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DCA (Sodium dichloroacetate)

別名: Dichloroacetic acid, bichloroacetic acid, BCA 中文名稱：二氯乙酸鈉

DCA (Sodium dichloroacetate)是 pyruvate dehydrogenase kinase (PDK) 的特異性抑制劑，對PDK2和PDK4的IC50值分別為183和80 μM；可抑制 Na+-K+-2Cl- cotransporter 和線粒體鉀離子通道軸。Sodium dichloroacetate 可增加活性氧的生成，引起癌細胞凋亡，并抑制腫瘤生長。

DCA (Sodium dichloroacetate) Chemical Structure

DCA (Sodium dichloroacetate) Chemical Structure

CAS: 2156-56-1

規(guī)格 價格 庫存 購買數(shù)量
100mg 794.47 現(xiàn)貨
1g 3030.55 現(xiàn)貨
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DCA (Sodium dichloroacetate)相關(guān)產(chǎn)品

相關(guān)信號通路圖

Dehydrogenase Signaling Pathways

Dehydrogenase信號通路圖

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
MCF7 Function assay 10 mM 12 hrs Inhibition of PDK1 in human MCF7 cells assessed as increase in oxygen consumption rate at 10 mM after 12 hrs 27006991
MCF7 Function assay 10 mM 12 hrs Inhibition of PDK1 in human MCF7 cells assessed as decrease in extracellular acidification rate at 10 mM after 12 hrs 27006991
MCF7 Function assay 10 mM 12 hrs Inhibition of PDK1 in human MCF7 cells assessed as decrease in proton production rate at 10 mM after 12 hrs 27006991
MCF7 Function assay 10 mM 12 hrs Inhibition of PDK1 in human MCF7 cells assessed as increase in ratio of oxygen consumption rate to extracellular acidification rate at 10 mM after 12 hrs 27006991
MCF7 Function assay 10 mM 12 hrs Inhibition of PDK1 in human MCF7 cells assessed as decrease in lactate production at 10 mM after 12 hrs 27006991
NCI-H1975 Antiproliferative assay 20 mM 72 hrs Antiproliferative activity against human NCI-H1975 cells assessed as reduction in cell viability at 20 mM after 72 hrs by MTT assay 30470491
MCF7 Antitumor assay 30 mg/kg two weeks Antitumor activity against human MCF7 cells xenografted in BALB/c nude mouse assessed as tumor growth inhibition at 30 mg/kg, iv administered every two days for two weeks measured after 14 days 31509699
MCF7 Function assay 30 uM 4 hrs Induction of metabolic reversal from aerobic glycolysis to oxidative phosphorylation in human MCF7 cells assessed as increase in extracellular acidification rate at 30 uM pretreated for 4 hrs followed by glucose addition after 25 mins by seahorse XF24 ext 31509699
MCF7 Function assay 30 uM 4 hrs Induction of metabolic reversal from aerobic glycolysis to oxidative phosphorylation in human MCF7 cells assessed as increase in extracellular acidification rate at 30 uM pretreated for 4 hrs followed by glucose addition after 25 mins followed by subsequent assay 31509699
MCF7 Function assay 30 uM 4 hrs Induction of metabolic reversal from aerobic glycolysis to oxidative phosphorylation in human MCF7 cells assessed as decline in extracellular acidification rate at 30 uM pretreated for 4 hrs followed by glucose addition after 25 mins followed by subsequent assay 31509699
MCF7 Function assay 30 uM 6 hrs Induction of metabolic reversal from aerobic glycolysis to oxidative phosphorylation in human MCF7 cells assessed as decrease in oxygen consumption rate at 30 uM pretreated for 6 hrs followed by oligomycin A addition after 25 mins followed by subsequent assay 31509699
MCF7 Function assay 90 mins Inhibition of PDK1 (unknown origin) expressed in human MCF7 cells using PDK tide as substrate measured after 90 mins in presence of ATP by ADP-Glo luminescent kinase assay 31509699
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生物活性

