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1420477-60-6

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1420477-60-6 Usage

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.

Uses

Acalabrutinib, is an experimental anti-cancer drug and a selective Bruton's tyrosine kinase (BTK) inhibitor. This kinase transmits signals from B-cell Receptor (BCR), and thus any genetic BTK mutation causes B-Cell immunodeficiency. Therefore, BTK inhibitors targeting B-cell signaling has shown great promise for the treatment of chronic lymphocytic leukemia (CLL).

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.

IC 50

3 nm

References

1) Wu et al.?(2016),?Acalabrutinib (ACP-196): a second-generation BTK inhibitor;?J. Hematol. Oncol.?9?21 2) Barf?et al.?(2017),?Acalabrutinib (ACP-196): A covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile;?J. Pharmacol. Exp. Ther.?363?240 3) Herman?et al.?(2017),?The Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia;?Clin. Cancer Res.?23?2831 4) Weber et al.?(2017),?Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity; Front. Immunol.?8?1454

Check Digit Verification of cas no

The CAS Registry Mumber 1420477-60-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,2,0,4,7 and 7 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1420477-60:
(9*1)+(8*4)+(7*2)+(6*0)+(5*4)+(4*7)+(3*7)+(2*6)+(1*0)=136
136 % 10 = 6
So 1420477-60-6 is a valid CAS Registry Number.

1420477-60-6SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 15, 2017

Revision Date: Aug 15, 2017

1.Identification

1.1 GHS Product identifier

Product name ACP-196

1.2 Other means of identification

Product number -
Other names ACP196.Acalabrutinib

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:1420477-60-6 SDS

1420477-60-6Downstream Products

1420477-60-6Relevant articles and documents

NOVEL PROCESS FOR THE PREPARATION OF ACALABRUTINIB AND ITS INTERMEDIATES

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, (2021/06/11)

The present invention relates to an improved and industrially viable process for the preparation of Acalabrutinib and its Intermediates. The present invention involves less expensive reagents, solvents and the process conditions can be easily adopted for commercial scale. The present invention relates to process for the preparation Acalabrutinib of formula (1) and process for the preparation of Acalabrutinib key starting material.

Method for preparing Acalabrutinib, in particular to method for preparing Acalabrutinib

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, (2020/07/24)

The invention relates to the field of chemical synthesis, in particular to a chemical synthesis method for preparing Acalabrutinib. The synthesis method of the compound 3 is optimized, wherein the cyano compound 2 is reduced to obtain the compound 3 by adopting a method of generating borane in situ under the conditions of indium trichloride and sodium borohydride. The method is simple and convenient to operate, a special reaction container and hydrogen are not needed for reduction, a high-risk material catalyst nickel is prevented from being adopted, and large-scale production is facilitated.In the preparation of the compound 15, water is used as a solvent, equivalent hydrogen peroxide is added to react the compound 13 with the compound 14 to prepare the compound 15, so that the method iseconomic and environment-friendly, the post-treatment is simple and convenient, and the reaction liquid is directly subjected to centrifugal operation; in addition, the yield is high and can reach 90% or above; and the compound 15 is high in purity and does not need to be further purified, so that the technology can satisfy the requirements of industrial production.

Preparation method capable of acalabrutinib being used for treating leukemia

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Paragraph 0045-0046, (2020/07/24)

The invention relates to a preparation method of acalabrutinib capable of being used for treating leukemia. The synthesis method of the compound 3 is optimized, so that according to the method, the cyano compound 2 is reduced to obtain the compound 3 by adopting a method of generating borane in situ under the conditions of indium trichloride and sodium borohydride. The method is simple and convenient to operate, a special reaction container and hydrogen are not needed for reduction, a high-risk catalyst nickel is prevented from being adopted, and large-scale production is facilitated; in the preparation of the compound 8, under the condition of a catalyst, large-scale preparation is realized by adding an ammonia water closed system, so that a method of introducing ammonia gas at an extremely low temperature is avoided, and large-scale production is facilitated.

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