Asciminib (ABL001) is a potent and selective allosteric BCR-ABL1 inhibitor, which inhibits Ba/F3 cells grown with an IC₅₀ of 0.25 nM^[1].

Asciminib binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. NMR and biophysical studies confirm that asciminib binds potently (dissociation constant=0.5-0.8nM) and selectively to the myristoyl pocket of ABL1 and induces the inactive C-terminal helix conformation. Asciminib binding mimics the structural consequences of myristate binding to the N terminus of ABL1. Consistent with this binding site, asciminib exhibits the same non-ATP-competitive biochemical kinetics as the BCR–ABL inhibitor GNF-2 but with approximately 100-fold greater potency. Asciminib lacks activity against more than 60 kinases, including SRC, and is similarly inactive against G-protein-coupled receptors, ion channels, nuclear receptors and transporters. In BCR–ABL1-transformed Ba/F3 cells grown without IL-3, asciminib has an anti-proliferative with IC₅₀ value of 0.25nM. In the CML blast-phase cell line KCL-22, asciminib inhibits phosphorylation of both STAT5 (Tyr694; pSTAT5) and BCR–ABL1 (Tyr245; pBCR–ABL1) after 1h using concentrations that correlate with those required for inhibition of cell proliferation. Asciminib is selectively active against all BCR–ABL1 lines (IC₅₀ value of 1–20nM), irrespective of the presence of either the p210 or the p190 BCR–ABL1 isoform.^[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.

Asciminib is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive acute lymphoblastic leukaemia. Single doses of 7.5, 15 and 30 mg/kg ABL001, administered to mice bearing KCL- 22 xenografts, inhibits pSTAT5 (Tyr694), which return to baseline at 10, 12 and 16-20h after administration of the dose, respectively. In mice implanted with KCL-22 tumors, the minimum dose of asciminib required for complete regression is 7.5 mg/kg twice a day (BID) or 30 mg/kg once a day (QD), and is tolerated at doses up to 250 mg/kg BID. Similarly, in xenografts derived from patients, treatment with 7.5 and 30 mg/kg asciminib leads to regressions that are maintained during dosing^[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.

449.84

C₂₀H₁₈ClF₂N₅O₃

1492952-76-7

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL (222.30 mM)

* “≥” means soluble, but saturation unknown.

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。

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    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.56 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.56 mM，饱和度未知) 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 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

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.56 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.56 mM，饱和度未知) 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.56 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.56 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  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玉米油中，混合均匀。

• [1]. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737.

Ba/F3 cells are treated with a range concentration of asciminib (0-10000 nM) for 48 h. Cell proliferation is measured using the Britelite luciferase detection assay^[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.

Mice: Asciminib efficacy in three patient-derived ALL systemic xenograft models (ALL-7015, AL-7119 and AL-7155) is assessed by FACS monitoring of the percentage of CD45+ cells per live cell in blood samples taken at varying time points after dosing with either 7.5 mg/kg BID (group 2) or 30 mg/kg BID (group 3) asciminib for 3 weeks^[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.

• [1]. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017 Mar 30;543(7647):733-737.