產(chǎn)品描述 DCA (Sodium dichloroacetate)是 pyruvate dehydrogenase kinase (PDK) 的特異性抑制劑，對PDK2和PDK4的IC50值分別為183和80 μM；可抑制 Na+-K+-2Cl- cotransporter 和線粒體鉀離子通道軸。Sodium dichloroacetate 可增加活性氧的生成，引起癌細胞凋亡，并抑制腫瘤生長。
靶點
PDK4 [4]
(Cell-free assay)		 PDK2 [4]
(Cell-free assay)
80 μM 183 μM
體外研究(In Vitro)
體外研究活性 DCA可引起人類肺部、乳腺和腦癌細胞的凋亡[1]。經(jīng)DCA處理后，癌細胞中的ROS水平升高、MMP去極化、在體內(nèi)外都能夠增加凋亡[2]。DCA抑制丙酮酸脫氫酶激酶（PDK）的活性，因而刺激線粒體丙酮酸脫氫酶（PDH）。當PDH處于關(guān)閉狀態(tài)時，PDH不再將丙酮酸轉(zhuǎn)化為acetyl-CoA（線粒體呼吸和葡萄糖依賴的氧化磷酸化過程所必需）。從而，DCA將細胞代謝從糖酵解轉(zhuǎn)換為葡萄糖氧化，降低線粒體膜電位，促進線粒體轉(zhuǎn)運孔的開放。這一系列代謝轉(zhuǎn)換有助于促凋亡介質(zhì)如cyt c和AIF的易位。因而，DCA可通過凋亡反應驅(qū)動癌細胞自殺[3]。
細胞實驗 細胞系 乳腺癌細胞
濃度 5 mM
孵育時間 24-72 h
方法

將細胞以3000細胞/孔的密度鋪于96孔板。用DCA和ATO處理24-72小時，然后換成新鮮的含30 μg/ml的中性紅培養(yǎng)基孵育3小時。PBS洗滌細胞，加入lysis buffer(acetic acid/methanol, 80%/20%)，在540 nm處檢測吸光值。
實驗圖片 檢測方法 檢測指標 實驗圖片 PMID
Western blot pPDH E1α / PDH E1α 25630799
體內(nèi)研究(In Vivo)
體內(nèi)研究活性 DCA在體內(nèi)體外可作為細胞生長抑制劑，而不引起程序性細胞死亡（凋亡）。DCA是一種安全性較高的藥物，沒有心臟、肺部、腎臟或骨髓毒性。最為嚴重的副作用包括周圍神經(jīng)病變，該作用為可逆過程。DCA在好幾種癌癥類型中，包括結(jié)腸癌、前列腺癌、卵巢癌、成神經(jīng)細胞瘤、肺癌、子宮頸癌、子宮內(nèi)膜、膽管癌、肉瘤和T細胞淋巴瘤具有抗癌活性。DCA的其他一些抗腫瘤作用也被報導，包括阻礙血管生成、改變HIF-1α的表達、pH調(diào)節(jié)劑V-ATPase和MCT1的改變、其他細胞生存調(diào)節(jié)子如PUMA、GLUT1、Bcl2和p53的改變。在大鼠高轉(zhuǎn)移乳腺癌模型中，DCA能夠顯著地減少肺部轉(zhuǎn)移性負擔[1]。在C57BL/6小鼠中，DCA-Na的體內(nèi)給藥可誘導20%的生存率提高并減少腫瘤直徑、體積和重量，而不影響其體重、并避免轉(zhuǎn)移[3]。
動物實驗 Animal Models C57BL/6 mice
Dosages 500 and 1000 mg/kg
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06073106 Not yet recruiting
Stroke|Traumatic Brain Injury|Knee Osteoarthritis|Breast Cancer
Tan Tock Seng Hospital|Rehabilitation Research Institute of Singapore (RRIS)|Woodlands Health (WH)
 December 2023 --
NCT05810623 Not yet recruiting
Upper Urinary Tract Urothelial Carcinoma|Bladder Cancer
David D''Andrea|Medical University of Vienna
 June 1 2023 Phase 3
NCT05646485 Recruiting
Bladder Cancer|Urothelial Carcinoma|Hematuria|Smoking Cessation
University of Texas Southwestern Medical Center
 May 5 2023 Not Applicable
NCT05460533 Recruiting
B-cell Acute Lymphoblastic Leukemia
Memorial Sloan Kettering Cancer Center|Novartis Pharmaceuticals
 July 12 2022 Phase 2

化學信息&溶解度

分子量 150.92 分子式

C2HCl2O2.Na
CAS號 2156-56-1 SDF Download DCA (Sodium dichloroacetate) SDF
Smiles C(C(=O)[O-])(Cl)Cl.[Na+]
儲存條件(自收到貨起)

體外溶解度
批次：
摩爾濃度計算器

體內(nèi)溶解度
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 只

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，注：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：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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