Description:
- Colorectal cancer treatment
Abstract
Our R&D team developed a cell-permeable Hdm2/HdmX E3 ligase inhibitor that shows in vitro activity in many cancer cell-lines (prostate carcinoma, osteosarcoma, lung carcinoma, colon carcinoma and ovarian carcinoma, among others) with p53 wt, mutated or null. This compound has shown activity in a colorectal cancer model in mice (HCT116/nude mice and CT26/Balb/c mice). Preliminary studies show that our compound is not immunogenic in Balb/C mice after ip dosing for 1 month 3 times per week at 25 mg/kg. Early in-vivo PK properties are favorable with 35% oral bioavailability.
Benefit
- Cyclotide anticancer treatment targeting p53 active against colon cancer
- Significantly reduced tumor volume
- Safe in early in-vivo studies. No detectable biochemical, hematologic or histological toxicities were detected
- Similar or better potency than current clinical
- candidates in p53 deficient cancer cells.
Market Application
Activation of tumor-suppressor p53 has recently been identified as an attractive targeted non-genotoxic cancer therapy because p53 possesses potent tumor-suppressing activity in vivo. p53 can inhibit cancer cell growth by cell cycle arrest or terminate their proliferation by inducing apoptosis and senescence. The p53-based therapy is particularly attractive for cancer types including retinoblastoma, neuroblastoma and leukemia/lymphoma.
Publications
The Potential of the Cyclotide Scaffold for Drug Development, Camarero and Campbell, 2019.
Other
Stage of Development
- Tested in vitro
- Validated in vivo
- Early in vivo PK/safety
- Available for exclusive license
Intellectual Property Status
US patent pending