• <dfn id="q240u"></dfn>
    • Fexagratinib (AZD4547)

      別名: ABSK 091

      Fexagratinib (AZD4547,ABSK 091)是一種新型選擇性的FGFR抑制劑,靶向作用于FGFR1/2/3,在無細胞試驗中IC50為0.2 nM/2.5 nM/1.8 nM,對FGFR4, VEGFR2(KDR)具有微弱的作用活性,對IGFR, CDK2和p38幾乎沒有作用活性。Phase 2/3。

      Fexagratinib (AZD4547)  Chemical Structure

      Fexagratinib (AZD4547) Chemical Structure

      CAS: 1035270-39-3

      規(guī)格 價格 庫存 購買數(shù)量
      10mM (1mL in DMSO) 1122.03 現(xiàn)貨
      5mg 901.31 現(xiàn)貨
      10mg 1395.39 現(xiàn)貨
      100mg 7125.05 現(xiàn)貨
      1g 12039.3 現(xiàn)貨
      更大包裝 有超大折扣

      400-668-6834

      [email protected]

      免費分裝
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      細胞實驗數(shù)據(jù)示例

      細胞系 實驗類型 給藥濃度 孵育時間 活性描述 文獻信息(PMID)
      SK-HEP-1 Function Assay 0-2 μM 48 h causes a decrease of FRS2,AKT, and ERK phosphorylation 26351320
      SNU449 Function Assay 0-2 μM 48 h causes a decrease of FRS2,AKT, and ERK phosphorylation 26351320
      SK-HEP-1 Clonogenic assay 1 μM 24 h decreases colony formation significantly 26351320
      SNU449 Clonogenic assay 1 μM 24 h decreases colony formation significantly 26351320
      A549 Cell viability Assay 0.1/1 μM 48 h enhances Erlotinib induced viability loss 26053020
      SGC-7901 Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 5-10 μM, inhibits cell viability dose dependently 25576915
      HGC-27 Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 5-10 μM, inhibits cell viability dose dependently 25576915
      MKN-28 Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 5-10 μM, inhibits cell viability dose dependently 25576915
      NCI-N87 Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 5-10 μM, inhibits cell viability dose dependently 25576915
      KATOIII Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 10-100 nM, inhibits cell viability dose dependently 25576915
      SNU-16 Growth Inhibition Assay 1 nM-10 μM 72 h IC50 of 10-100 nM, inhibits cell viability dose dependently 25576915
      4T1 Apoptosis Assay 1.25-20 μM 24 h induces apoptosis dose dependently 24642893
      HepG2 Growth Inhibition Assay 72 h IC50=8.73 μM 26351320
      Hur7 Growth Inhibition Assay 72 h IC50=7.25 μM 26351320
      PLC/PRF5 Growth Inhibition Assay 72 h IC50=6.55 μM 26351320
      Hep3B Growth Inhibition Assay 72 h IC50=6.43 μM 26351320
      SNU475 Growth Inhibition Assay 72 h IC50=5.4 μM 26351320
      SK-HEP-1 Growth Inhibition Assay 72 h IC50=0.084 μM 26351320
      SNU449 Growth Inhibition Assay 72 h IC50=0.082 μM 26351320
      KG1 Function assay 72 hrs Inhibition of FGFR1 in human KG1 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0002 μM. 27117427
      RT112 Function assay 72 hrs Inhibition of FGFR3 in human RT112 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0006 μM. 27117427
      KG1 Antiproliferative assay 72 hrs Antiproliferative activity against human KG1 cells expressing FGFR1 after 72 hrs, IC50 = 0.0019 μM. 29775937
      KG1 Antiproliferative assay 72 hrs Antiproliferative activity against human KG1 cells after 72 hrs by CCK-8 assay, IC50 = 0.0033 μM. 28687204
      SNU16 Antiproliferative assay 72 hrs Antiproliferative activity against human SNU16 cells after 72 hrs by CCK-8 assay, IC50 = 0.0034 μM. 28687204
      SNU16 Function assay 72 hrs Inhibition of recombinant FGFR2 in human SNU16 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0036 μM. 27117427
      SNU16 Antiproliferative assay 72 hrs Antiproliferative activity against human SNU16 cells expressing FGFR2 after 72 hrs, IC50 = 0.0062 μM. 29775937
      KG1 Antiproliferative assay 72 hrs Antiproliferative activity against FGFR1-translocated human KG1 cells after 72 hrs by CCK8/MTT assay, IC50 = 0.0064 μM. 27348537
      SNU16 Antiproliferative assay 72 hrs Antiproliferative activity against FGFR2-amplified human SNU16 cells after 72 hrs by CCK8/MTT assay, IC50 = 0.0134 μM. 27348537
      KATO III Function assay 72 hrs Inhibition of FGFR2 in human KATO III cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.0141 μM. 28714692
      KG1 Function assay 72 hrs Inhibition of FGFR1OP2 fused FGFR1 in human KG1 cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.0161 μM. 28714692
      KATO III Function assay 72 hrs Inhibition of FGFR2 in human KATO III cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0202 μM. 27117427
      SNU16 Function assay 72 hrs Inhibition of FGFR2 in human SNU16 cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.0254 μM. 28714692
      UM-UC-14 Antiproliferative assay 72 hrs Antiproliferative activity against human UM-UC-14 cells expressing FGFR3 after 72 hrs, IC50 = 0.0269 μM. 29775937
      RT112 Function assay 72 hrs Inhibition of FGFR3 in human RT112 cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.027 μM. 28714692
