Summary of chemical leads addressing apoptosis-relevant targets
Chemical lead . | Developing company or organization . | Target . | Stage . |
|---|---|---|---|
| BCL2 | |||
| Genasense (Bcl-2 antisense) | Genta (Aventis) | BCL2 | Phase 3 |
| Gossypol | National Cancer Institute/Ascenta | BCL2 | Phase 2 |
| Polyphenol E | Mayo (Mitsui Norin) | BCL2 | Phase 1 |
| HA14-1 analogues/CPM-1285 analogues | Raylight Chemokine Pharmaceuticals | BCL2 | Preclinical |
| BH3I-1/BH3I-2 | Harvard University | BCL2 | Preclinical |
| Antimycin A3 | University of Washington | BCL2 | Preclinical |
| Compound 6 | University of Michigan | BCL2 | Preclinical |
| Terphenyl derivative | Yale University | BCL2 | Preclinical |
| Apogossypol | Burnham/National Cancer Institute | BCL2 | Preclinical |
| SAHBs | Harvard University | BCL2 | Preclinical |
| A-779024 (ABT 737) | Abbott Laboratories | BCL2 | Preclinical |
| 3CI-AHPC/MM11453 | Burnham | NUR77/TR3 | Preclinical |
| IAP | |||
| Benzenesulphonamide derivatives | Novartis Genome Foundation | IAP | Preclinical |
| Tripeptides | Abbott Laboratories | IAP | Preclinical |
| Constrained peptideomimetic | University of Michigan | IAP | Preclinical |
| Embeline | University of Michigan | IAP | Preclinical |
| Di/triphenylureas (1396-11,12,34) | The Burnham Institute/TPIMS | IAP | Preclinical |
| Compound 3 | University of Texas Southwestern Medical Center | IAP | Preclinical |
| XIAP antisense (AEG35156/GEM640) | Aegera Therapeutics | XIAP | Phase 1 |
| Survivin antisense (ISIS 23722) | ISIS Pharmaceuticals (Lilly) | Survivin | Phase 1 |
| p53 | |||
| CP-31398 | Pfizer | p53 | Preclinical |
| Chlorofusin | University Chemical Laboratory, United Kingdom | MDM2 | Preclinical |
| Sulfonamide compound 1 | Virginia Commonwealth University | MDM2 | Preclinical |
| 2-phenoxybenzoyl-tryptophan derivatives | Schering-Plough Research Institute | MDM2 | Preclinical |
| Nutlins | Hoffmann-La Roche | MDM2 | Preclinical |
| Death receptor | |||
| TRAIL | Genentech/Amgen | pan-TRAILR | Phase 1 |
| HGS-ETR1/HGS-TR2J | Human Genome Sciences | TRAILR1/R2 | Phase 1 |
| 2-cyano-3, 12-dioxoolean-1,9-bien-28-oic acid (CDDO) | Dartmouth College/Reata Discovery | FLIP | Preclinical |
| Bryostatin | National Cancer Institute | PKC (TNF) | Phase 2 |
| ATRA | Ligand | RAR (TRAIL) | Approved |
| AKT | |||
| DPIs | University of Arizona | AKT/PKB | Preclinical |
| IL-6-hydroxymethyl-chiro-inositol 2(R)-2-O-methyl-3-O-octadecylcarbonate | University of Bologna | AKT/PKB | Preclinical |
| API-2 | University of South Florida | AKT/PKB | Preclinical |
| Wortmannin | University of Fribourg, Switzerland | PI3K | Preclinical |
| LY294002 | Lilly Research Laboratories | PI3K | Preclinical |
| PX866 | University of Arizona | PI3K | Preclinical |
| Geldanamycin (and 17-AAG) | NCI/KOSAN | HSP90 | Phase 1 |
| 17-AAG (hydroquinone) | Infinity | HSP90 | Phase 1 |
| ADD70 | Institut National de la Santé et de la Recherche Médicale U-517, France | HSP70 | Preclinical |
| IKK/NFκB | |||
