Remibrutinib | CAS#1787294-07-8 | BTK inhibitor

MedKoo Cat#: 585102 | Name: Remibrutinib

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Remibrutinib, also known as LOU064, is a Bruton's tyrosine kinase inhibitor. Remibrutinib has applications towards treating individuals with chronic spontaneous urticaria. Remibrutinib may represent a novel treatment option for patients with MS.

Chemical Structure

Remibrutinib

CAS#1787294-07-8

Theoretical Analysis

MedKoo Cat#: 585102

Name: Remibrutinib

CAS#: 1787294-07-8

Chemical Formula: C27H27F2N5O3

Exact Mass: 507.2082

Molecular Weight: 507.54

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

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00	2 Weeks
10mg	USD 950.00	2 Weeks

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Synonym

Remibrutinib; LOU064; LOU-064; LOU 064;

IUPAC/Chemical Name

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

InChi Key

CUABMPOJOBCXJI-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C(NC1=CC(F)=CC(C2=NC=NC(N)=C2OCCN(C)C(C=C)=O)=C1C)C3=CC=C(C4CC4)C=C3F

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Remibrutinib, is a potent and orally active bruton tyrosine kinase (BTK) inhibitor with an IC50 value of 1 nM. Remibrutinib inhibits BTK activity with an IC50 value of 0.023 μM in blood. Remibrutinib has the potential for Chronic urticaria (CU) treatment.

In vitro activity:

Remibrutinib and rilzabrutinib inhibit Btk-dependent pathways of platelet aggregation upon GPVI, VWF/GPIb, and FcγRIIA activation. Remibrutinib is more potent and shows a better profile of inhibition of Btk-dependent platelet activation vs. hemostatic impairment than rilzabrutinib; it has potential to be considered for further development as an antiplatelet drug. Reference: Front Cardiovasc Med. 2021 Sep 24;8:749022. https://pubmed.ncbi.nlm.nih.gov/34631841/

In vivo activity:

In the JeKo-1 xenografts, tumor uptake was blocked up to 62% by remibrutinib, indicating the BTK-dependent uptake of [18F]PTBTK3, an aromatic 18F-labeled tracer, in tumors. The cellular uptake of [18F]PTBTK3 was blocked up to 97% in JeKo-1 cells using remibrutinib. Reference: ACS Pharmacol Transl Sci. 2023 Feb 10;6(3):410-421. https://pubmed.ncbi.nlm.nih.gov/36926452/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.0	246.29

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 507.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Duan R, Goldmann L, Brandl R, Spannagl M, Weber C, Siess W, von Hundelshausen P. Effects of the Btk-Inhibitors Remibrutinib (LOU064) and Rilzabrutinib (PRN1008) With Varying Btk Selectivity Over Tec on Platelet Aggregation and in vitro Bleeding Time. Front Cardiovasc Med. 2021 Sep 24;8:749022. doi: 10.3389/fcvm.2021.749022. PMID: 34631841; PMCID: PMC8498029. 2. Li K, Wang M, Akoglu M, Pollard AC, Klecker JB, Alfonso P, Corrionero A, Prendiville N, Qu W, Parker MFL, Turkman N, Cohen JA, Tonge PJ. Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase. ACS Pharmacol Transl Sci. 2023 Feb 10;6(3):410-421. doi: 10.1021/acsptsci.2c00215. PMID: 36926452; PMCID: PMC10012250. 3. Maurer M, Berger W, Giménez-Arnau A, Hayama K, Jain V, Reich A, Haemmerle S, Lheritier K, Walsh P, Xia S, Storim J. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J Allergy Clin Immunol. 2022 Dec;150(6):1498-1506.e2. doi: 10.1016/j.jaci.2022.08.027. Epub 2022 Sep 9. Erratum in: J Allergy Clin Immunol. 2023 Feb;151(2):579. PMID: 36096203.

