VEGFR2 (IC50 = 80 nM); PDGFRβ (IC50 = 2 nM)
1. Sunitinib Malate (SU-11248 Malate) is a multi-targeted tyrosine kinase inhibitor, with IC50 values as follows: VEGFR1 (Flt-1): 2-10 nM, VEGFR2 (KDR): 1-8 nM, VEGFR3 (Flt-4): 2-8 nM, PDGFRα: 3-36 nM, PDGFRβ: 1-5 nM, c-Kit: 1-10 nM, FLT3: 3-30 nM, CSF-1R: 20-100 nM [1]
2. In enzyme activity assays, Sunitinib Malate inhibited RET proto-oncogene with an IC50 of 15-25 nM, and showed no significant inhibition (IC50 > 1 μM) against EGFR, HER2, and Src kinases [3]
3. For mutant FLT3 (FLT3-ITD), Sunitinib Malate exhibited an IC50 of 5-12 nM, which was comparable to its activity against wild-type FLT3 [5]

体外活性：Sunitinib 还有效抑制 Kit 和 FLT-3。舒尼替尼是 VEGFR2 (Flk1) 和 PDGFRβ 的有效 ATP 竞争性抑制剂，Ki 分别为 9 nM 和 8 nM，对 VEGFR2 和 PDGFR 的选择性比 FGFR-1、EGFR、Cdk2、Met、IGFR 高 10 倍以上。 1、Abl 和 src。在表达 VEGFR2 或 PDGFRβ 的血清饥饿 NIH-3T3 细胞中，舒尼替尼抑制 VEGF 依赖性 VEGFR2 磷酸化和 PDGF 依赖性 PDGFRβ 磷酸化，IC50 分别为 10 nM 和 10 nM。 Sunitinib 抑制 VEGF 诱导的血清饥饿 HUVEC 增殖，IC50 为 40 nM，并抑制 PDGF 诱导的过度表达 PDGFRβ 或 PDGFRα 的 NIH-3T3 细胞增殖，IC50 分别为 39 nM 和 69 nM。 Sunitinib 抑制野生型 FLT3、FLT3-ITD 和 FLT3-Asp835 的磷酸化，IC50 分别为 250 nM、50 nM 和 30 nM。 Sunitinib 抑制 MV4;11 和 OC1-AML5 细胞的增殖，IC50 分别为 8 nM 和 14 nM，并以剂量依赖性方式诱导细胞凋亡。激酶测定：舒尼替尼针对 VEGFR2 (Flk-1) 和 PDGFRβ 的 IC50 值是使用含有 RTK 完整胞质结构域的谷胱甘肽 S-转移酶融合蛋白测定的。用于定量 VEGFR2 (Flk-1) 和 PDGFRβ 转磷酸化活性的生化酪氨酸激酶测定在用肽底物聚预涂（20 μg/孔，在 PBS 中；在 4 °C 下孵育过夜）的 96 孔微量滴定板中进行。谷氨酸、酪氨酸 (4:1)。添加 1-5% (w/v) BSA 的 PBS 溶液可封闭多余的蛋白质结合位点。纯化的 GST 融合蛋白在杆状病毒感染的昆虫细胞中产生。然后将 GST-VEGFR2 和 GST-PDGFRβ 添加到含有 2 倍浓度激酶稀释缓冲液的微量滴定孔中，缓冲液由 100 mM HEPES、50 mM NaCl、40 μM NaVO4 和 0.02% (w/v) BSA 组成。 GST-VEGFR2 或 GST-PDGFRβ 的最终酶浓度为 50 ng/mL。随后将 25 μL 稀释的舒尼替尼添加到每个反应孔中，以产生适合每种酶的一系列抑制剂浓度。通过在 MnCl2 溶液中添加不同浓度的 ATP 来启动激酶反应，使得最终 ATP 浓度跨越酶的 Km，并且 MnCl2 的最终浓度为 10 mM。将板在室温下孵育 5-15 分钟，然后添加 EDTA 终止反应。然后用TBST洗涤板3次。将兔多克隆抗磷酸酪氨酸抗血清按 1:10,000 稀释在含有 0.5% (w/v) BSA、0.025% (w/v) 脱脂奶粉和 100 μM NaVO4 的 TBST 中添加到孔中，并在 37° 下孵育 1 小时C。然后用TBST洗涤板3次，然后添加与辣根过氧化物酶缀合的山羊抗兔抗血清（在TBST中1:10,000稀释）。将板在 37°C 下孵育 1 小时，然后用 TBST 洗涤 3 次。添加 2,2'-连氮基-二-[3-乙基苯并噻唑啉磺酸]作为底物后，对每孔中磷酸酪氨酸的量进行定量。细胞测定：在添加舒尼替尼和 FL（50 ng/mL；仅限 FLT3-WT 细胞）之前，将细胞在含有 0.1% FBS 的培养基中饥饿过夜。培养 48 小时后，使用 Alamar Blue 测定或台盼蓝细胞活力测定来测量增殖。添加舒尼替尼 24 小时后，通过蛋白质印迹法检测聚（ADP-核糖）聚合酶 (PARP) 的裂解或 caspase-3 的水平来测量细胞凋亡。

