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CCG-1423

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Chemical Structure| 285986-88-1 同义名 : -
CAS号 : 285986-88-1
货号 : A381687
分子式 : C18H13ClF6N2O3
纯度 : 99%+
分子量 : 454.75
MDL号 : MFCD01566719
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(230.9 mM)，配合低频超声，并水浴加热至45℃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

  • Rho-subclass
描述 Rho GTPases are molecular switches that regulate many essential cellular processes, including actin dynamics, gene transcription, cell-cycle progression and cell adhesion[3]. Rho-kinase has pleiotropic functions including the regulation of cellular contraction, motility, morphology, polarity, cell division, and gene expression[4]. CCG-1423 is a novel inhibitor of RhoA/C-mediated gene transcription that is capable of inhibiting invasion of PC-3 prostate cancer cells in a Matrigel model of metastasis. CCG-1423 selectively inhibited spontaneous PC-3 prostate cancer cell invasion through a Matrigel matrix in vitro, but not the Gαi-dependent LPA-stimulated SKOV-3 ovarian cancer cell invasion in vitro. At 100 μM, nearly complete inhibition of invasion was achieved with a lesser degree of toxicity than that induced by CCG-1423 at 10 μM[5]. Pharmacological SRF inhibition by CCG-1423 reduced nuclear MKL1 and improved glucose uptake and tolerance in insulin-resistant mice in vivo[6]. SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells[7]. Pharmacological MKL-inhibition with CCG-1423 significantly inhibited CCN1 promoter activity as well as mRNA and protein expression[8].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

11.00mL

2.20mL

1.10mL

21.99mL

4.40mL

2.20mL
参考文献

[1]Jin W, Goldfine AB, et al. Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance. J Clin Invest. 2011 Mar;121(3):918-29.

[2]Evelyn CR, Bell JL, et al. Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423. Bioorg Med Chem Lett. 2010 Jan 15;20(2):665-72.

[3]A L Bishop,et al. Rho GTPases and their effector proteins. Biochem J. 2000 Jun 1;348 Pt 2(Pt 2):241-55.

[4]Mutsuki Amano,et al. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken).2010 Sep;67(9):545-54.

[5]Evelyn CR, et al. Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423. Bioorg Med Chem Lett. 2010 Jan 15;20(2):665-72.

[6]Jin W, et al. Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance. J Clin Invest. 2011 Mar;121(3):918-29.

[7]Chong NW, et al. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway. PLoS One. 2012;7(7):e40966.

[8]Duggirala A, et al. cAMP-induced actin cytoskeleton remodelling inhibits MKL1-dependent expression of the chemotactic and pro-proliferative factor, CCN1. J Mol Cell Cardiol. 2014 Nov 18;79C:157-168.