- Rakovina Therapeutics Inc. (RKV) presents data supporting potential broad anticancer activity for its kt-4000 drug series
- kt-4000 represents a novel class of small molecule drug candidates
- The kt-4000 series aims to build upon demonstrated success of a trialed combined method while reducing the potential for multi-drug toxicity
- Effects led to cell cycle arrest and cell death in proficient cancer cells normally resistant to inhibitor treatment
- Select kt-4000 lead candidates are being advanced to evaluate activity in vivo
- Rakovina Therapeutics Inc. (RKV) is up 12.50 per cent trading at $0.18 per share as of 1:27 p.m. ET
Rakovina Therapeutics (RKV) has presented data supporting potential broad anticancer activity for its kt-4000 drug series.
The data presented suggested promising activity for bi-functional kt-4000 series compounds.
kt-4000 represents a novel class of small molecule drug candidates that combine potent inhibition of a family of proteins that support cellular processes (PARP) with DNA bonding functionality in a single molecule.
PARP is a key enzyme in the base-excision repair (BER) pathway, which is an important DNA damage response mechanism involved in the repair of single-strand breaks. Cells that are deficient in other repair mechanisms, such as homologous recombination (HR) repair, become highly dependent on BER for survival.
FDA-approved PARP inhibitors have become important in the treatment of HR-deficient tumors such as BRCA-mutant breast and ovarian cancers. However, PARP inhibitors are less active against HR-proficient cells that are not dependent on BER for DNA repair.
In previous studies, artificially induced DNA damage has led to the effective killing of HR-proficient cancer cells by PARP-inhibitors. Cancer chemotherapies known as alkylating agents induce DNA single-strand breaks, which activate BER. Published studies demonstrate that when PARP activity is also inhibited, the cell becomes “stalled” leading to cell death by apoptosis.
While this has been effective in a laboratory setting, the combination of the two types of treatment in clinical practice has been limited by toxicity.
Rakovina Therapeutics’ kt-4000 series aims to build upon the demonstrated success of the combined mechanism while reducing the potential for multi-drug toxicity.
Following treatment, the data presented demonstrate that the kt-4000 series drug candidates release an alkylating agent resulting in increased expression of a DNA damage marker, in cancer cells. The candidates simultaneously exhibited potent PARP inhibition at low concentrations. The combined effect led to cell cycle arrest and cell death in HR-proficient cancer cells, normally resistant to PARP inhibitor treatment.
Select kt-4000 lead candidates are being advanced to evaluate pharmacokinetics, preliminary safety profile and anti-tumor activity in vivo.
Rakovina Therapeutics Inc. (RKV) is up 12.50 per cent trading at $0.18 per share as of 1:27 p.m. ET.
