Atiratecan

Atiratecan (TP300) is a prodrug of camptothecin analog CH0793076 (HY-107096). Atiratecan does not inhibit acetylcholinesterase (AChE) activities. Atiratecan shows antitumor activity against both breast cancer resistance protein (BCRP)-positive and -negative xenografts in mouse xenograft models^[1]. In Vitro: Atiratecan (TP300) is stable in an acidic solution but is rapidly converted to CH0793076 under physiological pH conditions such as in sera^[1].
Atiratecan has antiproliferative activity against camptothecin-resistant cell lines. Atiratecan has IC₅₀s of 9.4 nM and 1.1 nM for A2780 and A2780/SN75 cells, respectively^[1].
In Vivo: Atiratecan (TP300; 47 mg/kg; IV; once per week for 3 weeks) shows more than 50% of tumor growth inhibition in all nine models, regardless of the expression of BCRP^[1].
Atiratecan (24 mg/kg; IV; once per week for 6 weeks) in combination with capecitabine results in synergistic eVects in the HCT116 human colon cancer and NCI-N87 human gastric cancer xenograft models and an additive eVect in the WiDr human colon cancer xenograft model which is BCRP-positive and CPT-11-insensitive^[1].
The eVective dose range of Atiratecan is between 0.30 and 47 mg/kg (MTD/ED₅₀=157). The toxic dose is 63 mg/kg for Atiratecan^[1].