Table 1. Clinical development and current indications of candidate CIMMs.
Data were obtained from ongoing or completed human clinical trials listed at http://www.clinicaltrials.gov.
| Metabolic pathway | Molecular target | Stage of clinical development; indication |
|---|---|---|
| mTOR | ||
| Rapamycin | mTORC1 | Approved; prophylaxis of organ rejection |
| Temsirolimus | mTORC1 | Approved; advanced renal cell carcinoma |
| Everolimus | mTORC1 | Approved; advanced renal cell carcinoma |
| Ridaforolimus | mTORC1 | Phase II; advanced solid and hematologic malignancies |
| OSI-027 | mTORC1 and mTORC2 | Phase I; advanced solid and hematologic malignancies |
| Oleandrin | p70S6K | Phase I; advanced solid tumors |
| AMPK | ||
| Metformin | AMPK | Approved; type II diabetes |
| AICAR | AMPK | Phase II; type II diabetes, Lesch-Nyhan syndrome |
| GW501516 | AMPK | Phase II; dyslipidemia |
| PI3K | ||
| SF1126 (LY294002 pro-drug) | PI3K | Phase I; advanced solid tumors |
| CAL-101 | PI3K (p110δ) | Phase I; hematologic malignancies |
| PX-866 | PI3K (p110α) | Phase I; advanced solid tumors |
| MK-2206 | AKT | Phase I; advanced solid tumors |
| Oleandrin | AKT | Phase I; advanced solid tumors |
| Wnt/β-catenin | ||
| Lithium | GSK-3α and -β | Approved; manic-depressive disorder |
| Valproic acid | GSK-3β | Approved; seizure disorder |
| Flavopiridol | GSK-3α and -β | Phase II; advanced solid and hematologic malignancies |
| Staurosporine | GSK-3α and -β | Phase II; advanced solid and hematologic malignancies |
| NP031112 | GSK-3β | Phase I/II; Alzheimer’s disease |
| TWS119 | GSK-3β | Preclinical |