AS-99 TFA

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AS-99 TFA

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
50mg	电议
100mg	电议

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 selectiveASH1Lhistone methyltransferaseinhibitor (IC₅₀= 0.79 μM,K_d= 0.89 μM) with anti-leukemic activity. AS-99 TFA blocks cell proliferation, inducesapoptosisand differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo^[1].

IC₅₀& Target

0.79 μM (ASH1L histone methyltransferase)^[1]

体外研究
(In Vitro)

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^[1].
AS-99 shows a several fold weaker effect on the proliferation of leukemia cells withoutMLL1translocations, such as SET2 and K562, with no or limited effects at 10 μM or higher concentrations^[1].
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^[1].
AS-99 TFA suppresses MLL fusion driven transcriptional programs^[1].
AS-99 results in a reduced number of H3K36me2 peaks when compared to the DMSO-treated cells^[1].

RT-PCR^[1]

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^[1].
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^[1].

Animal Model:	8- to 10-week old female NSG mice (bearing MV4;11 cells)^[1]
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.

分子量

707.71

性状

Solid

Formula

C₂₉H₃₁F₆N₅O₅S₂

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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-CDin 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 μL20% 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

*以上所有助溶剂都可在本网站选购。