In vitro protocol:

In vivo protocol:

1. Li K, Wang M, Akoglu M, Pollard AC, Klecker JB, Alfonso P, Corrionero A, Prendiville N, Qu W, Parker MFL, Turkman N, Cohen JA, Tonge PJ. Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase. ACS Pharmacol Transl Sci. 2023 Feb 10;6(3):410-421. doi: 10.1021/acsptsci.2c00215. PMID: 36926452; PMCID: PMC10012250. 2. Maurer M, Berger W, Giménez-Arnau A, Hayama K, Jain V, Reich A, Haemmerle S, Lheritier K, Walsh P, Xia S, Storim J. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J Allergy Clin Immunol. 2022 Dec;150(6):1498-1506.e2. doi: 10.1016/j.jaci.2022.08.027. Epub 2022 Sep 9. Erratum in: J Allergy Clin Immunol. 2023 Feb;151(2):579. PMID: 36096203.

1: Maurer M, Berger W, Giménez-Arnau A, Hayama K, Jain V, Reich A, Haemmerle S, Lheritier K, Walsh P, Xia S, Storim J. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J Allergy Clin Immunol. 2022 Dec;150(6):1498-1506.e2. doi: 10.1016/j.jaci.2022.08.027. Epub 2022 Sep 9. Erratum in: J Allergy Clin Immunol. 2023 Feb;151(2):579. doi: 10.1016/j.jaci.2022.12.001. PMID: 36096203. 2: Jain V, Giménez-Arnau A, Hayama K, Reich A, Carr W, Tillinghast J, Dahale S, Lheritier K, Walsh P, Zharkov A, Hugot S, Haemmerle S. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol. 2024 Feb;153(2):479-486.e4. doi: 10.1016/j.jaci.2023.10.007. Epub 2023 Oct 20. PMID: 37866460. 3: Kaul M, End P, Cabanski M, Schuhler C, Jakab A, Kistowska M, Kinhikar A, Maiolica A, Sinn A, Fuhr R, Cenni B. Remibrutinib (LOU064): A selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial. Clin Transl Sci. 2021 Sep;14(5):1756-1768. doi: 10.1111/cts.13005. Epub 2021 Apr 9. PMID: 33834628; PMCID: PMC8504815. 4: Nuesslein-Hildesheim B, Ferrero E, Schmid C, Huck C, Smith P, Tisserand S, Rubert J, Bornancin F, Eichlisberger D, Cenni B. Remibrutinib (LOU064) inhibits neuroinflammation driven by B cells and myeloid cells in preclinical models of multiple sclerosis. J Neuroinflammation. 2023 Aug 26;20(1):194. doi: 10.1186/s12974-023-02877-9. PMID: 37633912; PMCID: PMC10463946. 5: Angst D, Gessier F, Janser P, Vulpetti A, Wälchli R, Beerli C, Littlewood- Evans A, Dawson J, Nuesslein-Hildesheim B, Wieczorek G, Gutmann S, Scheufler C, Hinniger A, Zimmerlin A, Funhoff EG, Pulz R, Cenni B. Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2020 May 28;63(10):5102-5118. doi: 10.1021/acs.jmedchem.9b01916. Epub 2020 Mar 4. PMID: 32083858. 6: Dörner T, Kaul M, Szántó A, Tseng JC, Papas AS, Pylvaenaeinen I, Hanser M, Abdallah N, Grioni A, Santos Da Costa A, Ferrero E, Gergely P, Hillenbrand R, Avrameas A, Cenni B, Siegel RM. Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial. Ann Rheum Dis. 2024 Feb 15;83(3):360-371. doi: 10.1136/ard-2023-224691. PMID: 37932009; PMCID: PMC10894844. 7: Kolkhir P, Muñoz M, Asero R, Ferrer M, Kocatürk E, Metz M, Xiang YK, Maurer M. Autoimmune chronic spontaneous urticaria. J Allergy Clin Immunol. 2022 Jun;149(6):1819-1831. doi: 10.1016/j.jaci.2022.04.010. PMID: 35667749. 8: Mendes-Bastos P, Brasileiro A, Kolkhir P, Frischbutter S, Scheffel J, Moñino- Romero S, Maurer M. Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions. Allergy. 2022 Aug;77(8):2355-2366. doi: 10.1111/all.15261. Epub 2022 Feb 28. PMID: 35175630; PMCID: PMC9545595. 