ASP-9521

製品コードS6749 バッチS674901

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₁₉H₂₆N₂O₃
	分子量	330.42	CAS No.	1126084-37-4
Solubility (25°C)*	体外	DMSO	66 mg/mL (199.74 mM)
		Ethanol	66 mg/mL (199.74 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	ASP-9521 is a selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17β-HSD5).
in vitro	In vitro, ASP9521 inhibited the conversion of androstenedione into testosterone by recombinant human and cynomolgus monkey AKR1C3 in a concentration-dependent manner, with IC50 values of 11 and 49 nmol/L, respectively. In contrast, ASP9521 did not inhibit the conversion by rat and mouse homologues (AKR1C1 and AKR1C6, respectively) up to a concentration of 10 μmol/L. ASP9521 showed moderately high selectivity (>100-fold) for human AKR1C3 (IC50: 120 nmol/L) over the human isoform AKR1C2 (IC50: >20,000 nmol/L)^[1].
in vivo	In murine models harbouring CWR22R xenograft tumours, single oral administration of ASP9521 suppressed AD-induced intratumoural testosterone production in a dose-dependent manner. This inhibitory effect was maintained for 24 h after single oral administration of ASP9521. Over this 24 h period, ASP9521 concentration rapidly decreased in plasma from 771.8 ng/mL (mean) to undetectable levels, while its intratumoural concentration reached its maximal level within 15 min after administration of ASP9521 and remained stable for 24 h. In nude mice bearing HEK293 tumours with or without AKR1C3 expression, after single oral administration of ASP9521, plasma concentrations of ASP9521 reached maximum values within 0.25 h (mean: 767.3 ng/mL and 648.2 ng/mL for HEK293 and HEK293-AKR1C3 cells, respectively), but decreased rapidly thereafter. Accumulation of ASP9521 in tumour tissue may depend on AKR1C3 expression. After single oral administration of 1 mg/kg ASP9521 to rats, dogs and monkeys, the drug was rapidly absorbed. The bioavailability values were 35 %, 78 %, and 58 %, respectively. After iv administration of ASP9521 to rats, dogs and monkeys, plasma concentrations of the drug declined with t1/2 values of 0.2, 1.7 and 5.8 h, respectively^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	LNCaP-AKR1C3 cells stably expressing human AKR1C3
	濃度	0.3-100 nmol/L
	反応時間	24 h or 6 days
	実験の流れ	LNCaP-AKR1C3 cells stably expressing human AKR1C3 were seeded in 96-well plates at 1x 10⁴ cells/100 μL/well in RPMI-1640 medium supplemented with heat-inactivated charcoal-dextran-stripped FBS (1 % for the PSA expression assay and T measurement and 5 % for the cell proliferation assay). After 24 h incubation, AD was added to each well with or without ASP9521 (0.3-100 nmol/L). The cell culture media were collected 24 h after administration of AD to measure T concentration and 6 days after administration of AD to measure either PSA levels or cell proliferation.
動物実験	動物モデル	Male Balb/c athymic nude mice (4-6 weeks old) with CWR22R tumours
	投薬量	1, 3 or 10 mg/kg
	投与方法	oral administration

参考

[1] Kikuchi A, et al. Invest New Drugs. 2014, 32(5):860-70.

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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