Gemcitabine elaidate (C09-1135-912)

Gemcitabine elaidate (CP-4126) is lipophilic pro-agent of Gemcitabine. Gemcitabine elaidate is converted to Gemcitabine by esterases in order to be phosphorylated. Gemcitabine elaidate exhibits anti-tumor activity.In VitroGemcitabine elaidate (0.2 nM-1 mM; 72 h) inhibits the growth of gemcitabine sensitive and resistant cells, with IC 50 s of 0.0033, 16.0, 0.0042, 13.0, 0.0015, 0.03, 0.0025, 91, 0.0040, 0.0077, 0.028, and 0.088 μM for L1210/L5, L4A6, BCLO, Bara-C, C26-A, C26-G, A2780, AG6000, THX, LOX, MOLT4 and MOLT4/C8 cells, respectively. Gemcitabine elaidate (0.5 nM-1 μM; 72 h) increases S phase accumulation and dose-dependent cell kill in A549 and WiDR cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: A549 and WiDR cellsConcentration: 0.0005, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1.0 μM Incubation Time: 72 h Result: Induced a G2/M and S phase accumulation.In VivoGemcitabine elaidate (25-120 mg/kg; i.p. every 3 days for 5 doses) inhibits the solid tumor xenografts growth of non-small cell lung cancer (EKVX), non-classifiable sarcoma (MHMX), fibrous histiocytoma (TAX II-1), malignant melanoma (THX), prostate cancer (CRL-1435), pancreatic cancer (PANC-1) . Gemcitabine elaidate (10-20 mg/kg; p.o. every 3 days for 5 doses) shows acceptable toxicity and significant antitumor activity in the colon cancer xenograft Co6044 bearing mice . Gemcitabine elaidate (p.o. once daily for 5 doses) shows a favorable toxicity and antitumor activity, while the dose of 15 mg/kg is highly toxic in the human colon cancer xenograft Co6044 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female BALB/c nude (nu/nu) mice (5-8 weeks; 20-27 g) were bearing tumor of EKVX, H-146, MHMX, TAX II-1, OHS, THX, MA-11, CRL-1435, PANC-1 and MiaPaCa-2, respectively Dosage: 25-120 mg/kg Administration: I.p. every 3 days for 5 doses Result: Inhibited the growth of EKVX, MHMX, TAX II-1, THX, CRL-1435 and PANC-1, with T/C values of 7%, 1%, 30%, 7%, 9%, and 12%, respectively. Specification: 10mM in DMSO Molecular Formula: C27H43F2N3O5 Molecular Weight: 527.64