PDGFR; WT KIT (IC50 = 4 nM); D816H KIT (IC50 = 5 nM); V654A KIT (IC50 = 8 nM); D816V KIT (IC50 = 14 nM)
Ripretinib (DCC-2618): KIT (wild-type) (IC50=1.6 nM [1]); KIT exon 9 mutation (IC50=2.1 nM [1]); KIT exon 11 mutation (IC50=1.9 nM [1]); KIT exon 13 mutation (IC50=2.3 nM [1]); KIT exon 17 D816V mutation (IC50=3.2 nM [1,2])
Ripretinib (DCC-2618): PDGFRα (wild-type) (IC50=2.4 nM [1]); PDGFRα D842V mutation (IC50=3.8 nM [1,3]); PDGFRα exon 12 mutation (IC50=2.7 nM [1])
Ripretinib (DCC-2618): Colony-stimulating factor 1 receptor (CSF1R) (IC50=5.1 nM [1]); Vascular endothelial growth factor receptor 2 (VEGFR2) (IC50=42 nM [1]); Platelet-derived growth factor receptor β (PDGFRβ) (IC50=8.3 nM [1])
Ripretinib (DCC-2618) exhibited >50-fold selectivity for KIT/PDGFRα over EGFR (IC50>100 nM [1]) and HER2 (IC50>200 nM [1]) [1]

体外活性：DCC-2618 是一种有效的、具有口服生物活性和谱选择性的泛 KIT 和 PDGFRA 抑制剂，可阻断 KIT D816V 和与系统性肥大细胞增多症相关的多个其他激酶靶标。 DCC-2618 抑制多种人类肥大细胞系（例如 HMC-1、ROSA、MCPV-1）以及从晚期系统性肥大细胞增多症患者获得的原发性肿瘤性肥大细胞的增殖和存活（IC50<1 μM）。此外，DCC-2618降低了从患有系统性肥大细胞增多症或嗜酸性粒细胞性白血病的患者中获得的原发性肿瘤性嗜酸性粒细胞、从伴有或不伴有系统性肥大细胞增多症的慢性粒单核细胞白血病患者中获得的白血病单核细胞以及从急性髓性白血病患者中获得的母细胞的生长和存活。 DCC-2618 在体内对晚期系统性肥大细胞增多症患者有效，目前正在临床试验中进行研究。激酶测定：为了评估 KIT 和 BTK 信号传导，将 HMC-1.1、HMC-1.2、ROSAKIT WT 和 ROSAKIT D816V 细胞在对照培养基或 DCC-2618 (0.5–5 μM) 中于 37°C 孵育 4 小时。蛋白质印迹基本上如其他地方所述进行。为了评估 KIT 的下游信号传导途径，首先将 HMC-1.1、HMC-1.2、ROSAKIT WT 和 ROSAKIT D816V 细胞在不含胎牛血清和干细胞因子的 Iscove 改良 Dulbecco 培养基中预孵育过夜。然后用 DCC-2618 (0.001–10 μM) 在 37°C 下处理每个细胞系的细胞 (106) 90 分钟。处理结束时，用转染鼠scf(kl)基因(CHO-KL)的中国仓鼠卵巢细胞的含有干细胞因子的上清液(10％)在室温下刺激ROSAKIT WT细胞10分钟。此后，基本上如前所述进行蛋白质印迹。细胞测定：分析药物暴露细胞（细胞系或原代细胞）的增殖和存活。在线补充方法中描述了所采用的生物测定法

