acalabrutinib   

GtoPdb Ligand ID: 8912

Synonyms: ACP-196 | Calquence® | Example 6 [US20140155385 A1] [2]
acalabrutinib is an approved drug (FDA (2017))
Compound class: Synthetic organic
Comment: Acalabrutinib is an orally available second-generation, selective and irreversible inhibitor of Bruton tyrosine kinase (BTK) [6], being investigated for its potential antineoplastic activity (in multiple haematologic malignancies and solid tumours), as well as a potential therapy for rheumatoid arthritis. Acalabrutinib covalently bonds to Cysteine-481 in BTK.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 118.51
Molecular weight 465.19
XLogP 4.09
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CC#CC(=O)N1CCCC1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
Isomeric SMILES CC#CC(=O)N1CCC[C@H]1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
InChI InChI=1S/C26H23N7O2/c1-2-6-21(34)32-15-5-7-19(32)25-31-22(23-24(27)29-14-16-33(23)25)17-9-11-18(12-10-17)26(35)30-20-8-3-4-13-28-20/h3-4,8-14,16,19H,5,7,15H2,1H3,(H2,27,29)(H,28,30,35)/t19-/m0/s1
InChI Key WDENQIQQYWYTPO-IBGZPJMESA-N
References
1. Awan FT, Schuh A, Brown JR, Furman RR, Pagel JM, Hillmen P, Stephens DM, Woyach J, Bibikova E, Charuworn P et al.. (2019)
Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib.
Blood Adv, 3 (9): 1553-1562. [PMID:31088809]
2. Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. (2014)
4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk inhibitors.
Patent number: US20140155385 A1. Assignee: Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. Priority date: 19/07/2011. Publication date: 05/06/2014.
3. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016)
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.
N. Engl. J. Med., 374 (4): 323-32. [PMID:26641137]
4. Sharman JP, Banerji V, Fogliatto LM, Herishanu Y, Munir T, Walewska R, Follows G, Karlsson K, Ghia P, Corbett G et al.. (2019)
ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL).
Blood, 134 (Supplement_1): 31. [PMID:31724010]
5. UK Department of Health and Social Care. 
COVID-19 treatments could be fast-tracked through new national clinical trial initiative.
Accessed on 01/06/2020. Modified on 01/06/2020. gov.uk, https://www.gov.uk/government/news/covid-19-treatments-could-be-fast-tracked-through-new-national-clinical-trial-initiative
6. Wu J, Zhang M, Liu D. (2016)
Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.
J Hematol Oncol, 9: 21. [PMID:26957112]
7.  FDA Approves Calquence.
Accessed on 01/11/2017. Modified on 01/11/2017. www.drugs.com, https://www.drugs.com/newdrugs/fda-approves-calquence-acalabrutinib-adults-mantle-cell-lymphoma-4624.html?utm_source=ddc&utm_medium=email&utm_campaign=FDA+Approves+Calquence+%28acalabrutinib%29+for+Adults+with+Mantle+Cell+Lymphoma