Remibrutinib

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Remibrutinib
Remibrutinib.svg
Clinical data
ATC code
Identifiers
  • N-[3-[6-Amino-5-[2-[methyl(prop-2-enoyl)amino]ethoxy]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]-4-cyclopropyl-2-fluorobenzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
PDB ligand
Chemical and physical data
Formula C27H27F2N5O3
Molar mass 507.542 g·mol−1
3D model (JSmol)
  • CC1=C(C=C(C=C1NC(=O)C2=C(C=C(C=C2)C3CC3)F)F)C4=C(C(=NC=N4)N)OCCN(C)C(=O)C=C
  • InChI=1S/C27H27F2N5O3/c1-4-23(35)34(3)9-10-37-25-24(31-14-32-26(25)30)20-12-18(28)13-22(15(20)2)33-27(36)19-8-7-17(11-21(19)29)16-5-6-16/h4,7-8,11-14,16H,1,5-6,9-10H2,2-3H3,(H,33,36)(H2,30,31,32)
  • Key:CUABMPOJOBCXJI-UHFFFAOYSA-N

Remibrutinib is a small molecule drug that acts as a Bruton's tyrosine kinase (BTK) inhibitor. It is in development for the treatment of chronic spontaneous urticaria. [1] [2] In November 2023, Novartis announced that the compound "demonstrated clinically meaningful and statistically significant reduction in urticaria activity vs placebo" in a Phase III trial. [3]

Related Research Articles

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Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red and/or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and do not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Omalizumab</span> Monoclonal antibody medication

Omalizumab, sold under the brand name Xolair among others, is an injectable medication to treat severe persistent allergic forms of asthma, nasal polyps, urticaria (hives), and immunoglobulin E-mediated food allergy.

<span class="mw-page-title-main">Cold urticaria</span> Allergic reaction to low temperatures

Cold urticaria is a disorder in which large red welts called hives (urticaria) form on the skin after exposure to a cold stimulus. The hives are usually itchy and often the hands, feet and other parts of the body will become itchy and swollen as well. Hives vary in size from about 7 mm in diameter to as big as about 27 mm or larger.

<span class="mw-page-title-main">Aspirin-exacerbated respiratory disease</span> Chronic inflammatory disease affecting the sinuses and lungs

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated respiratory disease (N-ERD) or historically aspirin-induced asthma and Samter's Triad, is a long-term disease defined by three simultaneous symptoms: asthma, chronic rhinosinusitis with nasal polyps, and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease.

<span class="mw-page-title-main">Physical urticaria</span> Medical condition

Physical urticaria is a distinct subgroup of urticaria (hives) that are induced by an exogenous physical stimulus rather than occurring spontaneously. There are seven subcategories that are recognized as independent diseases. Physical urticaria is known to be painful, itchy and physically unappealing; it can recur for months to years.

<span class="mw-page-title-main">Bruton's tyrosine kinase</span> Kinase that plays a role in B cell development

Bruton's tyrosine kinase, also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

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Aquagenic urticaria, also known as water allergy and water urticaria, is a form of physical urticaria in which hives develop on the skin after contact with water, regardless of its temperature. The condition typically results from contact with water of any type, temperature or additive.

<span class="mw-page-title-main">Pressure urticaria</span> Medical condition

Pressure urticaria or delayed pressure urticaria is a physical urticaria caused by pressure applied to the skin, and is characterized by the development of swelling and pain that usually occurs 3 to 12 hours after local pressure has been applied.

<span class="mw-page-title-main">Bilastine</span> Antihistamine medication

Bilastine is an antihistamine medication used to treat hives (urticaria), allergic rhinitis and itchy inflamed eyes (allergic conjunctivitis) caused by an allergy. It is a second-generation antihistamine and takes effect by selectively inhibiting the histamine H1 receptor, preventing these allergic reactions. Bilastine has an effectiveness similar to cetirizine, fexofenadine, and desloratadine.

