The agent represents a nanoparticle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) and an anti-cancer compound (camptothecin). It was developed by Mark E. Davis, professor of Chemical Engineering at the California Institute of Technology, and associates at Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., hence the original name "IT-101". Its novel delivery mode allows the agent, and thus the toxic anti-cancer component, to be preferentially accumulated in cancer tissue. In turn, toxic side effect are expected to be reduced. The technology was licensed by Calando and Caltech to Cerulean Pharma Inc., in June, 2009.
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Camptothecin (CPT), an alkaloid extract with poor water solubility from plants such as camptotheca acuminata, exhibits anti-cancer activity possibly due, at least in part, by the inhibition of DNA topoisomerase I resulting in cell death. In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolysed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect and as a result, the anticancer drug is enhanced and retained in the tumor tissue.
Alternate drug name
CRLX101 was originally named "IT-101" and was changed to CRLX101 after licensing to Cerulean Pharma Inc. CRLX101 is the official name in clinical trials.
IT-101 and Dr. Mark E. Davis were included in the PBS documentary titled "Survival."
- Weiss GJ, Chao J, Neidhart JD, Ramanathan RK, Bassett D, Neidhart JA, Choi CH, Chow W, Chung V, Forman SJ, Garmey E, Hwang J, Kalinoski DL, Koczywas M, Longmate J, Melton RJ, Morgan R, Oliver J, Peterkin JJ, Ryan JL, Schluep T, Synold TW, Twardowski P, Davis ME, Yen Y (2013). "First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies". Invest. New Drugs. 31 (4): 986–1000. doi:10.1007/s10637-012-9921-8. PMC 3774600. PMID 23397498.