Developing protein arginine methyltransferase 1 (PRMT1) inhibitor TC-E-5003 as an antitumor drug using INEI drug delivery systems

Autor: Lixiao Zhou, Liyang Yu, Pengcheng Zhang, Chenggang Zhu, He Tao
Rok vydání: 2020
Předmět:
Drug
Male
Protein-Arginine N-Methyltransferases
Lung Neoplasms
media_common.quotation_subject
intratumoral chemotherapy
Pharmaceutical Science
Mice
Nude
Antineoplastic Agents
Breast Neoplasms
Oleic Acids
02 engineering and technology
RM1-950
Pharmacology
Intratumoral chemotherapy
030226 pharmacology & pharmacy
Rats
Sprague-Dawley
03 medical and health sciences
Inhibitory Concentration 50
Mice
inei
0302 clinical medicine
Drug Delivery Systems
Cell Line
Tumor
tc-e-5003
Medicine
Animals
Humans
nbca
media_common
Mice
Inbred ICR
Protein-arginine methyltransferase
business.industry
General Medicine
Enbucrilate
021001 nanoscience & nanotechnology
Xenograft Model Antitumor Assays
Rats
Repressor Proteins
Drug delivery
Female
Chemotherapeutic drugs
Therapeutics. Pharmacology
0210 nano-technology
business
new anti-tumor drugs
Research Article
Zdroj: Drug Delivery, Vol 27, Iss 1, Pp 491-501 (2020)
Drug Delivery
DOI: 10.6084/m9.figshare.12033798.v1
Popis: Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N′-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The in vitro experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC50 = 0.7022 µM for A549; IC50 = 0.6844 µM for NCL-H1299) and breast cancer (IC50 = 0.4128 µM for MCF-7; IC50 = 0.5965 µM for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.
Databáze: OpenAIRE
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