MKT-077 is a rhodacyanine dye and also a heat shock protein 70 (Hsp70) inhibitor which exhibits significant antitumor activity.

MKT-077 is a rhodacyanine dye and also a heat shock protein 70 (Hsp70) inhibitor which exhibits significant antitumor activity. MKT-077 treatment (0.1 to 10 µM dose ranges) for 48 hours can effectively decrease TT cell viability. MKT-077 treatment results in accumulation of cells in the G0/G1 phase in a dose-dependent manner, and also increases sub-G0/G1 phase population in TT cell culture in a dose-dependent manner. MKT-077 also downregulates cellular levels of the proliferation marker, Ki67, and the S-phase transcription factor, E2F-1, in TT and MZ-CRC-1 cells. Moreover, flow cytometry using different doses of MKT-077 reveales that TT cells can uptake and retain MKT-077 at significantly higher levels than MZ-CRC-1 cells^[1]. MKT-077 has EC₅₀ values of 1.4±0.2 and 2.2±0.2 μM against MDA-MB-231 and MCF7 breast cancer cells, respectivelyl^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Systemic administration of MKT-077 significantly delays the growth of TT xenografts in mice throughout the treatment. At the end of MKT-077 treatment, it is found that tumor weights are about two-times less in MKT-077-treated group than in control group. MKT-077 treatment also results in weight loss and general toxicity in animals^[1]. Results show that the succinate-induced, ADP-stimulated respiratory rate in mitochondria isolated from the liver of rats treated with a bolus i.v. injection of 15 mg MKT-077 1kg body weight each day for 5 days is significantly lower than that of untreated controls^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

432.00

C₂₁H₂₂ClN₃OS₂

147366-41-4

Room temperature in continental US; may vary elsewhere.

-20deg;C, sealed storage, away from moisture

*In solvent : -80deg;C, 6 months; -20deg;C, 1 month (sealed storage, away from moisture)

In Vitro:;

DMSO : 56.67 mg/mL (131.18 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (ultrasonic) (insoluble)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂：;10% DMSO ;; 40% PEG300 ;; 5% Tween-80 ;; 45% saline

  Solubility: ≥ 4.25 mg/mL (9.84 mM); Clear solution

  此方案可获得 ≥ 4.25 mg/mL (9.84 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 42.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂：;10% DMSO ;; 90% (20% SBE-β-CD in saline)

  Solubility: 4.25 mg/mL (9.84 mM); Suspended solution; Need ultrasonic

  此方案可获得 4.25 mg/mL (9.84 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 42.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Starenki D, et al. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo. Endocrinol Metab (Seoul). 2015 Dec;30(4):593-603.

  [2]. Li X, et al. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14;4(11).

  [3]. Weisberg EL, et al. In vivo administration of MKT-077 causes partial yet reversible impairment of mitochondrial function. Cancer Res. 1996 Feb 1;56(3):551-5.

Cells are incubated with 1 µM MKT-077 and 100 nM Mitotracker Green FM in culture medium for 30 minutes at 37°C in the dark, washed with PBS, switched into phenol-red free medium before visualizing fluorescence under a microscope. Pictures are acquired and processed with software. For flow cytometric measurement, MKT-077-treated cells are resuspended in 0.1% bovine serum albumin/PBS and analyzed by flow cytometry. Data from 20,000 cells are analyzed using FCS Express software^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

The 1×10⁷ TT cells in 200 µL Hank’s balanced salt solution are inoculated subcutaneously into the rear flanks of 6-week-old female athymic nude (nu/nu) mice. Once palpable, tumors are measured using calipers at intervals indicated in the text. When tumor volume reaches 100 mm³, mice are sorted into groups of 8 to achieve equal distribution of tumor size in all treatment groups. Group 1 receives only the vehicle (1:9 mixture of DMSO/saline) and group 2 receives MKT-077 (10 mg/kg body weight/dose). A 200 µL of ether solution is administered by intraperitoneal injection every 2 days (total 10 doses). At the end of the experiments, animals are euthanized by CO₂ asphyxiation^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Starenki D, et al. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo. Endocrinol Metab (Seoul). 2015 Dec;30(4):593-603.

  [2]. Li X, et al. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14;4(11).

  [3]. Weisberg EL, et al. In vivo administration of MKT-077 causes partial yet reversible impairment of mitochondrial function. Cancer Res. 1996 Feb 1;56(3):551-5.