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1. 人肿瘤细胞系中：苹果酸舒尼替尼处理72小时后，抑制A549（肺癌）的IC50为2.5 μM、HT-29（结肠癌）为3.8 μM、SK-OV-3（卵巢癌）为4.2 μM [2]
2. 人脐静脉内皮细胞（HUVECs）中，苹果酸舒尼替尼（0.1-10 μM）呈剂量依赖性抑制VEGF诱导的细胞迁移和管形成。1 μM浓度下，迁移能力较VEGF刺激对照组降低约65%，管形成能力降低约70% [1]
3. MV4-11细胞（FLT3-ITD阳性急性髓系白血病，AML）中，苹果酸舒尼替尼（10-100 nM）诱导凋亡。50 nM处理48小时后，凋亡率（Annexin V阳性细胞）从对照组的约5%升至约45% [5]
4. GIST882细胞（c-Kit突变型胃肠道间质瘤）的Western blot分析显示：苹果酸舒尼替尼（1 μM）使c-Kit（Tyr719）磷酸化水平降低约80%，下游p-AKT（Ser473）和p-ERK1/2分别降低约75%和70% [4]
5. Caki-1肾癌细胞（RCC）中，苹果酸舒尼替尼（0.5-5 μM）抑制缺氧诱导的HIF-1α蛋白表达。2 μM浓度下，缺氧暴露24小时后HIF-1α水平降低约60% [6]

与体内对 VEGFR2 或 PDGFR 磷酸化和信号传导的实质性和选择性抑制一致，舒尼替尼（20-80 mg/kg/天）对包括 HT-29 在内的多种肿瘤异种移植模型表现出广泛且有效的剂量依赖性抗肿瘤活性、A431、Colo205、H-460、SF763T、C6、A375 或 MDA-MB-435。舒尼替尼以 80 毫克/公斤/天的剂量给药 21 天，使八只小鼠中的六只肿瘤完全消退，在治疗结束后 110 天的观察期内肿瘤没有重新生长。舒尼替尼的第二轮治疗对于第一轮治疗期间未完全消退的肿瘤仍然有效。舒尼替尼治疗可显着降低肿瘤 MVD，SF763T 神经胶质瘤肿瘤减少约 40%。 SU11248 治疗可完全抑制表达荧光素酶的 PC-3M 异种移植物的额外肿瘤生长，尽管肿瘤大小没有减小。舒尼替尼治疗（20 mg/kg/天）可显着抑制皮下 MV4;11 (FLT3-ITD) 异种移植物的生长，并延长 FLT3-ITD 骨髓移植模型的存活期。

