Pivanex
(Synonyms: AN-9; Pivalyloxymethyl butyrate) 目录号 : GC68474Pivanex (AN-9) 是丁酸的衍生物，是口服有效的 HDAC 抑制剂。Pivanex 可下调 Bcr-Abl 蛋白，增强凋亡 (Apoptosis)。Pivanex 具有抗转移和抗血管生成的活性
Cas No.:122110-53-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pivanex (AN-9), a derivative of Butyric acid, is an orally active HDAC inhibitor. Pivanex down-regulates Bcr-Abl protein and enhances Apoptosis. Pivanex has antimetastic and antiangiogenic properties[1].
Pivanex (100-500 μM) exhibits significant anti-proliferation activity in K562 cells[1].
Pivanex (100-500 μM) also enhances apoptosis and caspase activity in K562 cells[1].
Pivanex (200 μM) induces enhancement in the G2-M phase, a moderate enhancement in the S phase and a slight reduction in G0-G1 of the cell cycle[1].
Pivanex (AN-9) has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines[2].
Cell Viability Assay[1]
| Cell Line: | K562 cells. |
| Concentration: | 100-500 μM. |
| Incubation Time: | 24 hours. |
| Result: | Reduced the number of K562 viable cells significantly. 100 μM Pivanex with 0.125 or 0.25 μM STI571 reduced the number of viable cells synergistically. |
Apoptosis Analysis[1]
| Cell Line: | K562 cells. |
| Concentration: | 100-500 μM. |
| Incubation Time: | 6-72 hours. |
| Result: | Increased the number of K562 apoptotic cells significantly. Increased the caspase activity in K562 cells significantly after only 4 h of incubation with 500 μM. |
Pivanex (AN9, 200 mg/kg, b.i.d, daily) significantly improves the survival of SMN7 SMA mice. Pivanex (AN9) treatment also marked delays the end stage of disease as defined by the onset of body mass loss[3].
| Animal Model: | SMN7 SMA mice (SMN2+/+; SMN7+/+; mSmn-/-)[3]. |
| Dosage: | 200 mg/kg. |
| Administration: | Oral administration, b.i.d, at 09.00 and 17.00 daily. |
| Result: | Improved the mean lifespan of treated SMN7 SMA mice by 84.6%. Delayed the onset of body mass loss in SMN7 SMA mice by 94.9%. |
[1]. Rabizadeh E, et al. Pivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line. Leuk Res. 2007 Aug;31(8):1115-23. Epub 2007 Jan 30.
[2]. Batova A, et al. The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. Blood. 2002 Nov 1;100(9):3319-24.
[3]. Edwards JD, et al. Effect of the Butyrate Prodrug Pivaloyloxymethyl Butyrate (AN9) on a Mouse Model for Spinal Muscular Atrophy. J Neuromuscul Dis. 2016 Nov 29;3(4):511-515.
| Cas No. | 122110-53-6 | SDF | Download SDF |
| 别名 | AN-9; Pivalyloxymethyl butyrate | ||
| 分子式 | C10H18O4 | 分子量 | 202.25 |
| 溶解度 | DMSO : ≥ 100 mg/mL (494.44 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.9444 mL | 24.7219 mL | 49.4438 mL |
| 5 mM | 0.9889 mL | 4.9444 mL | 9.8888 mL |
| 10 mM | 0.4944 mL | 2.4722 mL | 4.9444 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line
Leuk Res 2007 Aug;31(8):1115-23.PMID:17267032DOI:10.1016/j.leukres.2006.12.015.
Chronic myelogenous leukemia (CML) is associated with the high TK activity chimeric protein BCR-ABL, known to contribute to cell tumorogenicity, resistance to apoptosis and differentiation. STI571, the TK inhibitor, is the current treatment for CML. One possible approach to overcome STI571 resistance appearing in some cases, involves the combination of histone deacetylase inhibitors (HDI) and STI571. We demonstrated that in K562, the CML cell line, pivaloyloxymethyl butyrate (Pivanex)-induced apoptosis, differentiation and reduced BCR-ABL protein levels and that the combination of Pivanex with STI571 acted synergistically. These data suggest the possible benefit of combining this HDI with STI571 for treatment of CML.
Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer
Lung Cancer 2004 Sep;45(3):381-6.PMID:15301879DOI:10.1016/j.lungcan.2004.03.002.
This multicenter phase II trial evaluated the therapeutic activity and safety profile of pivaloyloxymethyl butyrate (Pivanex, AN-9) as a single agent in refractory non-small cell lung cancer (NSCLC). Pivanex (2.34 g/m2 per day) was administered as a 6-h continuous intravenous infusion, daily for 3 days, and repeated every 21 days until disease progression. Forty-seven patients were treated. More than 90% of patients had received both a platinum compound and a taxane and 32% had received three or more prior chemotherapy regimens. The most common toxicities were transient grade 1-2 fatigue (34%), nausea (17%), and dysgeusia (11%). Three patients had partial responses (6.4 and 95%; CI 1.4-18.7%) and 14 patients had stable disease for > or =12 weeks (30%). Median survival for all patients was 6.2 months with 1-year survival of 26%. For patients who received fewer than three prior chemotherapy regimens, median survival was 7.8 months and 1-year survival was 31%. Pivanex is well tolerated and appears to be active as a single agent in patients with advanced NSCLC refractory to previous chemotherapy. Based on its therapeutic activity and favorable safety profile, further studies of Pivanex in NSCLC, particularly in combination with current chemotherapeutic agents, are warranted.
The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer
Crit Rev Oncol Hematol 2008 Oct;68(1):29-36.PMID:18424067DOI:10.1016/j.critrevonc.2008.03.002.
Non-small-cell lung cancer (NSCLC) arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastases. The exponential growth in the level of research about the histone deacetylase (HDAC) enzymes, responsible for deacetylating core nucleosomal histones and other proteins, has been driven by the ability of HDAC inhibitors to modulate transcriptional activity. As a result, this therapeutic class is able to block angiogenesis and cell cycling, and promote apoptosis and differentiation. The mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known. Clinical experience indicates these agents generally well tolerated, and active in several haematological and solid tumours. HDAC inhibitors, under clinical evaluation in the treatment of NSCLC patients, are Pivanex, CI-994, vorinostat, and LBH589. Here, we discuss about the potential role of HDAC inhibitors focusing on their activity, tolerability, efficacy and future development, in the treatment of NSCLC.
Histone deacetylase inhibitors: the anticancer, antimetastatic and antiangiogenic activities of AN-7 are superior to those of the clinically tested AN-9 (Pivanex)
Clin Exp Metastasis 2008;25(7):703-16.PMID:18506586DOI:10.1007/s10585-008-9179-x.
Histone deacetylase inhibitory prodrugs that are metabolized to butyric acid and formaldehyde possess antineoplastic properties and low toxicity. We sought to characterize the antiangiogenic and antimetastatic activities of two lead prodrugs, pivaloyloxymethyl butyrate (AN-9) and butyroyloxymethyl-diethyl phosphate (AN-7) in murine cancer models. In the sc implanted human colon carcinoma HT-29 xenograft model AN-7, exhibited superior anticancer activity compared to AN-9, as was evident by the significantly greater inhibition of tumor growth and reduction of serum CEA. AN-7 was also more effective in reducing mean vessel density (MVD) by 7-fold, bFGF, Ki-67 (7-fold) and HIF-1alpha in immunohistochemically stained tumor sections. Semi-quantitative evaluation of the levels of bFGF, HDAC1 and HIF-1alpha by Western blot analysis showed a decrease in expression only in the tumors of mice treated with AN-7. The level of bFGF was reduced 3-fold in the tumor and that of TIMP1 was elevated (by 3-fold) in the serum of AN-7 treated mice. In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha. Yet, AN-7 was more potent than AN-9.