Elomotecan

Elomotecan (BN 80927 free base) is an orally active, potent inhibitor of topoisomerases I and II and a homocamptothecin (hCPT) analogue. Elomotecan possesses a dual inhibitory mechanism: it acts as a topoisomerase I poison by stabilizing the DNA-enzyme complex while simultaneously serving as a catalytic inhibitor of topoisomerase II. Elomotecan is used in research concerning various advanced and multidrug-resistant (MDR) solid tumors (such as prostate, colon, and breast cancers)^[1][2][3][4]. In Vitro:lomotecan (1-10 μM; 60 min) promotes and stabilizes the accumulation of Topo I-DNA cleavable complexes in live HT29 cells^[1].
Elomotecan (0.02-50 μM; 1 h) rapidly induces and highly stabilizes DNA-protein complexes (DPCs) in HT29 cells^[1].
Elomotecan (5.12 × 10^-13 to 1 × 10^-6 M; 72 h) exhibits potent antiproliferative activity against various human tumor cell lines (including HT29 (IC₅₀ = 21 nM), DU145 (IC₅₀ = 3 nM), PC3 (IC₅₀ = 81 nM), SKOV3 (IC₅₀ = 13 nM), A549 (IC₅₀ = 17 nM), MCF7 (IC₅₀ = 48 nM), T24 (IC₅₀ = 2.2 nM), K562 (IC₅₀ = 8.4 nM), HL60 (IC₅₀ = 7.4 nM)) and drug-resistant strains expressing MDR pumps (T24anp (IC₅₀ = 2.9 nM), K562adr (IC₅₀ = 18 nM), HL60adr (IC₅₀ = 1.3 nM), HL60dnr (IC₅₀ = 32 nM)) or Topo I mutations (KB-STP2 (IC₅₀ = 230 nM))^[1].
Elomotecan (0.64-400 nM; 16 h) exerts cytotoxic effects on cell survival in HT29 cells synchronized in the quiescent G0-G1 phase^[1].
Elomotecan (72 h) potently inhibits cell proliferation in human tumor cell lines (HT29 (IC₅₀ = 21 nM), DU145 (IC₅₀ = 3.13 nM), HL60 (IC₅₀ = 7.4 nM)) and their drug-resistant strains^[3].
Elomotecan (0.64-400 nM; 3-day culture following brief exposure) in synchronized quiescent G0/G1 HT29 It exhibits potent cytotoxic effects in cells^[3].
Elomotecan (3 h) maintains high stability of the lactone ring in human plasma systems^[4].
Elomotecan (1 h) induces the formation of substantial, largely irreversible DNA-protein complexes (DPCs) in HT29 cells^[4]. In Vivo:Elomotecan (BN 80927 free base) (5 mg/kg-40 mg/kg; p.o.; various regimens including once daily for 14 days, twice daily for 14 days, once weekly for 3 weeks, or a cycle of 4 days of dosing followed by 3 days off for 3 cycles; treatment and observation period up to 50 days) demonstrates potent tumor growth inhibition and survival prolongation in NCr nu/nu female athymic nude mouse models bearing subcutaneous human androgen-independent prostate cancer (PC3 and DU145) xenografts^[1].
Elomotecan (p.o.) exhibits potent antitumor activity, inducing tumor regression in mouse models of human prostate tumor (PC3 and DU145) xenografts^[3].