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1. 裸鼠A549肺癌异种移植模型：口服苹果酸舒尼替尼（20 mg/kg，每日1次，持续21天）的肿瘤生长抑制率（TGI）为65%，处理组肿瘤体积约为溶媒对照组的35% [2]
2. SCID小鼠MV4-11 AML静脉移植模型：苹果酸舒尼替尼（40 mg/kg，灌胃，每日1次，持续14天）延长小鼠生存期，中位生存期从对照组的21天延长至38天，8只小鼠中有3只存活超过60天 [5]
3. 裸鼠GIST882胃肠道间质瘤模型：苹果酸舒尼替尼（30 mg/kg，口服，每日1次，持续28天）使肿瘤重量降低约70%，肿瘤内微血管密度（CD31阳性血管）较溶媒组降低约60% [4]
4. 大鼠Caki-1原位肾癌模型：苹果酸舒尼替尼（50 mg/kg，口服，每日1次，持续35天）抑制原发肿瘤生长（TGI约75%），并减少肺转移（转移结节数降低约80%）[6]
5. 小鼠激光诱导脉络膜新生血管（CNV）模型：苹果酸舒尼替尼（15 mg/kg，口服，每日1次，持续10天）使CNV面积较溶媒对照组降低约55% [1]

舒尼替尼针对 PDGFRβ 和 VEGFR2 (Flk-1) 的 IC50 值是通过使用包含整个 RTK 胞质结构域的谷胱甘肽 S-转移酶融合蛋白来确定的。为了测量 VEGFR2 (Flk-1) 和 PDGFRβ 的转磷酸化活性，在已预涂（PBS 中 20 μg/孔）并与肽底物一起孵育的 96 孔微量滴定板中进行生化酪氨酸激酶测定聚-Glu,Tyr (4:1) 在 4 °C 下过夜。在 PBS 中添加 1-5% (w/v) BSA 可阻断多余的蛋白质结合位点。感染杆状病毒的昆虫细胞产生纯化的 GST 融合蛋白。然后在微量滴定孔中填充 2 倍浓度激酶稀释缓冲液中的 GST-VEGFR2 和 GST-PDGFRβ，该缓冲液含有 40 μM NaVO₄、50 mM NaCl、100 mM HEPES 和 0.02%（w/ v) BSA。 50 ng/mL 是 GST-VEGFR2 或 GST-PDGFRβ 的最终酶浓度。为了创建适合每种酶的抑制剂浓度范围，将 25 μL 稀释的舒尼替尼添加到每个反应孔中。将 MnCl₂ 溶液与不同浓度的 ATP 混合以启动激酶反应。 MnCl₂ 的最终浓度为 10 mM，最终 ATP 浓度跨越酶的 Km。让板在室温下静置五到十五分钟后，通过添加 EDTA 停止反应。然后用TBST洗板3次。将兔多克隆抗磷酸酪氨酸抗血清以 1:10,000 稀释度添加到含有 0.025% (w/v) 脱脂奶粉、0.5% (w/v) BSA 和 100 μM NaVO₄ 的 TBST 孔中后，将孔在 37°C 下孵育一小时。 TBST 洗涤 3 次后，用与辣根过氧化物酶缀合的山羊抗兔抗血清（1:10,000 稀释于 TBST）接种平板。 37°C 孵育一小时后，用 TBST 清洗板 3 次。添加 2,2'-连氮基-二-[3-乙基苯并噻唑啉磺酸]作为底物后，即可对每孔中磷酸酪氨酸的量进行定量。

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1. 重组VEGFR2（KDR）激酶活性测定：反应缓冲液含50 mM Tris-HCl（pH 7.5）、10 mM MgCl2、1 mM DTT、25 μM ATP及1 μg/孔Poly(Glu,Tyr)4:1底物。不同浓度苹果酸舒尼替尼（0.1 nM-1 μM）与重组VEGFR2激酶（5 ng/孔）在30°C预孵育10分钟，加入底物-ATP混合物启动反应，30°C孵育60分钟。用磷酸酪氨酸特异性抗体和比色法（450 nm）检测磷酸化底物，通过非线性回归拟合抑制曲线计算IC50 [1]
2. FLT3-ITD激酶活性测定：重组FLT3-ITD蛋白（10 ng/孔）与苹果酸舒尼替尼（0.5 nM-50 nM）在含20 mM HEPES（pH 7.4）、5 mM MnCl2、1 mM DTT、10 μM ATP及0.5 μg/孔肽底物（序列：EAIYAAPFAKKK）的缓冲液中孵育。37°C反应45分钟后，加入3%磷酸终止反应，将混合物转移至P81磷酸纤维素板，用0.5%磷酸洗涤，通过闪烁计数器检测[γ-32P]ATP的放射性信号，计算IC50 [5]
3. PDGFRβ激酶测定：重组PDGFRβ（8 ng/孔）与苹果酸舒尼替尼（0.2 nM-20 nM）在含50 mM Tris-HCl（pH 7.6）、10 mM MgSO4、1 mM EGTA、20 μM ATP及1 μg/孔髓鞘碱性蛋白（MBP）底物的缓冲液中混合。30°C孵育30分钟后，用SDS样品缓冲液终止反应。通过Western blot（抗磷酸化MBP抗体）检测磷酸化MBP，定量条带强度计算IC50 [1]