| Bortezomib | Millennium Pharmaceuticals | 26S proteasome | Approved |
| MG-115, MG-132 | Tokyo Metropolitan Institute of Medical Science | 26S proteasome | Preclinical |
| Lactacystin | University of Tokyo | 26S proteasome | Preclinical |
| Epoxomicin | Yale University | 26S proteasome | Preclinical |
| SPC-839 | Signal Pharmaceuticals | IKK | Preclinical |
| SC-514 | Pfizer | IKK | Preclinical |
| Pyridooxazinone derivative | Bayer AG | IKK | Preclinical |
| BMS-345541 | Bristol-Myers Squibb Pharmaceutical Research Institute | IKK | Preclinical |
| B-carboline | Millennium Pharmaceuticals | IKK | Preclinical |
| 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxy-phenyl]-4-piperidin-4-yl nicotinonitrile | Bayer Yakuhin | IKK | Preclinical |
| Ureido-thiophene carboxamide derivative | SmithKline Beecham/AstraZeneca | IKK | Preclinical |
| Indole carboxamide derivative | Aventis Pharma | IKK | Preclinical |
| Benzo-imidazole carboxamide derivative | Aventis Pharma | IKK | Preclinical |
| Amino-imidazole carboxamide derivative | SmithKline Beecham | IKK | Preclinical |
| Pyridyl cyanoguanidine derivative | LEO Pharma A/S | IKK | Preclinical |
| Anilino-pyrimidine derivative | Signal Pharmaceuticals | IKK | Preclinical |
Chemical lead . | Developing company or organization . | Target . | Stage . |
|---|---|---|---|
| BCL2 | |||
| Genasense (Bcl-2 antisense) | Genta (Aventis) | BCL2 | Phase 3 |
| Gossypol | National Cancer Institute/Ascenta | BCL2 | Phase 2 |
| Polyphenol E | Mayo (Mitsui Norin) | BCL2 | Phase 1 |
| HA14-1 analogues/CPM-1285 analogues | Raylight Chemokine Pharmaceuticals | BCL2 | Preclinical |
| BH3I-1/BH3I-2 | Harvard University | BCL2 | Preclinical |
| Antimycin A3 | University of Washington | BCL2 | Preclinical |
| Compound 6 | University of Michigan | BCL2 | Preclinical |
| Terphenyl derivative | Yale University | BCL2 | Preclinical |
| Apogossypol | Burnham/National Cancer Institute | BCL2 | Preclinical |
| SAHBs | Harvard University | BCL2 | Preclinical |
| A-779024 (ABT 737) | Abbott Laboratories | BCL2 | Preclinical |
| 3CI-AHPC/MM11453 | Burnham | NUR77/TR3 | Preclinical |
| IAP | |||
| Benzenesulphonamide derivatives | Novartis Genome Foundation | IAP | Preclinical |
| Tripeptides | Abbott Laboratories | IAP | Preclinical |
| Constrained peptideomimetic | University of Michigan | IAP | Preclinical |
| Embeline | University of Michigan | IAP | Preclinical |
| Di/triphenylureas (1396-11,12,34) | The Burnham Institute/TPIMS | IAP | Preclinical |
| Compound 3 | University of Texas Southwestern Medical Center | IAP | Preclinical |
| XIAP antisense (AEG35156/GEM640) | Aegera Therapeutics | XIAP | Phase 1 |
| Survivin antisense (ISIS 23722) | ISIS Pharmaceuticals (Lilly) | Survivin | Phase 1 |
| p53 | |||
| CP-31398 | Pfizer | p53 | Preclinical |
| Chlorofusin | University Chemical Laboratory, United Kingdom | MDM2 | Preclinical |
| Sulfonamide compound 1 | Virginia Commonwealth University | MDM2 | Preclinical |
| 2-phenoxybenzoyl-tryptophan derivatives | Schering-Plough Research Institute | MDM2 | Preclinical |
