Biological Activity

Irinotecan is an inhibitor of Topoisomerase I, preventing religation of the DNA strand by binding to topoisomerase I-DNA complex. Irinotecan inhibits the growth of LoVo and HT-29 cells, with IC50s of 15.8 ± 5.1 and 5.17 ± 1.4 μM, respectively. Irinotecan suppresses the proliferation of human umbilical vein endothelial cells (HUVEC), with an IC50 of 1.3 μM.

Irinotecan (CPT-11, 5 mg/kg) significantly inhibits the growth of tumors by intratumoral injection daily for 5 days, on two consecutive weeks in rats, and such effects also occur via continuous intraperitoneal infusion by osmotic minipump into mice. However, Irinotecan (10 mg/kg) shows no effect on the growth of tumor by i.p. Irinotecan (CPT-11, 100-300 mg/kg, i.p.) apparently suppresses tumor growth of HT-29 xenografts in athymic female mice by day 21.

Product Citations

• 

  Frontiers in Anti-Cancer Drug Discovery. 2015;64-114 .

  Concepts of Anticancer Treatment and Pharmacogenomics in Cancer Treatments
  Irinotecan purchased from AbMole

Chemical Information

Molecular Weight	586.68
Formula	C33H38N4O6
CAS Number	97682-44-5
Solubility (25°C)	DMSO ≥ 20 mg/mL
Storage	2-8°C, protect from light, dry, sealed

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Filemon S Dela Cruz, et al. Genome Med. A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma

[2] Mei-Yun Huang, et al. Apoptosis. Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis

[3] C Morales, et al. J Neurooncol. Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor