AS-99 TFA|西域试剂

AS-99 TFA,99.12%

产品编号：Bellancom-141429A| 分子式：C₂₉H₃₁F₆N₅O₅S₂| 分子量：707.71

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货号	包装	价格	库存与货期	购买量	操作
Bellancom-141429A		￥9400.00	杭州北京（现货）
Bellancom-141429A		￥15000.00	杭州北京（现货）

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AS-99 TFA

产品介绍

AS-99 TFA 是首创的、有效的、选择性的 ASH1L 组蛋白甲基转移酶抑制剂 (IC₅₀= 0.79 µM, K_d= 0.89 µM)，具有抗白血病活性。AS-99 TFA 在体内阻断细胞增殖，诱导细胞凋亡 (apoptosis) 和分化，下调 MLL 融合靶基因，减轻白血病。

生物活性

AS-99 TFA is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC₅₀= 0.79 µM, K_d= 0.89 µM) with anti-leukemic activity. AS-99 TFA blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo.

体外研究

AS-99 TFA is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 µM of AS-99 TFA on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L.
AS-99 shows a several fold weaker effect on the proliferation of leukemia cells without MLL1 translocations, such as SET2 and K562, with no or limited effects at 10 µM or higher concentrations.
AS-99 (1-8 µM; 7 days) TFA also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells.
AS-99 TFA suppresses MLL fusion driven transcriptional programs.
AS-99 results in a reduced number of H3K36me2 peaks when compared to the DMSO-treated cells.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

RT-PCR

Cell Line:	MOLM13 cells
Concentration:	2-6 µM
Incubation Time:	7 days
Result:	Led to a dose-dependent downregulation of canonical MLL fusion target genes required for leukemogenesis including MEF2C, DLX2, FLT3, and HOXA9.

体内研究
(In Vivo)

AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) TFA reduces leukemia burden in mice.
AS-99 TFA is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), suitable half-life (~5–6 h) and Cmax >10 µM.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	8- to 10-week old female NSG mice (bearing MV4;11 cells)
Dosage:	30 mg/kg
Administration:	I.p.; q.d., treated for 14 consecutive days
Result:	Reduced the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	8- to 10-week old female NSG mice (bearing MV4;11 cells)
Dosage:	30 mg/kg
Administration:	I.p.; q.d., treated for 14 consecutive days
Result:	Reduced the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	8- to 10-week old female NSG mice (bearing MV4;11 cells)
Dosage:	30 mg/kg
Administration:	I.p.; q.d., treated for 14 consecutive days
Result:	Reduced the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice.

性状

Solid

溶解性数据

In Vitro:

DMSO : 100 mg/mL (141.30 mM; Need ultrasonic)

H₂O : 12.5 mg/mL (17.66 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.4130 mL	7.0650 mL	14.1301 mL
5 mM	0.2826 mL	1.4130 mL	2.8260 mL
10 mM	0.1413 mL	0.7065 mL	1.4130 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (3.53 mM); Clear solution; Need ultrasonic

此方案可获得 2.5 mg/mL (3.53 mM) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
2.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (2.94 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (2.94 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液