Table 1. Comparison of selected... | American Society of Hematology

Table 1.

Comparison of selected BTK-targeting agents

Class	Drug	Binding to BTK	Half-life	Specificity	Toxicity	BTK mutations
First-generation	Ibrutinib	Irreversible at C481	Short	Low	Bleeding, cardiac	C481S
Second-generation	Acalabrutinib	Irreversible at C481	Short	High	Reduced	C481x, T474x
	Zanubrutinib	Irreversible at C481	Short	High	Reduced	C481x, L528W
Reversible	Pirtobrutinib	Reversible	Long	Very high	Reduced	T474, L528W, V416L, A428D, M477I, M437R, kinase-dead C481
	Nemtabrutinib	Reversible	Long	Low	Insufficient data	Not reported
Bifunctional	LP-168	Irreversible at wild-type C481. Reversible in C481S	Long	Very high	Reduced	Not reported
Protein degraders	NX-2127	Degrades BTK	Not reported	Not reported	Insufficient data	Not reported
	BGB-16673	Degrades BTK	Long	Not reported	Insufficient data	Not reported

Class	Drug	Binding to BTK	Half-life	Specificity	Toxicity	BTK mutations
First-generation	Ibrutinib	Irreversible at C481	Short	Low	Bleeding, cardiac	C481S
Second-generation	Acalabrutinib	Irreversible at C481	Short	High	Reduced	C481x, T474x
	Zanubrutinib	Irreversible at C481	Short	High	Reduced	C481x, L528W
Reversible	Pirtobrutinib	Reversible	Long	Very high	Reduced	T474, L528W, V416L, A428D, M477I, M437R, kinase-dead C481
	Nemtabrutinib	Reversible	Long	Low	Insufficient data	Not reported
Bifunctional	LP-168	Irreversible at wild-type C481. Reversible in C481S	Long	Very high	Reduced	Not reported
Protein degraders	NX-2127	Degrades BTK	Not reported	Not reported	Insufficient data	Not reported
	BGB-16673	Degrades BTK	Long	Not reported	Insufficient data	Not reported