Oblimersen

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Oblimersen
Clinical data
Trade namesGenasense
Other namesG3139
ATC code
Legal status
Legal status
  • Not marketed
Identifiers
CAS Number
  • 190977-41-4 checkY
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC172H221N62O91P17S17
Molar mass5684.58 g·mol−1
3D model (JSmol)
  • Cc1cn(c(=O)[nH]c1=O)[C@H]2C[C@@H]([C@H](O2)COP(=O)(O[C@H]3C[C@@H](O[C@@H]3COP(=O)(O[C@H]4C[C@@H](O[C@@H]4COP(=O)(O[C@H]5C[C@@H](O[C@@H]5COP(=O)(O[C@H]6C[C@@H](O[C@@H]6COP(=O)(O[C@H]7C[C@@H](O[C@@H]7COP(=O)(O[C@H]8C[C@@H](O[C@@H]8COP(=O)(O[C@H]9C[C@@H](O[C@@H]9COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1COP(=O)(O[C@H]1C[C@@H](O[C@@H]1CO)n1cc(c(=O)[nH]c1=O)C)S)n1ccc(nc1=O)N)S)n1cc(c(=O)[nH]c1=O)C)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)n1cnc2c1nc([nH]c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc([nH]c2=O)N)S)n1cc(c(=O)[nH]c1=O)C)S)n1cnc2c1nc([nH]c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc([nH]c2=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)O
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  • Key:MIMNFCVQODTQDP-NDLVEFNKSA-N ☒N
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Oblimersen (INN, trade name Genasense; also known as Augmerosen and bcl-2 antisense oligodeoxynucleotide G3139) is an antisense oligodeoxyribonucleotide being studied as a possible treatment for several types of cancer, including chronic lymphocytic leukemia, B-cell lymphoma, and breast cancer. It may kill cancer cells by blocking the production of Bcl-2—a protein that makes cancer cells live longer—and by making them more sensitive to chemotherapy.

History

The antisense oligonucleotide drug oblimersen was developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.

It was shown that the proliferation of human lymphoma cells (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of oblimersen, which is complementary to the first 6 codons of Bcl-2 mRNA.[1]

These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004.[2]

By the first quarter 2010, the drug had not received FDA approval due to disappointing results in a melanoma trial. Although its safety and efficacy have not been established for any use, Genta Incorporated still[when?] claims on its website that studies are currently under way to examine the potential role of oblimersen in a variety of clinical indications.

References

  1. ^ Dias N, Stein CA (November 2002). "Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". European Journal of Pharmaceutics and Biopharmaceutics. 54 (3): 263–9. doi:10.1016/S0939-6411(02)00060-7. PMID 12445555.
  2. ^ Mavromatis BH, Cheson BD (June 2004). "Novel therapies for chronic lymphocytic leukemia". Blood Reviews. 18 (2): 137–48. doi:10.1016/S0268-960X(03)00039-0. PMID 15010151.

External links

  • Augmerosen entry in the public domain NCI Dictionary of Cancer Terms