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Investigational

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Primary Target

Insulin-like growth factor I receptor

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SRC

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Serine/threonine-protein kinase Aurora-A

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Tyrosine-protein kinase ABL

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Exelixis

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XL-418

OLJ18SRI8A

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Status:

Investigational

Class (Stereo):

CHEMICAL (ACHIRAL)

XL418 is a dual protein kinase B (Akt) and ribosomal protein S6 Kinase (p70 S6K) inhibitor that also acts as an ATP-pocket binder with potential antineoplastic activity. XL418 was involved in phase I clinical trial in patients with solid tumors, howe...

ver, in Dec 2007, this study was discontinued, due to low drug exposure.

XL-228

33M2XSK003

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Status:

Investigational

Class (Stereo):

CHEMICAL (ACHIRAL)

Targets:

Serine/threonine-protein kinase Aurora-A

Tyrosine-protein kinase ABL

Insulin-like growth factor I receptor

Conditions:

Chronic myeloid leukemia

Philadelphia-chromosome-positive acute lymphocytic leukemia

XL-228 is a third generation inhibitor of Abl that shows efficacy in a variety of cell lines, including those exhibiting T315I mutations. XL-228, a tyrosine kinase inhibitor, is involved in binding to and inhibiting the activities of multiple tyrosin...

e kinases, such as the insulin-like growth factor 1 receptor (IGF1R), Src tyrosine kinase, and Bcr-Abl tyrosine kinase. Blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis. XL-228 is a multitargeted protein kinase inhibitor targeting IGF1R, the aurora kinases, IGF-1R, cSrc, BCR/Abl and SRC kinases. XL-228 displays anticancer chemotherapeutic activity and it was in clinical trials as a potential treatment for chronic myelogenous leukemia (CML). On 22 Feb 2011 phase I clinical studies for chronic myeloid leukaemia and cancer in USA were discontinued.

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