Afatinib Raw Material Powder CAS 439081-18-2

BIBW 2992 is the first irreversible ErbB series blocker approved. Studies have shown that the ErbB receptor family consists of four members: EGFR(ErbB1), HER2(ErbB2), ErbB3 and ErbB4. However, ErbB family members communicate with other ErbB family members to ensure the normal operation of cells, and abnormal ErbB family signal transduction is the key driving factor for the growth and spread of cancer cells. Afatinib raw material powder has two targets, EGFR and HER2, which can irreversibly block the abnormal information transmission in cells stimulated by the variation of epidermal growth factor receptor (EGFR) and the over-expression of tyrosine kinase of human epidermal receptor 2(HER2), and then permanently close the signal transmission channels on which cancer cells depend, so that cancer cells cannot grow and reproduce, and then delay and treat the development and spread of cancer cells.

What is the pharmacological action of Afatinib Raw Material Powder? 

Afatinib is a potent and irreversible double inhibitor of tyrosine kinase, which is the second representative of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2(HER2). It irreversibly inhibits the activity of this complex kinase by Michaelreaction with the sulfhydryl group of cysteine at the 797th position in EGFR. Afatinib Raw Material Powder was approved by FDA on July 12th, 2013. It is mainly used for the treatment of metastatic non-small cell lung cancer (NSCLC) patients with deletion of exon 19 of tumor epidermal growth factor receptor (EGFR) or mutation of exon 21 (L858R) confirmed by FDA-approved kit. In the field experiment, BIBW 2992 Powder also has a certain effect on advanced breast cancer patients with HEＲ2 positive.

Why is Afatinib raw material powder referred to as a lung cancer killer in medicine?

According to the statistics of the International Health Organization, lung cancer is the top cancer killer in the world. The incidence of lung cancer in men is higher than that in women, and the number of new lung cancer patients reaches more than 10 million every year. In the past, the treatment theory of lung cancer was relatively thin, and it was always thought that lung cancer was caused by a cause. According to the latest research, lung cancer includes many different types, and different types of lung cancer need specific treatment. A specific subtype of lung cancer can be judged by EGFR (a member EGFR(ErbB receptor family) mutation detection. And such patients are also the people who can benefit the most from Tovok powder treatment in clinical trials. According to the data of LUX-Lung3 trial, the survival time of patients who received BIBW-2992 raw material as the first-line treatment reached one year (the median progression-free survival (PFS) was 11.1 months), compared with patients who received Pemetrexed Disodium /Cisplatin for slightly more than half a year (PFS was 6.9 months).
In addition, the progression-free survival time of NSCLC patients with the two most common EGFR mutation types (Del19 or L858R) after receiving high-purity afatinib raw material powder is far more than one year (PFS is 13.6 months), while that of patients receiving Pemetrexed Dinatrium /cisplatin is slightly more than half a year (PFS is 6.9 months). In addition, compared with patients receiving standard chemotherapy regimen, the symptoms of lung cancer and quality of life of patients using Hot sales BIBW-2292 have also been improved. In addition, the side effects of this product are extremely low, and only 1% of patients stopped the experimental process because of the related diarrhea caused by Afatinib products.

Why is Afatinib Raw Material Powder classified as the second generation product of EGFR?

When it comes to EGFR targeted drugs for lung cancer, the first generation product Gefitinib; The second-generation product Afatinib (BIBW 2992) and the third-generation product Osimertinib (AZD-9291) are both shining stars.

However, why do we classify afatinib as the second generation drug of EGFR? According to the relevant scientific literature, there are three generations of EGFR TKI at present, and the researchers differ in the mechanism of drug action except according to the time sequence. The details are as follows:

Generation 1: EGFR mutant protein that inhibits the mainstream (reversible)

Second generation: Inhibit the mainstream EGFR mutant protein (irreversible), and also inhibit EGFR-related proteins.

The third generation: it inhibits the mainstream EGFR mutant protein, and it is still effective (irreversible) against T790M-resistant mutant protein.
Compared with the first generation products, afatinib has two obvious characteristics:
1. It is irreversibly combined with EGFR protein, and once it is combined with mutant protein, it is very strong. We can combine Afatinib Raw Material Powder with mutant protein just like the combination of key and keyhole. The reason why the first generation of drugs can take effect is because they can effectively occupy this keyhole. However, the first-generation drugs are weak in binding force and easy to fall off, while the second-generation drugs have strong binding force with mutant proteins, which becomes a key that will not fall off easily. If they are firmly combined, they may have better and more lasting inhibitory effects in theory.
Secondly, in addition to EGFR protein, BIBW 2992 Raw Material Powder can also inhibit related proteins such as HER2 and HER4, so it can deal with other mutations other than EGFR, that is, a key can be inserted into multiple keyhole, which may also delay the drug resistance of some patients.

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