Table 1.
Examples of SMIs targeted BCL-2 family members in clinical trials or pre-clinical studies
| SMI | Target(s) | Clinical Trials or Pre-Clinical studies | ||
|---|---|---|---|---|
| Cancer Type | Combination Drug | Clinical Trials* | ||
| Gossypol | BCL-2 BCL-XL MCL-1 BCL-W BCL-B |
Adrenocortical carcinoma | N/A | II |
| Lymphoma | Paclitaxel, carboplatin | I | ||
| Advanced SCLC, solid tumors | Cisplatin, etoposide | I | ||
| Advanced prostate cancer | Bicalutamide | II | ||
| Obatoclax | BCL-2 MCL-1 BCL-XL BCL-W BCL-B BFL-1 |
Advanced SCLC | Carboplatin, etoposide | I/II |
| AML | N/A | II | ||
| CLL | N/A | I/II | ||
| Hodgkins lymphoma | N/A | II | ||
| MCL, Lymphoma | Bortezomib | I/II | ||
| NSCLC | Docetaxel | I/II | ||
| SCLC | Topotecan hydrochloride | I/II | ||
| ABT-263 (ABT-737) | BCL-2 BCL-XL BCL-W |
CLL, SCLC, Leukemia | N/A | II,I,II |
| Lymphoma, CLL, solid tumors | Ketoconaxole | I | ||
| CLL | Fludarabine, Cyclophosphomide, Rituximab | I | ||
| Solid tumors | Doxetaxel, Gemcitabine, Etoposide, Cisplatin, Paclitaxel | I | ||
| Lymphoma; CLL | Rifampin | I; II | ||
| ABT-199 | BCL-2 | SLL, NHL, CLL, AML | N/A | I; II |
| B-cell Lymphoma | Rituximab | IB | ||
| Maritoclax | MCL-1 | Melanoma | Single and with ABT-737; In vitro and In vivo | N/A |
| AML | Single; In vitro | |||
| Clitocine | MCL | hepatocellular carcinoma | Single; In vitro and In vivo | N/A |
| UMI-77 | MCL | Pancreatic cancer | Single; In vitro and In vivo | N/A |
*
The information for clinical trials is adapted from www.clinicaltrials.gov
Abbreviations: AML – acute myeloid leukemia, CLL – chronic lymphocytic leukemia, MCL – mantle cell lymphoma, NSCLC – non-small cell lung cancer, NHL – non-Hodgkins lymphoma, SCLC –small cell lung cancer, SLL – small lymphocytic leukemia, N/A–not available
Note: None of the MCL-1 inhibitors listed is in clinical trials yet, thus we provided the information on preclinical studies for these instead. More details can be found in reviews (Belmar and Fesik, 2014; Thomas et al., 2013).