Reagent | Principle | Company/Reference | Experimental Effects | Clinical Trial/Status |
---|---|---|---|---|
Bcl-2 blocker | Small molecule inhibitors of Bcl-2/Bcl-xL | Idun/Abbott | Induction of tumor cell apoptosis | Preclinical |
GX01 series of compounds | Small molecule inhibitors binding antiapoptotic Bcl-2 proteins | Gemin X | Preclinical | |
Bcl-2 small-molecule antagonist | Structure-based designed nonpeptidic Bcl-2 antagonists | Structural Bioinformatics | Preclinical | |
Tetrocarcin-A derivatives | Natural fungal compound inhibitor of Bcl-2 | Kyowa Hakko Kogyo Co. | Inhibits mitochondrial functions regulated by Bcl-2, potentiates apoptosis | Preclinical |
Chelerythrine | Plant alkaloid inhibiting Bcl-2/Bax interaction | Chan et al., 2003 | Inhibitor of Bcl-xL/Bak-BH3 interaction, induces cell death in Bcl-2 and Bcl-xL-overexpressing cells | Preclinical |
Antimycin A derivatives | Natural and synthetic Bcl-2/Bcl-xL inhibitors | Tzung et al., 2001 | Bind to the BH3 pocket of Bcl-2 and Bcl-xL and induce apoptosis | Preclinical |
HA14—1 | Chemical compound binding the Bcl-2 BH3 pocket | Wang et al., 2000b | Induces apoptosis in tumor cells, synergistic with drugs | Preclinical |
Synthetic compound | Identified in an HTS, binds to the BH3 of Bcl-2 | Enyedy et al., 2001 | Induces cell death in Bcl-2-overexpressing cells | Preclinical |
Genasense | Bcl-2 18-mer antisense oligonucleotide | Aventis/Genta Inc. | Kills drug-resistant chronic lymphocytic leukemia cells, delays development of fatal lymphoma in mice, increases dacarbazine effectiveness in melanoma models | Phase-3: FDA fast-track status for melanoma, multiple myeloma, chronic lymphocytic leukemia. Phase 3 for non-small cell lung cancer, phase 2 for hormone-refractory prostate cancer |
ISIS 22783 | Splice-specific Bcl-x antisense oligonucleotide | ISIS; Taylor et al., 1999 | Redirects Bcl-x mRNA processing to proapoptotic Bcl-xS, and sensitizes tumor cells for apoptosis | Preclinical |
Bispecific Bcl-2/Bcl-xL antisense | Antisense construct against both Bcl-2 and Bcl-xL | Zangemeister-Wittke et al., 2000 | Promotion of apoptosis in cell lines | Preclinical |
BH3 peptides from Bax, Bak, Bid or Bad | BH3 peptides coupled to protein transduction domains or to fatty acids | Holinger et al., 1999; Wang et al., 2000a | Apoptosis induction in tumor cell lines and mouse xenografts | Preclinical |
SAHBs | Peptidomimetic BH3-mimeticum | Walensky et al., 2004 | Induces Bax/Bak oligomerization, apoptosis in cell lines and growth suppression of leukemic xenografts | Preclinical |
BH3Is | Compounds interfering with Bak-BH3/Bcl-xL interaction | Degterev et al., 2001 | Induction of apoptosis | Preclinical |
Companies: Abbott Laboratories (www.abbott.com), Aventis (www.aventis.com), Gemin X Biotechnologies (www.geminx.com), Genta Incorporated (www.genta.com), Idun Pharmaceuticals, Inc. (www.idun.com), ISIS Pharmaceuticals (www.isispharm.com), Kyowa Hakko Kogyo Co., Ltd. (www.kyowa.co.jp), Structural Bioinformatics, Inc. (www.strubix.com).