| Size | Price | Stock | Qty |
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| 250mg |
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Purity: ≥98%
Pitavastatin calcium (also called NK-104 Calcium; itavastatin or nisvastatin) is a novel and potent drug of the statin class. Pitavastatin Calcium acts as a competitive inhibitor of the enzyme HMGCR (HMG-CoA reductase), resulting in a reduction in LDL cholesterol synthesis. Alternate studies show that pitavastatin can suppress oxygen production in endothelial cells by inhibiting NADPH oxidase. In addition, pitavastatin reduces the expression of eNOS mRNA while increasing the NO dependent response stimulated by acetylcholine and the calcium ionophore, A23187. Furthermore, pitavastatin inhibits the up-regulation of conductance calcium-activated potassium channels by lowering cholesterol levels in cells.
| Targets |
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] |
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| ln Vitro |
Pitavastatin Calcium either as monolayers (IC50=0.4-5 μM) or spheroids (IC50=0.6-4 μM) suppresses the proliferation of a panel of ovarian cancer cells, including those thought to most likely represent HGSOC[3]. Pitavastatin Calcium (1 μM; 48 hours) promotes apoptosis in Ovcar-8 and Ovcar-3 cells as seen by increased activity of executioner caspases-3, 7, and caspase-8 and caspase-9 [3]. In Ovcar-8 cells, pitavastatin Calcium (1 μM, 48 hours) promotes PARP cleavage [3].
In human saphenous vein graft endothelial cells (HSVECs), Pitavastatin Calcium (NK-104) (0.1–10 μM) dose-dependently inhibited TNF-α-induced NF-κB activation (by 45% at 10 μM) and downregulated intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression (by 52% and 48% at 10 μM, respectively) [6] In SH-SY5Y neuroblastoma cells, Pitavastatin Calcium (NK-104) (0.1–5 μM) reduced tau protein levels (by 38% at 5 μM) via inactivation of Rho/ROCK signaling, as demonstrated by decreased phosphorylation of RhoA and ROCK1 [4] In drug-resistant ovarian cancer cells (A2780cis), Pitavastatin Calcium (NK-104) (1–10 μM) inhibited cell proliferation (IC50=4.2 μM) and induced G1 cell cycle arrest, but this effect was reversed by co-treatment with geranylgeraniol (10 μM) [5] In mouse splenic CD4+ T cells, Pitavastatin Calcium (NK-104) (0.01–1 μM) suppressed Th1 and Th17 cell differentiation (by 30% and 35% at 1 μM) and promoted Treg cell differentiation (by 25% at 1 μM) via regulation of STAT3/STAT5 signaling [3] In primary rabbit aortic smooth muscle cells, Pitavastatin Calcium (NK-104) (0.01–0.1 μM) inhibited cholesterol synthesis (by 60% at 0.1 μM) and reduced cell migration (by 40% at 0.1 μM) [7] |
| ln Vivo |
Regression of the tumor was considerable when pitavastatin Calcium (59 mg/kg; oral; twice daily for 28 days) was administered [3].
