SML1684

GSK2850163

≥98% (HPLC)

• Sinônimo(s): (R)-2-(3,4-Dichlorobenzyl)-N-(4-methylbenzyl)-2,7-diazaspiro[4.5]decane-7-carboxamide
• Fórmula empírica (Notação de Hill): C₂₄H₂₉Cl₂N₃O
• Número CAS: 2121989-91-9
• Peso molecular: 446.41
• Código UNSPSC: 12352200
• ID de substância PubChem: 329826014
• NACRES: NA.77

Propriedades

• Nível de qualidade: 100
• Ensaio: ≥98% (HPLC)
• Formulário: oil
• cor: colorless to light yellow
• temperatura de armazenamento: 2-8°C
• cadeia de caracteres SMILES: ClC1=CC(CN(C2)CC[C@]32CN(C(NCC4=CC=C(C)C=C4)=O)CCC3)=CC=C1Cl
• InChI: 1S/C24H29Cl2N3O/c1-18-3-5-19(6-4-18)14-27-23(30)29-11-2-9-24(17-29)10-12-28(16-24)15-20-7-8-21(25)22(26)13-20/h3-8,13H,2,9-12,14-17H2,1H3,(H,27,30)/t24-/m1/s1
• chave InChI: YFDASBFQKMHSSJ-XMMPIXPASA-N

Descrição

Ações bioquímicas/fisiológicas

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

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.

Informações de segurança

• Frases de perigo: H413
• Declarações de precaução: P273 - P501
• Classificações de perigo: Aquatic Chronic 4
• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable