Maytansine-the alloy warhead from non-medicinal to ADC!

Subsequently, in April 2014, Trastuzumab Emtansine was approved for marketing in Japan for the treatment of HER2-positive inoperable or recurrent breast cancer patients; in May 2019, the FDA approved Trastuzumab Emtansine for the adjuvant treatment of HER2-positive early breast cancer; In December 2019, EMA approved the drug for the adjuvant treatment of HER2-positive early breast cancer, patients with residual invasive disease in the breast and/or lymph nodes after receiving neoadjuvant therapy based on taxanes and HER2-targeted therapy; 2020 In August, Japan approved an application for adjuvant treatment of HER2-positive early breast cancer
.

In terms of global sales, this product has been on the market since 2013 and will exceed 1 billion U.
S.
dollars in 2018 and 1.
8 billion U.
S.
dollars in 2020.
It is estimated that the sales in the next five years will be between 2.
2 and 3 billion U.
S.
dollars
.

Based on the clinical performance and market performance of Trastuzumab Emtansine with the above-mentioned maytansine as the warhead, a number of maytansine ADC drugs have entered clinical phase II/III, and the warhead is still concentrated in DM1/DM4; and the target is further expanded to FOLR1, CD37, CD56, CD19, CD138, Mesothelin, CA6, etc.
; indications have also been further extended to ovarian cancer, endometrial cancer, lung cancer, diffuse B-cell lymphoma, follicular lymphoma, non-Hodgkin’s lymphoma tumors, multiple myeloma, leukemia, pancreatic cancer, and so on
.

Six, summary

The above is the brief research and development process of maytansine from being too active, narrow safety window, and obvious toxicity to be applied to clinical treatment as an ADC alloy warhead
.
In fact, in addition to maytansine, there are many strong cytotoxic substances used in clinical development, such as dolphin, auristatin, calicheamicin, beonomycin, camptothecin derivatives Wait, these related studies are very worthy of attention
.
And as more and more unpreparable medicines have become possible in recent years, many fields that have been studied for many years or even have been suspended are likely to become blue ocean markets.
Then, whether it is for industry insiders or industry investors, technological breakthroughs and Rapid development requires extra attention and in-depth research
.

Reference source:

1.
Bioorg.
Med.
Chem.
Lett.
24 (2014) 5357-5363.

2.
Acta Pharmaceutica Sinica B 2020;10(9):1589-1600.

3.
Drug Discovery Today Volume 26, Number 2 February 2021.

4.
Biomedicine & Pharmacotherapy 133 (2021) 110973

5.
Pharraac.
Ther.
Vol.
55, pp.
31-51, 1992.

6.
CNKI partial information.