BTK inhibitors have been successful Can Syk work miracles?

The world's highest sales of tinib drugs, is now the first BTK inhibitor to be marketed ~ ibrutinib; drug development for BTK inhibitors is also a very hot competition track, in order to get a share! Finding targets around BTK and avoiding the competition track is naturally a routine and potential strategy.

01 B cell malignant tumor & autoimmune disease & Syk

B-cell related malignancies, including chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and mantle cell lymphoma (MCL), etc.

As for autoimmunity, its occurrence is closely related to the abnormal activation of the immunoglobulin G-Fc receptor gamma (IgG-FcR gamma) signaling pathway.

02 Syk signal path characteristics

Syk belongs to the category of B cell receptors.

Figure 2.

(Image source: FEBS Letters 584 (2010) 4933-4940)

03 Distribution and structural characteristics of Syk kinase

Syk belongs to the same PTK family as ZAP-70; it is widely expressed in hematopoietic cells such as mast cells, basophils, B cells and platelets, especially in the field of B cells; the coding gene is Syk 9q22 located on the human chromosome

Figure 3.

04 Syk inhibitor development status

Aiming at the development of Syk inhibitors, there are now drugs approved for the market.

Figure 4.

Fostamatinib, developed code-named R788, is a non-selective oral Syk inhibitor (Kd is 15nM).

In addition, the drugs currently developed for the target of Syk: Phase III~I clinical varieties, mainly Entospletinib from Gilead, PRT-2761 from Portola Pharmaceuticals Inc, HMPL-523 from Hutchison Medipharma Enterprises Ltd, and SKI-O from Oscotec Inc.

05 Examples of domestic innovative drug development

In the above-mentioned clinical research selective Syk inhibitor information, people in the industry will find a familiar company, namely Hutchison Medipharma~Hutchison Whampoa.

Figure 5.

(Image source: http:// Summary

In summary, it is a small microcosm of the development of Syk targets and their inhibitors

Reference materials:

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FDA official website

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Official websites/annual reports of major companies