Quilizumab (INN) is a humanized monoclonal antibody designed for the treatment of asthma. It binds to IGHE.

Ligelizumab is a humanized IgG1 monoclonal antibody designed for the treatment of severe asthma and chronic spontaneous urticaria. It is an anti-IgE that binds to IGHE an acts as an immunomodulator. It is delivered as a subcutaneous biologic injection.

<span class="mw-page-title-main">Chronic spontaneous urticaria</span> Medical condition

Chronic spontaneous urticaria(CSU) also known as Chronic idiopathic urticaria(CIU) is defined by the presence of wheals, angioedema, or both for more than six weeks. The most common symptoms of chronic spontaneous urticaria are angioedema and hives that are accompanied by itchiness.

Mast cell activation syndrome (MCAS) is a term referring to one of two types of mast cell activation disorder (MCAD); the other type is idiopathic MCAD. MCAS is an immunological condition in which mast cells, a type of white blood cell, inappropriately and excessively release chemical mediators, such as histamine, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological, and respiratory problems.

Tse Wen Chang is a Taiwanese immunologist. His early research involving the Immunoglobulin E (IgE) pathway and antibody-based therapeutics lead to the development of omalizumab, a medication that has been approved for the treatment of severe allergic asthma and severe chronic spontaneous urticaria. Chang is a cofounder of Tanox, a biopharmaceutical company specialized in anti-IgE therapies for the treatment of allergic diseases.

<span class="mw-page-title-main">Giorgio Walter Canonica</span> Italian allergist and pulmonologist

Giorgio Walter Canonica is an Italian allergist, pulmonologist and professor of Respiratory Medicine at Humanitas University, Milan, Italy and Director Personalized Medicine Asthma & Allergy Center at Humanitas Research Hospital IRCCS-Milano Italy since December 2016. He is known for his research work related to innovative treatment strategies for allergic diseases which includes biological response modifier in form of targeted immunotherapy with primary emphasis on sublingual immunotherapy (SLIT). He has served as Secretary General and President elect of World Allergy Organisation for six consecutive years and has served as president of the same organization during 2007–09. He is also the vice-president of INTERASMA.

Lirentelimab is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.

<span class="mw-page-title-main">Autoimmune urticaria</span> Autoimmune disease causing hives and itching

Autoimmune urticaria, also known as chronic autoimmune urticaria, is a type of chronic urticaria characterized by the presence of autoantibodies in the patient's immune system that target the body's own mast cells, leading to episodes of hives (urticaria). This immunologically distinct type of urticaria is considered autoimmune because the immune system, which normally protects the body from foreign organisms, mistakenly attacks the body's own cells, causing inflammation and other symptoms.

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References

  1. Maurer, Marcus; Berger, William; Giménez-Arnau, Ana; Hayama, Koremasa; Jain, Vipul; Reich, Adam; Haemmerle, Sibylle; Lheritier, Karine; Walsh, Pauline; Xia, Summer; Storim, Julian (December 2022). "Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria". The Journal of Allergy and Clinical Immunology. 150 (6): 1498–1506.e2. doi: 10.1016/j.jaci.2022.08.027 . hdl: 10230/55511 . ISSN   1097-6825. PMID   36096203.
  2. Maurer, Marcus; Giménez-Arnau, Ana; Jain, Vipul; Tillinghast, Jeffrey; Tolcachier, Alberto; Nigen, Simon; Hayam, Koremasa; Lheritier, Karine; Walsh, Pauline; Haemmerle, Sibylle (February 2022). "Remibrutinib Treatment Improves Quality of Life in Patients with Chronic Spontaneous Urticaria". Journal of Allergy and Clinical Immunology. 149 (2): AB179. doi:10.1016/j.jaci.2021.12.589. S2CID   246522006.
  3. "Novartis data show potential of remibrutinib as an oral treatment for chronic spontaneous urticaria providing significant symptom improvement as early as Week 2". Novartis. Retrieved 11 November 2023.