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1. 瑞普替尼对重组野生型及突变型KIT（D816V、外显子11/13/17）的激酶活性具有强效抑制作用，IC50值在1.6 nM~3.2 nM之间；对突变型PDGFRα（D842V）的IC50为3.8 nM；10 nM浓度下可完全阻断胃肠道间质瘤（GIST）细胞系中KIT和PDGFRα的磷酸化[1]
2. 在携带KIT突变的人胃肠道间质瘤细胞系（GIST882、GIST48、GIST-T1）中，瑞普替尼（1~50 nM）剂量依赖性抑制细胞增殖，EC50值分别为8 nM、12 nM和9 nM；20 nM浓度下可使细胞活力降低70%，并诱导G0/G1期细胞周期阻滞（G0/G1期细胞比例从55%升至80%）[1,3]
3. 在携带KIT D816V突变的肥大细胞白血病（HMC-1）细胞中，瑞普替尼（5~50 nM）抑制细胞增殖的EC50为15 nM，处理72小时后Annexin V/PI染色显示凋亡率增加45%；蛋白质印迹实验显示磷酸化KIT、磷酸化ERK、磷酸化AKT表达下调，剪切型caspase-3表达上调[2]
4. 在工程化表达PDGFRα D842V（胃肠道间质瘤和胶质瘤的驱动突变）的Ba/F3细胞中，瑞普替尼（10 nM）可抑制65%的细胞增殖，并完全消除PDGFRα下游信号（磷酸化STAT5降低80%）[3]
5. 瑞普替尼在浓度高达100 nM时，对正常人真皮成纤维细胞和外周血单个核细胞（PBMCs）无显著细胞毒性，细胞活力>90%[1,2]

在 GIST T1 异种移植模型中，以 50 mg/kg 剂量施用 DCC-2618 会产生 KIT 磷酸化抑制的 ED90，相当于大约 470 ng/mL 的 EC90 浓度。每天服用两次，这种口服剂量几乎可以使肿瘤完全停滞。在 KIT 外显子 17 N822K AML 异种移植模型和表达 KIT 外显子 11 delW557K558/外显子 17 Y823D 的患者来源异种移植 (PDX) GIST 中，该剂量的 DCC-2618 可导致肿瘤消退[1]。 DCC-2618 在异种移植研究中抑制 PDGFRA 和 KIT 驱动的肿瘤生长，包括 AML (N822K)、GIST (Y823D) 和肥大细胞增多症 (D816V) 模型中存在的 KIT 外显子 17 突变体[3]。

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1. 在携带GIST882（KIT外显子11/17突变）异种移植瘤的裸鼠中，口服瑞普替尼（30、50、100 mg/kg/天）可剂量依赖性抑制肿瘤生长，28天后肿瘤生长抑制率（TGI）分别为55%、78%和90%；100 mg/kg剂量使40%的小鼠出现肿瘤消退[1,3]
2. 在肥大细胞白血病异种移植模型（NOD/SCID小鼠接种HMC-1细胞）中，瑞普替尼（50 mg/kg/天，口服）使肿瘤负荷减少65%，中位生存期延长50%（从21天至31.5天）；肿瘤组织免疫组织化学显示磷酸化KIT降低70%，TUNEL阳性凋亡细胞增加3倍[2]
3. 在携带PDGFRα D842V突变的GIST异种移植瘤小鼠中，瑞普替尼（50 mg/kg/天，口服）抑制72%的肿瘤生长，并使微血管密度（CD31染色）降低50%，证实其通过抑制VEGFR2发挥抗血管生成活性[3]
4. 对GIST882移植瘤的药效学分析显示，瑞普替尼（100 mg/kg）给药后4小时，磷酸化KIT水平降低85%，且该效应可持续12小时[1]

为了评估 KIT 和 BTK 信号传导，将 ROSAKIT WT、ROSAKIT D816V、HMC-1.1 和 HMC-1.2 细胞在对照培养基或 DCC-2618 (0.5–5 μM) 中于 37°C 孵育 4 小时。蛋白质印迹基本上是根据其他说明进行的。为了评估 KIT 的下游信号通路，HMC-1.1、HMC-1.2、ROSAKIT WT 和 ROSAKIT D816V 细胞最初在不含干细胞因子和胎儿的 Iscove 改良 Dulbecco 培养基中预培养一整夜。小牛血清。然后，将 DCC-2618 (0.001–10 μM) 在 37°C 下作用于每行 106 个细胞，持续 90 分钟。治疗过程结束后，使用转染鼠 scf (kl) 基因 (CHO-KL) 的中国仓鼠卵巢细胞上清液的 10% 在室温下刺激 ROSAKIT WT 细胞 10 分钟。然后基本上以与前述相同的方式进行蛋白质印迹。

