Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Ref Type | Journal Article | ||||||||||||
PMID | (26555154) | ||||||||||||
Authors | Myers SH, Brunton VG, Unciti-Broceta A | ||||||||||||
Title | AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective. | ||||||||||||
|
|||||||||||||
URL | |||||||||||||
Abstract Text | Dysregulation of the AXL receptor tyrosine kinase has been associated with many types of cancer. It has not been until recently, however, that targeting AXL has come under the spotlight because of ever accumulating evidence of its strong correlation with poor prognosis and drug resistance. The entry of the first AXL-branded inhibitor in clinical trials in 2013 marked an important milestone for the clinical validation of AXL as an anticancer target. Nevertheless, to weigh the current contribution and potential future impact of AXL inhibition in the clinic, it is fundamental to recognize that several kinase inhibitors approved or in clinical development have AXL as either a prominent secondary or even the primary target. Through this review, the chemical and biological properties of the main inhibitors targeting AXL (either intentionally or unintentionally) will be discussed, along with the prospects and challenges to translate AXL inhibitors into a bona fide therapeutic option. |
Molecular Profile | Treatment Approach |
---|
Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
---|
Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
---|---|---|---|
Bosutinib | Bosutinib | 1 | 12 |
Glesatinib | Glesatinib | 0 | 2 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
BMS-777607 | ASLAN002 | AXL Inhibitor 30 MET Inhibitor 59 RON Inhibitor 11 TYRO3 Inhibitor 8 | BMS-777607 (ASLAN002) is a small molecule that inhibits MET, MST1R (RON), TYRO3, and AXL, resulting in decreased downstream pathway activation, potentially resulting in decreased tumor cell growth and metastasis (PMID: 19260711, PMID: 20515943, PMID: 24233399, PMID: 26555154). | |
Bosutinib | Bosulif | SKI-606|PF-5208763 | ABL Inhibitor (pan) 9 AXL Inhibitor 30 BCR-ABL Inhibitor 31 BTK inhibitor 36 SRC Inhibitor 31 TNK2 Inhibitor 6 | Bosulif (bosutinib) inhibits SRC and ABL kinases and has additional activity against other kinases including AXL, TNK2, and BTK, resulting in decreased pathway activation and inhibition of tumor cell proliferation (PMID: 12543790, PMID: 19039322, PMID: 26555154). Bosulif (bosutinib) is FDA-approved for use in adult and pediatric patients 1 year of age and older with Ph+ (BCR-ABL) chronic myelogenous leukemia (FDA.gov). |
Glesatinib | MGCD-265|MGCD 265 | AXL Inhibitor 30 MET Inhibitor 59 RON Inhibitor 11 VEGFR Inhibitor (Pan) 36 | Glesatinib (MGCD265) inhibits several tyrosine kinases including MET (type II inhibitor), MST1R (RON), and AXL, as well as VEGFR1-3, and TIE2, which may result in decreased tumor growth (PMID: 25806189, PMID: 26555154, PMID: 32306194). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|