2020
DOI: 10.1158/1538-7445.am2020-ct132
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Abstract CT132: Orelabrutinib, a potent and selective Bruton's tyrosine kinase inhibitor with superior safety profile and excellent PK/PD properties

Abstract: Bruton's tyrosine kinase (BTK) as a therapeutic target for B-cell malignancies, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other non-Hodgkin's lymphomas (NHL), has been clinically validated. Orelabrutinib (ICP-022) is a novel, potent and highly selective BTK inhibitor with excellent pharmacokinetics/pharmacodynamics (PK/PD) properties distinguished from other BTK inhibitors. Here we report the results from preclinical studies, together with safet… Show more

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Cited by 26 publications
(27 citation statements)
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“…However, acalabrutinib [ 6 , 25 , 26 ] and zanubrutinib [ 9 ] exhibit minimal inhibition of TEC, EGFR and Src family kinases, in contrast to ibrutinib (Table 1 ). Other examples of highly selective, irreversible covalent BTK inhibitors include tirabrutinib [ 14 ] and orelabrutinib [ 18 ] (Table 1 ). Metabolism of the currently approved covalent BTK inhibitors primarily involves CYP3A enzymes (Table 1 ), and there exists the potential for clinically significant drug interactions between the BTK inhibitor and CYP3A inhibitors or inducers [ 4 , 5 , 7 , 8 , 10 , 17 , 27 , 28 ].…”
Section: Drug Characteristics and Pharmacological Propertiesmentioning
confidence: 99%
“…However, acalabrutinib [ 6 , 25 , 26 ] and zanubrutinib [ 9 ] exhibit minimal inhibition of TEC, EGFR and Src family kinases, in contrast to ibrutinib (Table 1 ). Other examples of highly selective, irreversible covalent BTK inhibitors include tirabrutinib [ 14 ] and orelabrutinib [ 18 ] (Table 1 ). Metabolism of the currently approved covalent BTK inhibitors primarily involves CYP3A enzymes (Table 1 ), and there exists the potential for clinically significant drug interactions between the BTK inhibitor and CYP3A inhibitors or inducers [ 4 , 5 , 7 , 8 , 10 , 17 , 27 , 28 ].…”
Section: Drug Characteristics and Pharmacological Propertiesmentioning
confidence: 99%
“…Orelabrutinib (ICP-022, Biogen/Innocare Pharma) is an orally available, secondgeneration BTK inhibitor being developed for the treatment of B cell malignancies and autoimmune diseases. In a KINOMEscan assay conducted in parallel against numerous kinases at a 1 µM drug concentration, Orelabrutinib was more selective than ibrutinib [74]. 2020 In this study, BTK was the only kinase targeted by orelabrutinib (with >90% inhibition).…”
Section: Orelabrutinibmentioning
confidence: 66%
“…Orelabrutinib (ICP-022, Biogen/Innocare Pharma, Beijing, China) is another highly selective irreversible, covalent BTKi (Cys481 IC50 = 1.6 nM) under investigation for the treatment of B-cell malignancies and autoimmune diseases [ 41 ]. In a KINOME scan assay conducted in parallel against numerous kinases at a drug concentration of 1 μM, orelabrutinib was found to be more selective than ibrutinib.…”
Section: Characteristics Of Btk Inhibitorsmentioning
confidence: 99%