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C-myb antisense (G4460) is part of Genta's DNA/RNA Medicines program, which uses drugs that are based on chemical modifications of DNA or RNA to selectively knock out the function of genes that may be involved in cancer cause or progression. C-myb antisense is a prototype antisense compound that targets a proto-oncogene known as c-myb, C-myb is a protein that directly binds to cellular DNA and is believed to be regulate expression of other genes that are critically involved in the growth and differentiation of primitive cells. These downstream genes include Bcl-2, Bcl-XL, c-myc, cyclin A1, cyclin D1, cdc2, and Cox-2. Over-expression of c-myb blocks differentiation, promotes proliferation, and decreases apoptosis.
C-myb antisense has been tested in two preliminary clinical trials in patients with drug-resistant hematologic cancers. Genta plans to pursue further clinical development of C-myb antisense in patients with both hematologic cancers and solid tumors. Potential clinical targets for C-myb antisense include CML, malignant melanoma, neuroblastoma, and cancers of the breast, pancreas and colon.
C-myb antisense has received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of chronic myelocytic leukemia (CML). Designation as an Orphan Drug, which is intended to facilitate product development, provides eligibility for a seven- year period of market exclusivity after approval, grants and tax credits for research and development, and reduced filing fees for marketing applications.
References:
Oh IH, Reddy EP: The myb gene family in cell growth, differentiation and apoptosis.
Oncogene 18: 3017-33, 1999.
Luger SM, O’Brien S, Ratajczak J, et al.: Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study.
Blood 15;99:1150-8, 2002.
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