Acalabrutinib (ACP-196)

Catalog No.S8116 Batch:S811601

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Technical Data

Formula

C26H23N7O2
Molecular Weight 465.51 CAS No. 1420477-60-6
Solubility (25°C)* In vitro DMSO 93 mg/mL (199.78 mM)
Ethanol 93 mg/mL (199.78 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Acalabrutinib (ACP-196) is a selective second-generation Bruton's tyrosine kinase (BTK) inhibitor with an IC50 of 3 nM, which prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. ACP-196 has improved target specificity over ibrutinib with 323-, 94-, 19- and 9-fold selectivity over the other TEC kinase family members (ITK, TXK, BMX, and TEC, respectively) and no activity against EGFR.
Targets
BTK [1]
(in a human whole-blood CD69 B cell activation assay)
3nM
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[1].
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[3].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    primary human CLL cells,T cells, NK cells, and epithelial cells

  • Concentrations

    --

  • Incubation Time

    --

  • Method

    --
Animal Study:

[2]
  • Animal Models

    canine model of B cell NHL

  • Dosages

    2.5, 5, 10 mg/kg.

  • Administration

    orally administered 

Customer Product Validation

Data from [Data independently produced by , , BioMed Research International, 2018, Article ID 1023490]

Selleck's Acalabrutinib (ACP-196) has been cited by 45 publications

BMX controls 3βHSD1 and sex steroid biosynthesis in cancer [ J Clin Invest, 2023, 133(2)e163498] PubMed: 36647826
XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression [ Leukemia, 2023, 10.1038/s41375-023-01984-z] PubMed: 37528310
In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival [ Hemasphere, 2023, 7(9):e938] PubMed: 37637994
The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors [ Hemasphere, 2023, 7(8):e931] PubMed: 37492437
FDA-approved Abl/EGFR/PDGFR kinase inhibitors show potent efficacy against pandemic and seasonal influenza A virus infections of human lung explants [ iScience, 2023, 26(4):106309] PubMed: 36968089
HZ-A-018, a novel inhibitor of Bruton tyrosine kinase, exerts anti-cancer activity and sensitizes 5-FU in gastric cancer cells [ Front Pharmacol, 2023, 14:1142127] PubMed: 37033615
Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib [ PLoS One, 2023, 18(8):e0290872] PubMed: 37651403
In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival [ Hemasphere, 2023, 7(9):e938] PubMed: 37637994
Bruton's TK regulates myeloid cell recruitment during acute inflammation [ Br J Pharmacol, 2022, 179(11):2754-2770] PubMed: 34897650
The Inhibition of Bruton Tyrosine Kinase Alleviates Acute Liver Failure via Downregulation of NLRP3 Inflammasome [ J Immunol, 2022, 209(6):1156-1164] PubMed: 35977799

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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