      UM-UC-14 Function assay 72 hrs Inhibition of FGFR3 mutant in human UM-UC-14 cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.0271 μM. 28714692
      RT112 Antiproliferative assay 72 hrs Antiproliferative activity against human RT112 cells after 72 hrs by MTT assay, GI50 = 0.0292 μM. 27599742
      H1581 Function assay 72 hrs Inhibition of FGFR1 in human H1581 cells assessed as suppression of cell proliferation after 72 hrs by SRB/CCK-8 assay, IC50 = 0.0329 μM. 27117427
      NCI-H1581 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H1581 cells expressing FGFR1 after 72 hrs, IC50 = 0.04 μM. 29775937
      B16F10 Cytotoxicity assay 72 hrs Cytotoxicity against mouse B16F10 cells after 72 hrs by MTT assay, IC50 = 0.051 μM. 25736993
      A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.062 μM. 25736993
      NCI-H1581 Function assay 72 hrs Inhibition of FGFR1 in human NCI-H1581 cells assessed as inhibition of cell proliferation after 72 hrs by cell counting kit-8 assay, IC50 = 0.0626 μM. 28714692
      RT112 Antiproliferative assay 72 hrs Antiproliferative activity against human RT112 cells expressing FGFR3 after 72 hrs, IC50 = 0.0838 μM. 29775937
      RT112 Antiproliferative assay 72 hrs Antiproliferative activity against FGFR3-amplified human RT112 cells after 72 hrs by CCK8/MTT assay, IC50 = 0.0884 μM. 27348537
      NCI-H1581 Antiproliferative assay 72 hrs Antiproliferative activity against FGFR1-amplified human NCI-H1581 cells after 72 hrs by CCK8/MTT assay, IC50 = 0.0921 μM. 27348537
      HeLa 229 Cytotoxicity assay 72 hrs Cytotoxicity against human HeLa 229 cells after 72 hrs by MTT assay, IC50 = 0.14 μM. 25736993
      BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing VEGFR2 after 72 hrs, IC50 = 0.222 μM. 29775937
      SGC7901 Antiproliferative assay 72 hrs Antiproliferative activity against human SGC7901 cells after 72 hrs by MTT assay, IC50 = 2.8 μM. 27829519
      MGC803 Antiproliferative assay 72 hrs Antiproliferative activity against human MGC803 cells after 72 hrs by MTT assay, IC50 = 6.2 μM. 27829519
      BGC823 Antiproliferative assay 72 hrs Antiproliferative activity against human BGC823 cells after 72 hrs by MTT assay, IC50 = 7.9 μM. 27829519
      HL7702 Cytotoxicity assay 72 hrs Cytotoxicity against human HL7702 cells after 72 hrs by MTT assay, IC50 = 18.21 μM. 25736993
      HEC1A Normal FGFR2 Growth Inhibition Assay GI50﹥10 μM 26294741
      Ishikawa FGFF2 over exp. Growth Inhibition Assay GI50=4.5 ± 1.51 μM 26294741
      MFE280 FGFR2 S252W Growth Inhibition Assay GI50=0.218 ± 0.073 μM 26294741
      MFE296 FGFR2 N550K Growth Inhibition Assay GI50=0.730 ± 0.057 μM 26294741
      AN3-CA FGFR2 N550K, K310R Growth Inhibition Assay GI50=0.031 ± 0.023 μM 26294741
      TT RET C634W Growth Inhibition Assay GI50=2.9 ± 0.904 μM 26294741
      MV4-11 FLT3/ITD Growth Inhibition Assay GI50=0.459 ± 0.046 μM 26294741
      MOLM14 FLT3/ITD Growth Inhibition Assay GI50=0.484 ± 0.157 μM 26294741
      BaF3 Parental Growth Inhibition Assay GI50﹥10 μM 26294741
      BaF3 RET-TEL Growth Inhibition Assay GI50=0.39 ± 0.048 μM 26294741
      BaF3 FLT3-TEL Growth Inhibition Assay GI50=4.6 ± 0.577 μM 26294741
      4T1 Growth Inhibition Assay IC50=0.64±0.11 μM 24642893
      MDA-MB-468 Growth Inhibition Assay IC50=4.9±0.85 μM 24642893
      HCT116 Growth Inhibition Assay IC50=15.9±1.82 μM 24642893
      SW620 Growth Inhibition Assay IC50>20 μM 24642893
      MDA-MB-231 Growth Inhibition Assay IC50>20 μM 24642893
      CT26 Growth Inhibition Assay IC50>20 μM 24642893
      SW480 Growth Inhibition Assay IC50>20 μM 24642893
      KG1a Growth Inhibition Assay IC50=0.018 μM 22369928
      Sum52-PE Growth Inhibition Assay IC50=0.041 μM 22369928
      KMS11 Growth Inhibition Assay IC50=0.281 μM 22369928
      MCF7 Growth Inhibition Assay IC50>30 μM 22369928
      U-2 OS qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
      A673 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
      Saos-2 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
      BT-37 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
      RD qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
      SK-N-SH qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
      BT-12 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
      OHS-50 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
      fibroblast cells qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
      Rh41 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
      Rh30 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
      SJ-GBM2 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
      NB-EBc1 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
      LAN-5 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
      Rh18 qHTS ssay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
      點擊查看更多細胞系數(shù)據(jù)

