Mefuparib hydrochloride
(Synonyms: MPH) 目录号 : GC62252
Mefuparib hydrochloride (MPH) 是一种具有口服活性的，底物竞争性和选择性的 PARP1/2 抑制剂，IC50 分别为 3.2 nM 和 1.9 nM。Mefuparib hydrochloride 诱导细胞凋亡 (apoptosis)，并在体内外具有显着的抗癌活性。
Cas No.:1449746-00-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Mefuparib hydrochloride (MPH) is an orally active, substrate-competitive and selective PARP1/2 inhibitor with IC50s of 3.2 nM and 1.9 nM, respectively. Mefuparib hydrochloride induces apoptosis and possesses prominent anticancer activity in vitro and in vivo[1][2].
Mefuparib hydrochloride (1-10 μM; 48 hours) causes cell apoptosis[1]. Mefuparib hydrochloride (MPH; 1-10 μM; 24 hours) causes V-C8 cells into typical G2/M arrest[1]. Mefuparib hydrochloride (1-10 μM; 24 hours) causes the accumulation of DSB marked by the increased levels of γH2AX in the MDA-MB-436 (BRCA1-/-) cells in a concentration-dependent manner[1]. Mefuparib hydrochloride exerts potent in vitro proliferation-inhibitory effects on cancer cells derived from different human tissues with an average IC50 of 2.16 μM (0.12 μM~3.64 μM)[1]. Mefuparib hydrochloride inhibits PARP3 (IC50>10 μM), PARP6 (IC50>10 μM), TNKS1 (IC50=1.6 μM), TNKS2 (IC50=1.3 μM)[1].
Mefuparib hydrochloride (MPH; 40-160 mg/kg; orally; once every other day; for 21 days) displays dose- and time-dependent killing on V-C8 xenografts accompanied by complete disappearance of some xenografts, especially in the high-dose group[1]. Mefuparib hydrochloride (160 mg/kg; orally; once every other day; for 21 days) inhibits the growth of the BR-05-0028 breast patient-derived xenograft (PDX) without obvious loss of body weight[1]. Mefuparib hydrochloride (10, 20, 40 mg/kg; oral) has a T1/2 of 1.07-1.3 hours and a C max of 116-725 ng/mL for SD rats[1]. Mefuparib hydrochloride (5, 10, 20 mg/kg; oral) has a T1/2 of 2.16-2.7 hours and a C max of 114-608 ng/mL for cynomolgus monkeys[1].
[1]. He JX, et al. Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution. Oncotarget. 2017 Jan 17;8(3):4156-4168.
[2]. Nie D, et al. Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy. Nano Lett. 2020 Feb 12;20(2):936-946.
| Cas No. | 1449746-00-2 | SDF | |
| 别名 | MPH | ||
| 分子式 | C17H16ClFN2O2 | 分子量 | 334.77 |
| 溶解度 | 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 | 2.9871 mL | 14.9356 mL | 29.8713 mL |
| 5 mM | 0.5974 mL | 2.9871 mL | 5.9743 mL |
| 10 mM | 0.2987 mL | 1.4936 mL | 2.9871 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。
Covid-19 and Artificial Intelligence: Genome sequencing, drug development and vaccine discovery
J Infect Public Health 2022 Feb;15(2):289-296.PMID:35078755DOI:10.1016/j.jiph.2022.01.011.
