Application of h018JAK as active ingredient in preparation of medicine for treating myelofibrosis
By developing a highly selective JAK1 inhibitor h018JAK, which specifically inhibits the JAK-STAT signaling pathway and blocks the cascade amplification effect of inflammatory cytokines in RA patients, it solves the problem of long-term use of existing RA therapeutic drugs, and provides a Safe and effective treatment options improve the quality of life of RA patients.
Patent Information
- Application Number
- CN202310936242.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-28
- Publication Date
- 2025-02-14
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Existing RA therapeutic drugs have side effects in long-term use, which is difficult to meet the long-term treatment needs of patients, especially those who have poor response to traditional DMARD and TNF inhibitor treatment.
Develop a highly selective JAK1 inhibitor h018JAK, which specifically inhibits the JAK-STAT signaling pathway and blocks the cascade amplification of cytokines such as TNF-α, IL-1, and IL-6, thereby improving the joints of RA patients symptom.
h018JAK as a JAK1 inhibitor, provides a safe and effective treatment option that can improve the health-related quality of life of patients with RA, especially those who have poor response to traditional treatments, and have high safety.
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedicine, and specifically relates to an application of h018JAK as an active ingredient in the preparation of a drug for treating myelofibrosis. Background Art
[0002] At present, the treatment of RA is still a medical problem at home and abroad, and there is no cure so far. According to the treatment guidelines of various countries, the main goal of treating RA is to control inflammation, prevent joint structure damage, maintain mechanism function, and improve the patient's long-term quality of life as much as possible. Therapeutic drugs include nonsteroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), small molecule JAK inhibitors, TNFα and other biological agents, and herbal preparations.
[0003] As a chronic progressive disease, long-term drug maintenance is the key to achieving treatment goals and delaying disease progression. However, all types of drugs may cause additional damage to patients due to side effects during long-term use. For example, nonsteroidal anti-inflammatory drugs and glucocorticoids have strong anti-inflammatory and analgesic effects, but they cannot improve the course of RA. Long-term use will cause greater adverse reactions, such as poor digestion and joint damage, and are not suitable for long-term use; DMARDs are the main treatment for RA, which can quickly control the patient's condition and delay the development of the disease, but long-term use will cause adverse reactions such as digestive tract discomfort, infection, malignant tumors and cardiovascular disease. There are still many unmet treatment needs and problems that need to be solved in the treatment of RA.
[0004] As the first small molecule inhibitor targeting the JAK-STAT pathway to be launched on the market, tofacitinib is an innovation and progress in the treatment of RA. However, it is pan-selective for the JAK family and has certain safety risks. Its instructions contain a black box warning about the risks of serious infection, malignancy, and thrombosis. With the in-depth study of JAK family kinases, it was found that selectively targeting the same subtype of JAK kinase has significant advantages in reducing toxic side effects. Therefore, the development of highly selective JAK1 inhibitors for autoimmune diseases such as rheumatoid arthritis has a major unmet clinical need. Summary of the invention
[0005] The purpose of the present invention is to provide an application of h018JAK as an active ingredient in the preparation of a drug for treating myelofibrosis.
[0006] To achieve the above object, the present invention provides the following technical solutions:
[0007] A use of h018JAK as an active ingredient in the preparation of a drug for treating myelofibrosis.
[0008] The h018JAK is used as an inhibitor to specifically inhibit the JAK-STAT signaling pathway, thereby blocking the cascade amplification mediated by tumor necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6 cytokines, thereby improving the symptoms of damaged joints in RA patients.
[0009] Compared with the prior art, the present invention has the following beneficial effects:
[0010] JAK1 inhibitors provide a treatment option for RA patients, breaking the traditional treatment pathways of rheumatic drugs and biological drugs. They are still effective for patients who have poor responses to traditional DMARD and TNF inhibitor treatments, improving patients' health-related quality of life, and have proven safety. Oral treatments are more popular among patients. DETAILED DESCRIPTION
[0011] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0012] Example.
[0013] A use of h018JAK as an active ingredient in the preparation of a drug for treating myelofibrosis.
[0014] The h018JAK is used as an inhibitor to specifically inhibit the JAK-STAT signaling pathway, thereby blocking the cascade amplification mediated by tumor necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6 cytokines, thereby improving the symptoms of damaged joints in RA patients.
[0015] H018 is an oral, highly selective JAK1 inhibitor used to treat autoimmune diseases such as rheumatoid arthritis (RA). JAKs belong to the cytoplasmic tyrosine kinase family and play an important role in regulating intracellular signal transduction. The immune system disorders of RA patients are mainly mediated by cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6. These cytokines interact with each other and activate the JAK-STAT signaling pathway through different pathways.
[0016] JAK1 inhibitors specifically inhibit the JAK-STAT signaling pathway, blocking the cascade amplification of the above cytokines, thereby improving the symptoms of damaged joints in RA patients. Based on the currently disclosed chemical structure of JAK1 inhibitors, the skeleton structure of the drug molecule is maintained, and a series of compounds with patentable space are found by using ring opening, ring closing, mother nucleus conformation retention, bioelectronic isostery, and dominant molecular fragments. The compounds with patentable space are modified for drugability in the hope of improving the compound's activity, in vivo metabolism, toxicity and other drugability properties.
Claims
1. A use of h018JAK as an active ingredient in the preparation of a drug for treating myelofibrosis.
2. The use of h018JAK according to claim 1 as an active ingredient in the preparation of a drug for treating myelofibrosis, characterized in that The h018JAK is used as an inhibitor to specifically inhibit the JAK-STAT signaling pathway, thereby blocking the cascade amplification mediated by tumor necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6 cytokines, thereby improving the symptoms of damaged joints in RA patients.