ML216 (CID-49852229) is a potent, selective and cell permeable inhibitor of the DNA unwinding activity of BLM helicase with IC₅₀s of 2.98 μM and 0.97 μM for BLM^full-length and BLM^636-1298, respectively. ML216 inhibits ssDNA-dependent ATPase activity of BLM with a K_i of 1.76 µM. Antitumor avtivity^[1][2].

IC50: 2.98 μM (BLM^full-length) and 0.97 μM (BLM^636-1298)^[1]

ML216 (12.5-50 µM; 24-72 hours; PSNG5 and PSNG13cells) treatment inhibits the proliferation of PSNF5 cells in a concentration-dependent manner, but not of PSNG13 cells^[1].
ML216 treatment leads to a statistically significant increase in the frequency of sister chromatid exchanges (SCEs) in PSNF5 cells, but not in PSNG13 cells^[1].
ML216 increases the sensitivity of PSNF5 cells to aphidicolin but has no sensitizing effect on isogenic PSNG13 cells devoid of BLM^[1].
ML216 inhibits both the full length WRN (IC₅₀ of 5 μM) and a truncated WRN^500-946 (IC₅₀ of 12.6 μM), with the former being 2.5-fold more sensitive to inhibition. BLM is a little more sensitive than WRN to inhibition by ML216 (1.7-fold based on IC₅₀ values). Despite the detectable inhibition of WRN by ML216, this compound appears selective for BLM in human cells. ML216 inhibits proliferation of WRN⁺ and WRN⁻ cells equally well, and similarly sensitized both cell types to aphidicolin^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Although ML216 inhibits unwinding by the sequence-related BLM and WRN helicases similarly in vitro, the apparent dependence on BLM for ML216 to exert its biological effects in human cells suggests BLM specificity for the drug’s mechanism of action in vivo. A co-crystal structure of BLM in complex with inhibitor would be informative. Cellular cues in vivo may induce a specific conformation of WRN that makes it resistant to ML216^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

383.32

C₁₅H₉F₄N₅OS

1430213-30-1

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 20 mg/mL (52.18 mM; Need ultrasonic)

*

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。-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 mg/mL (5.22 mM); Suspended solution; Need ultrasonic

  此方案可获得 2 mg/mL (5.22 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 20.0 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

• [1]. Nguyen GH, et al. A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem Biol. 2013 Jan 24;20(1):55-62.

  [2]. Banerjee T, et al. A new development in DNA repair modulation: discovery of a BLM helicase inhibitor. Cell Cycle. 2013 Mar 1;12(5):713-4.