Table 1.
Activators and inhibitors of protein kinase C (PKC) and their applications in clinical trials.
| Diseases | PKC Activators or Inhibitors/Other Agents | Phases | Clinical Benefits | References |
|---|---|---|---|---|
| Cancer | ||||
| Metastatic triple negative breast cancer | UCN-01/irinotecan | II | No significant clinical benefits | [48] |
| Advanced ovarian cancer | UCN-01/topotecan | II | No significant clinical benefits | [51] |
| Mutant FLT3-positive acute myeloid leukemia | Midostaurin/standard chemotherapy | III | Significantly prolonged overall and event-free survival | [56] |
| Advanced systemic mastocytosis | Midostaurin | II | Significant clinical benefits and no unexpected toxicity | [61] |
| High-risk diffuse large B-cell lymphoma | Enzastaurin (LY317615) | III | No significant clinical benefits | [80] |
| Multiple myeloma, lung cancer with brain metastases, epithelial ovarian or primary peritoneal carcinoma, metastatic breast cancer, and relapsed or refractory mantle cell lymphoma and advanced cutaneous T-cell lymphoma | Enzastaurin | II | No significant clinical benefits | [81,82,83,84,85,86] |
| Advanced non-small-cell lung cancer | Enzastaurin/erlotinib | II | No significant clinical benefits | [87] |
| Glioblastoma multiforme and gliosarcoma | Enzastaurin/temozolomide + radiation therapy | II | No significant clinical benefits | [88] |
| Castration-resistant metastatic prostate cancer | Enzastaurin/docetaxel + prednisone | II | No significant clinical benefits | [89] |
| Advanced ovarian cancer | Enzastaurin/paclitaxel + carboplatin | II | No significant clinical benefits | [90] |
| Metastatic colorectal cancer | Enzastaurin/5-fluorouracil + leucovorin + bevacizumab | II | No significant clinical benefits | [91] |
| Advanced non-small cell lung cancer | Enzastaurin/pemetrexed | II | No significant clinical benefits | [92] |
| Advanced or metastatic pancreatic cancer | Enzastaurin/gemcitabine | II | No significant clinical benefits | [93] |
| Metastatic malignant melanoma, renal cell carcinoma, and colorectal cancer, non-Hodgkin’s lymphoma, relapsed multiple myeloma, advanced sarcoma and advanced head and neck cancer, metastatic or recurrent squamous cell carcinoma of the head and neck, squamous cell carcinoma of the cervix, and recurrent epithelial ovarian carcinoma | Bryostatin-1 | II | No significant clinical benefits | [205,206,207,208,209,210,211,212,213,214] |
| Advanced pancreatic carcinoma, non-small cell lung cancer, and esophageal cancer, advanced or recurrent carcinoma of the cervix, and advanced gastric or gastroesophageal junction adenocarcinoma | Bryostatin-1/paclitaxel | II | No significant clinical benefits | [215,216,217,219,220] |
| Renal cell carcinoma | Bryostatin-1/interleukin-2 | II | No significant clinical benefits | [218] |
| Recurrent platinum-sensitive or resistant ovarian cancer | Bryostatin-1/cisplatin | II | Modest response rate but high toxicity in platinum-pretreated patients | [221] |
| Aggressive B-cell non-Hodgkin lymphoma relapsing after autologous stem cell transplantation | Bryostatin-1/vincristine | II | Overall response rate of 31% (efficacy in select patients) | [222] |
| Diabetic retinopathy and neuropathy | ||||
| Moderate to severe non-proliferative diabetic retinopathy | Ruboxistaurin (LY 333531) | III | Reduced occurrence of sustained moderate vision loss but not significant | [106] |
| Diabetic retinopathy (retinopathy level 20 to 47D or 35B to 53E) | Ruboxistaurin | III | Approximately 50% reduction of sustained moderate vision loss but not significant | [107] |
| Diabetes and symptomatic diabetic peripheral neuropathy | Ruboxistaurin | III | No significant and progressive improvement in symptoms | [108] |
| Neurological diseases | ||||
| Alzheimer’s disease | Bryostatin-1 | IIa | Cognitive improvement in the first 24 weeks | [226] |
| Bryostatin-1 | II | Improved the full analysis set and the Severe Impairment Battery scores at 15 weeks | [227] | |
| Postherpetic neuralgia | KAI-1678 | II | No significant reduction in pain intensity | [141] |
| Transplant rejection | ||||
| De novo kidney transplantation | Sotrastaurin (AEB071) | II | Low efficacy and high adverse events | [114] |
| De novo kidney transplantation | Sotrastaurin/tacrolimus | II | Limited benefits over standard immunosuppressive therapy and high adverse events | [116] |
| De novo kidney transplantation | Sotrastaurin/everolimus | II | High efficacy failure rates and adverse events | [117] |
| De novo liver transplantation | Sotrastaurin/tacrolimus | II | High efficacy failure rates and adverse events | [115] |
| Cardiovascular diseases | ||||
| Myocardial infarction | Delcasertib (KAI-9803) | II | No significant clinical benefits | [140] |
| Infections | ||||
| Human immunodeficiency virus (HIV) infection | Bryostatin-1 | I | No effect on the transcription of latent HIV-1 | [230] |