Basic Characteristics

Product Name	Acalabrutinib(ACP-196)
CAS Number	1420477-60-6
Molecular Formula	C26H23N7O2
Formula Weight	465.5
Synonyms	Acalabrutinib; 1420477-60-6; ACP-196; Calquence; UNII-I42748ELQW.
Appearance	Brown powder(Tea color)
Storage and Handling	Store in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

 

Acalabrutinib(ACP-196) Description

Acalabrutinib, also known as ACP-196, is a novel irreversible second-generation Bruton’s tyrosine kinase (BTK) inhibitor, which prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and that, was rationally designed to be more potent and selective than ibrutinib. This drug in clinical trials phase III for treatment the treatment of relapsed chronic lymphocytic leukemia. Also in combination with others drugs, Acalabrutinib in phase II of clinical trials for the treatment Glioblastoma Multiforme, Mantle Cell Lymphoma, Squamous Cell Carcinoma of the Head and Neck, Rheumatoid Arthritis and some others.

 

Acalabrutinib(ACP-196) Mechanism of Action

Acalabrutinib is a small molecule inhibitor of BTK. Both acalabrutinib and its active metabolite, ACP-5862, act to form a covalent bond with a cysteine residue (Cys481) in the BTK active site, leading to inhibition of BTK enzymatic activity.As a result, acalabrutinib inhibits BTK-mediated activation of downstream signaling proteins CD86 and CD69, which ultimately inhibits malignant B-cell proliferation and survival

Whereas ibrutinib is typically recognized as the first-in-class BTK inhibitor, acalabrutinib is considered a second generation BTK inhibitor primarily because it demonstrates highter selectivity and inhibition of the targeted activity of BTK while having a much greater IC50 or otherwise virtually no inhibition on the kinase activities of ITK, EGFR, ERBB, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1.

In effect, acalabrutinib was rationally designed to be more potent and selective than ibrutinib, all the while demonstrating fewer adverse effects – in theory – because of the drug’s minimized off target effects.

 

Acalabrutinib(ACP-196) Application

Acalabrutinib is used to treat people with mantle cell lymphoma (MCL; a fast-growing cancer that begins in the cells of the immune system) who have already been treated with at least one other chemotherapy medication. It is also used alone or with obinutuzumab (Gazyva) to treat chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells) and small lymphocytic lymphoma (SLL: a type of cancer that begins in the white blood cells). Acalabrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.

 

Acalabrutinib(ACP-196) Side Effects & Warning

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

 

More common

▪ bleeding gums

▪ collection of blood under the skin

▪ coughing up blood

▪ difficulty in breathing or swallowing

▪ dizziness

▪ headache

▪ increased menstrual flow or vaginal bleeding

▪ itching, pain, redness, or swelling

▪ large, flat, blue or purplish patches in the skin

▪ nosebleeds

▪ paralysis

▪ prolonged bleeding from cuts

▪ red or black, tarry stools

▪ red or dark brown urine

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

 

More common

▪ constipation

▪ diarrhea

▪ difficulty in moving

▪ joint pain or swelling

▪ muscle cramp, pain, or stiffness

▪ nausea

▪ rash

▪ stomach pain

▪ unusual tiredness or weakness

▪ vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

 

Reference

[1] Fischer K Al-Sawaf O Bahlo J et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions.N Engl J Med. 2019; 380: 2225-2236.

[2] House DW (2016-02-25). “AstraZeneca and Acerta Pharma’s acalabrutinib tagged an Orphan Drug in Europe for three indications”. Seeking Alpha. Retrieved 2016-11-21.

[3] “EU/3/16/1626”. European Medicines Agency (EMA). 4 May 2016. Retrieved 15 April 2020.

[4] Byrd JC, Harrington B, O’Brien S, Jones JA, Schuh A, Devereux S, et al. (January 2016). “Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia”. The New England Journal of Medicine. 374 (4): 323–32.

[5] “Acalabrutinib Orphan Drug Designation and Approval”. U.S. Food and Drug Administration (FDA). Retrieved 15 April 2020.

[6] Walker I, Roland D (2015-12-17). “AstraZeneca to Buy Stake in Acerta Pharma”. Wall Street Journal. ISSN 0099-9660. Retrieved 2016-11-19.

[7] Hallek M Fischer K Fingerle-Rowson G et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010; 376: 1164-1174.

[8] Burger JA Tedeschi A Barr PM et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia.N Engl J Med. 2015; 373: 2425-2437.

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