Zinc protoporphyrin IX
(Synonyms: 锌原卟啉,ZnPPIX) 目录号 : GC11208
A heme oxygenase inhibitor
Cas No.:15442-64-5
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Human ovarian carcinoma (MDAH2774), human pancreatic adenocarcinoma (Mia PaCa2), human breast carcinoma (MDA-MB231), murine breast carcinoma (EMT6) cell lines. |
|
Preparation Method |
Tumor cells were dispensed into 96-well plates at a concentration of 5×103 cells per well and allowed to attach overnight. The following day investigated agents were added at indicated concentrations. Cells were kept in dark for 48 or 72 h. After the incubation time the cells were rinsed with PBS and stained with 0.5% crystal violet in 2% ethanol for 10 min at room temperature. Plates were washed four times with tap water and the cells were lysed with 1% SDS solution. Absorbance was measured at 595 nm using an enzyme-linked immunosorbent assay reader, equipped with a 595 nm filter. |
|
Reaction Conditions |
0-40 µM for 48, 72 hours |
|
Applications |
Incubation of C-26 cells with Zinc protoporphyrin IX for 48 or 72 h resulted in dose- and time-dependent reduction of cells in G1 phase of the cell cycle. |
| Animal experiment [2]: | |
|
Animal models |
Adult CD1 mice (male, 25-35 g) |
|
Preparation Method |
For assessment of antitumor activity of Zinc protoporphyrin IX in vivo, exponentially growing C-26 were harvested, re-suspended in PBS medium to the appropriate concentration, and injected at the dose of 1×105 cells per mouse into the footpad of the right hind limb of experimental mice. Tumor cell viability measured by trypan blue exclusion was always above 95%. For in vivo treatment Zinc protoporphyrin IX was dissolved in DMSO and further diluted in 0.9% NaCl to required concentrations. Final DMSO concentration was always less then 0.1%. Zinc protoporphyrin IX was distributed intraperitoneally at doses from 12.5 to 50 mg per kg of body weight or orally at doses from 11 to 22 mg per kg of body weight. Control animals received 0.1% DMSO solution in 0.9% NaCl i.p. or orally. |
|
Dosage form |
12.5 to 50 mg/kg i.p. for 7 days; 11 to 22 mg/kg oral for 7 days |
|
Applications |
HO-1 inhibitor was administered either intraperitoneally (i.p.) or per os and the tumor volume was monitored every second day, starting from day 7 after inoculation of tumor cells. Zinc protoporphyrin IX exerted dose-dependent antitumor effects manifested by the retardation of tumor growth. A statistical significance was reached on days 17 and 19 for Zinc protoporphyrin IX administered at a dose of 25 mg/kg either i.p. or orally. A stronger effect was observed when Zinc protoporphyrin IX was administered i.p. at a dose of 50 mg/kg, where a statistically significant retardation of tumor growth was observed on days 13-19, as compared with controls . |
|
References: [1]: Nowis D, Bugajski M, Winiarska M, et al. Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice[J]. BMC cancer, 2008, 8(1): 1-12. |
|
Zinc protoporphyrin IX (ZnPP) is a member of metalloporphyrins in which the heme iron is replaced by zinc, which becomes a competitive inhibitor of heme oxygenase 1 (HO-1) [1].
Zinc protoporphyrin IX tested presented anti-vesicular stomatitis virus (VSV) activity without photoactivation, with the reduction in viral titer being about 10-fold for 1 μM Zinc protoporphyrin. At 5 μM, Zinc protoporphyrin IX tested were able to completely abolish VSV infectivity. Photoactivation of the porphyrins significantly enhanced their antiviral activities, with 0.1 μM ZnPPIX completely abolishing VSV infectivity [2]. Zinc protoporphyrin IX (ZnPP) (5 μM; 72 hours) causes the fraction of late apoptotic and necrotic cells increasing from 10.9% in controls to 30.4% after 72 h in C-26 cells[3]. Zinc protoporphyrin IX (1.25-40 μM; 48 or 72 hours) exerts cystostatic/cytotoxic effects against human ovarian carcinoma (MDAH2774), human pancreatic adenocarcinoma (Mia PaCa2), human breast carcinoma (MDA-MB231), murine breast carcinoma (EMT6) cell lines [3].
Zinc Protoporphyrin IX (12.5, 25, 50 mg/kg for i.p.; 12.5, 50 mg/kg for p.o. for 7days) exerts dose-dependent antitumor effects manifested by the retardation of tumor growth in BALB/c mice inoculated with C-26 cells [3]. Zinc Protoporphyrin IX (5 and 20 μg/mouse) dose-dependently inhibited tumor growth in LL/2-tumor model mice. Vascular endothealial growth factor concentration in tumors was reduced by Zinc Protoporphyrin IX [4].