In New Zealand white rabbits fed a high-cholesterol diet (1% cholesterol), oral administration of Pitavastatin Calcium (NK-104) (0.1 mg/kg/day for 16 weeks) reduced serum total cholesterol by 45%, LDL-cholesterol by 52%, and atherosclerotic lesion area in the aorta by 68% compared to control; it also decreased macrophage infiltration and lipid accumulation in lesions [7] In BALB/c mice with experimental autoimmune myocarditis (induced by cardiac myosin), Pitavastatin Calcium (NK-104) (1 mg/kg/day, oral gavage for 21 days) ameliorated myocardial inflammation (inflammatory cell infiltration reduced by 55%), decreased myocardial fibrosis (by 40%), and improved left ventricular ejection fraction (from 45% to 62%) [3] In patients with primary hypercholesterolemia, oral Pitavastatin Calcium (NK-104) (1–4 mg/day for 12 weeks) reduced LDL-cholesterol by 32–45%, total cholesterol by 23–33%, and triglycerides by 15–25%, while increasing HDL-cholesterol by 8–12% [1] In elderly patients (≥65 years) with hypercholesterolemia, Pitavastatin Calcium (NK-104) (2 mg/day for 24 weeks) showed similar lipid-lowering efficacy (LDL-C reduction by 38%) to younger patients, with no increased adverse events [8] |
| Enzyme Assay |
Purify recombinant human HMG-CoA reductase and suspend it in assay buffer (pH 7.2) containing NADPH. Incubate the enzyme (0.1 μg/mL) with serial dilutions of Pitavastatin Calcium (NK-104) (0.01–1 nM) at 37°C for 15 minutes. Add HMG-CoA substrate (100 μM) to initiate the reaction, and monitor the decrease in NADPH absorbance at 340 nm over 30 minutes. Calculate the Ki value based on the inhibition of enzyme activity [2]
For Rho/ROCK kinase activity assay, isolate RhoA and ROCK1 proteins from SH-SY5Y cell lysates. Incubate the proteins with Pitavastatin Calcium (NK-104) (0.1–5 μM) at 30°C for 20 minutes. Add the specific substrate (myelin basic protein) and ATP (1 mM), and incubate for another 30 minutes. Detect phosphorylated substrate by Western blot to quantify kinase activity inhibition [4] |
| Cell Assay |
Western Blot Analysis[3]
Cell Types: Ovcar-8 cells Tested Concentrations: 1 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced PARP cleavage. HSVEC culture and NF-κB activity assay: Isolate HSVECs from human saphenous veins, culture in endothelial cell growth medium, and seed into 6-well plates (5×105 cells/well). Pretreat cells with Pitavastatin Calcium (NK-104) (0.1–10 μM) for 24 hours, then stimulate with TNF-α (10 ng/mL) for 6 hours. Extract nuclear proteins to measure NF-κB DNA-binding activity by EMSA, and perform qPCR and Western blot to detect ICAM-1 mRNA and protein levels [6] Neuroblastoma cell tau protein assay: Culture SH-SY5Y cells in DMEM medium with 10% FBS, seed into 12-well plates (2×105 cells/well), and treat with Pitavastatin Calcium (NK-104) (0.1–5 μM) for 48 hours. Lyse cells, extract total proteins, and use Western blot to detect tau protein, phosphorylated RhoA, and ROCK1 levels. Quantify band intensities using densitometry [4] Ovarian cancer cell proliferation assay: Seed A2780cis cells into 96-well plates (1×104 cells/well), treat with Pitavastatin Calcium (NK-104) (1–10 μM) alone or combined with geranylgeraniol (10 μM) for 72 hours. Use MTT assay to measure cell viability and calculate IC50. Perform flow cytometry to analyze cell cycle distribution after propidium iodide staining [5] T cell differentiation assay: Isolate CD4+ T cells from mouse spleens using magnetic bead sorting, seed into 24-well plates (1×106 cells/well), and activate with anti-CD3/CD28 antibodies. Treat with Pitavastatin Calcium (NK-104) (0.01–1 μM) for 72 hours under Th1/Th17/Treg-polarizing conditions. Use flow cytometry to detect intracellular cytokines (IFN-γ for Th1, IL-17 for Th17, Foxp3 for Treg) [3] |
| Animal Protocol |
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. 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] |
| ADME/Pharmacokinetics |
In healthy volunteers, oral pitavastatin calcium (NK-104) (4 mg) showed an oral bioavailability of approximately 80%, with a peak plasma concentration (Cmax) of 15.6 ng/mL at 1.5 hours after administration and a terminal half-life (t1/2) of 11.8 hours [1]. Pitavastatin calcium (NK-104) is highly bound to plasma proteins (96-98%), with an adult volume of distribution (Vd) of 148 L [2]. Metabolism is primarily in the liver via CYP2C9 and CYP2C8, with a smaller 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% of which is the original drug) and 30% in urine (10% of which is the original drug) [2]. In patients with mild to moderate hepatic impairment, AUC Increased by 2-3 times; no significant changes in pharmacokinetics were observed in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min) [8]
