Protein kinase Cδ is a therapeutic target in malignant melanoma with NRAS mutation.

ABSTRACT: NRAS is the second most frequently mutated gene in melanoma. Previous reports have demonstrated the sensitivity of cancer cell lines carrying KRAS mutations to apoptosis initiated by inhibition of protein kinase Cδ (PKCδ). Here, we report that PKCδ inhibition is cytotoxic in melanomas with primary NRAS mutations. Novel small-molecule inhibitors of PKCδ were designed as chimeric hybrids of two naturally occurring PKCδ inhibitors, staurosporine and rottlerin. The specific hypothesis interrogated and validated is that combining two domains of two naturally occurring PKCδ inhibitors into a chimeric or hybrid structure retains biochemical and biological activity and improves PKCδ isozyme selectivity. We have devised a potentially general synthetic protocol to make these chimeric species using M

SUBMITTER: Takashima A 

PROVIDER: S-EPMC4160068 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature