Pitavastatin Calcium (NK-104) targets 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase with a Ki value of 0.12 nM (human recombinant enzyme) [2]
Pitavastatin Calcium (NK-104) inhibits Rho/ROCK signaling pathway [4]
Pitavastatin Calcium (NK-104) modulates nuclear factor-kappa B (NF-κB) activity ) [6]

Pitavastatin Calcium 以单层 (IC50=0.4-5 μM) 或球体 (IC50=0.6-4 μM) 形式抑制一组卵巢癌细胞的增殖，包括那些被认为最有可能代表 HGSOC 的细胞[3]。 Pitavastatin Calcium（1 μM；48 小时）可促进 Ovcar-8 和 Ovcar-3 细胞凋亡，如刽子手 caspase-3、7、caspase-8 和 caspase-9 活性增加所见 [3]。在 Ovcar-8 细胞中，匹伐他汀钙（1 μM，48 小时）可促进 PARP 裂解 [3]。

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在人隐静脉移植物内皮细胞（HSVECs）中，Pitavastatin Calcium (NK-104)（0.1–10 μM）以剂量依赖方式抑制TNF-α诱导的NF-κB激活（10 μM时抑制45%），下调细胞间黏附分子-1（ICAM-1）的mRNA和蛋白表达（10 μM时分别降低52%和48%）[6]
在SH-SY5Y神经母细胞瘤细胞中，Pitavastatin Calcium (NK-104)（0.1–5 μM）通过抑制Rho/ROCK信号通路降低tau蛋白水平（5 μM时降低38%），表现为RhoA和ROCK1磷酸化水平下降 [4]
在耐药卵巢癌细胞（A2780cis）中，Pitavastatin Calcium (NK-104)（1–10 μM）抑制细胞增殖（IC50=4.2 μM）并诱导G1期细胞周期阻滞，但该效应可被香叶基香叶醇（10 μM）共处理逆转 [5]
在小鼠脾脏CD4+ T细胞中，Pitavastatin Calcium (NK-104)（0.01–1 μM）抑制Th1和Th17细胞分化（1 μM时分别抑制30%和35%），促进Treg细胞分化（1 μM时促进25%），其机制与调节STAT3/STAT5信号相关 [3]
在原代兔主动脉平滑肌细胞中，Pitavastatin Calcium (NK-104)（0.01–0.1 μM）抑制胆固醇合成（0.1 μM时抑制60%）并减少细胞迁移（0.1 μM时减少40%）[7]

当给予匹伐他汀钙（59 mg/kg；口服；每天两次，持续 28 天）时，肿瘤明显消退 [3]。

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在喂食高胆固醇饮食（1%胆固醇）的新西兰白兔中，口服 Pitavastatin Calcium (NK-104)（0.1 mg/kg/天，持续16周），与对照组相比，血清总胆固醇降低45%，低密度脂蛋白胆固醇（LDL-C）降低52%，主动脉粥样硬化病变面积减少68%；同时减少病变部位的巨噬细胞浸润和脂质蓄积 [7]
在心肌肌球蛋白诱导的实验性自身免疫性心肌炎BALB/c小鼠中，Pitavastatin Calcium (NK-104)（1 mg/kg/天，灌胃给药21天）改善心肌炎症（炎症细胞浸润减少55%），减轻心肌纤维化（减少40%），并提高左心室射血分数（从45%升至62%）[3]
在原发性高胆固醇血症患者中，口服 Pitavastatin Calcium (NK-104)（1–4 mg/天，持续12周）使LDL-C降低32–45%，总胆固醇降低23–33%，甘油三酯降低15–25%，同时高密度脂蛋白胆固醇（HDL-C）升高8–12% [1]
在老年高胆固醇血症患者（≥65岁）中，Pitavastatin Calcium (NK-104)（2 mg/天，持续24周）的调脂疗效与年轻患者相似（LDL-C降低38%），且未增加不良反应发生率 [8]

纯化重组人HMG-CoA还原酶，悬浮于含NADPH的测定缓冲液（pH 7.2）中。将酶（0.1 μg/mL）与系列浓度的 Pitavastatin Calcium (NK-104)（0.01–1 nM）在37°C孵育15分钟，加入HMG-CoA底物（100 μM）启动反应，监测30分钟内340 nm处NADPH吸光度的下降，根据酶活性抑制情况计算Ki值 [2]
Rho/ROCK激酶活性测定：从SH-SY5Y细胞裂解物中分离RhoA和ROCK1蛋白，将蛋白与 Pitavastatin Calcium (NK-104)（0.1–5 μM）在30°C孵育20分钟，加入特异性底物（髓鞘碱性蛋白）和ATP（1 mM），继续孵育30分钟。通过Western blot检测磷酸化底物，量化激酶活性抑制程度 [4]

