The DOI matches its Crossref record; 148 of the 148 references it cites were found in a registry or an index.
Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects
Open accessAbstract
The cytoplasmic protein-tyrosine kinase BTK plays an essential role for differentiation and survival of B-lineage cells and, hence, represents a suitable drug target. The number of BTK inhibitors (BTKis) in the clinic has increased considerably and currently amounts to at least 22. First-in-class was ibrutinib, an irreversible binder forming a covalent bond to a cysteine in the catalytic region of the kinase, for which we have identified 228 active trials listed at ClinicalTrials.gov. Next-generation inhibitors, acalabrutinib and zanubrutinib, are approved both in the United States and in Europe, and zanubrutinib also in China, while tirabrutinib is currently only registered in Japan. In most cases, these compounds have been used for the treatment of B-lymphocyte tumors. However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib. Adverse effects (AEs) have predominantly implicated inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4. However, the binding pattern of BTKis to various additional kinases does not correlate with the common assumption that skin manifestations and diarrhoeas are off-target effects related to EGF receptor inhibition. Moreover, dermatological toxicities, diarrhoea, bleedings and invasive fungal infections often develop early after BTKi treatment initiation and subsequently subside. Conversely, cardiovascular AEs, like hypertension and various forms of heart disease, often persist.
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Citations
Cites
Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia
Byrd, J. C., Furman, R. R., Coutre, S. E., Flinn, I. W., Burger, J. A., Blum, K. A., Grant, B., Sharman, J. P., Coleman, M., Wierda, W. G., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215637 · Cited by 2,270
Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia
Byrd, J. C., Brown, J. R., O'Brien, S., Barrientos, J. C., Kay, N. E., Reddy, N. M., Coutre, S., Tam, C. S., Mulligan, S. P., Jaeger, U., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400376 · Cited by 1,639
Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia
Burger, J. A., Tedeschi, A., Barr, P. M., Robak, T., Owen, C., Ghia, P., Bairey, O., Hillmen, P., Bartlett, N. L., Li, J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1509388 · Cited by 1,583
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BRUTON, O. C. (1952) · Pediatrics · doi:10.1542/peds.9.6.722 · Cited by 1,492
Vetrie, D., Vořechovský, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarström, L., Kinnon, C., Levinsky, R., Bobrow, M., et al. (1993) · Nature · doi:10.1038/361226a0 · Cited by 1,461
Self-citationResistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275 · cited 1×
“The commonest cause of resistance is the C481 to serine substitution in BTK (Woyach et al., 2014, 2017; Hamasy et al., 2017; Quinquenel et al., 2019).”
BackgroundAdvani, R. H., Buggy, J. J., Sharman, J. P., Smith, S. M., Boyd, T. E., Grant, B., Kolibaba, K. S., Furman, R. R., Rodriguez, S., Chang, B. Y., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.7906 · Cited by 1,128 · cited 1×
“Ibrutinib (Imbruvica R (cid:13) ), the first-in-class BTK inhibitor (BTKi), is an irreversible binder, which has revolutionized the therapeutic landscape for B-cell malignancies (Honigberg et al., 2010; Advani et al., 2013).”
BackgroundIbrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL
Woyach, J. A., Ruppert, A. S., Heerema, N. A., Zhao, W., Booth, A. M., Ding, W., Bartlett, N. L., Brander, D. M., Barr, P. M., Rogers, K. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1812836 · Cited by 962
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia
Byrd, J. C., Harrington, B., O’Brien, S., Jones, J. A., Schuh, A., Devereux, S., Chaves, J., Wierda, W. G., Awan, F. T., Brown, J. R., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1509981 · Cited by 897
Cited by
Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Brown, J. R., Eichhorst, B., Hillmen, P., Jurczak, W., Kaźmierczak, M., Lamanna, N., O’Brien, S. M., Tam, C. S., Qiu, L., Zhou, K., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2211582 · Cited by 489
Targeted protein degradation: advances in drug discovery and clinical practice
Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326
Bruton tyrosine kinase inhibitors for multiple sclerosis
Krämer, J., Bar-Or, A., Turner, T. J., & Wiendl, H. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00800-7 · Cited by 206
Microglia in multiple sclerosis: protectors turn destroyers
Yong, V. W. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.023 · Cited by 185
Bruton’s tyrosine kinase inhibition in multiple sclerosis
Schneider, R., & Oh, J. (2022) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-022-01229-z · Cited by 47
Metadata
- Authors
- Estupiñán, H. Y., Berglöf, A., Zain, R., & Smith, C. I. E.
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2021-03-11
- Volume
- 9
- Pages
- 630942-630942
- ISSN
- 2296-634X (ISSN-L)
- OpenAlex
- W3139157067
- Cited by
- 267
- References
- 148
- FWCI
- 19.00
- Type
- journal article
- Language
- en
- Open access
- gold
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
