Acalabrutinib
- CAS No.
- 1420477-60-6
- Chemical Name:
- Acalabrutinib
- Synonyms
- ACP196;ACP-196;CS-1558;EOS-60753;Calquence;acalabrutinib;α-Dimethylglycine;ACP196,Acalabrutinib;ACP196 1420477-60-6;Acalabrutinib (ACP-196)
- CBNumber:
- CB22756514
- Molecular Formula:
- C26H23N7O2
- Molecular Weight:
- 465.51
- MOL File:
- 1420477-60-6.mol
- Modify Date:
- 2024/7/24 13:33:21
| Melting point | >133°C (dec.) |
|---|---|
| Density | 1.37±0.1 g/cm3(Predicted) |
| storage temp. | Refrigerator |
| solubility | Soluble in DMSO (up to at least 25 mg/ml) |
| pka | 11.47±0.70(Predicted) |
| form | solid |
| color | Yellow |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| InChIKey | WDENQIQQYWYTPO-IBGZPJMESA-N |
| SMILES | C(NC1=NC=CC=C1)(=O)C1=CC=C(C2=C3N(C([C@@H]4CCCN4C(=O)C#CC)=N2)C=CN=C3N)C=C1 |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|---|---|
| Signal word | Warning |
| Hazard statements | H302-H315-H319-H335 |
| Precautionary statements | P261-P305+P351+P338 |
Acalabrutinib Chemical Properties,Uses,Production
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.
General Description
Class: non-receptor tyrosine kinase
Treatment: CLL, SLL, MCL
Oral bioavailability = 25%
Elimination half-life = 0.9 h
Protein binding = 97.5%
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.
Metabolism
Acalabrutinib has an absolute bioavailability of 25% and an elimination half-life of 0.9 h. Because of its better oral bioavailability but much shorter half-life than ibrutinib, acalabrutinib is taken at a lower dosage (100 mg) than ibrutinib (420 mg) but twice a day (vs. QD for ibrutinib).
The major circulating metabolite in the plasma is the pyrrolidine ring-opened product 1. This metabolite also exhibited covalent BTK inhibition with potency 2-fold lower than acalabrutinib, and its kinase selectivity profile is similar to acalabrutinib. This active metabolite has a half-life of 6.9 h, much longer than the parent drug. However, the extent of its contribution to on-target covalent inhibition of BTK in humans remains to be established.
Acalabrutinib Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| AVD pharmaceuticals Pvt Ltd | +919860835260 | Pune, India | 102 | 58 | Inquiry |
| Salvavidas Pharmaceutical Pvt., Ltd. | +91-2612538898 +91-9327127459 | Gujarat, India | 34 | 58 | Inquiry |
| Vijaya Pharma And Life Science | +91-8939866271 +91-8939866271 | Tamil Nadu, India | 320 | 58 | Inquiry |
| Svak Life Sciences | +91-9963463333 +91-9705383777 | Hyderabad, India | 101 | 58 | Inquiry |
| SynZeal Research Pvt Ltd | +1 226-802-2078 | Gujarat, India | 6522 | 58 | Inquiry |
| Pharma Affiliates | 172-5066494 | Haryana, India | 6761 | 58 | Inquiry |
| CLEARSYNTH LABS LTD. | +91-22-45045900 | Hyderabad, India | 6351 | 58 | Inquiry |
| Pharmaffiliates Analytics and Synthetics P. Ltd | +91-172-5066494 | Haryana, India | 6773 | 58 | Inquiry |
| Triveni Interchem Private Limited (Group Of Triveni... | 08046042087 | Gujarat, India | 497 | 58 | Inquiry |
| Clearsynth Labs Research Centre | 08048372785Ext 201 | Mallapur, India | 9 | 58 | Inquiry |
Related articles
- Acalabrutinib: Uses, Interactions, Mechanism of Action
- Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of non-Hodgkin lymphoma, inclu....
- Dec 22，2021