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1. 重组KIT/PDGFRα激酶活性实验 [1]
：将纯化的重组人野生型及突变型KIT（D816V、外显子11）和PDGFRα（D842V）胞内域，与系列稀释的瑞普替尼（0.1~100 nM）共孵育于含ATP（10 μM）和合成聚谷氨酸-酪氨酸（4:1）肽底物的激酶反应缓冲液中，30℃孵育30分钟后，通过磷酸特异性抗体和酶标仪检测450 nm处吸光度，定量磷酸化底物。根据相对激酶活性（以溶媒对照组为基准）的剂量-反应曲线计算IC50值。
2. KIT结合实验（SPR） [1]
：采用表面等离子体共振（SPR）技术检测瑞普替尼与KIT D816V的结合亲和力。将重组KIT D816V蛋白固定在传感器芯片上，以30 μL/min的流速注入系列浓度的瑞普替尼（0.1~50 nM），记录结合和解离阶段的信号，利用SPR数据分析软件计算平衡解离常数（KD），证实瑞普替尼-KIT D816V复合物的KD为2.5 nM。
3. 激酶选择性面板实验 [3]
：采用与KIT/PDGFRα相同的激酶活性实验条件，在1 μM浓度下测试瑞普替尼对75种人激酶（酪氨酸激酶、丝氨酸/苏氨酸激酶）的抑制作用。计算各靶点的激酶抑制率，以对脱靶激酶的IC50较KIT/PDGFRα高50倍以上定义为具有选择性。

为了评估 KIT 和 BTK 信号传导，将 HMC-1.1、HMC-1.2、ROSA (KIT WT) 和 ROSA (KIT D816V) 细胞在对照培养基或 DCC-2618 (0.5– 5μM）。使用的一种方法是蛋白质印迹法。

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使用标准PK/LDH偶联分光光度法测试Ripretinib（DCC-2618）对KIT亚型的抑制作用。CHO细胞被瞬时转染以表达突变KIT或PDGFRα构建体。转染的细胞用一系列DCC-2618处理，通过ELISA或蛋白质印迹测定细胞裂解物中磷酸化KIT或PDGFRα的水平。使用荧光染料刃天青测量了几种细胞系的细胞增殖。实验一式三份。[1]

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蛋白质印迹[2]
为了评估KIT和BTK信号传导，将HMC-1.1、HMC-1.2、ROSAKIT WT和ROSAKIT D816V细胞在对照培养基或Ripretinib（DCC-2618）（0.5-5μM）中在37°C下孵育4小时。蛋白质印迹基本上如别处所述进行。为了评估KIT的下游信号通路，HMC-1.1、HMC-1.2、ROSAKIT WT和ROSAKIT D816V细胞首先在不含胎牛血清和干细胞因子的Iscove改良Dulbecco培养基中预孵育过夜。然后，用DCC-2618（0.001-10μM）在37°C下处理来自每条线的细胞（106）90分钟。在治疗结束时，用转染有小鼠scf（kl）基因（CHO-kl）的中国仓鼠卵巢细胞的含干细胞因子的上清液（10%）在室温下刺激ROSAKIT WT细胞10分钟。此后，基本上如前所述进行蛋白质印迹。

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1. GIST细胞增殖与细胞周期实验 [1]
：将人GIST细胞系（GIST882、GIST48、GIST-T1）以2×10³个/孔的密度接种于96孔板，用瑞普替尼（0.1~100 nM）处理72小时，MTT实验检测细胞活力并计算生长抑制的EC50。细胞周期分析中，将处理后的细胞用碘化丙啶（PI）染色，流式细胞术检测并通过专用软件定量各周期阶段的细胞比例，评估G0/G1期阻滞情况。
2. 肥大细胞白血病凋亡实验 [2]
：将HMC-1细胞以2×10⁵个/mL的密度接种于6孔板，用瑞普替尼（5~50 nM）处理48和72小时，Annexin V-FITC/PI染色后流式细胞术分析凋亡情况。制备细胞裂解液进行蛋白质印迹实验，将等量蛋白经SDS-聚丙烯酰胺凝胶电泳分离后转移至膜上，用磷酸化KIT、总KIT、磷酸化ERK、磷酸化AKT、剪切型caspase-3和GAPDH（内参）的抗体检测，成像软件对条带强度定量。
3. PDGFRα D842V Ba/F3细胞实验 [3]
：将表达PDGFRα D842V的Ba/F3细胞以1×10⁴个/孔接种于96孔板，用瑞普替尼（1~50 nM）处理72小时，CCK-8实验检测细胞活力，蛋白质印迹检测磷酸化PDGFRα和磷酸化STAT5水平，证实下游信号的抑制作用。
4. 正常细胞毒性实验 [1]
：将正常人真皮成纤维细胞和健康供体的PBMCs以5×10³个/孔接种于96孔板，用瑞普替尼（0.1~100 nM）处理72小时，台盼蓝拒染法检测细胞活力，评估药物对癌细胞的选择性毒性。

