ChemicalBook CAS DataBase List 534605-78-2

534605-78-2

Name	TP3076
CAS	534605-78-2
Molecular Formula	C26H26N4O4
MDL Number	MFCD32661889
Molecular Weight	458.51
MOL File	534605-78-2.mol

Chemical Properties

Boiling point	845.3±75.0 °C(Predicted)
density	1.46±0.1 g/cm3(Predicted)
pka	11.22±0.20(Predicted)

Hazard Information

Description

TP-300, also known as CH-0793076; TP-3076, is a DNA topoisomerase I inhibitor potentially for the treatment of colorectal cancer, gastric cancer. TP300 is stable in an acidic solution but is rapidly converted to CH0793076 under physiological pH conditions such as in sera. This efficient prodrug activation would minimize interpatient differences in pharmacokinetic and toxicity profiles. Unlike CPT-11, TP300 does not exhibit cholinergic interaction or cause acute diarrhea at effective doses. In mouse xenograft models, TP300 showed antitumor activity against both BCRP-positive and -negative xenografts, whereas CPT-11 was less active against BCRP-positive xenografts.

Uses

CH-0793076 (TP3076), a hexacyclic camptothecin analog, is active drug and major metabolite of TP300. CH-0793076 inhibits DNA topoisomerase I with an IC50 of 2.3 μM. CH-0793076 is efficacious against cells expressing BCRP (breast cancer resistance protein)[1].

in vivo

TP300 (1-100 mg/kg; bolus intravenous injection once per week for 3 weeks, for a total of three doses), a water-soluble prodrug of CH0793076, shows more than 50% of tumor growth inhibition in all nine models, regardless of the expression of BCRP (WiDr, HT-29, NCI-H460 and AsPC-1, HCT116, COLO 201, HCT-15, Calu-6 and NCI-N87)^[1].

IC 50

Topoisomerase I: 2.3 μM (IC₅₀)

References

[1] Endo M, et al. A water soluble prodrug of a novel camptothecin analog is efficacious against breast cancer resistance protein-expressing tumor xenografts. Cancer Chemother Pharmacol. 2010 Jan;65(2):363-71. DOI:10.1007/s00280-009-1042-5

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