体外活性：坎地沙坦与 CHO-AT1 细胞中的血管紧张素 II AT1 受体高度特异性结合，K−1 为 0.001 min−1。坎地沙坦不会影响细胞活力或增殖，但会增加 KU-19-19 细胞培养基中 VEGF 和 IL-8 的表达。坎地沙坦 (0.1 nM) 可使血管紧张素 II 的最大收缩反应降低约 50%。激酶测定：将细胞铺板于 24 孔板中并培养直至汇合。实验前，室温下用每孔 0.5 mL 的 DMEM 洗涤细胞 3 次。除去培养基后，加入 400 μL 结合 DMEM，然后将板在 37 ℃ 下放置 15 分钟。对于饱和结合测定，将细胞与终体积为 0.5 mL 的逐渐浓度的 [3H]坎地沙坦（终浓度在 0.15 nM 至 15 nM 之间）在 37℃ 下孵育 5 分钟至 180 分钟。对于竞争性结合测定，添加 50 μL 缓冲液或 50 μL 含有浓度不断增加的未标记坎地沙坦的缓冲液。 30分钟后，加入50μL含有[3H]坎地沙坦（终浓度1.1nM）或[3H]坎地沙坦（终浓度1.0nM）的缓冲液，并将细胞在37℃下进一步孵育30分钟。细胞测定：将 KU-19-19 细胞以每孔 2 × 104 的细胞密度接种到 96 孔板中，并使其生长过夜。然后用不同浓度的坎地沙坦处理细胞不同的时间。通过 Alamar Blue 测定法测定细胞活力，以检查坎地沙坦的细胞毒性和抗增殖作用。在酶标仪中测定每个孔的吸光度值。

在降低神经元损伤、病变体积和小胶质细胞活化方面，坎地沙坦（腹腔注射；1 mg/kg/天；持续 1、3 或 28 dpi）具有神经保护作用，保护 CBF 并改善 TBI 动物模型。经营行为[3]。

Animal/Disease Models: C57BL/6 mice (nineweeks old, male, 22–28 g)[3]
Doses: 1 mg/kg
Route of Administration: ip; 1 mg/kg/day; continuously for 1, 3 or 28 dpi.
Experimental Results: decreased the lesion volume after CCI injury by approximately 50%, diminished the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and decreased the expression of the cytokine TGFß1 while increasing expression of TGFB3 . demonstrated good motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury.

Absorption, Distribution and Excretion
The volume of distribution of candesartan is 0.13 L/kg. Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses. In rats, it has been demonstrated that candesartan crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that candesartan passes across the placental barrier and is distributed in the fetus.
Following administration of candesartan cilexetil, the absolute bioavailability of candesartan was estimated to be 15%. After tablet ingestion, the peak serum concentration (Cmax) is reached after 3 to 4 hours. Food with a high fat content does not affect the bioavailability of candesartan after candesartan cilexetil administration.
Total plasma clearance of candesartan is 0.37 mL/min/kg, with a renal clearance of 0.19 mL/min/kg. When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Following an oral dose of (14)C-labeled candesartan cilexetil, approximately 33% of radioactivity is recovered in urine and approximately 67% in feces. Following an intravenous dose of (14)C-labeled candesartan, approximately 59% of radioactivity is recovered in urine and approximately 36% in feces. Biliary excretion contributes to the elimination of candesartan.
It is not known whether candesartan is excreted in human milk, but candesartan has been shown to be present in rat milk.

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Metabolism / Metabolites
Candesartan cilexetil is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to candesartan, a selective AT1 subtype angiotensin II receptor antagonist. Candesartan is mainly excreted unchanged in urine and feces (via bile). It undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.
Candesartan has known human metabolites that include 3-[[4-[2-[2-[(3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]tetrazol-5-yl]phenyl]phenyl]methyl]-2-ethoxy-1H-benzimidazol-3-ium-4-carboxylic acid and (2S,3S,4S,5R)-6-[2-Ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carbonyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid.

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Biological Half-Life
The elimination half-life of candesartan is approximately 9 hours.

Hepatotoxicity
Candesartan has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: C (Probable cause of rare instances of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Preliminary evidence suggests that candesartan passes poorly into milk and is barely detectable in the plasma of breastfed infants. Use of candesartan is not a reason to discontinue nursing, but use caution in newborn and preterm infants.
◉ 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.

[1]. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66.

[2]. Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors. Brain Res. 2000 Jul 14;871(1):29-38.

[3]. Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice. Neuropsychopharmacology. 2012 Dec;37(13):2817-29.

Candesartan is a benzimidazolecarboxylic acid that is 1H-benzimidazole-7-carboxylic acid substituted by an ethoxy group at position 2 and a ({2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl}methyl) group at position 1. It is a angiotensin receptor antagonist used for the treatment of hypertension. It has a role as an antihypertensive agent, an angiotensin receptor antagonist, an environmental contaminant and a xenobiotic. It is a benzimidazolecarboxylic acid and a biphenylyltetrazole. It is a conjugate acid of a candesartan(2-).
Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is available as a prodrug in the form of [candesartan cilexetil].
Candesartan is an Angiotensin 2 Receptor Blocker. The mechanism of action of candesartan is as an Angiotensin 2 Receptor Antagonist.
Candesartan is an angiotensin II receptor blocker used widely in the therapy of hypertension and heart failure. Candesartan is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury.
Candesartan is a synthetic, benzimidazole-derived angiotensin II receptor antagonist prodrug with antihypertensive activity. Candesartan selectively competes with angiotensin II for the binding of the angiotensin II receptor subtype 1 (AT1) in vascular smooth muscle, blocking angiotensin II-mediated vasoconstriction and inducing vasodilatation. In addition, antagonism of AT1 in the adrenal gland inhibits angiotensin II-stimulated aldosterone synthesis and secretion by the adrenal cortex; sodium and water excretion increase, followed by a reduction in plasma volume and blood pressure.
See also: Candesartan Cilexetil (active moiety of).

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Mechanism of Action
Although these agents /angiotensin II receptor antagonists/ are similar to ACE inhibitors in that they decrease the effects of angiotensin II, rather than decreasing the formation of angiotensin II, drugs antagonize angiotensin II at the type I angiotensin receptor. This allows the drugs to inhibit the vasoconstrictive and aldosterone promoting effects of angiotensin II without interfering with bradykinin degradation, significantly reducing the adverse effects of cough and angioedema seen with ACE inhibitor therapy. ... /Angiotensin II receptor antagonists/
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the ATI receptor than for the AT2 receptor. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.

C24H20N6O3

440.45

440.159

139481-59-7

Candesartan Cilexetil;145040-37-5;Candesartan-d4;1346604-70-3;Candesartan-d5;1189650-58-5

2541

White to off-white solid powder

1.4±0.1 g/cm3

754.8±70.0 °C at 760 mmHg

183-185°C

410.3±35.7 °C

0.0±2.7 mmHg at 25°C

1.719

5.01

118.81

2

7

7

33

660

0

HTQMVQVXFRQIKW-UHFFFAOYSA-N

InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)

2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid

CV11974; CV-11974, CV 11974, Trade names: Blopress, Atacand, Amias, and Ratacand

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: ≥ 2.5 mg/mL (5.68 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 (5.68 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 3 中的溶解度: 30%Propylene glycol, 5%Tween 80, 65% D5W:30 mg/mL

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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。