XL228 / Exelixis - LARVOL DELTA

The PKN1- TRAF1 signaling axis as a potential new target for chronic lymphocytic leukemia. (PubMed, Oncoimmunology) - "Through a screen of 700 kinase inhibitors, we identified two inhibitors, OTSSP167, and XL-228, that inhibited PKN1 in the nanomolar range and induced dose-dependent loss of TRAF1 in RAJI cells. Although correlative, these findings suggest the PKN1-TRAF1 signaling axis as a potential new target for CLL. These findings also suggest the use of the orally available inhibitor OTSSP167 in combination treatment with venetoclax for TRAF1 overexpressing CLL."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2 • CASP3 • CD40 • MCL1 • RELA

Exelixis: Annual Report 2014 (Exelixis, Inc) - Discontinued development of XL228 in oncology

Discontinued • Oncology

The Identification of Novel Epigenetic Therapies for ALK-Driven Haematological Malignancies (ASH 2019) - "Results Several of the validated drugs have previously been used/trialled in the clinic for the treatment of various cancers, e.g. aurora kinase (XL-228), topoisomerase (Mitoxantrone HCl) and HDAC (Romidepsin) inhibitors – these functioned as internal controls for the drug screens. However, an assortment of novel drugs was also identified that have not previously been described in the context of the treatment of ALK-driven haematological malignancies; including the FLT3 inhibitor KW2449 which caused a >75% decrease in viability in all the tested cell lines and as such may serve as a novel front line therapy...Furthermore, we investigated the combinatorial potential of the identified DNMT inhibitor with ALK TKIs such as Brigatinib and observed the inhibitor acting synergistically (as per Bliss-Independence calculations) resulting in a further decrease in cell viability...Data reveal a potent inhibitor of DNA methylation as a candidate drug that suppresses the growth of..."

ALK • FLT3