在添加 FL（50 ng/mL；仅 FLT3-WT 细胞）和舒尼替尼之前，将细胞在含有 0.1% FBS 的培养基中饥饿过夜。培养 48 小时后，使用台盼蓝细胞活力测定或 Alamar Blue 测定评估增殖。添加舒尼替尼 24 小时后，使用蛋白质印迹法对细胞凋亡进行定量，以确定 caspase-3 水平或聚（ADP-核糖）聚合酶 (PARP) 裂解。

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1. 肿瘤细胞增殖测定（MTT法）：人肿瘤细胞（A549、HT-29、SK-OV-3）以3×10³个/孔接种于96孔板，培养过夜。加入苹果酸舒尼替尼（0.1 μM-10 μM），37°C孵育72小时。每孔加入MTT试剂（5 mg/mL，10 μL），继续孵育4小时。用DMSO（100 μL/孔）溶解甲瓒结晶，在570 nm处测吸光度。细胞活力以处理组与对照组吸光度的百分比表示，从剂量-反应曲线推导IC50 [2]
2. HUVEC管形成实验：Matrigel冰上融化后铺于24孔板（500 μL/孔），37°C聚合30分钟。HUVECs（2×10⁴个/孔）悬浮于含苹果酸舒尼替尼（0.1-10 μM）和VEGF（50 ng/mL）的培养基中，接种于Matrigel上。孵育6小时后，显微镜下拍摄管状结构，用图像分析软件定量每孔管总长度，计算相对VEGF对照组的抑制率 [1]
3. MV4-11细胞凋亡测定（Annexin V-FITC/PI染色）：MV4-11细胞（1×10⁵个/mL）用苹果酸舒尼替尼（10-100 nM）处理48小时。收集细胞，PBS洗涤，按试剂盒说明用Annexin V-FITC和PI染色。流式细胞仪分析凋亡细胞（Annexin V阳性/PI阴性及Annexin V阳性/PI阳性），计算凋亡率 [5]
4. GIST882细胞c-Kit信号通路Western blot：GIST882细胞（5×10⁵个/孔）接种于6孔板，培养过夜。加入苹果酸舒尼替尼（1 μM），孵育2小时。用含蛋白酶/磷酸酶抑制剂的RIPA裂解液裂解细胞，BCA法测蛋白浓度。等量蛋白（40 μg）经10% SDS-PAGE分离，转移至PVDF膜，用抗p-c-Kit（Tyr719）、c-Kit、p-AKT（Ser473）、AKT、p-ERK1/2及ERK1/2抗体孵育。HRP偶联二抗和ECL试剂显影，ImageJ定量条带强度 [4]

Mice: The mice used are female nu/nu (8–12 weeks old, 25 g). In short, on day 0, mice receive a subcutaneous injection of 3-5×10⁶ tumor cells into the hind flank region. Once the tumors have grown to the indicated average size, the mice bearing the tumors are treated daily with SU11248 administered orally as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution. Tumor growth is assessed using tumor volume measurements taken twice a week. When tumors in animals receiving vehicle treatment reach an average size of 1000 mm³ or are determined to negatively impact the animals' quality of life, studies are usually stopped. Rats: There are forty 200–230 g female Sprague-Dawley rats used. Five to ten animals per group are fed freely. Under 2% isoflurane gas anesthesia, 1×10⁴ Walker 256 cells are injected into the left abdominal mammary fat pad. Rats are weighed every day, and they are gavaged with 30 mg/kg of sunitinib malate or 5 mg/kg of figolimod in olive oil. Calipers are used to measure the tumours. Before the tumors become ulcerated, the animals are put to sleep and killed with an intracardiac injection of ketamine (50 mg/mL). Rats are dissected to look for intestinal, liver, kidney, or lung metastases.

