [PMID:11756493]
5. Maroney AC, Finn JP, Connors TJ, Durkin JT, Angeles T, Gessner G, Xu Z, Meyer SL, Savage MJ, Greene LA et al.. (2001)
Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family.
J Biol Chem, 276 (27): 25302-8. [PMID:11325962]
6. Parkinson Study Group PRECEPT Investigators. (2007)
Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease.
Neurology, 69 (15): 1480-90. [PMID:17881719]
7. Pirvola U, Xing-Qun L, Virkkala J, Saarma M, Murakata C, Camoratto AM, Walton KM, Ylikoski J. (2000)
Rescue of hearing, auditory hair cells, and neurons by CEP-1347/KT7515, an inhibitor of c-Jun N-terminal kinase activation.
J Neurosci, 20 (1): 43-50. [PMID:10627579]
8. Saporito MS, Brown EM, Miller MS, Carswell S. (1999)
CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo.
J Pharmacol Exp Ther, 288 (2): 421-7. [PMID:9918541]
9. Siu M, Sengupta Ghosh A, Lewcock JW. (2018)
Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration.
J Med Chem, 61 (18): 8078-8087. [PMID:29863360]