Table 2.
Main classes of PKC inhibitors used in the clinic
| Name Reference | Structure | PKC Selectivity (site) |
Isozyme Selectivity |
|---|---|---|---|
| Balanol76,221 |  |
An inhibitor of PKC and PKA (ATP-binding) | e.g., N-Tosyl derivative221 βII>βI>η>δ>α>ε>>>PKA |
| Riluzole77 |  |
Likely inhibits other S/T kinases (ATP-binding) | Preferential inhibitor of PKCα |
| Staurosporin222 |  |
(ATP-binding) | Pan-PKC inhibitor |
| Enzastaurin223 |  |
(ATP-binding) | 3- to 5-fold selectivity for βPKC inhibition |
| δV1-128 (KAI-9803 or Delcasertib*) | SFNSYELGSL-carrier** | δPKC inhibitor (RACK-binding) | >1,000X over other isozymes |
| εV1-2224 (KAI-1678*) | EAVSLKPT-carrier** | εPKC inhibitor (RACK-binding) | >100X over other isozymes |
| HDAPIGYD-Carrier** | εPKC activator (intramolecular interaction in PKC) | >100X over other isozymes | |
| Aprinocarsen225 | Anti-sense oligonucleotide that targets αPKC mRNA | PKCα inhibitor (expression) | PKCα |
| Midostaurin (PKC412)152,226 |  |
(ATP-binding) | A number of protein kinases, including PKC |
| UCN-01227 (7-hydroxy-staurosporin) |  |
(ATP-binding) | A number of protein kinases including tyrosine kinases and classical PKC at a similar IC50 (25–50nM) |
| Rottlerin72226 5, 7, dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-methyl-5-acetlybenzyl)-8-cinnamoyl-1,2-chromene |  |
PKCδ inhibitor (ATP-binding) | PKC δ, but also calcium calmodulin kinase VI at a similar IC50 (5µM). |
| Bryostatin 1228 |  |
C1 domain | 2-fold selectivity for PKCε over PKC α,δ84 |
*
The exact composition of KAI compounds is unavailable.
**
Carrier is the TAT-derived peptide, CYGRKKRQRRR229