Publication of preclinical research results of ivetinib, a new anti lung cancer drug

Hangzhou, September 14, 2016 / Meitong news agency / -- recently, the preclinical research results of ivetinib (ac0010), the first third representative skin growth factor receptor (EGFR) inhibitor in China, independently developed by Essen Pharmaceutical Research Co., Ltd., were published in the American mainstream cancer journal molecular cancer therapeutics This paper describes in detail the preclinical research process of ivetinib as a new generation of EGFR inhibitors and the preliminary results of the first human clinical trial In this paper, the chemical structure of avidini and the molecular structure design, screening, optimization process and principle of T790M, a drug-resistant gene mutation of lung cancer, were first disclosed A series of molecular cell biological methods and animal models were used to demonstrate the unique advantages of molecular structure design and the potential of the drug Through systematic preclinical research, avetinib with unique chemical structure embodies three important anti lung cancer pharmacological characteristics that the first and second generation EGFR inhibitors do not possess: 1 Highly selective inhibition of EGFR mutation gene leads to lung cancer, while it has no effect on normal EGFR with physiological function, and its selection advantage is as high as 300 times So the side effects of ivetinib are very small 2 To overcome the drug resistance mutation of EGFR gene in lung cancer, effectively inhibit the growth of drug-resistant lung cancer cells, so as to overcome the drug resistance of lung cancer 3 Irreversible inhibition of EGFR gene mutation in lung cancer can permanently block the carcinogenic pathway of EGFR gene mutation, which has better therapeutic effect At the same time, the paper also published the preliminary clinical results of ivetinib In patients with advanced lung cancer, ivetinib also showed the characteristics and advantages obtained in cell level and animal research Industry insiders said that the preclinical and preclinical clinical research results published by ivetinib in molecular cancer therapeutics showed the innovative research process of ivetinib and its characteristics of safety, low toxicity and excellent effect At present, ivetinib is carrying out phase II / III clinical research in China and phase I clinical research in the United States, which is progressing smoothly Ac0010 is a pyrologyrimidine ba sed environmental growth factor receiver (EGFR) inhibitor, structurally distinct from previously reported pyrimidine-ba sed irreversible EGFR inhibitors such as osimertinib and rociletinib.AC0010 selectively inhibits EGFR active and T790M mutations with up to 298-fold increase in potency compared to wild-type EGFR.In a xenografte model, oral administration of AC0010 at daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR active and T790M mutations for over 143 days with no weight loss.Three major me tabolites of AC0010 were tested and showed no wild-type EGFR inhibition and off-target effects such as inhibition of IGF-1R.AC0010 is safe in non-small cell lung Cancer (NSCLC) patients at the dose range between 50 mg and 550 mg o nce per day and no hyperglycemia and other severe adverse effects were detected such as grade 3 QT promotion The objective respo nses were observed in NSCLC patients with EGFR T790M education http://mct.aacrjournals.org/content/early/2016/08/27/1535-7163.MCT-16-0281