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Table 1 Drugs currently in clinical trials targeting tumor suppressor/oncogene pathways or proteins within the mitochondrial pathway of apoptosis

From: Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy?

  Target Drug Mechanism Clinical trial
Tumor suppressors/oncogenes p53 ADVEXIN (Ade5CMV-p53)1 Gene therapy for introduction of wtp53 Phase III
P13K Idelalisib (GS-1101)2 Inhibitor of PI3Kδ Phase II
Buparlisib3 ATP competitive inhibitor of class I PI3K Phase II
SAR245408 (XL 147)4 ATP competitive inhibitor of class I PI3K Phase I/II
P13K/mTOR BEZ2353 Dual kinase inhibitor to PI3K and mTOR Phase II
BGT2263 Dual kinase inhibitor to PI3K and mTOR Phase I
PF-046915025 Dual kinase inhibitor to PI3K and mTOR Phase I/II
SAR2454096 Dual kinase inhibitor to PI3K and mTOR Phase II
AKT Perifosine7 Inhibitor to AKT Phase I/II
Receptor tyrosine kinases (e.g., EGFR) Iressa (Gefitinib)8 ATP competitive tyrosine kinase inhibitor Phase I/II
Tarceva (Erlotinib)9 ATP competitive EGFR inhibitor Phase II/III
Cetuximab10 Monoclonal-antibody against EGFR prevents receptor dimerization Phase II/III
Tykerb (Lapatinib)11 Inhibitor to receptor phosphorylation Phase I/II
Vectibix (Panitumumab)12 Monoclonal antibody against EGFR inhibits receptor activation Phase II
  RAS Salirasib13 Blocks RAS membrane association Phase II
Sarasar (Lonafarnib)14 Inhibitor to farnesyl transferase Phase II
Zarnestra (Tipifarnib)15 Inhibitor to farnesyl transferase Phase II/III
BRAFV600E Zelboraf (Vemurafenib)9 ATP-competitive selective inhibitor Phase II
RAF Nexavar (Sorafenib)16 Multi-kinase inhibitor Phase II/III
Tafinlar (Dabrafenib)11 ATP competitive kinase inhibitor Phase I/II
  MEK Mekinist (Trametinib)11 MEK inhibitor Phase II/III
Mitochondrial pathway Anti-apoptotic BCL-2 proteins Navitoclax (ABT-263)17 Inhibits BCL-2, BCL-w, and BCL-xL Phase I/II
ABT-19917 Inhibits BCL-2 Phase I
Gossypol(AT-101)18 Inhibits BCL-2, BCL-xL, MCL-1 and BCL-w Phase I/II
Obatoclax19 Inhibits BCL-2, BCL-xL, and MCL-1 Phase I/II
XIAP GEM640 (AEG35156)20 Blocks expression of XIAP Phase I/II
IAPs LCL-1613 Peptidomimetic of SMAC-inhibits IAPs Phase I/II
Birinapant (TL32711)21 Peptidomimetic of SMAC-inhibits IAPs Phase II
  1. Records were obtained from the National Cancer Institute and NIH clinical trials databases (http://www.cancer.gov; https://clinicaltrials.gov).
  2. 1Introgen Therapeutics, TX, USA, 2Gilead, CA, USA, 3Novartis, Basel, Switzerland, 4Exelixis, CA, USA, 5Pfizer, NY, USA, 6Sanofi, Paris, France, 7Aeterna Zentaris, Quebec, Canada, 8Astra Zeneca, London, UK, 9Genentech, CA, USA, 10Imclone Systems Inc., NY, USA, 11GlaxoSmithKline, Middlesex, UK, 12Amgen, CA, USA, 13Concordia Pharmaceuticals, FL, USA, 14Merck, NJ, USA, 15Johnson & Johnson, NJ, USA, 16Onyx Pharmaceuticals, CA, USA, 17AbbVie, IL, USA, 18Ascenta Therapeutics, PA, USA, 19Gemin X Pharmaceuticals, Quebec, Canada, 20Aegera Therapeutics, Quebec, Canada, 21TetraLogic Pharmaceuticals, PA, USA.