Multiple myeloma treatment drugs although there are small molecules "drug king" but the development is still hot.

Text . . . Drug-mad multiple myeloma (MM), the second most common malignant tumor in the blood system in many countries, is a malignant disease of abnormal proliferation of cloned plasma cells.
is not currently curable, but treatment and drug development is very hot! Whether it's the classic salidadamine, the introduction guidelines for the mono-anti-drug Dretoyo monoanti, or the intervention of CAR-T therapy, or the launch of the new drug Selinexor in 2019, the drug development process in this area has never stopped, and from a certain point of view, there has been a qualitative improvement.
China's multiple myeloma diagnosis and treatment guidelines (revised in 2020) issued every 2 to 3 years of China MM diagnosis and treatment guidelines updated, to improve the level of China's MM diagnosis and treatment is of great significance; Guidelines for diagnosis and treatment (revised in 2020); the main changes in the guidelines are the addition of the Daretoyu monoantigen combination therapy section and related considerations, the addition of CAR-T immunotherapy in the recurring MM section of the treatment, and the emphasis on autologic hematopoietic stem cell transplantation (ASCT) as an irreplaceable position for transplant patients.
has been listed MM drug heavy "China multiple myeloma diagnosis and treatment guidelines" (revised in 2020) although the direction of treatment recommendations, but from the perspective of drug development MM drug development, from the saridamine.
, which is used in the development of MM drugs, its legend and success for drug researchers, can learn far more than thinking about its drug harm events! New base company dares to grab such a hot potato again, and secondary development to make it a god medicine again, and although there is no longer the protection of compound patents, but also from other ways to obtain a period of market exclusive, this wave of operation is really strong! On this basis, the introduction of nadamine and pomadamine, 3 varieties completely solidified the new base company in the field of multiple myeloma position! In particular, the amine, since the listing, has grown into the world's annual sales of nearly 10 billion U.S. dollars of varieties, and once became a small molecular drug king.
2.1: The mechanism by which immunomodulation drugs work on MM (Photo: Drug Discovery Today Volume 25, Number 2 February 2020) and, in other categories of "Zomi" drugs in the MM field, represent boroniczomi.
, a protease inhibitor developed by Millennium Pharmaceuticals, was first approved for market by the FDA in 2003 and then approved by EMA and PMDA respectively, with Millennium Pharmaceuticals and Janssen in charge of marketing.
the variety since its listing, it is also a heavy bomb-grade variety, with annual global sales of about $2.3 billion to $2.4 billion over the past five years, mainly in the U.S. market.
2.2: The mechanism by which protease inhibitors work on MM (Photo: Drug Discovery Today Volume 25, Number 2 February 2020) In addition to the above two important types of "domamine" and "Zomi" drugs, this entry into the Chinese guidelines and highlighted the mono-anti-class drug - Daleitoyu monoantigen, which is CD38 monoclonal antibody, the development company for Jansen, approved by the FDA in 2015, in July 2019 by China's NMPA approved the listing, the commodity name ®.
five years since the product went on sale, global annual sales have reached nearly $3 billion, a recognition of the market.
Figure 2.3 The mechanism of action of The Drug Discovery Today Volume 25, Number 2 February 2020) in addition to the above MM representative drugs, in addition to the above MM representative drugs, in recent years also listed a number of new drugs, especially the 2019 market Selinexor, its target is XPO1, breaking the traditional classic target, for MM drug development has expanded an important direction, highlighted below.
Table 1: Multiple myeloma therapy drug (chemical) listed globally for nearly 20 years 2019 MM drug Selinexor "salideamine-lynamin-pomadamine" The attack, coupled with the clamping of "Zomi" drugs, has divided mm's drug market by half; the late intervention of mono-anti-class drugs, and the introduction of treatments such as CAR-T, mm's new drug development "desire" seems to be getting smaller and smaller.
2019 FDA-approved output protein-1 (XPO1) antagonist Selinexor has brought new ideas to MM's treatment.
Selinexor was developed by Karyopharm Therapeutics to treat the incurable MMs of five existing therapies (including boronazome, carphetamine, lanadamine, pomadamide, and dharetoyoda), which has the right to develop the variety in Chinese mainland and Macau (including all adaptations) as early as 2018.
noted that Selinexor's NDA application for B-cell lymphoma has been reviewed as a priority by the FDA and that multiple adaptations are clinically ongoing.
to briefly describe the mechanism of Selinexor's role.
in the presence of the active small G-protein Ran, the tumor inhibitor FOXO or p53 as a cargo protein is combined with the pockets of XPO-1, while the active Ran-GTP-XPO-1-protein complex passes through the nucleus through THEC and is transported from the nucleus to the cytokine, which drives energy from the concentration gradient of Ran-GTP; The -1-protein complex is dissocented, while Thelinexor binds to XPO-1-Cys528 and occupies the XPO-1 binding pocket, preventing the formation of the Ran-GTP-XPO-1-protein complex;
3.1 XPO1 mechanism of action model (image source:) the future direction of MM drug treatment, that is, the current drug development for multiple myeloma in general state.
Although the company's three products in the MM market, but the intervention of single anti-drugs, CAR-T therapy promotion, making MM treatment more diversified, and just launched in 2019 Selinexor, but also for the treatment of the cancer species has brought a new choice.
increase in the variety of treatment methods, naturally laid the foundation for combination therapy, I believe that MM's future drug treatment direction will be integrated with the above-mentioned treatments, of course, if there is a similar to the birth of Selinexor innovative drugs, will certainly bring greater help to the treatment of this cancer species! References: 1. China's Guidelines for the Diagnosis and Treatment of Multiple Myeloma (revised in 2020) 2. Enterprise Annual Report Data 3.New generation drugs for treatment of multiple myeloma. Drug Discovery Today Volume 25, Number 2 February 2020.4. A new drug for the treatment of multiple myeloma - nuclear output protein XPO-1 inhibitor Celliniso. Oncology Pharmacy 20195. Targeting nuclear import and export in hematological malignancies.6.Pharmaproject Date / Cortellis Date7.