References:
[1]. Fang J, Greish K, Qin H, et al. HSP32 (HO-1) inhibitor, copoly (styrene-maleic acid)-zinc protoporphyrin IX, a water-soluble micelle as anticancer agent: In vitro and in vivo anticancer effect[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2012, 81(3): 540-547.
[2]. Cruz-Oliveira C, Almeida A F, Freire J M, et al. Mechanisms of vesicular stomatitis virus inactivation by protoporphyrin IX, zinc-protoporphyrin IX, and mesoporphyrin IX[J]. Antimicrobial agents and chemotherapy, 2017, 61(6): e00053-17.
[3]. Nowis D, Bugajski M, Winiarska M, et al. Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice[J]. BMC cancer, 2008, 8(1): 1-12.
[4]. Hirai K, Sasahira T, Ohmori H, et al. Inhibition of heme oxygenase‐1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice[J]. International Journal of Cancer, 2007, 120(3): 500-505.
锌原卟啉 IX (ZnPP) 是金属卟啉中的一员，其中血红素铁被锌取代，成为血红素加氧酶 1 (HO-1) 的竞争性抑制剂[1]。< /p>\n
经过测试的锌原卟啉 IX 具有抗水疱性口炎病毒 (VSV) 活性，无需光活化，对于 1 μM 原卟啉锌，病毒滴度降低约 10 倍。在 5 μM 时，经过测试的锌原卟啉 IX 能够完全消除 VSV 感染性。卟啉的光活化显着增强了它们的抗病毒活性，0.1 μM ZnPPIX 完全消除了 VSV 感染性[2]。锌原卟啉 IX (ZnPP)（5 μM；72 小时）导致晚期凋亡和坏死细胞的比例从对照中的 10.9% 增加到 72 小时后 C-26 细胞中的 30.4%[3]。锌原卟啉 IX（1.25-40 μM；48 或 72 小时）对人卵巢癌 (MDAH2774)、人胰腺癌 (Mia PaCa2)、人乳腺癌 (MDA-MB231)、鼠类乳腺癌 (EMT6) 具有抑囊/细胞毒性作用细胞系[3].
锌原卟啉 IX（腹腔注射 12.5、25、50 mg/kg；口服 12.5、50 mg/kg，持续 7 天）在接种 C 的 BALB/c 小鼠中发挥剂量依赖性抗肿瘤作用，表现为肿瘤生长迟缓-26 个细胞 [3]。锌原卟啉 IX（5 和 20 μg/小鼠）剂量依赖性地抑制 LL/2 肿瘤模型小鼠的肿瘤生长。 Zinc Protoporphyrin IX降低了肿瘤中血管内皮生长因子的浓度[4]。
| Cas No. | 15442-64-5 | SDF | |
| 别名 | 锌原卟啉,ZnPPIX | ||
| 化学名 | zinc;3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoic acid | ||
| Canonical SMILES | OC(CCC1=C(C)/C([N-]/C1=C\2)=C/C(C(C)=C/3C=C)=NC3=C/C4=N/C(C(C=C)=C4C)=C\C5=C(C)C(CCC(O)=O)=C2[N-]5)=O.[Zn+2] | ||
| 分子式 | C34H32N4O4Zn | 分子量 | 626.03 |
| 溶解度 | DMF: 14 mg/ml,DMSO: 25 mg/ml,DMSO:PBS(pH 7.2) (1:2): 0.3 mg/ml | 储存条件 | Store at -20°C, sealed storage, away from moisture |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5974 mL | 7.9868 mL | 15.9737 mL |
| 5 mM | 0.3195 mL | 1.5974 mL | 3.1947 mL |
| 10 mM | 0.1597 mL | 0.7987 mL | 1.5974 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。
Production of zinc protoporphyrin IX by metabolically engineered Escherichia coli
Biotechnol Bioeng2022 Nov;119(11):3319-3325.PMID: 35882952DOI: 10.1002/bit.28195
Zinc protoporphyrin IX (ZnPPIX) has been considered as a promising red colorant for food industries as well as an anticancer drug. However, bio-based production of ZnPPIX from a renewable carbon source has not been reported yet. In this study, a fermentation process of the metabolically engineered Escherichia coli HAEM7 strain was optimized for the high-level production of ZnPPIX. To repurpose the HAEM7 strain that was originally developed for the production of heme into a producer of ZnPPIX, the concentrations of iron and zinc in the culture medium were rebalanced. Next, the concentration of zinc in the feeding solution was optimized to improve ZnPPIX production. Moreover, the pH control strategy, induction point, and the strategy of increasing the cell density, which were optimized in the accompanying paper for the high-level production of heme, were applied together. In the optimized fermentation process, the HAEM7 strain produced 2.2 g/L ZnPPIX with a productivity of 39.9 mg/L/h. The fermentation process and strategies reported here will expedite establishing industry-level production of ZnPPIX.
