SML1684

GSK2850163

≥98% (HPLC)

• 別名: (R)-2-(3,4-Dichlorobenzyl)-N-(4-methylbenzyl)-2,7-diazaspiro[4.5]decane-7-carboxamide
• 実験式（ヒル表記法）: C₂₄H₂₉Cl₂N₃O
• CAS番号: 2121989-91-9
• 分子量: 446.41
• UNSPSCコード: 12352200
• PubChem Substance ID: 329826014
• NACRES: NA.77

特性

• 品質水準: 100
• アッセイ: ≥98% (HPLC)
• 形状: oil
• 色: colorless to light yellow
• 保管温度: 2-8°C
• SMILES記法: ClC1=CC(CN(C2)CC[C@]32CN(C(NCC4=CC=C(C)C=C4)=O)CCC3)=CC=C1Cl

詳細

生物化学的／生理学的作用

GSK2850163 is a highly selective inhibitor of inositol requiring enzyme-1 alpha (IRE1α) with dual activity: it inhibits IRE1α kinase activity with an IC50 value of 20 nM and RNase activity with an IC50 value of 200 nM. IRE1α is a dual serine/threonine-protein kinase/endoribonuclease with two enzymatic domains: a trans-autophosphorylation domain and and endoribonuclease (RNase) domain. When activated, usually in response to endoplasmic reticulum (ER) stress such as the unfolded protein response (UPR), IRE1α oligomerizes and activates mRNA splicing of adaptive XBP1 transcription factor, which upregulates ER chaperones and ER associated degradation (ERAD) genes that promote degradation of ER unfolded proteins and facilitate recovery from ER stress. However, if ER stress is too high or chronic, IRE1α is hyperactivated, increasing many ER mRNAs, resulting in apoptosis. GSK2850163 interacts with IRE1α catalytic residues Lys599 and Glu612, displacing the kinase activation loop to the inactive DFG-out conformation. The rearrangement of the kinase domain-dimer interface also results in the RNAse domains rotating away from each other, inhibiting the RNase activity.

IRE1α-selective inhibitor of XBP1 splicing.
Homoharringtonine is a cephalotaxine ester that is also known as (HHT; 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate). In gefitinib-resistant lung cancer cells, homoharringtonine promotes apoptosis and prevents signal transducer and activator of transcription (STAT3) through IL-6 (interleukin-6) /JAK1 (janus kinase 1)/STAT3 signal pathway. It plays an important role in the treatment of malaria.

安全性情報

• 危険有害性情報: H413
• 注意書き: P273 - P501
• 危険有害性の分類: Aquatic Chronic 4
• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable