In vitro: In the in vitro signaling assay on primary human CLL cells, acalabrutinib inhibits tyrosine phosphorylation of downstream targets of ERK, IKB, and AKT. Acalabrutinib demonstrates higher selectivity for BTK with IC50 determinations on nine kinases with a cysteine residue in the same position as BTK. Importantly, unlike ibrutinib, acalabrutinib does not inhibit EGFR, ITK, or TEC. acalabrutinib has no effect on EGFR phosphorylation on tyrosine residues Y1068 and Y1173. Compared with ibrutinib, acalabrutinib has much higher IC50(>1000 nM) or virtually no inhibition on kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1.
In vivo: oral administration of ACP-196 in mice results in dose-dependent inhibition of anti-IgM-induced CD86 expression in CD19+ splenocytes with an ED50 of 0.34 mg/kg compared to 0.91 mg/kg for ibrutinib. A similar model is used to compare the duration of Btk inhibition after a single oral dose of 25 mg/kg. ACP-196 inhibits CD86 expression >90% at 3h postdose.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||90 mg/mL in DMSO|
Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.
Wu J, et al. J Hematol Oncol. 2016 Mar 9;9:21. PMID: 26957112.
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.
Byrd JC, et al. N Engl J Med. 2016 Jan 28;374(4):323-32. PMID: 26641137.
|Related BTK Products|
Evobrutinib is a selective BTK inhibitor with an IC50 of 37.9 nM.
BMS-986142 is a potent, selective, reversible BTK inhibitor, shows BTK IC50 = 0.5nM; human WB IC50 = 90 nM.
GDC-0853 is an orally BTK inhibitor with potential antineoplastic activity.
|Btk inhibitor 2
Btk inhibitor 2 (BGB-3111) is a Brutons tyrosine kinase (BTK) inhibitor.
BMS-935177 is a potent, reversible Bruton's Tyrosine Kinase (BTK) inhibitor with an IC50 value of 2.8 nM and demonstrates good kinase selectivity. It is more potent against BTK than other kinase, including the other Tec family kinases (TEC, BMX, ITK, and TXK) over which the compound is between 5- and 67-fold selective.
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