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規格	10mM*1mLinDMSO 5mg 10mg 25mg 50mg 100mg
CAS	1338934-59-0
別名	N/A
化學名	N/A
分子式	C18H19NO7
分子量	361.35
溶解度	DMSO : 16.67 mg/mL (46.13 mM)
儲存條件	Store at -20°C
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request

產品描述：

MKC8866 is an inositol requiring enzyme 1 (IRE-1α) inhibitor with an IC50 of less than 0.1 μM.

Protein folding stress in the endoplasmic reticulum of a cell initiates a signal transduction cascade termed the unfolded protein response or UPR. A key enzyme, inositol requiring enzyme 1 (IRE-1α), relieves protein folding stress by enhancing molecular chaperone activity and therefore protects cells from stress induced apoptosis. MKC8866 is useful for treating at least B cell autoimmune diseases, certain cancers, and some viral infections. MKC8866 (Compound 167) inhibits IRE-1α in the in vitro assay with an IC50 of <0.1 μM. MKC8866 (Compound 167) IRE-1α in an in vivo XBP-1 splicing assay (e.g., in myeloma cells) with an EC50<10 μM[1].

MKC8866 is a selective IRE1 RNase inhibitor that exhibits acceptable pharmacokinetic and toxicity profiles. To determine the efficacy of MKC8866 treatment in vivo, MDA-MB-231 tumor xenografts are established in athymic nude mice. Once tumors have reached a palpable size (225-250 mm3), animals are randomized into treatment groups and treated with vehicle alone, 300 mg/kg MKC8866 alone, 10 mg/kg Paclitaxel alone or a combination of Paclitaxel and MKC8866. Treatments in all groups are administered until tumors reach maximal size (2000 mm3) or on day 60, whichever came first. MKC8866 is well tolerated after 60 consecutive oral doses and, based on pharmacokinetic allometric scaling, systemic exposures are well above anticipated clinical therapeutic levels. Following MDA-MB-231 tumor formation, mice are treated with Paclitaxel alone (7.5 mg/kg) for days 1-10, or a combination of Paclitaxel (days 1-10) and MKC8866 (300 mg/kg, days 1-28). After withdrawal of Paclitaxel treatment on day 10, an initial reduction in tumor volume is apparent in both treatment groups. Tumor re-growth, evident after day 18 in those animals receiving no further treatment, is repressed in the treatment group still receiving MKC8866. Tumor re-growth is only apparent in this group following cessation of MKC8866 on day 28[2].

[1]. Zeng, Qingping, et al. IRE-1α inhibitors. US9867803. [2]. Logue SE, et al. Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy. Nat Commun. 2018 Aug 15;9(1):3267.

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原創作者：上海莼試生物技術有限公司

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賬戶名：上海生物

開戶行：中國銀行山東省分行營業部

賬號：2169 2341 6278

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MKC8866 (IRE-1α inhibitor 1)

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