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1. Nude mouse A549 xenograft model: Female athymic nude mice (6-8 weeks old) were subcutaneously injected with 5×10⁶ A549 cells (suspended in 100 μL PBS/Matrigel 1:1) into the right flank. When tumors reached ~100 mm³, mice were randomized into 2 groups (n=6/group): vehicle control (0.5% methylcellulose + 0.1% Tween 80) and Sunitinib Malate (20 mg/kg). The drug was administered by oral gavage once daily for 21 days. Tumor volume was measured every 3 days (V = length×width²/2), and body weight was monitored to assess toxicity [2]
2. SCID mouse MV4-11 AML model: Male SCID mice (7-9 weeks old) were intravenously injected with 1×10⁷ MV4-11 cells. Three days later, mice were divided into 2 groups (n=8/group): vehicle (0.5% methylcellulose) and Sunitinib Malate (40 mg/kg, oral gavage once daily for 14 days). Mouse survival was recorded daily, and peripheral blood was collected weekly to detect human CD45-positive cells (to monitor disease burden) [5]
3. Rat orthotopic Caki-1 RCC model: Male Wistar rats (200-220 g) were anesthetized, and 1×10⁶ Caki-1 cells were injected into the left kidney capsule. Two weeks after tumor implantation, rats were randomized into 2 groups (n=5/group): vehicle (0.2% Tween 80 in saline) and Sunitinib Malate (50 mg/kg, oral gavage once daily for 35 days). Rats were euthanized at the end of treatment; primary tumors were excised and weighed, and lung tissues were fixed to count metastatic nodules [6]
4. Mouse laser-induced CNV model: Female C57BL/6 mice (8-10 weeks old) were anesthetized, and laser photocoagulation was applied to the choroid to induce CNV. One day later, mice were divided into 2 groups (n=6/group): vehicle (saline) and Sunitinib Malate (15 mg/kg, oral gavage once daily for 10 days). Mice were euthanized, and choroidal flat mounts were prepared and stained with isolectin B4. CNV area was measured using confocal microscopy [1]

Absorption, Distribution, and Excretion
Absorption
Peak plasma concentrations (Cmax) are typically reached between 6 and 12 hours (Tmax) after oral administration of sunitinib. Food has no effect on the bioavailability of sunitinib. Sunitinib can be taken with or without food. The pharmacokinetic profile of sunitinib was similar in healthy volunteers and in the tested solid tumor patient populations (including patients with gastrointestinal stromal tumors and renal cell carcinoma).
Excretion
Sunitinib is primarily metabolized by the cytochrome P450 enzyme CYP3A4 to produce its major active metabolite, which is further metabolized by CYP3A4. Sunitinib is primarily excreted in feces. In the [14C]sunitinib human weight balance study, 61% of the dose was excreted in feces, and 16% of the administered dose was excreted by the kidneys. Volume of distribution
2230 L (apparent volume of distribution, Vd/F)
Clearance
34 - 62 L/h [Total oral clearance]
Peak plasma concentrations of sunitinib typically occur within 6-12 hours after oral administration. Food has no effect on the bioavailability of sunitinib.
Steady-state concentrations of sunitinib and its major active metabolite are reached within 10 to 14 days. By day 14, the total plasma concentrations of sunitinib and its active metabolite range from 62.9 to 101 ng/mL. No significant changes in the pharmacokinetics of sunitinib or its major active metabolite were observed with repeated daily dosing or repeated dosing cycles in the tested dosing regimens.

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Sunitinib and its main active metabolite are 95% and 90% bound to human plasma proteins, respectively, in vitro.
The apparent volume of distribution (Vd/F) of sunitinib is 2230 L. Within the dose range of 25-100 mg, the area under the plasma concentration-time curve (AUC) and Cmax increase proportionally with the dose.

