GlpBio

PF-477736

目录号: GC14234纯度: >99.00%同义词: PF 00477736
A selective inhibitor of checkpoint kinase 1
PF-477736
Cas No.: 952021-60-2
规格价格库存数量操作
1mg¥308.00现货
1
5mg¥828.00现货
1
10mg¥1,440.00现货
1
50mg¥4,680.00现货
1
10mM (in 1mL DMSO)¥911.00现货
1
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文献被引

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    187(9):2288-2304 (2024)
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    183(7):1867-1883 (2020)
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产品描述 Description

PF-477736 is a potent, selective ATP-competitive and small-molecule inhibitor of Chk1 with a Ki of 0.49±0.29nM for the in vitro kinase activity of Chk1 [1].

PF-477736 has shown a selective inhibition of Chk1 with the IC50 values of 0.49nM, 9.9μM and 47nM for Chk1, CDK1 and Chk2, respectively. In a dot-blot assay, PF-477736 has been reported to inhibit camptothecin-induced G2 arrest with the EC50 values of 45nM, 38nM and 42nM in P53-mutated human lymphoma CA46 cells, HeLa cells and HT29 cells. Apart from these, PF-477736 has been found to selectively target p53-defective cancer cells while having minimal cytotoxic effects on normal (p53-competent) cells. In addition, PF-00477736 has been revealed to dose-dependently enhance the antitumor activity of a MTD of gemcitabine with no apparent exacerbation of systemic toxicity as assessed by monitoring body weight in the Colo205 xenograft [1].

References:
[1] Blasina A1, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther. 2008 Aug;7(8):2394-404.

实验参考方法 Experimental Reference Method

Kinase experiment [1]:

Kinase assays

CHK1 activity was measured by a pyruvate kinase-lactate dehydrogenase coupled, continuous spectrophotometric assay method where the phosphorylation of a CHK1 peptide substrate (Syntide-2, PLARTLSVAGLPGKK) was coupled to the oxidation of NADH and the corresponding change in absorbance intensity was measured at 340 nm. The assay was performed in a 96-well plate for 20 minutes at 30°C in 0.1 mL of assay buffer containing 50 mM TRIS pH 7.5, 0.4 M NaCl, 4 mM PEP, 0.15 mM NADH, 28 units of lactate dehydrogenase/mL, 16 units of pyruvate kinase/mL, 3 mM DTT, 0.125 mM Syntide-2, 0.15 mM ATP and 25 mM magnesium chloride. Assays were initiated with 1nM of CHK1 kinase domain. The inhibition of CHK1 activity was determined by measuring initial velocities in the presence of varying concentrations of PF-477736.
Cell experiment [2]:

Cell lines

HT29 cell lines

Preparation method

The solubility of this compound in DMSO is >5.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

69 nM, 24h

Applications

The gemcitabine and PF-477736 combination induced significant potentiation of the cytotoxic activity of gemcitabine, indicating that the combination treatment caused a permanent cellular damage that cannot be overcome even after drug removal. The cell kill induced by the combination treatment is time and dose dependent.
Animal experiment [2]:

Animal models

Colo205 Xenograft Models in Athymic Nude Mice

Dosage form

i.p., 4-60 mg/kg，q3d × 4

Application

In xenografts, PF-477736 enhanced the antitumor activity of gemcitabine in a dose-dependent manner.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Blasina A1, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther. 2008 Aug;7(8):2394-404.

产品文档 Product Documents

Purity:>99.00%

化学性质Chemical Properties

CAS 号
952021-60-2
同义词
PF 00477736
化学名
(R)-2-amino-2-cyclohexyl-N-(2-(1-methyl-1H-pyrazol-4-yl)-6-oxo-5,6-dihydro-4H-[1,2]diazepino[4,5,6-cd]indol-8-yl)acetamide
SMILES
O=C(C(C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])([H])N([H])[H])N([H])C2=C([H])C3=C4C(N=C(C5=C([H])N(C([H])([H])[H])N=C5[H])C4=C([H])N([H])N([H])C3=O)=C2[H]
分子式
C22H25N7O2
分子量
419.48 g/mol
溶解性
≥ 5.2mg/mL in DMSO
保存条件
Store at -20°C
General tips
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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
为了提高溶解度，请将管子加热至 37°C，然后在超声波浴中震荡一段时间。
Shipping Condition
评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备 RT，或根据请求配备蓝冰。

计算工具摩尔浓度 / 稀释 / 分子量 / 单位换算 / 体内配方 / 溶解度

g/mol