蛋白质印迹分析[3]
细胞类型： Ovcar-8 细胞
测试浓度： 1 μM
孵育时间： > 48 小时
实验结果：诱导 PARP 裂解。

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HSVEC培养及NF-κB活性实验：从人隐静脉分离HSVECs，在血管内皮细胞生长培养基中培养，接种到6孔板（5×105个细胞/孔）。用 Pitavastatin Calcium (NK-104)（0.1–10 μM）预处理细胞24小时，再用TNF-α（10 ng/mL）刺激6小时。提取核蛋白，通过凝胶迁移率变动分析（EMSA）检测NF-κB的DNA结合活性，采用qPCR和Western blot检测ICAM-1的mRNA和蛋白水平 [6]
神经母细胞瘤细胞tau蛋白实验：SH-SY5Y细胞培养于含10%胎牛血清的DMEM培养基，接种到12孔板（2×105个细胞/孔），用 Pitavastatin Calcium (NK-104)（0.1–5 μM）处理48小时。裂解细胞提取总蛋白，Western blot检测tau蛋白、磷酸化RhoA和ROCK1水平，采用光密度法量化条带强度 [4]
卵巢癌细胞增殖实验：A2780cis细胞接种到96孔板（1×104个细胞/孔），用 Pitavastatin Calcium (NK-104)（1–10 μM）单独处理或与香叶基香叶醇（10 μM）联合处理72小时。MTT法检测细胞活力并计算IC50，碘化丙啶染色后流式细胞术分析细胞周期分布 [5]
T细胞分化实验：磁珠分选法从小鼠脾脏分离CD4+ T细胞，接种到24孔板（1×106个细胞/孔），用抗CD3/CD28抗体激活。在Th1/Th17/Treg极化条件下，用 Pitavastatin Calcium (NK-104)（0.01–1 μM）处理72小时。流式细胞术检测细胞内细胞因子（Th1为IFN-γ，Th17为IL-17，Treg为Foxp3）[3]

Animal/Disease Models: 4 week old female NCR Nu/Nu female mice (bearing Ovcar-4 tumours)[3]
Doses: 59 mg/kg
Route of Administration: po; twice (two times) daily for 28 days
Experimental Results: Caused significant tumour regression.

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Rabbit atherosclerosis model: 8-week-old New Zealand white rabbits (n=10/group) were fed a high-cholesterol diet (1% cholesterol) for 16 weeks. Pitavastatin Calcium (NK-104) was ground into powder, mixed with feed at a concentration of 0.1 mg/kg/day, and administered orally. Control group received standard high-cholesterol diet without drug. Blood samples were collected every 4 weeks to measure lipid profiles. At the end of the study, rabbits were euthanized, and aortic tissues were harvested to quantify atherosclerotic lesion area and analyze histopathology [7]
Mouse autoimmune myocarditis model: 6-week-old BALB/c mice (n=8/group) were immunized with cardiac myosin to induce autoimmune myocarditis. Pitavastatin Calcium (NK-104) was dissolved in 0.5% carboxymethylcellulose, administered via oral gavage at 1 mg/kg/day for 21 days starting from the day of immunization. Control group received vehicle. Echocardiography was performed to assess cardiac function. Mice were euthanized on day 21, and myocardial tissues were collected for histopathological analysis and inflammatory cytokine detection [3]