| Nutlins | Hoffmann-La Roche | MDM2 | Preclinical |
| Death receptor | |||
| TRAIL | Genentech/Amgen | pan-TRAILR | Phase 1 |
| HGS-ETR1/HGS-TR2J | Human Genome Sciences | TRAILR1/R2 | Phase 1 |
| 2-cyano-3, 12-dioxoolean-1,9-bien-28-oic acid (CDDO) | Dartmouth College/Reata Discovery | FLIP | Preclinical |
| Bryostatin | National Cancer Institute | PKC (TNF) | Phase 2 |
| ATRA | Ligand | RAR (TRAIL) | Approved |
| AKT | |||
| DPIs | University of Arizona | AKT/PKB | Preclinical |
| IL-6-hydroxymethyl-chiro-inositol 2(R)-2-O-methyl-3-O-octadecylcarbonate | University of Bologna | AKT/PKB | Preclinical |
| API-2 | University of South Florida | AKT/PKB | Preclinical |
| Wortmannin | University of Fribourg, Switzerland | PI3K | Preclinical |
| LY294002 | Lilly Research Laboratories | PI3K | Preclinical |
| PX866 | University of Arizona | PI3K | Preclinical |
| Geldanamycin (and 17-AAG) | NCI/KOSAN | HSP90 | Phase 1 |
| 17-AAG (hydroquinone) | Infinity | HSP90 | Phase 1 |
| ADD70 | Institut National de la Santé et de la Recherche Médicale U-517, France | HSP70 | Preclinical |
| IKK/NFκB | |||
| Bortezomib | Millennium Pharmaceuticals | 26S proteasome | Approved |
| MG-115, MG-132 | Tokyo Metropolitan Institute of Medical Science | 26S proteasome | Preclinical |
| Lactacystin | University of Tokyo | 26S proteasome | Preclinical |
| Epoxomicin | Yale University | 26S proteasome | Preclinical |
| SPC-839 | Signal Pharmaceuticals | IKK | Preclinical |
| SC-514 | Pfizer | IKK | Preclinical |
| Pyridooxazinone derivative | Bayer AG | IKK | Preclinical |
| BMS-345541 | Bristol-Myers Squibb Pharmaceutical Research Institute | IKK | Preclinical |
| B-carboline | Millennium Pharmaceuticals | IKK | Preclinical |
| 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxy-phenyl]-4-piperidin-4-yl nicotinonitrile | Bayer Yakuhin | IKK | Preclinical |
| Ureido-thiophene carboxamide derivative | SmithKline Beecham/AstraZeneca | IKK | Preclinical |
| Indole carboxamide derivative | Aventis Pharma | IKK | Preclinical |
| Benzo-imidazole carboxamide derivative | Aventis Pharma | IKK | Preclinical |
| Amino-imidazole carboxamide derivative | SmithKline Beecham | IKK | Preclinical |
| Pyridyl cyanoguanidine derivative | LEO Pharma A/S | IKK | Preclinical |
| Anilino-pyrimidine derivative | Signal Pharmaceuticals | IKK | Preclinical |
Chemical leads against targets are listed. The approximate stage of clinical development is indicated. It should be noted that some of the chemical leads interact with additional protein targets not listed here. Some targets such as the proteasome, NFκB, and HSP90 operate on many other proteins besides the apoptosis-relevant proteins. Only antisense and protein compounds that are in clinical development are listed. Gene therapy is excluded. 17-AAG indicates 17-allylamino-17-demethoxygeldanamycin; ATRA, all-trans-retinoic acid; DPI, diphenyleneiodonium; API-2, alkaline protease inhibitor 2; RAR retinoic acid receptor; PI3K, phosphatidylinositol 3′-kinase. The listing is not comprehensive.