      生物活性

      產(chǎn)品描述 Fexagratinib (AZD4547,ABSK 091)是一種新型選擇性的FGFR抑制劑,靶向作用于FGFR1/2/3,在無細胞試驗中IC50為0.2 nM/2.5 nM/1.8 nM,對FGFR4, VEGFR2(KDR)具有微弱的作用活性,對IGFR, CDK2和p38幾乎沒有作用活性。Phase 2/3。
      特性 AZD4547高選擇性作用于 FGFR1-3,比作用于FGFR4選擇性高。AZD4547有效作用于野生型和突變型FGFR酪氨酸激酶活性。
      靶點
      FGFR1 [1]
      (Cell-free assay)
      FGFR3 [1]
      (Cell-free assay)
      FGFR2 [1]
      (Cell-free assay)
      KDR [1]
      (Cell-free assay)
      0.2 nM 1.8 nM 2.5 nM 24 nM
      體外研究(In Vitro)
      體外研究活性

      與 FGFR1-3相比, AZD4547作用于FGFR4,活性微弱,IC50為165 nM。AZD4547 只抑制重組 VEGFR2 (KDR) 激酶活性, IC50為 24 nM,在體外選擇性作用于一組多種代表性的人類激酶。0.1 μM AZD4547 作用于一系列重組激酶,包括 ALK, CHK1, EGFR, MAPK1, MEK1, p70S6K, PDGFR, PKB, Src, Tie2,和 PI3K,沒有作用活性。相應(yīng)地,在細胞磷酸化實驗中,可觀察到AZD4547 作用于FGFR1-3的選擇性比作用于 FGFR4, IGFR, 和 KDR高。AZD4547在體外,只有作用于表達去調(diào)控FGFRs 如KG1a, Sum52-PE,和KMS11的腫瘤細胞,具有有效抗增殖活性,IC50 為18-281 nM,而對MCF7 及100 種以上其他腫瘤細胞無活性。AZD4547 處理人類腫瘤細胞,有效抑制FGFR 和 MAPK 磷酸化,這種作用存在劑量依賴性。AZD4547 也有效抑制FRS2 和 PLCγ磷酸化,及下游FGFR信號。另外, AZD4547作用于乳腺細胞系,MCF7和Sum52-PE 而不是KG1a和 KMS11細胞,影響AKT磷酸化。AZD4547處理Sum52-PE 和 KMS11細胞,顯著誘導(dǎo)凋亡,作用于KG1a細胞,顯著提高細胞周期在G1期停滯而不是凋亡, 而作用于MCF7細胞,對細胞周期分布和凋亡都沒有作用效果。[1]

      激酶實驗 AZD4547 激酶活性
      使用濃度等于或低于相對Km 的ATP,測定AZD4547抑制 FGFR1-3的人類重組激酶活性的效果。
      細胞實驗 細胞系 KG1a, Sum52-PE, KMS11, 和MCF7
      濃度 溶于DMSO,終濃度為 ~1 μM
      孵育時間 72 小時
      方法