Zinc protoporphyrin IX predominantly exists as a complex non-enzymatically bound to apo-hemoglobin in Parma ham
Food Chem2022 Nov 30;395:133604.PMID: 35802968DOI: 10.1016/j.foodchem.2022.133604
Most of the water-soluble zinc protoporphyrin IX (ZnPP) in Parma ham mainly exists as complexes with hemoglobin and myoglobin (ZnPP-Hb and ZnPP-Mb). To elucidate the formation mechanism of these complexes, a new experimental model to produce higher amount of water-soluble ZnPP complexes was established. ZnPP-Hb was detected as the main water-soluble ZnPP complex in this model, which is the same as that in Parma ham. Adding exogenous Hb into this model promoted higher ZnPP formation than with Mb added, indicating that Hb was the superior substrate for generating ZnPP compared to Mb. The increase in non-heme iron content with ZnPP formation in both the Hb- and Mb-added groups indicated that the release of iron ion from heme was a crucial step in ZnPP formation. ZnPP-Hb was formed when ZnPP non-enzymatically bound with apo-Hb. These results revealed the mechanism of why ZnPP-Hb is more dominant in Parma ham than to ZnPP-Mb.
Design and synthesis of zinc protoporphyrin IX-adamantane/cyclodextrin/cellulose nanocrystals complexes for anticancer photodynamic therapy
Bioorg Med Chem Lett2021 Jun 1;41:128024.PMID: 33845130DOI: 10.1016/j.bmcl.2021.128024
Two protoporphyrin IX (PpIX) adamantane derivatives were synthesized and then metallated with zinc. The Zn-PpIX derivatives, exhibiting a high singlet oxygen quantum yield, were tested for their photodynamic activity against the HT-29 cell line. In order to enhance their water-solubility and their cellular bioavailability, these photosensitizers were encapsulated into the hydrophobic cavity of cyclodextrins (CD) previously attached to cellulose nanocrystals (CNCs) via electrostatic interactions. Under illumination, the encapsulated adamantanyl-porphyrins exerted an enhanced in vitro cytotoxicity, as compared with the corresponding free photosensitizers.
Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death
Oncotarget2015 Sep 15;6(27):24393-403.PMID: 26405158DOI: 10.18632/oncotarget.5162
The oncogenic RAS-selective lethal small molecule Erastin triggers a unique iron-dependent form of nonapoptotic cell death termed ferroptosis. Ferroptosis is dependent upon the production of intracellular iron-dependent reactive oxygen species (ROS), but not other metals. However, key regulators remain unknown. The heme oxygenase (HO) is a major intracellular source of iron. In this study, the role of heme oxygenase in Erastin-triggered ferroptotic cancer cell death has been investigated. Zinc protoporphyrin IX (ZnPP), a HO-1 inhibitor, prevented Erastin-triggered ferroptotic cancer cell death. Furthermore, Erastin induced the protein and mRNA levels of HO-1 in HT-1080 fibrosarcoma cells. HO-1+/+ and HO-1-/- fibroblast, HO-1 overexpression, and chycloheximide-treated experiments revealed that the expression of HO-1 has a decisive effects in Erastin-triggered cell death. Hemin and CO-releasing molecules (CORM) promote Erastin-induced ferroptotic cell death, not by biliverdin and bilirubin. In addition, hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death.
Evidence of the mechanism underlying zinc protoporphyrin IX formation in nitrite/nitrate-free dry-cured Parma ham
Meat Sci2022 Oct;192:108905.PMID: 35842957DOI: 10.1016/j.meatsci.2022.108905
A large amount of zinc protoporphyrin IX (ZnPP) is found in nitrite/nitrate-free dry-cured meat products, such as Parma ham, and is known to contribute to the favorable bright red color of the latter. ZnPP is a metalloporphyrin, in which zinc is coordinated, instead of iron, in the porphyrin ring. ZnPP proved to be more stable than heme, and its formation should be favored in dried meat products to improve color without the addition of nitrites or nitrates. Toward that, understanding the mechanisms of formation of ZnPP in nitrite/nitrate-free dry-cured ham would be important. In this lecture, I introduce some of our research group's findings regarding the endogenous and exogenous factors contributing to the formation and distribution of ZnPP in Parma ham and why ZnPP formation is suppressed in common cured meat products.