Gemcitabine elaidate (CP-4126) hydrochloride 是 Gemcitabine 的亲脂性前药。Gemcitabine elaidate hydrochloride 通过酯酶转化为 Gemcitabine 以被磷酸化。Gemcitabine elaidate hydrochloride 可以口服给药，具有抗肿瘤活性。

Gemcitabine elaidate (CP-4126) hydrochloride is lipophilic pro-drug of Gemcitabine. Gemcitabine elaidate hydrochloride is converted to Gemcitabine by esterases in order to be phosphorylated. In contrast to gemcitabine, CP-4126 could be administered orally, with a schedule and dose dependent toxicity and antitumor activity [1] [2].

Gemcitabine elaidate (0.2 nM-1 mM; 72 h) hydrochloride inhibits the growth of gemcitabine-sensitive and drug-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 [1]. Gemcitabine elaidate (0.5 nM-1 μM; 72 h) hydrochloride increases S phase accumulation and dose-dependent cell death in A549 and WiDR cells [2]. Cell Cycle Analysis [2] Cell Line: A549 and WiDR cells Concentration: 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.

Gemcitabine elaidate (25-120 mg/kg; i.p. every 3 days for 5 doses) hydrochloride has been shown to be effective against 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) [1]. Gemcitabine elaidate (10-20 mg/kg; p.o. every 3 days for 5 doses) hydrochloride exhibits acceptable toxicity and significant antitumor activity in the colon cancer xenograft Co6044 bearing mice [1]. Gemcitabine elaidate (p.o. once daily for 5 doses) hydrochloride shows a favorable toxicity and antitumor activity, while the dose of 15 mg/kg is highly toxic in the human colon cancer xenograft Co6044 [1]. 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 [1] 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.

T15378L

C27H44ClF2N3O5

564.11

CO-101 hydrochloride;Gemcitabine elaidate hydrochloride(210829-30-4(free base));Gemcitabine 5'-elaidate hydrochloride;CP-4126 hydrochloride

DMSO:10 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years