3oxi
Design and Synthesis of Disubstituted Thiophene and Thiazole Based Inhibitors of JNK for the Treatment of Neurodegenerative DiseasesDesign and Synthesis of Disubstituted Thiophene and Thiazole Based Inhibitors of JNK for the Treatment of Neurodegenerative Diseases
Template:ABSTRACT PUBMED 21071223
DiseaseDisease
[MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
FunctionFunction
[MK10_HUMAN] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.[1]
About this StructureAbout this Structure
3oxi is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Hom RK, Bowers S, Sealy JM, Truong AP, Probst GD, Neitzel ML, Neitz RJ, Fang L, Brogley L, Wu J, Konradi AW, Sham HL, Toth G, Pan H, Yao N, Artis DR, Quinn K, Sauer JM, Powell K, Ren Z, Bard F, Yednock TA, Griswold-Prenner I. Design and synthesis of disubstituted thiophene and thiazole based inhibitors of JNK. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7303-7. Epub 2010 Oct 21. PMID:21071223 doi:10.1016/j.bmcl.2010.10.066