      使用多種濃度AZD4547處理細胞72小時。通過 MTS 增殖實驗獲得抗增殖的IC50值。熒光激活細胞分選(FACS)中,細胞與70%乙醇混合,然后與碘化丙啶/RNase A標(biāo)記溶液溫育。使用 FACSCalibur 儀器和CellQuest分析軟件測定細胞周期譜。為了分析凋亡,輕輕收集細胞和培養(yǎng)基,離心,然后沖洗細胞顆粒。細胞進行Annexin膜聯(lián)蛋白 V-異硫氰酸熒光素(FITC)染色和碘化丙啶吸收。使用FACSCalibur儀器測定 膜聯(lián)蛋白 V染色陽性細胞比例,使用CellQuest分析軟件進行象限分類。

      實驗圖片 檢測方法 檢測指標(biāo) 實驗圖片 PMID
      Western blot p-FGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK pFRS2 28900173
      Growth inhibition assay Cell viability Cell viability 28900173
      體內(nèi)研究(In Vivo)
      體內(nèi)研究活性

      AZD4547按3 mg/kg劑量口服處理攜帶KMS11腫瘤的小鼠,每天兩次,與空白對照組相比,顯著抑制53%腫瘤生長,AZD4547 按 12.5 mg/kg劑量每天處理一次,或按 6.25 mg/kg劑量每天處理兩次,則完全抑制腫瘤,這與p-FGFR3的藥效學(xué)調(diào)節(jié)劑量正相關(guān),且降低 KMS11腫瘤細胞增殖。而且, AZD4547按 12.5 mg/kg劑量口服處理給藥FGFR1融合KG1a 移植瘤模型,每天一次,抑制65% 腫瘤生長。在有效劑量水平,AZD4547不表現(xiàn)出抗血管生成的效果。AZD4547 對血壓沒有顯著作用效果,因此在體內(nèi)缺乏 抗-KDR 活性。相應(yīng)地, AZD4547按6.25 mg/kg劑量口服處理對Cediranib敏感的移植瘤模型,包括 Calu-6, HCT-15 和 LoVo,每天兩次,沒有作用活性。[1]

      動物實驗 Animal Models 皮下注射LoVo, HCT-15, Calu-6, KMS11 或 KG1a的雌性Swiss衍生裸鼠和SCID小鼠
      Dosages 1.5-50 mg/kg
      Administration 口服飼喂,每天一次或兩次
      NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
      NCT02824133 Completed
      Recurrent IDHwt Gliomas With FGFR3-TACC3 Fusion|Recurrent IDHwt Gliomas With FGFR1-TACC1 Fusion
      Assistance Publique - H?pitaux de Paris
      September 2015 Phase 1|Phase 2
      NCT01824901 Completed
      Recurrent Non-small Cell Lung Cancer|Squamous Cell Lung Cancer
      ECOG-ACRIN Cancer Research Group|National Cancer Institute (NCI)|Eastern Cooperative Oncology Group
      January 15 2014 Phase 1|Phase 2
      NCT01795768 Unknown status
      Gastric Cancer|Oesophageal Cancer|Breast Cancer|Squamous Cell Carcinoma of the Lung
      Royal Marsden NHS Foundation Trust|AstraZeneca
      September 2012 Phase 2
      NCT01213160 Completed
      Cancer|Advanced Solid Malignancies
      AstraZeneca
      November 2010 Phase 1
      • https://pubmed.ncbi.nlm.nih.gov/22369928/

      化學(xué)信息&溶解度

      分子量 463.57 分子式

      C26H33N5O3

      CAS號 1035270-39-3 SDF Download Fexagratinib (AZD4547) SDF
      Smiles CC1CN(CC(N1)C)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)CCC4=CC(=CC(=C4)OC)OC
      儲存條件(自收到貨起)

      體外溶解度
      批次:

      DMSO : 93 mg/mL ( (200.61 mM) ;DMSO吸濕會降低化合物溶解度,請使用新開封DMSO)

      Water : Insoluble

      Ethanol : Insoluble

      摩爾濃度計算器

      體內(nèi)溶解配方
      批次:

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

      動物體內(nèi)配方計算器

      實驗計算

      摩爾濃度計算器

      質(zhì)量 濃度 體積 分子量

      動物體內(nèi)配方計算器(澄清溶液)

      第一步:請輸入基本實驗信息(考慮到實驗過程中的損耗,建議多配一只動物的藥量)

      mg/kg g μL

      第二步:請輸入動物體內(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,請聯(lián)系Selleck為您提供正確的澄清溶液配方)

      % DMSO % % Tween 80 % ddH2O
      %DMSO %

      計算結(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,:如該濃度超過該批次藥物DMSO溶解度,請先聯(lián)系Selleck);

      體內(nèi)配方配制方法: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: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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