Objectives: To clarify the work done by using AI for identifying the genomic sequences, development of drugs and vaccines for COVID-19 and to recognize the advantages and challenges of using such technology. Methods: A non-systematic review was done. All articles published on Pub-Med, Medline, Google, and Google Scholar on AI or digital health regarding genomic sequencing, drug development, and vaccines of COVID-19 were scrutinized and summarized. Results: The sequence of SARS- CoV-2 was identified with the help of AI. It can help also in the prompt identification of variants of concern (VOC) as delta strains and Omicron. Furthermore, there are many drugs applied with the help of AI. These drugs included Atazanavir, Remdesivir, Efavirenz, Ritonavir, and Dolutegravir, PARP1 inhibitors (Olaparib and CVL218 which is Mefuparib hydrochloride), Abacavir, Roflumilast, Almitrine, and Mesylate. Many vaccines were developed utilizing the new technology of bioinformatics, databases, immune-informatics, machine learning, and reverse vaccinology to the whole SARS-CoV-2 proteomes or the structural proteins. Examples of these vaccines are the messenger RNA and viral vector vaccines. AI provides cost-saving and agility. However, the challenges of its usage are the difficulty of collecting data, the internal and external validation, ethical consideration, therapeutic effect, and the time needed for clinical trials after drug approval. Moreover, there is a common problem in the deep learning (DL) model which is the shortage of interpretability. Conclusion: The growth of AI techniques in health care opened a broad gate for discovering the genomic sequences of the COVID-19 virus and the VOC. AI helps also in the development of vaccines and drugs (including drug repurposing) to obtain potential preventive and therapeutic agents for controlling the COVID-19 pandemic.
Novel PARP1/2 inhibitor Mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution
Oncotarget 2017 Jan 17;8(3):4156-4168.PMID:27926532DOI:10.18632/oncotarget.13749.
The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that Mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity. Notably, MPH displayed high water solubility (> 35 mg/ml) and potent PARP1/2 inhibition in a substrate-competitive manner. It reduced poly(ADP-ribose) (PAR) formation, enhanced γH2AX levels, induced G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells. Proof-of-concept studies confirmed the MPH-caused synthetic lethality. MPH showed potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide. A good relationship between the anticancer activity and the PARP inhibition of MPH suggested that PAR formation and γH2AX accumulation could serve as its pharmacodynamic biomarkers. Its high bioavailability (40%~100%) and high tissue distribution in both monkeys and rats were its most important pharmacokinetic features. Its average concentrations were 33-fold higher in the tissues than in the plasma in rats. Our work supports the further clinical development of MPH as a novel PARP1/2 inhibitor for cancer therapy.
Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy
Nano Lett 2020 Feb 12;20(2):936-946.PMID:31671946DOI:10.1021/acs.nanolett.9b03817.
Despite rapid advancements in antitumor drug delivery, insufficient intracellular transport and subcellular drug accumulation are still issues to be addressed. Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) have shown promising potential in tumor therapy due to their immune escape and homotypic binding capacities. However, their efficacy is still limited due to inefficient tumor penetration and compromised intracellular transportation. Herein, a yolk-shell NP with a mesoporous silica nanoparticle (MSN)-supported PEGylated liposome yolk and CCM coating, CCM@LM, was developed for chemotherapy and exhibited a homologous tumor-targeting effect. The yolk-shell structure endowed CCM@LM with moderate rigidity, which might contribute to the frequent transformation into an ellipsoidal shape during infiltration, leading to facilitated penetration throughout multicellular spheroids in vitro (up to a 23.3-fold increase compared to the penetration of membrane vesicles). CCM@LM also exhibited a cellular invasion profile mimicking an enveloped virus invasion profile. CCM@LM was directly internalized by membrane fusion, and the PEGylated yolk (LM) was subsequently released into the cytosol, indicating the execution of an internalization pathway similar to that of an enveloped virus. The incoming PEGylated LM further underwent efficient trafficking throughout the cytoskeletal filament network, leading to enhanced perinuclear aggregation. Ultimately, CCM@LM, which co-encapsulated low-dose doxorubicin and the poly(ADP-ribose) polymerase inhibitor, Mefuparib hydrochloride, exhibited a significantly stronger antitumor effect than the first-line chemotherapeutic drug Doxil. Our findings highlight that NPs that can undergo facilitated tumor penetration and robust intracellular trafficking have a promising future in cancer chemotherapy.