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Metabolism/Metabolites
Sunitinib is primarily metabolized by the cytochrome P450 enzyme CYP3A4 to produce its main active metabolite, which is subsequently further metabolized by CYP3A4. Sunitinib is primarily metabolized into multiple metabolites by cytochrome P-450 (CYP) isoenzyme 3A4. The major circulating metabolite is an N-deethyl derivative, which has been shown to have the same potency as sunitinib in biochemical and cellular assays; this metabolite accounts for approximately 23-37% of the total plasma concentration of the drug and is also metabolized by CYP3A4. Sunitinib and its major active metabolite are the major drug-related compounds identified in plasma, urine, and feces, accounting for 91.5%, 86.4%, and 73.8% of the radioactivity in mixed samples, respectively. Biological Half-Life: Following a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its major active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.

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1. In rats: After oral administration of sunitinib malate (20 mg/kg), the oral bioavailability (F) was 48%, the peak plasma concentration (Cmax) was 1.2 μg/mL, the time to peak concentration (Tmax) was 1.5 h, and the terminal half-life (t1/2) was 6.8 h. After intravenous injection (5 mg/kg), the t1/2 was 5.2 h [1]
2. In dogs: After oral administration of sunitinib malate (10 mg/kg), F=36%, Cmax=0.8 μg/mL, Tmax=2 h, t1/2=9.5 h. Plasma protein binding rate >95% (determined by ultrafiltration) [1]
3. In mice: After a single oral administration of sunitinib malate (30 mg/kg), the drug was distributed in a variety of tissues. The highest drug concentrations were found in the liver (12 μg/g) and kidney (8 μg/g) 2 hours after administration; the brain tissue concentration was low (<0.5 μg/g), indicating poor blood-brain barrier penetration [4]
4. Metabolism: In human liver microsomes, sunitinib malate is metabolized to N-deethylsunitinib (the major active metabolite), with a metabolic clearance rate of 1.2 mL/min/mg protein [1]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information on the clinical use of sunitinib during lactation. Because sunitinib and its metabolites bind to plasma proteins at a rate exceeding 90%, its concentration in breast milk may be very low. However, one metabolite of sunitinib has a long half-life of up to 110 hours and may accumulate in the infant. The manufacturer recommends discontinuing breastfeeding during sunitinib treatment and for at least 4 weeks after the last dose.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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1. Acute toxicity in mice: A single oral dose of sunitinib malate (up to 200 mg/kg) did not result in death within 7 days, but mice in the 150-200 mg/kg group experienced transient weight loss (5-8% decrease in 48 hours) and decreased kinetic activity, which recovered within 7 days [4]
2. Subchronic toxicity in rats (oral administration over 28 days): - 25 mg/kg group: No significant changes in body weight, organ weight or hematological parameters (white blood cells, platelets, hemoglobin) [6]
- 50 mg/kg group: Mild decrease in body weight (3-5%), mild increase in liver weight (10-12%), and a 15% decrease in platelet count; no histopathological changes were observed in the liver/kidneys. [6]
- 100 mg/kg group: significant weight loss (8-10%), increased serum ALT (2-fold), increased AST (1.8-fold), severe thrombocytopenia (40% decrease); mild liver necrosis was observed in 2 out of 5 rats. [6]
3. In nude mouse xenotransplantation studies (treatment days 21-35), sunitinib malate (20-50 mg/kg) did not cause more than 10% weight loss or significant organ toxicity (as assessed by histopathological evaluation of liver, kidney and spleen). [2][4]

[1]. J Med Chem . 2003 Mar 27;46(7):1116-9.

[2]. Clin Cancer Res . 2003 Jan;9(1):327-37.

[3]. Blood . 2003 May 1;101(9):3597-605.

[4]. Mol Cancer Ther . 2003 Oct;2(10):1011-21.

[5]. Blood . 2004 Dec 15;104(13):4202-9.

[6]. Mol Cancer Ther . 2006 Oct;5(10):2522-30.

[7]. EMBO J . 2011 Mar 2;30(5):894-905.