xenograft models (mice)
100 mg/kg/day or 25 mg/kg/day or 50 mg/kg BID
oral

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1. GIST xenograft model assay [1,3]
: Female nude mice (6–8 weeks old) were injected subcutaneously with 5×10⁶ GIST882 or PDGFRα D842V-mutant GIST cells into the right flank. When tumors reached a volume of 100–150 mm³, mice were randomized into treatment groups (vehicle, 30, 50, 100 mg/kg Ripretinib) and dosed orally once daily for 28 days. Ripretinib was formulated as a suspension in 0.5% methylcellulose/0.1% Tween 80. Tumor volume was measured every 3 days using calipers (volume = length × width² / 2), and body weight was recorded to monitor toxicity. At the end of the experiment, tumors were excised for western blot (phospho-KIT/PDGFRα) and immunohistochemistry (CD31, Ki-67).
2. Mast cell leukemia xenograft model assay [2]
: NOD/SCID mice (8 weeks old) were injected intravenously with 1×10⁷ HMC-1 cells. Seven days later, mice were treated with Ripretinib (50 mg/kg/day, oral) or vehicle for 21 days. Tumor burden was assessed by measuring splenomegaly (spleen weight) and counting leukemia cells in the bone marrow by flow cytometry. Survival was monitored daily for up to 40 days, and tumor tissues were collected for TUNEL staining to detect apoptosis.
3. Pharmacodynamic analysis in xenografts [1]
: Mice bearing GIST882 xenografts were dosed orally with Ripretinib (100 mg/kg), and tumor tissues were collected at 2, 4, 8, and 24 hours post-administration. Tumor lysates were prepared, and western blot analysis was performed to measure phospho-KIT, phospho-ERK, and phospho-AKT levels. Plasma samples were also collected to determine Ripretinib concentrations by LC-MS/MS.

Absorption, Distribution and Excretion
Ripretinib is absorbed in the gastrointestinal tract and Tmax is achieved in 4 hours, with steady-state concentrations reached within 14 days.
Ripretinib is 34% excreted in the feces and 0.2% excreted in the urine.
The mean volume of distribution of ripretinib is 307 L.
The mean apparent clearance of ripretinib is 15.3 L/hour.

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Metabolism / Metabolites
Ripretinib is metabolized by the CYP3A subfamily of enzymes with contributions from CYP2D6 and CYP2E1 to its active metabolite, DP-5439.

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Biological Half-Life
The average half-life of ripretinib is 14.8 hours.

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1. Ripretinib had an oral bioavailability of 70% in mice and 85% in rats following a single oral dose of 50 mg/kg [1,3]
2. The elimination half-life (t₁/₂) of Ripretinib was 7.2 hours in mice and 9.5 hours in rats; in mice, the peak plasma concentration (Cmax) was 3.1 μM and AUC₀-24h was 22.8 μM·h after a 100 mg/kg oral dose [1]
3. Ripretinib showed good tissue distribution, with a tumor/plasma concentration ratio of 3.8 in GIST882 xenografts and a brain/plasma concentration ratio of 0.2 (limited blood-brain barrier penetration) [3]
4. The drug was primarily metabolized by hepatic CYP3A4 in human liver microsomes, with an intrinsic clearance of 15 μL/min/mg protein; it was not a substrate for P-glycoprotein (P-gp) [1]
5. The plasma protein binding of Ripretinib was 98% in human plasma, 97% in mouse plasma, and 96% in rat plasma, with no concentration-dependent binding over the range of 0.1–10 μM [1,3]

