Rebastinib (DCC-2036) is an orally active, non-ATP-competitive Bcr-Ablinhibitor forAbl1^WTandAbl1^T315IwithIC₅₀s of 0.8 nM and 4 nM, respectively. Rebastinib also inhibitsSRC, KDR,FLT3, andTie-2, and has low activity to seen towardsc-Kit.

IC50: 0.75±0.11 nM (ABL1^WT), 2±0.3 nM (FLT3), 4±0.3 nM (KDR), 6±0.3 nM (TIE2), 34±6 nM (SRC)^[1]

Rebastinib potently (IC₅₀0.82 nM) inhibits u-ABL1^native, which is thought to exist predominantly in the inactive type II conformation. In addition, Rebastinib also strongly inhibits p-ABL1^native(IC₅₀2 nM), which more readily adopts an active, Type I conformation^[1].
Rebastinib potently inhibits both u-ABL1^T315I(IC₅₀5 nM) and p-ABL1^T315I(IC₅₀4 nM), both of which exist predominately in the Type I conformation due to stabilization of an activating hydrophobic spine by the T315I mutation^[1].
In addition to ABL1, Rebastinib also inhibits the SRC family kinases LYN, SRC, FGR, and HCK, and PDGFRα, and PDGFRβ with IC₅₀of 29±1, 34±6, 38±1, 40±1, 70±10 and 113±10 nM, respectively. Notably, Rebastinib spared c-KIT (IC₅₀481 nM)^[1].
Rebastinib effectively inhibits the proliferation of Ba/F3 cells expressing native BCR-ABL1^native(IC₅₀5.4 nM). Rebastinib also inhibits proliferation of the Ph⁺cell line K562 (IC₅₀5.5 nM)^[1].
Rebastinib also inhibits proliferation of several common TKI-resistant mutants of BCR-ABL1, including G250E, Q252H, Y235F, E255K, V299L, F317L, and M351T, at IC₅₀s ranging from 6-150 nM. Rebastinib effectively inhibits autophosphorylation of BCR-ABL1^native(IC₅₀29 nM) and BCR-ABL1^T315I(IC₅₀18 nM), as well as the phosphorylation of STAT5 in both cell lines (IC₅₀28 nM and 13 nM, respectively)^[1].

A single dose of Rebastinib (DCC-2036; oral; 100 mg/kg) affords circulating plasma levels that exceeds 12 μM for up to 24 hours, and effectively inhibits BCR-ABL1 signaling for up to 8 hours in Ba/F3-BCR-ABL1^T315Ileukemia cells isolated from BM and spleen of tumor-bearing mice^[1].
Treatment of mice bearing Ba/F3-BCR-ABL1^T315Ileukemia cells with Rebastinib at 100 mg/kg once daily by oral gavage significantly prolonged their survival, while STI571 at 100 mg/kg twice daily is ineffective^[1].
In this aggressive allograft model, Rebastinib is as effective for treatment of BCR-ABL^T315Ileukemia as STI571 at 100 mg/kg twice daily in BCR-ABL1^nativeleukemia, and reduces the leukemia cell burden in the spleens of treated mice^[1].

553.59

Solid

C₃₀H₂₈FN₇O₃

1020172-07-9

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(90.32 mM;ultrasonic and warming and heat to 80℃)

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。-80℃ 储存时，请在 6 个月内使用，-20℃ 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: ≥ 2.08 mg/mL (3.76 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.76 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
• 2.

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

  Solubility: ≥ 2.08 mg/mL (3.76 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.76 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 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