Table 2.

Summary of BTKIs in clinical trials [64,75,76].

Name	Synonyms	Type of Inhibitor	Indications	Activity (IC50)
Spebrutinib	CC-292 AVL-292	Irreversible	CLL, NHL	BTK IC50 = 9.2 nM
				ITK IC50 = 1050 nM
				TEC IC50 = 8.4 nM
Evobrutinib	M2951 MSC-2364447C	Irreversible	RA, MS	BTK IC50 = 8.9 nM
Vecabrutinib	SNS-062	Reversible	CLL, SLL	BTK IC50 = 1.9 nM
Pirtobrutinib	LOXO-305	Reversible	CLL, MCL	BTK IC50 = 3.15 nM
				ITK IC50 > 5000 nM
				TEC IC50 = 1234 nM
Fenebrutinib	GDC-0853	Reversible	RA, SLE, CSU	BTK IC50 = 2.3 nM
				ITK IC50 = 1000 nM
				TEC IC50 = 1000 nM

CLL—chronic lymphocytic leukemia; CSU—chronic spontaneous urticaria; MCL—mantle cell lymphoma; MS—multiple sclerosis; NHL—non-Hodgkin lymphoma; RA—rheumatoid arthritis; SLE—systemic lupus erythematosus SLL—small lymphocytic lymphoma; IC₅₀—half-maximal inhibitory concentration, the inhibitor concentration that causes a 50% decrease in enzyme activity. Various kinase activity tests are utilized to assess the selectivity of the inhibitors; hence, reported IC₅₀ statistics are widely diverse; e.g., the IC₅₀ values for ibrutinib against ITC range from 0.5 nM to 218 nM [5,76]. BTK—Bruton’s tyrosine kinase; ITK—interleukin-2-inducible T-cell kinase, TEC—cytoplasmic tyrosine kinase.