9: Gimeno R, Ribas-Llauradó C, Pesque D, Andrades E, Cenni B, Ambros B, Pujol R, Giménez-Arnau AM. Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response. Clin Transl Allergy. 2023 Mar;13(3):e12227. doi: 10.1002/clt2.12227. PMID: 36973953; PMCID: PMC9985467. 10: Bernstein JA, Maurer M, Saini SS. BTK signaling-a crucial link in the pathophysiology of chronic spontaneous urticaria. J Allergy Clin Immunol. 2024 May;153(5):1229-1240. doi: 10.1016/j.jaci.2023.12.008. Epub 2023 Dec 21. PMID: 38141832. 11: Lai X, Liu J, Li W, Qiao M, Qiu M, Lu L. Metabolite profiling of remibrutinib in rat and human liver microsomes using liquid chromatography combined with benchtop orbitrap high-resolution mass spectrometry. Biomed Chromatogr. 2023 Dec;37(12):e5737. doi: 10.1002/bmc.5737. Epub 2023 Aug 31. PMID: 37651996. 12: Wedi B. Emerging treatments for chronic urticaria. Expert Opin Investig Drugs. 2022 Mar;31(3):281-290. doi: 10.1080/13543784.2022.2042513. Epub 2022 Feb 18. PMID: 35166638. 13: Gabizon R, London N. A Fast and Clean BTK Inhibitor. J Med Chem. 2020 May 28;63(10):5100-5101. doi: 10.1021/acs.jmedchem.0c00597. Epub 2020 May 13. PMID: 32401033; PMCID: PMC7304894. 14: Huth F, Schiller H, Jin Y, Poller B, Schuhler C, Weis W, Woessner R, Drollmann A, End P. Novel Bruton's Tyrosine Kinase inhibitor remibrutinib: Drug- drug interaction potential as a victim of CYP3A4 inhibitors based on clinical data and PBPK modeling. Clin Transl Sci. 2022 Jan;15(1):118-129. doi: 10.1111/cts.13126. Epub 2021 Aug 25. PMID: 34432364; PMCID: PMC8742645. 15: Duan R, Goldmann L, Brandl R, Spannagl M, Weber C, Siess W, von Hundelshausen P. Effects of the Btk-Inhibitors Remibrutinib (LOU064) and Rilzabrutinib (PRN1008) With Varying Btk Selectivity Over Tec on Platelet Aggregation and in vitro Bleeding Time. Front Cardiovasc Med. 2021 Sep 24;8:749022. doi: 10.3389/fcvm.2021.749022. PMID: 34631841; PMCID: PMC8498029. 16: Schiller H, Huth F, Schuhler C, Drollmann A, Kaul M, Woessner R, Shah B, Weis W, End P. Novel Bruton's tyrosine kinase inhibitor remibrutinib: Assessment of drug-drug interaction potential as a perpetrator of cytochrome P450 enzymes and drug transporters and the impact of covalent binding on possible drug interactions. Eur J Pharm Sci. 2022 May 1;172:106155. doi: 10.1016/j.ejps.2022.106155. Epub 2022 Mar 3. PMID: 35247543. 17: von Hundelshausen P, Siess W. Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease. Cancers (Basel). 2021 Mar 4;13(5):1103. doi: 10.3390/cancers13051103. PMID: 33806595; PMCID: PMC7961939. 18: Geladaris A, Torke S, Weber MS. Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression? CNS Drugs. 2022 Oct;36(10):1019-1030. doi: 10.1007/s40263-022-00951-z. Epub 2022 Sep 30. PMID: 36178589; PMCID: PMC9550714. 19: Lin EV, Suresh RV, Dispenza MC. Bruton's tyrosine kinase inhibition for the treatment of allergic disorders. Ann Allergy Asthma Immunol. 2024 Jul;133(1):33-42. doi: 10.1016/j.anai.2024.03.002. Epub 2024 Mar 14. PMID: 38492772; PMCID: PMC11222055. 20: Li K, Wang M, Akoglu M, Pollard AC, Klecker JB, Alfonso P, Corrionero A, Prendiville N, Qu W, Parker MFL, Turkman N, Cohen JA, Tonge PJ. Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase. ACS Pharmacol Transl Sci. 2023 Feb 10;6(3):410-421. doi: 10.1021/acsptsci.2c00215. PMID: 36926452; PMCID: PMC10012250.