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

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.

Protein kinase Cδ inactivation inhibits cellular proliferation and decreases survival in human neuroendocrine tumors.

The concept of targeting cancer therapeutics toward specific mutations or abnormalities in tumor cells, which are not found in normal tissues, has the potential advantages of high selectivity for the tumor and correspondingly low secondary toxicities. Many human malignancies display activating mutations in the Ras family of signal-transducing genes or over-activity of p21(Ras)-signaling pathways. Carcinoid and other neuroendocrine tumors have been similarly demonstrated to have activation of Ras signaling directly by mutations in Ras, indirectly by loss of Ras-regulatory proteins, or via constitutive activation of upstream or downstream effector pathways of Ras, such as growth factor receptors or PI(3)-kinase and Raf/mitogen-activated protein kinases.

A divergent strategy for the synthesis of secologanin derived natural products.

The syntheses of D,L-geissoschizol, D,L-corynantheidol, D,L-dihydrocorynantheol, D,L-protoemetinol, and D,L-3-epi-protoemetinol have been accomplished from a single synthetic intermediate.

Synthesis of (+/-)-Oleocanthal via a Tandem Intramolecular Michael Cyclization-HWE Olefination.

A synthesis of racemic oleocanthal has been accomplished in eleven steps from 1,3 propanediol by a key tandem intramolecular Michael cyclization-Horner Wadsworth Emmons olefination.