Ripretinib

別名: DCC-2618

目錄號(hào)：S8757 Purity: 99.82%

Ripretinib是一種具有口服活性的Kit (c-Kit)和PDGFR-alpha抑制劑，對(duì)WT Kit (c-Kit)、V654A Kit (c-Kit)、T670I Kit (c-Kit)、D816H Kit (c-Kit)和D816V Kit (c-Kit)的IC50分別為4 nM、8 nM、18 nM、5 nM和14 nM。

Ripretinib Chemical Structure

CAS: 1442472-39-0

規(guī)格	價(jià)格	庫(kù)存
10mM (1mL in DMSO)	3333.33	現(xiàn)貨
5mg	1859.41	現(xiàn)貨
25mg	5651.24	現(xiàn)貨
100mg	13022.99	現(xiàn)貨
1g	31900	現(xiàn)貨
更大包裝有超大折扣
400-668-6834 [email protected]

產(chǎn)品質(zhì)控

批次：純度： 99.82%

99.82

Ripretinib相關(guān)產(chǎn)品

相關(guān)產(chǎn)品	Masitinib Amuvatinib (MP-470) OSI-930 Sitravatinib (MGCD516) ISCK03 PDGFR inhibitor 1	點(diǎn)擊展開(kāi)
相關(guān)化合物庫(kù)	激酶抑制劑庫(kù) 酪氨酸激酶抑制劑分子庫(kù) PI3K/Akt 抑制劑庫(kù) 細(xì)胞周期化合物庫(kù) 血管生成相關(guān)化合物庫(kù)	點(diǎn)擊展開(kāi)

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	孵育時(shí)間	活性描述	文獻(xiàn)信息(PMID)
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.003 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.006 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.013 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.014 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.023 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.031 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.04 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.045 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.048 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.075 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.078 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.098 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.13 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.188 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.205 μM.	30204441
Cytotoxicity assay	BA/F3	72 hrs	Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 8.037 μM.	30204441
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生物活性

產(chǎn)品描述

靶點(diǎn)

PDGFR ^[2]	WT KIT ^[1] (Cell-free assay)	D816H KIT ^[1] (Cell-free assay)	V654A KIT ^[1] (Cell-free assay)	D816V KIT ^[1] (Cell-free assay)	點(diǎn)擊更多
	4 nM	5 nM	8 nM	14 nM	點(diǎn)擊更多

體外研究(In Vitro)
體外研究活性	DCC-2618有效并廣泛地抑制KIT原發(fā)性和耐藥性突變體，如發(fā)生在外顯子9、11、13、14、17和18的突變，以及發(fā)生在PDGFRA外顯子12、14、18的原發(fā)性突變^[3]。DCC-2618以納摩爾級(jí)別的效力抑制多種性質(zhì)的KIT：WT (IC50 4 nM), V654A (8 nM), T670I (18 nM), D816H (5 nM), D816V (14 nM)。在瞬時(shí)轉(zhuǎn)染了KIT原發(fā)性突變體和二次突變的CHO細(xì)胞中，DCC-2618抑制了外顯子17、外顯子9/13、外顯子9/14，外顯子9/17，外顯子11/17突變的KIT，包括位于外顯子17的D816V, D816G, D820A, D820E, D820Y, N822K, N822Y, N822H和Y823D原發(fā)性或二次突變。在MO7e細(xì)胞系中，DCC-2618抑制野生型KIT的磷酸化（IC50=36 nM）。在人源GIST細(xì)胞系中，包括GIST T1(缺失外顯子11)、GIST 430（缺失外顯子11/外顯子13 V654A）和GIST 48（外顯子11 V560D/外顯子17 D820A）, DCC-2618也能有效抑制KIT的激活。在小鼠肥大細(xì)胞增多癥中，DCC-2618可有效抑制P815細(xì)胞(表達(dá)外顯子17 D816Y 突變KIT)的增殖，IC50為2 nM^[1]。在多種人類肥大細(xì)胞系（HMC-1, ROSA, MCPV-1）和從晚期系統(tǒng)性肥大細(xì)胞增多癥患者體內(nèi)分離的原代腫瘤肥大細(xì)胞中，DCC-2618可抑制其增殖和生存^[2]。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	HMC-1.1, HMC-1.2, ROSA (KIT WT)和 ROSA (KIT D816V)細(xì)胞
	濃度	0.5-5 μM
	孵育時(shí)間	4 h
	方法	將細(xì)胞培養(yǎng)于對(duì)照組培養(yǎng)基中或加入0.5-5 μM DCC-2618，置于37℃培養(yǎng)4小時(shí)。結(jié)束后，收集細(xì)胞提取蛋白質(zhì)，進(jìn)行Western blotting分析。
實(shí)驗(yàn)圖片	檢測(cè)方法	檢測(cè)指標(biāo)	實(shí)驗(yàn)圖片	PMID
實(shí)驗(yàn)圖片	Western blot	KIT / BTK STAT5 / AKT / ERK		29439183

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	在體內(nèi)，50 mg/kg DCC-2618可在GIST T1移植瘤模型抑制KIT磷酸化，達(dá)到90%的有效劑量（ED90），EC50約為470 ng/mL。每日兩次口服給藥，DCC-2618可幾乎完全地造成腫瘤瘀滯^[1]。在移植瘤模型中，DCC-2618可阻止KIT和PFGFRA驅(qū)動(dòng)的腫瘤生長(zhǎng)^[3]。
動(dòng)物實(shí)驗(yàn)	Animal Models	小鼠移植瘤模型
	Dosages	100 mg/kg/day 或 25 mg/kg/day 或 50 mg/kg BID
	Administration	口服

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05080621	Withdrawn	Gastrointestinal Stromal Tumors	Deciphera Pharmaceuticals LLC	November 2021	Phase 1\|Phase 2
NCT04633122	Completed	Gastrointestinal Stromal Tumor(GIST)	Zai Lab (Shanghai) Co. Ltd.\|Zai Lab (Hong Kong) Ltd.	November 25 2020	Phase 2
NCT02571036	Completed	Gastrointestinal Stromal Tumors\|Advanced Systemic Mastocytosis\|Advanced Cancers	Deciphera Pharmaceuticals LLC	November 2015	Phase 1

參考文獻(xiàn)
[1]http://cancerres.aacrjournals.org/content/75/15_Supplement/2690 [2]https://pubmed.ncbi.nlm.nih.gov/29439183/ [3]https://www.deciphera.com/wp-content/uploads/2018/04/DCC-2618-Pre-Clinical-AACR-2018.pdf

參考文獻(xiàn)

[1]http://cancerres.aacrjournals.org/content/75/15_Supplement/2690
[2]https://pubmed.ncbi.nlm.nih.gov/29439183/
[3]https://www.deciphera.com/wp-content/uploads/2018/04/DCC-2618-Pre-Clinical-AACR-2018.pdf

化學(xué)信息&溶解度

分子量	510.36	分子式	C₂₄H₂₁BrFN₅O₂
CAS號(hào)	1442472-39-0	SDF	--
Smiles	CCN1C2=CC(=NC=C2C=C(C1=O)C3=CC(=C(C=C3Br)F)NC(=O)NC4=CC=CC=C4)NC
儲(chǔ)存條件(自收到貨起)	3年 -20°C 粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲(chǔ)存條件(自收到貨起)	3年 -20°C 粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 100 mg/mL ( (195.94 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL ( (195.94 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解配方
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

給藥劑量 mg/kg 動(dòng)物平均體重 g 每只動(dòng)物給藥體積 μL 動(dòng)物數(shù)量只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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* 必填項(xiàng)

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