同义名 :	LT-253; LOR-253
	CAS号 :	916151-99-0
	货号 :	A350879
	分子式 :	C22H14FN5
	纯度 :	99%+
	分子量 :	367.38
	MDL号 :	MFCD25976826
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that consist of 6 members, PAKs 1-6, which are positioned at an intersection of multiple signaling pathways implicated in oncogenesis[2]. APTO-253 is a phase I clinical stage small molecule that selectively induces CDKN1A (p21), promotes G0-G1 cell-cycle arrest, and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. APTO-253 was found to elicit a concentration- and time-dependent reduction in MYC mRNA expression and protein levels. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253)3][3]. Treatment of cells with APTO-253 caused DNA damage, which led us to ask whether cells deficient in homologous recombination (i.e., loss of BRCA1/2 function) were hypersensitive to this drug. It was found that loss of either BRCA1 or BRCA2 function in multiple isogenic paired cell lines resulted in hypersensitivity to APTO-253 of a magnitude similar to the effects of PARP inhibitors, olaparib. Raji cells selected for 16-fold acquired resistance had 16-fold reduced accumulation of Fe(253)3 RNA-seq analysis revealed that overexpression of the ABCG2 drug efflux pump is a key mechanism of resistance. ABCG2-overexpressed HEK-293 cells were resistant to APTO-253, and inhibition of ABCG2 reversed resistance to APTO-253 in Raji/253R[4]. Treatment of ovarian cancer cells with APTO-253, a small molecule inducer of KLF4, enhanced the efficacy of both chemotherapy drugs. KLF4 expression mediated by lentiviral vector or induced by APTO-253 resulted in G1 phase arrest in ovarian cancer cells[5].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.72mL 0.54mL 0.27mL	13.61mL 2.72mL 1.36mL	27.22mL 5.44mL 2.72mL

参考文献

[1]Sakata VM, da Silva FT, et al. High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids. Graefes Arch Clin Exp Ophthalmol. 2015 May;253(5):785-90. [2]Chetan K Rane,et al. P21 activated kinase signaling in cancer. Semin Cancer Biol. 2019 Feb;54:40-49. [3]Andrea Local,et al. APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells. Mol Cancer Ther. 2018 Jun;17(6):1177-1186. [4]Cheng-Yu Tsai,et al. APTO-253 Is a New Addition to the Repertoire of Drugs that Can Exploit DNA BRCA1/2 Deficiency. Mol Cancer Ther. 2018 Jun;17(6):1167-1176. [5]Baojin Wang,et al. KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells. Biochem Biophys Res Commun. 2017 Mar 11;484(3):486-492.