Bruton tyrosine kinase (BTK) (IC50 = 1 nM)

Remibrutinib (Example 6) inhibited Btk enzyme activity in the biochemical enzyme assay, with an IC50 value of 1 nM [1]. Remibrutinib reduced blood Btk enzyme activity in an in vitro B cell activation test, with an IC50 value of 0.023 μM. Sector Lewis was put under anesthesia, and whole blood was extracted from the abdominal aorta [1].

Remibrutinib inhibits Bruton’s tyrosine kinase with high selectivity, potency, and covalent inhibition. In clinical trials, it ameliorated mast cell-mediated inflammatory effects in chronic urticaria. Remibrutinib inhibits mast cell and basophil degranulation, including release of histamine and other proinflammatory mediators, mediated by pathogenic IgE or IgG directed against the FcεR1 or IgE. Remibrutinib is a selective Bruton's tyrosine kinase inhibitor. The FDA approved remibrutinib on September 30, 2025 as the only oral, targeted treatment for chronic spontaneous urticaria. Bruton's tyrosine kinase plays a role in B cell receptor and Fc receptor signalling, releasing histamine and pro-inflammatory mediators. Remibrutinib has also been investigated in other inflammatory conditions, such as autoimmune encephalomyelitis and Sjögren's syndrome.

[1]. Novel amino pyrimidine derivatives. Patent WO2015079417A1.

[2]. New treatments for chronic urticaria. Ann Allergy Asthma Immunol. 2020 Jan;124(1):2-12.

Drug Indication
Treatment of Multiple Sclerosis Treatment of Chronic Spontaneous Urticaria (CSPI) Remibutinib is a kinase inhibitor. Remibutinib's mechanism of action is as a Bruton's tyrosine kinase inhibitor and a P-glycoprotein inhibitor. Remibutinib is a small molecule drug that has completed Phase III clinical trials (covering all indications) and has six investigational indications. The approval of Remibutinib is a significant advancement in the treatment of chronic spontaneous urticaria. "It rapidly relieves symptoms, helping patients control daily hives and itching," said Giselle Mosnaim, MD, MSc, allergist and immunologist at Endeavor Health, clinical associate professor at the University of Chicago Pritzker School of Medicine, and investigator of the REMIX trial. "This is significant because it goes beyond existing injectable therapies, providing patients with an oral option that can be easily integrated into their daily lives." Purpose: Chronic urticaria (CU) is a common, heterogeneous, and distressing disease. Antihistamines and omalizumab are the main treatment options for chronic urticaria (CU). However, more treatment options are needed. This article reviews off-label use of approved drugs, new therapies currently under development, and promising new targets. Data Sources: We searched the MEDLINE database for recent reports on successful applications of CU treatment and promising new therapies and targets for development. We also searched ClinicalTrials.gov for recent and ongoing randomized clinical trials of CU. Study Selection: We screened and reviewed relevant articles. Results: Omalizumab is the first-line treatment for patients with antihistamine-resistant chronic spontaneous urticaria (CSU) and its use in treating chronic inducible urticaria in children under 12 years of age with CSU should be explored, and higher doses should be considered. Off-label use of dupilumab, relizumab, mepolizumab, and benazepril may be effective for chronic urticaria (CU). Two novel anti-IgE monoclonal antibodies, linfalimumab and UB-221, are currently undergoing clinical trials for CU. Other potential drugs under development for the treatment of chronic urticaria (CU) include: antagonists of chemokine receptor homologs expressed on TH2 cells, anti-Siglec-8 monoclonal antibody (AK002), Bruton's tyrosine kinase inhibitors (fenbubrutinib and Lou064), spleen tyrosine kinase inhibitors, and dupilumab. Potential targets for future treatment include Mas-associated G protein-coupled receptor X2; histamine 4 receptor; C5a and its receptor; inhibitory mast cell receptors other than Siglec-8; interleukin-33, interleukin-25, thymic stromal lymphopoietin, and stem cell factors. Conclusion: There is an urgent need for novel and effective therapies for chronic urticaria (CU). Some drugs have entered clinical trials (e.g., linigzumab), and more drugs should be developed by leveraging the numerous potential targets recently discovered and characterized.

C27H27F2N5O3

507.531792879105

507.208

C, 63.90; H, 5.36; F, 7.49; N, 13.80; O, 9.46

1787294-07-8

118107483

White to off-white solid powder

3.9

2

8

9

37

815

0

FC1=C(C(NC2C=C(C=C(C3C(=C(N)N=CN=3)OCCN(C(C=C)=O)C)C=2C)F)=O)C=CC(=C1)C1CC1

CUABMPOJOBCXJI-UHFFFAOYSA-N

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)

N-(3-{6-amino-5-[2-(N-methylprop-2-enamido)ethoxy]pyrimidin-4-yl}-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide

LOU064; LOU-064; Remibrutinib; 1787294-07-8; NVP-LOU064-NXA; LOU064-NXA; LOU 064

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~246.29 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)