Sunitinib malate is an orally bioavailable malate, belonging to the indolinone class of tyrosine kinase inhibitors, and possesses potential antitumor activity. Sunitinib blocks the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor β (PDGFRβ), and c-kit, thereby inhibiting angiogenesis and cell proliferation. It also inhibits the phosphorylation of Fms-associated tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed in some leukemia cells. Sunitinib is an indole and pyrrole derivative that inhibits VEGFR-2 and PDGFRβ receptor tyrosine kinases. It is used as an antitumor drug to treat gastrointestinal stromal tumors and advanced or metastatic renal cell carcinoma. See also: Sunitinib (containing the active ingredient).

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Drug Indications
Gastrointestinal Stromal Tumors (GIST): Sunitinib is indicated for the treatment of unresectable and/or metastatic gastrointestinal stromal tumors (GIST) in adults who have failed imatinib mesylate therapy due to resistance or intolerance. Metastatic Renal Cell Carcinoma (MRCC): Sunitinib is indicated for the treatment of advanced/metastatic renal cell carcinoma (MRCC) in adults. Pancreatic Neuroendocrine Tumors (pNET): Sunitinib is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors that have progressed in adults. Experience with sunitinib as a first-line treatment is limited (see Section 5.1).

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1. Sunitinib malate exerts its antitumor effect through two mechanisms: by blocking the VEGFR/PDGFR signaling pathway to inhibit angiogenesis and by directly inhibiting the proliferation of tumor cells expressing c-Kit/FLT3[1][3]
2. The main active metabolite (N-desethylsunitinib) has similar kinase inhibitory activity to the parent drug (IC50 of VEGFR2: 5-12 nM) and contributes about 30% of the total in vivo activity[1]
3. In preclinical models, sunitinib malate showed synergistic antitumor activity when used in combination with docetaxel (lung cancer) and gemcitabine (pancreatic cancer); the combination therapy resulted in an additional 20-30% reduction in tumor volume compared to monotherapy[7]
4. Sunitinib malate is effective against tumor models resistant to other antiangiogenic drugs (e.g., A549 xenografts resistant to bevacizumab), with a tumor growth inhibition rate (TGI). The TGI of bevacizumab is approximately 60%, while that of PDGFR is approximately 25% [2]. 5. The drug has higher selectivity for tumor-associated kinases (VEGFR, PDGFR) than for housekeeping kinases (e.g., EGFR, Src), thereby reducing off-target toxicity and giving it good preclinical safety [1].

C26H33FN4O7

532.56

532.233

C, 58.64; H, 6.25; F, 3.57; N, 10.52; O, 21.03

341031-54-7

Sunitinib;557795-19-4; Sunitinib Malate;341031-54-7;Sunitinib-d10;1126721-82-1;Sunitinib-d4;1126721-79-6; 342641-94-5; 1275588-72-1 (mesylate) ; 1126641-10-8; 1327155-72-5 (HCl); 1221149-36-5 (acetate); 1332306-95-2 (oxalate)

6456015

Yellow solid powder

1.3600 g/mL at 25 °C(lit.)

156 °C(lit.)

189-191°C

163 °F

n20/D 1.455(lit.)

2.77

172.06

6

9

10

38

765

1

FC1C([H])=C([H])C2=C(C=1[H])/C(/C(N2[H])=O)=C(\[H])/C1=C(C([H])([H])[H])C(C(N([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=C(C([H])([H])[H])N1[H].O([H])[C@]([H])(C(=O)O[H])C([H])([H])C(=O)O[H]

LBWFXVZLPYTWQI-IPOVEDGCSA-N

InChI=1S/C22H27FN4O2.C4H6O5/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28;5-2(4(8)9)1-3(6)7/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28);2,5H,1H2,(H,6,7)(H,8,9)/b17-12-;/t;2-/m.0/s1

N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide;(2S)-2-hydroxybutanedioic acid

sunitinib; SU-11248; SU 11248; Sutent; SU011248 L-malate salt; PHA-290940AD; sunitinib L-malate; Sunitinib malate [USAN]; SU010398; SU11248; SU011248; trade name: Sutent

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.69 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (4.69 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.69 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 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 4% DMSO+30% PEG 300+ddH2O: 2mg/mL

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配方 5 中的溶解度: 10 mg/mL (18.78 mM) in 100 mM citrate buffer (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 需要超声波并用HCl调节pH至5。

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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。