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XL228
- Development stage
- Discontinued
- Lead developer
- Exelixis
- Modality
- Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
- Administration
- Intravenous
01
Overview
XL228 is a small molecule, investigational anticancer compound developed as a multi-targeted tyrosine kinase inhibitor. It potently inhibits several kinases implicated in cancer cell proliferation, survival, and metastasis—including insulin-like growth factor type 1 receptor (IGF1R), BCR-Abl (including the T315I mutant form associated with resistance to other therapies), Src family kinases, Aurora kinases, and fibroblast growth factor receptors 1–3 (FGFR1–3). By blocking these targets, XL228 disrupts key signaling pathways involved in tumor growth and resistance mechanisms. The drug was primarily investigated for use in chronic myeloid leukemia (CML), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and various solid tumors. Clinical development reached phase I trials but was discontinued for all indications[1][5][6][7][9].
- Other names
- XL228XL-228XL 228
02
Targets
AURKA (Aurora kinase A)ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)IGF-1R (Insulin-like growth factor 1 receptor)BCR-ABL1 T315I (Bcr-Abl T315I mutant protein)LYN (LYN proto-oncogene, Src family tyrosine kinase)FGFR2 (Keratinocyte growth factor receptor)
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