Avapritinib (BLU-285) is a highly potent, selective, and orally active KIT and PDGFRA activation loop mutant kinases inhibitor with IC₅₀s of 0.27 and 0.24 nM for KIT D816V and PDGFRA D842V, respectively. Avapritinib (BLU-285) binds the active conformation of the kinase and shows antitumor activity. Avapritinib (BLU-285) attenuates the transport function of both ABCB1 and ABCG2^[1][2].

IC50: 0.27 nM (KIT D816V), 0.24 nM (PDGFRA D842V)^[1]

Avapritinib (BLU-285) has demonstrated biochemical in vitro activity on the KIT exon 17 mutant enzyme, KIT D816V (IC₅₀=0.27 nM). Cellular activity of Avapritinib on KIT D816 mutants is measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC₅₀=4 and 22 nM, respectively. In Kasumi-1 cells, a t(8;21)-positive AML cell line with a KIT exon 17 N822K mutation, Avapritinib potently inhibits KIT N822K mutant autophosphorylation (IC₅₀=40 nM), downstream signaling, as well as cellular proliferation (IC₅₀=75 nM)^[3].

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.

In vivo Avapritinib (BLU-285) is well tolerated and has demonstrated dose dependent antitumor efficacy. Complete tumor growth inhibition and ≥75% KIT kinase inhibition is observed with 10 mg/kg once daily, oral dosing of Avapritinib in the aggressive KIT exon 17 mutant driven P815 mastocytoma model grown as a solid tumor allograft as well as in a disseminated model of disease. Disease burden, measured by whole body luciferase imaging (photons/second/mm²), increases 86-fold in the vehicle control animals over the 24 day dosing period with widespread disease detectable in both femurs, the pelvis and circulating in peripheral blood. Avapritinib at both doses (10 or 30 mg/kg orally, once daily) results in a marked reduction of disease burden throughout the study. Avapritinib at either 10 or 30 mg/kg results in tumor regression in all animals with disease abrogation indistinguishable from background signal measurements in several animals by the end of study. Avapritinib is also well tolerated in this in vivo model and has no adverse effects on body weight at either dose^[3].

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.

498.56

C₂₆H₂₇FN₁₀

1703793-34-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 83.33 mg/mL (167.14 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 (5.01 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.01 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 (5.01 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.01 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 (5.01 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.01 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]. Wu CP, et al. Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-MediatedMultidrug Resistance in Cancer Cell Lines. Mol Pharm. 2019 Jul 1;16(7):3040-3052.

  [2]. Evans EK, et al. A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med. 2017 Nov 1;9(414). pii: eaao1690.

  [3]. Erica Evans, et al. Blu-285, a Potent and Selective Inhibitor for Hematologic Malignancies with KIT Exon 17 Mutations.Blood 2015 126:568.

Mice^[1]
A Kasumi-1 luc⁺ AML NOG SCID mouse femoral injection model is used to assess the efficacy of Avapritinib (BLU-285) in KIT exon 17-mutated CBF-AML. Following a 21 day post injection latency period, mice are dosed with Avapritinib orally, once daily at 10 mg/kg or 30 mg/kg through day 45.

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]. Wu CP, et al. Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-MediatedMultidrug Resistance in Cancer Cell Lines. Mol Pharm. 2019 Jul 1;16(7):3040-3052.

  [2]. Evans EK, et al. A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med. 2017 Nov 1;9(414). pii: eaao1690.

  [3]. Erica Evans, et al. Blu-285, a Potent and Selective Inhibitor for Hematologic Malignancies with KIT Exon 17 Mutations.Blood 2015 126:568.