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E64FC26

CAS No. : 2285446-62-8

產品活性：E64FC26 is a potent pan-inhibitor of the protein disulfide isomerase (PDI) family, with IC₅₀s of 1.9, 20.9, 25.9, 16.3, and 25.4 μM against PDIA1, PDIA3, PDIA4, TXNDC5, and PDIA6, respectively. E64FC26 shows anti-myeloma activity.

研究領域：Apoptosis  |  Metabolic Enzyme/Protease  |  Cell Cycle/DNA Damage

作用靶點：Apoptosis  |  PDI

In Vitro: E64FC26 (0.01-100 µM; 24 hours) shows anti-MM activity , with an EC₅₀ of 0.59 μM.E64FC26 is more cytotoxic against a genetically diverse panel of multiple myeloma (MM) cell lines (KMS11, OPM2, MM.1S BzR, MM.1S, SA-13, U266 BzR, ANBL6, KMS12PE, U266, 8226 DxR, 8226 BzR, KMS12BM, H929,8226 cells) when compared to non-malignant cells.

In Vivo: E64FC26 (2 mg/ kg; i.p.; three days a week for 7days) shows anti-MM effect in NSG mice model, and increases median survival by 2 weeks.
The combination of E64FC26 and Bortezomib produced the greatest improvement in survival, extending the median survival by 20 days.
Pharmacokinetic of E64FC26 was measured in CD-1 mice. E64FC26 was administered i.v. (2 mg/kg; gray tracing) or p.o. (5 mg/ kg; blue tracing) and plasma drug concentrations were measured over a 24 h period. In CD-1 mice demonstrated adequate oral bioavailabilty of 34% with systemic exposure approaching a maximum concentration (Cmax) of 400 nM after a single oral dose of 5 mg/kg with a terminal half-life of 9.5 h.
Vk*MYC transgenic mice are treated with E64FC26 (2 mg/kg, i.p., 3 days/week) for two consecutive weeks. E64FC26 treatment induces an immediate anti-MM response, decreasing serum M-protein in all mice by an average of 33 ± 7.9%.

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