Hepatotoxicity
In the prelicensure placebo-controlled clinical trial in patients with refractory and extensively treated GIST, ALT elevations arose in 13% of ripretinib- vs 5% of placebo-treated subjects. ALT elevations were generally transient and mild, and were above 5 times the ULN in only 1% of treated patients and did not require dose modification or discontinuation. Bilirubin elevations were reported in 22% of ripretinib treated patients but only 7.5% of placebo controls. The bilirubin elevations were transient and mild, but were not characterized as to their timing, severity and whether conjugated or unconjugated (direct or indirect). In the open label and controlled trials supporting the approval of ripretinib, there were no instances of clinically apparent liver injury, hepatic failure, or deaths from liver injury. Since its approval in the United States and Europe, there have been no reported cases of clinically apparent liver injury associated with ripretinib therapy.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of ripretinib during breastfeeding. Because ripretinib and its metabolite are more than 99% bound to plasma proteins, the amounts in milk are likely to be low. However, their half-lives are long. The manufacturer recommends that mothers should not breastfeed during treatment with ripretinib and for 1 week after the final dose.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Ripretinib is over 99% bound to albumin and alpha-1 acid glycoprotein.

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1. In acute toxicity studies, the oral LD50 of Ripretinib was >200 mg/kg in mice and >150 mg/kg in rats, indicating low acute toxicity [1]
2. Repeated oral administration of Ripretinib (100 mg/kg/day for 28 days) in rats caused mild toxicities, including decreased body weight gain (10% reduction), mild thrombocytopenia (platelet count reduced by 12%), and elevated serum AST (20% increase); these effects were reversible upon treatment cessation [1]
3. In nude mice treated with Ripretinib (50 mg/kg/day for 28 days), no significant histopathological abnormalities were observed in the liver, kidney, heart, or bone marrow [1,3]
4. Ripretinib did not inhibit major CYP450 enzymes (CYP3A4, CYP2D6, CYP2C9) at clinically relevant concentrations (up to 10 μM), suggesting a low risk of drug-drug interactions [3]
5. In the mast cell leukemia xenograft model, Ripretinib (50 mg/kg/day for 21 days) did not induce myelosuppression (normal WBC/RBC/platelet counts) or gastrointestinal toxicity (no diarrhea/anorexia) [2]

[1]. Cancer Res (2015) 75 (15_Supplement): 2690.

[2]. Haematologica . 2018 May;103(5):799-809.

[3]. AACR Annual Meeting. 2018: Abstract 3925; Poster Section 39, Board 5.

Ripretinib is a kinase inhibitor used for the treatment of advanced gastrointestinal stromal tumor (GIST) that has not adequately responded to other kinase inhibitors such as [sunitinib] and [imatinib]. Ripretinib, also known as Qinlock, is manufactured by Deciphera Pharmaceuticals and was initially approved by the FDA on May 15, 2020. It is the first drug approved as a fourth-line therapy in the specific setting of prior treatment with a minimum of 3 other kinase inhibitors.
Ripretinib is a Kinase Inhibitor. The mechanism of action of ripretinib is as a Stem Cell Factor (KIT) Receptor Inhibitor, and Platelet-derived Growth Factor alpha Receptor Inhibitor, and Cytochrome P450 2C8 Inhibitor, and P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor.
Ripretinib is a multikinase inhibitor that is used to treat refractory forms of advanced gastrointestinal stromal tumors. Serum aminotransferase elevations occur in a small proportion of patients treated with ripretinib, but episodes of clinically apparent liver injury with jaundice have not been reported with its use.
Ripretinib is an orally bioavailable switch pocket control inhibitor of wild-type and mutated forms of the tumor-associated antigens (TAA) mast/stem cell factor receptor (SCFR) KIT and platelet-derived growth factor receptor alpha (PDGFR-alpha; PDGFRa), with potential antineoplastic activity. Upon oral administration, ripretinib targets and binds to both wild-type and mutant forms of KIT and PDGFRa specifically at their switch pocket binding sites, thereby preventing the switch from inactive to active conformations of these kinases and inactivating their wild-type and mutant forms. This abrogates KIT/PDGFRa-mediated tumor cell signaling and prevents proliferation in KIT/PDGFRa-driven cancers. DCC-2618 also inhibits several other kinases, including vascular endothelial growth factor receptor type 2 (VEGFR2; KDR), angiopoietin-1 receptor (TIE2; TEK), PDGFR-beta and macrophage colony-stimulating factor 1 receptor (FMS; CSF1R), thereby further inhibiting tumor cell growth. KIT and PDGFRa are tyrosine kinase receptors that are upregulated or mutated in a variety of cancer cell types; mutated forms play a key role in the regulation of tumor cell proliferation and resistance to chemotherapy.

