Table 1. Commonly used inhibitors of aPKCs.
| Inhibitor | IC50* | Specificity | Reference |
|---|---|---|---|
| ZIP | ∼ 1 μM (PKMζ)† | All aPKCs, other PKCs, other kinases | Ling et al. [59] |
| Lisman [133] | |||
| Wu-Zhang et al. [57] | |||
| Yao et al. [58] | |||
| Farah et al. [47] | |||
| Chelerythrine | >40 μM (PRKCZ) | Reported to be ∼1 μM† (for PKMζ) | Thompson and Fields [61] |
| Pfizer 01 | ∼22 nM (PRKCZ) | ∼7x for PRKCZ over PRKCI | Trujillo et al. [63] |
| Pfizer 03 | ∼2.26 nM (PRKCZ) | n/a | Trujillo et al. [63] |
| Pfizer 09 (PZ09) | ∼5.18 nM (PRKCZ) | ∼10x for PRKCZ over PRKCI | Trujillo et al. [63] |
| CRT0066854 | ∼0.132 μM (PRKCI) | ∼4.7x for PRKCI | Kjær et al. [70] |
| ∼0.623 μM (PRKCZ) | |||
| CRT0066390 | ∼2.5 μM (PRKCI) | ∼2.8x for PRKCI | Kjær et al. [70] |
| ∼7.1 μM (PRKCZ) | |||
| CRT0329868 | ∼8.4 nM (PRKCI) | n/a | Mirza et al. [71] |
| 2-amino-3-carboxy-4-phenylthiophenes | Titchenell et al. [65] | ||
| 6 | ∼6 μM (PRKCZ) | ∼1.6x for PRKCZ over PRKCI | |
| 10 | ∼6 μM (PRKCZ) | n/a | |
| 14 | ∼5 μM (PRKCZ) | ∼2.2x to 1.6x for PRKCI over PRKCZ | |
| 29 | ∼2 μM (PRKCZ) | n/a | |
| 30 | ∼1 μM (PRKCZ) | Approx. equivalent | |
| 32 | ∼2 μM (PRKCZ) | ∼2x for PRKCI over PRKCz | |
| 33 | ∼4 μM (PRKCZ) | n/a | |
| PS171 | <50 μM (PRKCZ) | ∼2.5x for PRKCZ over PRKCI | Lopez-Garcia et al. [40] |
| PS168 | <50 μM (PRKCZ) | ∼5x for PRKCZ over PRKCI | Lopez-Garcia et al. [40] |
| 4-benzimidazolyl-3-phenylbutanoic acid analog series | Fröhner et al. [72] | ||
| 1d | ∼33 μM (PRKCZ) | ||
| 1n | ∼38 μM (PRKCZ) | ||
| 1o | ∼55 μM (PRKCZ) | ||
| 1p | ∼39 μM (PRKCZ) | ||
| 1q | ∼18 μM (PRKCZ) | ||
| 1s | ∼43 μM (PRKCZ) | ||
| 1w | ∼23 μM (PRKCZ) | ||
| 1x | ∼33 μM (PRKCZ) | Most PRKCZ selective (no effect on PRKCI) | |
| 1yc | ∼25 μM (PRKCZ) | ||
| 1y-e1 | ∼20 μM (PRKCZ) | ||
| 1y-e2 | ∼37 μM (PRKCZ) | ||
| ICA-1 | ∼0.1 μM (PRKCI) | Does not inhibit PRKCZ at low conc. | Pillai et al. [67] |
| [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate | |||
| ACPD | ∼2.5 μM (PRKCZ/I)† | Approx. equivalent | Ratnayake et al. [66] |
| 2-acetyl-1,3-cyclopentanedione | |||
| DNDA | ∼2.5 μM (PRKCZ/I)† | Approx. equivalent | Ratnayake et al. [66] |
| 3,4-diaminonaphthalene-2,7-disulfonic acid | |||
List of compounds described as inhibitors of aPKCs, the concentration that inhibits 50 percent enzymatic activity of the kinase (IC50), respective specificities and associated references are listed. Since this list was compiled from several studies, each using different conditions, the IC50 are only to be used as approximation and not directly compared with each other. While most IC50s were derived from in vitro assays, those indicated by † are from in vivo studies.
*
Kinase assays were performed at various ATP concentrations and should not be compared across studies.
†In vivo IC50.