Zoligratinib (Debio 1347) is an orally available and selective FGFR inhibitor with IC₅₀s of 9.3, 7.6, and 22 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.

Zoligratinib is well balanced in cellular antiproliferative activity against SNU-16 and stability in human liver microsome. The selectivity of 8 to inhibit FGFR over KDR is suggested to be caused by the difference in the interaction with M535 in FGFR1 and L889 in KDR^[1]. The IC₅₀ of Zoligratinib is 29 nM for FGF-dependent proliferation and 780 nM for VEGF-dependent proliferation^[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.

Zoligratinib treatment shows a dose-dependent tumor regression (tumor growth inhibition (TGI)=106% at 30 mg/kg and 147% at 100 mg/kg) without apparent body weight loss. Zoligratinib treatment also shows significant in vivo efficacy in xenograft mice models with FGFR genetic alterations, such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion)^[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.

356.38

C₂₀H₁₆N₆O

1265229-25-1

Room temperature in continental US; may vary elsewhere.

DMSO : 25 mg/mL (70.15 mM; ultrasonic and warming and heat to 50°C)

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: ≥ 2.08 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.84 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-CD in saline)

  Solubility: ≥ 2.08 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.84 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 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: ≥ 2.08 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.84 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Nakanishi Y, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther. 2014 Nov;13(11):2547-58.

  [2]. Nakanishi Y, et al. Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1. Mol Cancer Ther. 2015 Mar;14(3):704-12.

  [3]. Nakanishi Y, et al. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor. Mol Cancer Ther. 2015 Dec;14(12):2831-9.

The cell lines are added to the wells of 96-well plates containing 0.076−10,000 nM tested compounds (CH5183284) and incubated at 37°C. After 4 days’ incubation, Cell Counting Kit-8 solution is added, and after incubation for several more hours, absorbance at 450 nm is measured. The antiproliferative activity is calculated using the formula (1-T/C) × 100 (%), where T and C represent absorbance at 450 nm of the cells treated with drugs (T) and that of untreated control cells (C)^[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.

Rats: Male Wistar rats (340-390 g) implanted with a telemetry transmitter are used for the assessment of effects on blood pressure (BP). Vehicle (0.5% carmellose sodium, 0.5% polysorbate 20, and 0.9% benzyl alcohol in purified water) or CH5183284/Debio 1347 (10 and 30 mg/kg) are administered by oral gavage once a day for 4 consecutive days. Data for blood pressure are automatically analyzed and continuously recorded at 5-minute intervals^[2].

Mice: The in vivo efficacy is evaluated in mice bearing an SNU-16 xenograft. CH5183284 is orally administered once daily for 11 days, and the body weight of mice and the volume of the tumors are measured twice a week^[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]. Nakanishi Y, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther. 2014 Nov;13(11):2547-58.

  [2]. Nakanishi Y, et al. Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1. Mol Cancer Ther. 2015 Mar;14(3):704-12.

  [3]. Nakanishi Y, et al. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor. Mol Cancer Ther. 2015 Dec;14(12):2831-9.