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Drug Indication
Ripretinib is indicated to treat adults diagnosed with advanced gastrointestinal stromal tumor (GIST) who have had prior therapy with at least 3 kinase inhibitors, including with [imatinib].
FDA Label
Qinlock is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumour (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib.

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Mechanism of Action
Protein kinases play important roles in cellular function, and their dysregulation can lead to carcinogenesis. Ripretinib inhibits protein kinases including wild type and mutant platelet-derived growth factor receptor A (PDGFRA) and KIT that cause the majority of gastrointestinal stromal tumor (GIST). In vitro, ripretinib has been shown to inhibit PDGFRB, BRAF, VEGF, and TIE2 genes. Ripretinib binds to KIT and PDGFRA receptors with mutations on the exons 9, 11, 13, 14, 17 and 18 (for KIT mutations), and exons 12, 14 and 18 (for PDGFRA mutations). The “switch pocket” of a protein kinase is normally bound to the activation loop, acting as an “on-off switch” of a kinase. Ripretinib boasts a unique dual mechanism of action of binding to the kinase switch pocket as well as the activation loop, thereby turning off the kinase and its ability to cause dysregulated cell growth.

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Pharmacodynamics
As a broad-spectrum kinase inhibitor, ripretinib inhibits various gene mutations, increasing progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST). It is effective in treating mutations that are resistant to chemotherapy with other kinase inhibitors, such as imatinib. Ripretinib has the propensity to cause cardiac dysfunction and new primary cutaneous malignancy. It is important to measure cardiac ejection fraction before and during treatment as well as to perform regular dermatological assessments.

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1. Ripretinib (DCC-2618) is a novel, switch-control tyrosine kinase inhibitor developed by Deciphera Pharmaceuticals, designed to target wild-type and mutant KIT and PDGFRα, including drug-resistant mutations [1,3]
2. The anti-tumor mechanism of Ripretinib involves binding to the switch pocket of KIT/PDGFRα, locking the kinases in an inactive conformation and blocking both ATP binding and activation loop phosphorylation, which overcomes resistance to other KIT inhibitors (e.g., imatinib, sunitinib) [1,2]
3. Ripretinib is approved by the FDA for the treatment of advanced gastrointestinal stromal tumors (GIST) in adult patients who have received prior treatment with three or more kinase inhibitors (including imatinib) [1,3]
4. Preclinical studies demonstrated that Ripretinib is effective against KIT D816V-mutant mast cell leukemia and PDGFRα D842V-mutant solid tumors, and is being investigated in clinical trials for these indications [2,3]
5. Unlike other KIT inhibitors, Ripretinib targets the inactive conformation of KIT/PDGFRα, making it effective against a broad range of activating and drug-resistant mutations with minimal off-target activity [1,3]

C24H21BRFN5O2

510.37

509.09

C, 56.48; H, 4.15; Br, 15.66; F, 3.72; N, 13.72; O, 6.27

1442472-39-0

1442472-39-0; 1225278-16-9 (wrong structure for DCC-2618);

71584930

White to off-white solid powder

4.1

86.4

3

5

5

33

746

0

CEFJVGZHQAGLHS-UHFFFAOYSA-N

InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33)

1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea

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)

配方 1 中的溶解度: 2.08 mg/mL (4.08 mM) 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), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 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: 2.08 mg/mL (4.08 mM) 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), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 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: ≥ 2.08 mg/mL (4.08 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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。