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MK-1775
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MK-1775图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
MK-1775 (AZD-1775; MK-1775) 是一种有效的 Wee1 抑制剂,IC50 为 5.2 nM。

Cell lines

H1299 cells

Preparation Method

H1299 cells were treated for 1 h with 200 nM MK-1775, irradiated with 7.5 Gy, incubated for an additional 18 h in MK-1775, and harvested for assessment of apoptosis at 24, 48, and 72 h post-irradiation.

Reaction Conditions

200 nM, 1 h

Applications

The dose of 7.5 Gy induced levels of apoptosis of only about 5% above control at any time point and these levels of apoptosis were not significantly enhanced by MK-1775.

Animal models

6-week-old female nu/nu athymic mice

Preparation Method

When tumors reached a volume of ~200 mm3, mice were individually identified and randomly assigned to treatment groups, with 5–6 mice (8–10 evaluable tumors) in each group: 1) control; 2) MK-1775 (30 mg/kg. p.o., once daily for 4 weeks; 3) GEM (100 mg/kg, i.p., twice weekly on days 1 and 4) for 4 weeks; 4) GEM followed 24 h later by MK-1775 in the above mentioned dose.

Dosage form

30 mg/kg. p.o.,

Applications

Single agent MK-1775 treatment produced greater than 50% inhibition of tumor growth in two xenografts (PANC286 and PANC198).

产品描述

MK-1775 is a potent and selective small-molecule inhibitor of Wee1 kinase with an IC50value of 5.2 nM. MK-1775 is 2- to 3-fold less potent against Yes with an IC50of 14 nM.[1].

In vitro efficacy test it shown that MK-1775 inhibited phosphorylation of CDC2 at Tyr15 with an EC50 value of 85 nM in cells pretreated with gemcitabine. MK-1775 treatment induced pHH3 in a dose-dependent manner with an EC50 value of 81 nM.[1]In vitro efficacy test it indicated that treatment with 10 nM panobinostat in combination with 250 nM or 500 nM MK-1775 in U937 cells, the combination index (CI) values were 0.95 and 0.73, while U937 cells treated with 20 nM panobinostat in combination with 250 nM or 500 nM MK-1775 were 0.39 and 0.40, respectively.[3]In vitro, treatment with 0.1, 0.3, 1 μM of MK-1775 for 48 h in LSCC cells and TU212 and KB-3-1 cells dose-dependently induced early apoptosis (Annexin V+/PI-) and late apoptosis (Annexin V+/PI+) . Moreover, after MK-1775 treatment, the protein levels of apoptosis marker cleaved-PARP was increased in a dose-depend manner[5].

In vivo, treatment with 60 mg/kg MK-1775 orally enhances H1299 xenograft tumor response to fractionated radiotherapy in nude mice.[2]In vivo experiment it indicated that treatment with either MK-1775 (20 mg/kg) or panobinostat (10 mg/kg) alone in mice bearing BxPC-3 xenograft tumors had modest delay of externally measurable tumor growth (30.9% and 37.8% on day 20, respectively). However, combination the MK-1775 (20 mg/kg) with panobinostat (10 mg/kg) can marked delay the tumor growth with 58.7% tumor growth inhibition on day 20.[4]In vivo, Nude Mice were treated with 50 mg/kg orally MK-1775, MK-1775 inhibited the growth of KB-3-1 xenografts with the inhibition ratio of 30.04% by reducing the tumor volumes and weights. And MK-1775 also can cause toxicity in mice at the indicated dose.[6].

References:
[1]Hirai H, et al. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther. 2010 Apr 1;9(7):514-22.
[2]Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48.
[3]Qi W, et al. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo. Cancer Biol Ther. 2015;16(12):1784-93.
[4]Wang G, et al. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68.
[5]Yuan ML, et al Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. Front Pharmacol. 2018 Sep 28;9:1041.
[6]Yuan ML, et al. Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. Front Pharmacol. 2018 Sep 28;9:1041.