SN-38

Research use only, not for human use.

LE-SN38 is NeoPharm’s NeoLipid liposomal formulation of SN-38, the active metabolite of irinotecan (Camptosar), a chemotherapeutic pro-drug approved for the treatment of advanced colorectal Y.

LE-SN38 is the Company’s NeoLipid Liposomal formulation of SN-38, the active, but poorly soluble, metabolite of Camptosar, a chemotherapeutic pro-drug, which is used as a first-line and second-line treatment for advanced colorectal Y. A pro-drug is a compound that is converted into the active drug in the body. However, Camptosar is converted into SN-38 in colorectal Y cells at different rates in different patients, and this variability in conversion rates may result in suboptimal treatment. By employing the Company’s proprietary NeoLipid technology to directly deliver SN-38, the Company hopes to minimize treatment variability. A Phase I clinical trial was completed in 2005 and showed the potential for decreased side effects, particularly diarrhea, compared to published results of Camptosar. The results of that trial were presented at the American Society of Clinical Oncology (ASCO) meeting in June 2005, and were used to determine the Phase II study dose. (In Vitro):The IC50 values for LoVo, HCT116, and HT29 cell lines is 20 nM, 50 nM, 130 nM, respectively. In all three SN-38 (NK012) resistant cell lines Top1 activity is maintained in the presence of high concentrations of SN-38.(In Vivo):SN-38 (NK012), the active and toxic metabolite of the anticancer prodrug Irinotecan. At 30 minutes after administration, Irinotecan plasma concentrations in Slco1a/1b(?/?) mice are 1.9-fold higher than in the wild-type mice (1.89 vs. 1.01 μM, respectively), whereas SN-38 (NK012) plasma concentrations of Slco1a/1b(?/?) mice are 8-fold higher compare with wild-type mice (0.4 μg/mL vs. 0.05 μg/mL, respectively). Overall plasma exposure [AUC(5-240)] of Irinotecan is 1.7-fold higher in Oatp1a/1b knockout mice versus wild-type mice (209.8±6.7 vs. 120.9±4.4 μM/min; P<0.01), and 2.9-fold higher for SN-38 (50±2.9 vs. 12±2 μM/min; P<0.001).

The IC50 values for LoVo, HCT116, and HT29 cell lines is 20 nM, 50 nM, 130 nM, respectively. In all three SN-38 resistant cell lines Top1 activity is maintained in the presence of high concentrations of SN-38.

SN-38, the active and toxic metabolite of the anticancer prodrug Irinotecan. At 30 minutes after administration, Irinotecan plasma concentrations in Slco1a/1b(?/?) mice are 1.9-fold higher than in the wild-type mice (1.89 vs. 1.01 μM, respectively), whereas SN-38 plasma concentrations of Slco1a/1b(?/?) mice are 8-fold higher compare with wild-type mice (0.4 μg/mL vs. 0.05 μg/mL, respectively). Overall plasma exposure [AUC(5-240)] of Irinotecan is 1.7-fold higher in Oatp1a/1b knockout mice versus wild-type mice (209.8±6.7 vs. 120.9±4.4 μM/min; P<0.01), and 2.9-fold higher for SN-38 (50±2.9 vs. 12±2 μM/min; P<0.001).

7-Ethyl-10-Hydroxycamptothecin | 7-ethyl-10-hydroxy-20(S)-Camptothecin | NK 012

Cell Cycle/DNA Damage

Topoisomerase

Topo I

Cancer

——

86639-52-3

392.4

C22H20N2O5

>98% (HPLC)

DMSO: 21 mg/mL (53.51 mM)

O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CC)C5=CC(O)=CC=C5N=C4C3=C2)=O

(S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

(-20℃)

With Ice Pack

≥ 2 years