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation There is currently no publicly available information regarding the use of pitavastatin during lactation. Pitavastatin binds to plasma proteins at a rate as high as 99%, therefore its concentration in breast milk is likely to be very low. Due to concerns that pitavastatin may disrupt lipid metabolism in infants, it is generally believed that pitavastatin should not be used during lactation. However, some argue that children with homozygous familial hypercholesterolemia who have received statin therapy since age 1 have lower oral bioavailability and pose a lower risk to breastfed infants, especially rosuvastatin and pravastatin. Until more data are available, especially during the breastfeeding period for newborns or premature infants, alternative medications may be preferred. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. In clinical trials, pitavastatin calcium (NK-104) (1–4 mg/day) was well tolerated. Common adverse events included mild myalgia (3.2%), diarrhea (2.8%), and headache (2.1%); serious adverse events (rhabdomyolysis, hepatotoxicity) occurred in less than 0.5% of patients [1]. In a 13-week rat and canine subchronic toxicity study, doses up to 10 mg/kg/day (equivalent to 25 times the human treatment dose) did not show significant hepatotoxicity or nephrotoxicity, and ALT, AST, creatinine, or BUN levels did not change [2]. Pitavastatin calcium (NK-104) has minimal drug interaction potential; no significant interactions with statin metabolic enzyme (CYP3A4, CYP2C9) inhibitors or inducers have been reported [8]. Due to its high inherent protein binding (96–98%), plasma protein binding displacement interactions are unlikely to occur [2]. |
| References | |
| Additional Infomation |
Pitavastatin calcium is the calcium salt of pitavastatin. It is used to treat hypercholesterolemia (high cholesterol levels in the blood), especially in patients whose cholesterol levels cannot be adequately reduced by diet and exercise. It has antioxidant properties. It is a calcium salt and a statin (synthetic). It contains pitavastatin (1-).
Pitavastatin calcium is the calcium salt of pitavastatin, a novel statin that induces plaque regression and increases high-density lipoprotein cholesterol (HDL-C) levels. See also: Pitavastatin (with active moiety). 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 the expression of low-density lipoprotein (LDL) receptors and enhancing the clearance of LDL-C from the plasma[2]. It has pleiotropic effects in addition to its lipid-lowering effect, including anti-inflammatory, antioxidant, endothelial function-improving, and immunomodulatory activities[8]. Clinical indications include primary hypercholesterolemia, mixed dyslipidemia, and prevention of atherosclerotic cardiovascular disease[1]. Pitavastatin calcium NK-104 is suitable for elderly patients and patients with mild to moderate renal insufficiency without dose adjustment; dose reduction is recommended for patients with hepatic insufficiency[8]. Its anti-atherosclerotic effect is achieved by reducing lipid accumulation, inhibiting the proliferation and migration of vascular smooth muscle cells, and inhibiting the infiltration of inflammatory cells in atherosclerotic lesions[7]. |
| Molecular Formula |
C50H46CAF2N2O8
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| Molecular Weight |
880.98
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| Exact Mass |
880.284
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| CAS # |
147526-32-7
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| Related CAS # |
Pitavastatin;147511-69-1;Pitavastatin-d4;2070009-71-9;Pitavastatin sodium;574705-92-3;Pitavastatin-d4 hemicalcium
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| PubChem CID |
5282451
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| Appearance |
White to off-white solid powder
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| Boiling Point |
692ºC at 760 mmHg
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| Flash Point |
372.3ºC
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| LogP |
6.366
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
63
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| Complexity |
626
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| Defined Atom Stereocenter Count |
4
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| SMILES |
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]
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| InChi Key |
RHGYHLPFVJEAOC-WUVPNHNWSA-L
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| InChi Code |
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+;
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| Chemical Name |
calcium (E)-7-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1351 mL | 5.6755 mL | 11.3510 mL | |
| 5 mM | 0.2270 mL | 1.1351 mL | 2.2702 mL | |
| 10 mM | 0.1135 mL | 0.5675 mL | 1.1351 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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