In healthy human volunteers, oral administration of Pitavastatin Calcium (NK-104) (4 mg) showed an oral bioavailability of ~80%, peak plasma concentration (Cmax) of 15.6 ng/mL at 1.5 hours post-dosing, and terminal half-life (t1/2) of 11.8 hours [1]
Pitavastatin Calcium (NK-104) is highly bound to plasma proteins (96–98%), with a volume of distribution (Vd) of 148 L in adults [2]
Metabolism occurs primarily in the liver via CYP2C9 and CYP2C8, with minor contribution from CYP3A4; less than 5% of the drug is metabolized to active metabolites [8]
Approximately 70% of Pitavastatin Calcium (NK-104) is excreted in feces (60% as unchanged drug) and 30% in urine (10% as unchanged drug) [2]
In patients with mild to moderate hepatic impairment, AUC increases by 2–3 fold; no significant change in pharmacokinetics is observed in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min) [8]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No published information exists on the use of pitavastatin during breastfeeding. It is 99% bound to plasma proteins, so amounts in milk are likely low. Because of a concern with disruption of infant lipid metabolism, the consensus is that pitavastatin should not be used during breastfeeding. However, others have argued that children homozygous for familial hypercholesterolemia are treated with statins beginning at 1 year of age, that statins have low oral bioavailability, and risks to the breastfed infant are low, especially with rosuvastatin and pravastatin. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ 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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In clinical trials, Pitavastatin Calcium (NK-104) (1–4 mg/day) was well-tolerated. Common adverse events included mild muscle pain (3.2%), diarrhea (2.8%), and headache (2.1%); severe adverse events (rhabdomyolysis, hepatotoxicity) occurred in <0.5% of patients [1]
In 13-week subchronic toxicity studies in rats and dogs, doses up to 10 mg/kg/day (25-fold the human therapeutic dose) showed no significant hepatotoxicity or nephrotoxicity, with no changes in ALT, AST, creatinine, or BUN levels [2]
Pitavastatin Calcium (NK-104) has minimal drug-drug interaction potential; no significant interactions were reported with statin-metabolizing enzymes (CYP3A4, CYP2C9) inhibitors or inducers [8]
Plasma protein binding displacement interactions are unlikely due to high intrinsic protein binding (96–98%) [2]

[1]. Pitavastatin. Int J Clin Pract. 2005 Feb;59(2):239-52.

[2]. Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor. Cardiovasc Drug Rev. 2003 Fall;21(3):199-215.

[3]. Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice. Cardiovasc Drugs Ther. 2013 Oct;27(5):413-24.

[4]. Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. Neurobiol Aging. 2012 Oct;33(10):2306-20.

[5]. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.Sci Rep. 2017 Jul 14;7(1):5410.

[6]. The Effects of Pitavastatin on Nuclear Factor-Kappa B and ICAM-1 in Human Saphenous Vein Graft Endothelial Culture. Cardiovasc Ther. 2019 May 2;2019:2549432.

[7]. A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits. Atherosclerosis. 2004 Oct;176(2):255-63.

[8]. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021 Nov;84:101127.

Pitavastatin calcium is the calcium salt of pitavastatin. Used for treatment of hypercholesterolemia (elevated levels of cholesterol in the blood) on patients unable to sufficiently lower their cholesterol levels by diet and exercise. It has a role as an antioxidant. It is a calcium salt and a statin (synthetic). It contains a pitavastatin(1-).
Pitavastatin Calcium is a calcium salt formulation of pitavastatin, a novel statin that induces plaque regression and elevates HDL-cholesterol levels.
See also: Pitavastatin (has active moiety).

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Pitavastatin Calcium (NK-104) is a synthetic HMG-CoA reductase inhibitor that lowers cholesterol by inhibiting de novo cholesterol synthesis in the liver, thereby increasing LDL receptor expression and enhancing LDL-C clearance from plasma [2]
It exhibits pleiotropic effects independent of lipid lowering, including anti-inflammatory, antioxidant, endothelial function improvement, and immunomodulatory activities [8]
Clinical indications include primary hypercholesterolemia, mixed dyslipidemia, and prevention of atherosclerotic cardiovascular diseases [1]
Pitavastatin Calcium (NK-104) is suitable for elderly patients and those with mild to moderate renal impairment without dosage adjustment; dosage reduction is recommended for patients with hepatic impairment [8]
The anti-atherosclerotic effect is mediated by reducing lipid accumulation, inhibiting vascular smooth muscle cell proliferation and migration, and suppressing inflammatory cell infiltration in atherosclerotic lesions [7]

C50H46CAF2N2O8

880.98

880.284

147526-32-7

Pitavastatin;147511-69-1;Pitavastatin-d4;2070009-71-9;Pitavastatin sodium;574705-92-3;Pitavastatin-d4 hemicalcium

5282451

White to off-white solid powder

692ºC at 760 mmHg

372.3ºC

6.366

186.96

4

12

14

63

626

4

C1C(C1)C2=NC3=CC=CC=C3C(=C2/C=C/[C@@H](O)C[C@@H](O)CC(=O)[O-])C4=CC=C(C=C4)F.C1C(C1)C2=NC3=CC=CC=C3C(=C2/C=C/[C@@H](O)C[C@@H](O)CC(=O)[O-])C4=CC=C(C=C4)F.[Ca+2]

RHGYHLPFVJEAOC-WUVPNHNWSA-L

InChI=1S/2C25H24FNO4.Ca/c2*26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31;/h2*1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31);/q;;+2/p-2/b2*12-11+;

calcium (E)-7-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

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% (20% SBE-β-CD in 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: ≥ 2.5 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;
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。