CEP-1347

Identification

Name
CEP-1347
Accession Number
DB05403
Type
Small Molecule
Groups
Investigational
Description

CEP-1347 is a semi-synthetic compound shown to protect multiple nerve cell types from a variety of insults leading to programmed cell death (apoptosis) which could improve the survival of dopamine neurons prior to and after transplantation.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
200HA2LIMK
CAS number
Not Available
Weight
Average: 615.762
Monoisotopic: 615.186162561
Chemical Formula
C33H33N3O5S2
InChI Key
WMBUVOLZSWTKMP-KQFGJPIXSA-N
InChI
InChI=1S/C33H33N3O5S2/c1-5-42-15-17-7-9-23-19(11-17)27-28-21(14-34-31(28)37)26-20-12-18(16-43-6-2)8-10-24(20)36-30(26)29(27)35(23)25-13-22(32(38)41-39-4)33(36,3)40-25/h7-12,22,25H,5-6,13-16H2,1-4H3,(H,34,37)/t22-,25+,33+/m1/s1
IUPAC Name
methyl (15S,16S,18S)-10,23-bis[(ethylsulfanyl)methyl]-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.1¹⁵,¹⁸.0²,⁶.0⁷,²⁷.0⁸,¹³.0¹⁹,²⁶.0²⁰,²⁵]octacosa-1,6,8(13),9,11,20(25),21,23,26-nonaene-16-carboperoxoate
SMILES
[H][[email protected]@]12C[[email protected]](C(=O)OOC)[[email protected]](C)(O1)N1C3=C(C=C(CSCC)C=C3)C3=C4CNC(=O)C4=C4C5=C(C=CC(CSCC)=C5)N2C4=C13

Pharmacology

Indication

Investigated for use/treatment in asthma and parkinson's disease.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

CEP-1347, an orally active molecule, is a selective and potent inhibitor of the stress-activated protein kinase pathway, an intracellular signaling pathway that is an essential component of the stress response leading to neuronal death. In-vitro cell culture systems and in-vivo mouse and non-human primate models of Parkinson's disease have shown that CEP-1347 protects dopamine neurons in the substantia nigra, the area of the brain affected by Parkinson's disease.

TargetActionsOrganism
UMitogen-activated protein kinase 12Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Bozyczko-Coyne D, O'Kane TM, Wu ZL, Dobrzanski P, Murthy S, Vaught JL, Scott RW: CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Abeta-induced cortical neuron apoptosis. J Neurochem. 2001 May;77(3):849-63. [PubMed:11331414]
External Links
PubChem Compound
133005
PubChem Substance
175426995
ChemSpider
117379

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3TerminatedTreatmentParkinson's Disease (PD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0111 mg/mLALOGPS
logP5.35ALOGPS
logP6.26ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)13.91ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.72 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity171.22 m3·mol-1ChemAxon
Polarizability88.35 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9693
Blood Brain Barrier+0.6995
Caco-2 permeable-0.5691
P-glycoprotein substrateSubstrate0.6925
P-glycoprotein inhibitor IInhibitor0.5838
P-glycoprotein inhibitor IINon-inhibitor0.9543
Renal organic cation transporterNon-inhibitor0.7471
CYP450 2C9 substrateNon-substrate0.8371
CYP450 2D6 substrateNon-substrate0.8243
CYP450 3A4 substrateSubstrate0.7203
CYP450 1A2 substrateNon-inhibitor0.6332
CYP450 2C9 inhibitorNon-inhibitor0.5752
CYP450 2D6 inhibitorNon-inhibitor0.8831
CYP450 2C19 inhibitorNon-inhibitor0.5698
CYP450 3A4 inhibitorInhibitor0.6903
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.626
Ames testNon AMES toxic0.6308
CarcinogenicityNon-carcinogens0.744
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8432 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9963
hERG inhibition (predictor II)Non-inhibitor0.5125
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Indolocarbazoles
Alternative Parents
Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Indoles / Benzenoids / Tetrahydrofurans / Heteroaromatic compounds / Peroxycarboxylic acids and derivatives / Pyrroles / Lactams
show 13 more
Substituents
Indolocarbazole / Pyrrolo[2,3-a]carbazole / Pyrroloindole / Isoindolone / Indole / Isoindoline / Isoindole or derivatives / Benzenoid / Heteroaromatic compound / Tetrahydrofuran
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK12
Uniprot ID
P53778
Uniprot Name
Mitogen-activated protein kinase 12
Molecular Weight
41939.84 Da

Drug created on November 18, 2007 11:24 / Updated on December 01, 2017 15:35