KeyGen

R&D

Transcription Factors New Drug R&D Technology

Innovative anti-cancer oligonucleotide targeting transcription factor KGCGS102.

"Transcription factors are attractive targets both because they are less numerous than other signaling activators and are at a focal point of many cancer pathways," says Darnell.
"Like kicking Achilles in the heel, striking at these targets would constitute a more global approach to fighting cancer.”says Rockefeller University: Darnell, James E.

KGCGS102 is the first anti-cancer decoy nucleotide drug developed by KeyGen holding the intellectual property. It has been patented in China, US, Europe and Japan. The anti-cancer target of KG102 is the transcription factor AP-1. It inhibits cancer cell proliferation and induces cancer cell apoptosis by change the expression of cell cycle related genes.

It has been shown to have a very selective anti-cancer effect on lung cancer and hepatocarcinoma with very low toxicity. NOTE: It is currently in preclinical stage.
The progress of KGCGS 102 in oligonucleotide chemistry, quality control, in vitro and in vivo pharmacological evaluation, and mechanism research and toxicity study provides the theoretical and experimental basis for the preclinical research. The molecular mechanism of K102 has shown that K102 is able to specifically bind to the key regulatory factor of oncogenes.

Currently KeyGen is analyzing the downstream genes regulated by this targeted transcription factor by the utilization of DNA micro-array and HGRD. The effect of K102 on multiple gene expression at mRNA and protein level has confirmed its molecular mechanism. K102 is able to enter the cancer cells, inhibit the proliferation of cancer cells and induce cancer cell apoptosis.

In-vitro assay showed that K102 inhibited the proliferation of lung cancer, hepatocarcinoma, melanoma and glioma cells. The inhibitory percentage of K102 on lung cancer and hepatocarcinoma cells reached 85%. In-vivo assay by using nude mice xenografts of NCI-H460 and A549 showed that K102 had significant anti-cancer effect on NCI-H460 human lung cancer growth which is above the standard of SFDA and NCI at the dose of 50 mg/kg (NCI standard T/C%<50%, SFDA standard T/C%<60%). The results are repeatable and showed the dose-effect relationship.

The exploration of purification and QC method has gained successful progress, which solved the problem of low purity of this kind of drug. The purity of the raw material has reached 95%, which guarantees the ongoing of the other downstream research.

KeyGen has consulted with the international experts in this field and set up the authentic purity detection method (capillary electrophoresis and HPLC) and structure analysis method by large numbers of repeated experiments. The toxicity study shows that the LD 50 of K102 is over 500 mg/kg and the maximum tolerable dose (MTD) has not been detected which proves that K102 has very low toxicity on mice. This is a prominent advantage of this drug compared with the other traditional anti-cancer drugs. The above work provides an optimistic foreground of this new anti-cancer drug candidate.