AZD7507

CSF-1R

AZD7507（化合物 31）对 hERG 和 NaV1.5 表现出抑制活性，IC50 分别 >30 和 26 μM。它还抑制 3T3 细胞的增殖，这些细胞已被设计为表达 CSF-1R 并用 CSF-1 刺激（IC50，32 nM）[1]。

AZD7507 在大鼠中表现出良好的口服 PK，生物利用度为 42%，体内清除率为 7 mL/min/kg。犬 L 型 Ca 通道测定中的 IC50 大于 20 μM[1]。使用 AZD7507 处理时，携带 CC-LP-1 和 SNU-1079 细胞的小鼠表现出体积和质量显着减少，并且 CD68⁺ 巨噬细胞计数显着减少，但 WITT-1 细胞则不然[2]。

Mice: Male CD1 nude mice are given subcutaneous injections of 5 × 105 human ICC cells suspended in a 1:1 mixture of culture media and RGF Matrigel (Gibco) derived from human cell lines WITT-1, CC-LP-1, or SNU-1079 (n = 24 in each case). Two flanks are used to engraft cells, which are then given three weeks to grow into tumors. Using the online program GraphPad, mice are randomized into three groups once palpable tumors have developed. IV injection of liposomal clodronate at 4 μL/g is administered to xenografted mice. Intravenous saline alone or liposomes without clodronate (4 μL/g) are used as the treatment's control. For three weeks, each of these treatments is administered every 48 hours. The CSFR1 inhibitors GW2580 and AZD7507 are prepared in sterile water with 0.1% Tween-80 and 0.5% methylcellulose. The dosage of GW2580 is 160 mg/kg per day, while AZD7507 is administered twice daily at a dose of 100 mg/kg. Water containing 0.1% Tween-80 and 0.5% methylcellulose is given to control animals. Intraperitoneal injections of C-59 (20 mg/kg) or ICG-001 (5 mg/kg) are administered. The physiological saline serves as the vehicle for this. The vehicle is given to control animals alone. Inhibitors and the vehicle are administered three times a week in all cases[2].

[1]. Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4591-6.

[2]. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. Send to J Clin Invest. 2015 Mar 2;125(3):1269-85.

C23H27FN6O3

454.497287988663

454.21

C, 60.78; H, 5.99; F, 4.18; N, 18.49; O, 10.56

1041852-85-0

1041852-85-0

25001557

Light yellow to yellow solid powder

2.2

117

3

9

7

33

652

0

CPDGCAFPSYOTGO-UHFFFAOYSA-N

InChI=1S/C23H27FN6O3/c1-14-3-4-17(16(24)11-14)26-21-15-12-19(30-7-5-29(6-8-30)9-10-31)20(33-2)13-18(15)27-28-22(21)23(25)32/h3-4,11-13,31H,5-10H2,1-2H3,(H2,25,32)(H,26,27)

4-(2-fluoro-4-methylanilino)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-7-methoxycinnoline-3-carboxamide

AZD-7507; AZD7507; AZD 7507

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 91~130 mg/mL (200.2~286.0 mM)

配方 1 中的溶解度: ≥ 2.17 mg/mL (4.77 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 21.7 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.17 mg/mL (4.77 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL澄清DMSO储备液加入900 μL玉米油中，混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。