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CZ415

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Chemical Structure| 1429639-50-8 同义名 : -
CAS号 : 1429639-50-8
货号 : A569091
分子式 : C22H29N5O4S
纯度 : 99%+
分子量 : 459.562
MDL号 : MFCD30533321
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(228.48 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • mTOR

    mTOR, pIC50:8.07
描述 The mammalian target of rapamycin (mTOR/FRAP1) is a serine/threonine protein kinase, which belongs to a family of phosphoinositide 3-kinase-related kinases (PIKK). mTOR is the catalytic subunit of two signaling complexes called mTORC1 and mTORC2, which play a critical role in regulation of cell metabolism, proliferation, survival and migration. CZ415 is a potent and highly selective ATP-competitive mTOR inhibitor with Kdapp value of 6.9 nM, and shows efficacy in a semi-therapeutic collagen induced arthritis (CIA) mouse model[3]. CZ514 (1-1000 nM) dose-dependently inhibited human papillary thyroid carcinoma cell line TPC-1 cell growth, induced cleavage of both caspase-3 and caspase-9 and disrupted cycle progression. Consistently, oral administration of CZ415 (20 mg/kg body weight, daily for 24 days) significantly reduced TPC-1 xenograft tumor volume in mice more than 60%[4]. CZ415 dose-dependently inhibited HepG2 cell survival with IC50 of 233.75 ±22.54 nM. HepG2 tumor growth in SCID mice was decreased to 13.93 ± 3.72 mm3 after oral administration of CZ415 (10 mg/kg body weight, daily), compared with 43.52 ± 4.5 mm3 in vehicle control mice[5]. It was also found that CZ415 (from 1 to 300 nM) dose-dependently inhibited head and neck squamous cell carcinoma cell line SCC-9 survival[6].
作用机制 CZ415 inhibits mTOR activity in an ATP-competitive manner.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.88mL

2.18mL

1.09mL

21.76mL

4.35mL

2.18mL
参考文献

[1]Cansfield AD, Ladduwahetty T, et al. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett. 2016 Jun 10;7(8):768-73.

[2]Yin G, Fan J, et al. ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo. Oncotarget. 2017 May 30;8(47):82027-82036.

[3]Cansfield AD, Ladduwahetty T, Sunose M, Ellard K, Lynch R, Newton AL, Lewis A, Bennett G, Zinn N, Thomson DW, Rüger AJ, Feutrill JT, Rausch O, Watt AP, Bergamini G. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett. 2016 Jun 10;7(8):768-73. doi: 10.1021/acsmedchemlett.6b00149. PMID: 27563401; PMCID: PMC4983736.

[4]Li X, Li Z, Song Y, Liu W, Liu Z. The mTOR Kinase Inhibitor CZ415 Inhibits Human Papillary Thyroid Carcinoma Cell Growth. Cell Physiol Biochem. 2018;46(2):579-590. doi: 10.1159/000488625. Epub 2018 Mar 28. PMID: 29617677.

[5]Zhang W, Chen B, Zhang Y, Li K, Hao K, Jiang L, Wang Y, Mou X, Xu X, Wang Z. The anti-hepatocellular carcinoma cell activity by a novel mTOR kinase inhibitor CZ415. Biochem Biophys Res Commun. 2017 Jun 3;487(3):494-499. doi: 10.1016/j.bbrc.2017.03.156. Epub 2017 Mar 30. PMID: 28366631.

[6]Xie J, Li Q, Ding X, Gao Y. Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells. Cell Physiol Biochem. 2018;46(2):676-686. doi: 10.1159/000488724. Epub 2018 Mar 29. PMID: 29621758.