**Acknowledgements**

*Cutaneous Melanoma*

therapeutics for melanoma.

to the inhibitor [87].

inhibitors [88].

**5. State of atypical PKC inhibitors**

which initiated as a result of PKC-ι inhibition using specific inhibitors. These results indicate that PKC-ι is being regulated in a rather complex manner, which involves itself as a key component. PKC-ι specific inhibition using ICA-1S and ICA-1T leads to a decrease in its own production, and during this process, PKC-ι inhibition also triggers multiple anti-tumor/pro-apoptotic signaling. This makes PKC-ι one of the central key points of interest to specifically target and diminish as a means of treating melanoma. The results also strongly suggest that PKC-ι is a prime novel biomarker that can be targeted to design and develop personalized and targeted

We have discussed the effects of five aPKC specific inhibitors throughout this

Atypical PKCs were first considered as a novel therapeutic target by Stallings-Mann et al. in 2006. They screened aurothiomalate as a potent inhibitor of the interaction between PB1 domain of PKC-ι and Par6 [87]. Half maximal inhibitory concentration (IC50) of aurothiomalate ranged from 300 nM to 100 μM and indicated that some cell lines are insensitive (i.e. H460 and A549 lung cancer cells)

Blázquez et al. tested calphostin C and chelerythrine against West Nile virus (WNV) which significantly inhibit WNV multiplication in cell culture without affecting cell viability. They report that PKCs have also been implicated in different steps during viral replication. Calphostin C and chelerythrine two wide range PKC inhibitors that target all three PKC classes. Results indicate that atypical PKCs are involved in WNV multiplication process which can be effectively retard using said

Kim et al. reported the application of Echinochrome A as an inducer of cardiomyocyte differentiation from mouse embryonic stem cells. Echinochrome A was

*Structures of the aPKC specific inhibitors (ACPD, DNDA, ζ-Stat, ICA-1S and ICA-1T). chemical structures of ACPD (a) and DNDA are specific to both PKC-ι and PKC-ζ, ζ-Stat (C) is specific to PKC-ζ while ICA-1S (D) and ICA-1T (E) are specific to PKC-ι. molecular weights (MW) of ACPD (140.14 g/mol), DNDA (318.32 g/mol), ζ-Stat (MW = 384.34 g/mol), ICA-1S (MW = 256.26 g/mol) and ICA-1T (MW = 336.24 g/*

chapter. The structures of these compounds are shown in **Figure 5**.

**34**

**Figure 5.**

*mol), respectively.*

The authors acknowledge the generous financial contributions from the Frederick H. Leonhardt Foundation, David Tanner Foundation, Bradley Zankel Foundation, Inc., Kyrias Foundation, Brotman Foundation of California, Baker Hughes Foundation, Irving S. Cooper Family Foundation, and the Creag Foundation.
