同义名 :	AN-2728; PF-06930164; Crisaborole, Eucrisa
	CAS号 :	906673-24-3
	货号 :	A203325
	分子式 :	C14H10BNO3
	纯度 :	98%
	分子量 :	251.05
	MDL号 :	MFCD17169940
	存储条件：	Pure form Inert atmosphere, 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	Cyclic nucleotide phosphodiesterases(PDEs) are enzymes that regulate the cellular levels of the second messengers, cAMP and cGMP, by controlling their rates of degradation. The single known mechanism for removing cellular 3′, 5′-cyclic adenosine monophosphate (cAMP), a critical intracellular messenger for regulation of immune responses, is through degradation to AMP via the PDE family of enzymes. The four phosphodiesterase 4 (PDE4) enzymes (A/B/C/D) play a critical role in degrading cAMP in lymphocytes, endothelial cell, keratinocytes and smooth muscle cells. The long forms of each PDE4 subtype can be phosphorylated by PKA and ERK phosphorylation. AN-2728 is a topically administered, boron-containing, anti-inflammatory compound, with an IC50 of 0.49 μM that inhibits PDE4 activity and thereby suppresses the release of TNF-alpha (IC50 0.54 μM), IL-2 (IC50 0.61 μM), IFN-γ (IC50 0.83 μM) and other cytokines. In a vivo study, ear edema mice were dosed 1 mg/ear × 2 and 78% inhabitation rate of AN-2728 was achieved, which suggested that these compounds have good anti-inflammatory activity. In a vitro study, AN-2728 at 10 nM reacted with ATP substrate (40 nM) and result showed AN2728 inhibit the major isoforms of PDE4 in vitro, suggesting that AN-2728 is an efficient PDE4 inhibitor.
作用机制	AN2728 competes with cAMP to inhibit the PDE4B1-catalytic domain.

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT03645057	Atopic Dermatitis	Phase 3	Not yet recruiting	August 31, 2020	-
NCT03250663	Mild to Moderate Atopic Dermat... 展开 >>itis 收起 <<	Phase 1	Recruiting	August 1, 2019	United States, North Carolina ... 展开 >> Wake Forest University Heath Sciences Recruiting Winston-Salem, North Carolina, United States, 27157 收起 <<
NCT03770858	-		Not yet recruiting	December 2019	United States, Illinois ... 展开 >> Northwestern University Not yet recruiting Chicago, Illinois, United States, 60611 Contact: Dermatology CTU    312-503-5944    NUdermatologyCTU@northwestern.edu 收起 <<

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	3.98mL 0.80mL 0.40mL	19.92mL 3.98mL 1.99mL	39.83mL 7.97mL 3.98mL

参考文献

[1]Nazarian R, Weinberg JM. AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. Curr Opin Investig Drugs. 2009 Nov;10(11):1236-42. [2]Akama T, Baker SJ, et al. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2129-32.