| In Vivo |
EC2629 as a promising first-in-class SMDC comprising a potent DNA crosslinking pharmacophore for the treatment of FR-positive tumors. EC2629 displays potent anti-tumor activity against KB tumor xenografts in mice and rats. EC2629 treatment of nude mice bearing FR-positive KB human xenografts leads to cures in 100% of the test animals with very low dose levels (0.3 µmol/kg) following a convenient once a week schedule. Further, EC2629-treated animals do not lose any significant weight throughout the dosing period and beyond[1]. Female Rats pharmacokinetic parameter of EC2629[1]. Dose (mg/kg) Gender t1/2 (h) Tmax (h) Cmax (ng/mL) C0 (ng/mL) AUClast (h·ng/mL) AUCinf (h·ng/mL) Vz (L/kg) Cl (L/h/kg) 0.05 F 0.627 0.033 545 662 260 287 0.157 0.174 M 1.02 0.033 595 669 305 384 0.191 0.130 0.10 F 0.525 0.033 1,330 1,570 596 633 0.120 0.158 M 0.706 0.033 1,390 1,690 617 699 0.146 0.143 0.25 F 0.530 0.033 3,230 3,740 1,640 1,750 0.109 0.143 M 0.770 0.033 3,580 4,310 1,670 1930 0.144 0.129 0.50 F 0.611 0.033 6,070 7,060 3,230 3,540 0.125 0.141 M 1.40 0.033 7,080 8,450 5,450 5,510 0.183 0.0907 Animal Model: Four- to eight-week-old female nu/nu mice and rats[1] Dosage: 0.3 µmol/kg for mice or 0.15 µmol/kg for rats Administration: Administered intravenously; following a once a week (SIW), 2-week schedule Result: Untreated control mice reached a tumor size of 1,500 mm3 by 23-30 days PTI (post tumor implant), whereas treatment with EC2629 led to 100% cures. Control tumors in rats reached the target tumor size of 15,000 mm3 by 25-28 days PTI, while EC2629-treated rats yielded 2 complete responses (CRs) and 1 partial response (PR).
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