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Fosciclopirox Sale

(Synonyms: CPX-POM) 目录号 : GC63366

Fosciclopirox(CPX-POM) selectively delivers the active metabolite, Ciclopirox (CPX) that targets γ-secretase complex (Presenilin 1 and Nicastrin)2. It is used in the treatment of urothelial cancer and a number of solid and hematologic malignancies.

Fosciclopirox Chemical Structure

Cas No.:1380539-06-9

规格 价格 库存 购买数量
5 mg
¥900.00
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10 mg
¥1,530.00
现货
25 mg
¥3,150.00
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50 mg
¥4,950.00
现货
100 mg
¥8,550.00
现货

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产品描述

Fosciclopirox(CPX-POM) selectively delivers the active metabolite, Ciclopirox (CPX) that targets γ-secretase complex (Presenilin 1 and Nicastrin)2. It is used in the treatment of urothelial cancer and a number of solid and hematologic malignancies.

[1] Weir SJ, et al. Cell Death Dis. 2021 May 31;12(6):562.

Chemical Properties

Cas No. 1380539-06-9 SDF
别名 CPX-POM
分子式 C13H20NO6P 分子量 317.27
溶解度 DMSO : 100 mg/mL (315.19 mM; Need ultrasonic) 储存条件 Store at -20°C
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 3.1519 mL 15.7594 mL 31.5189 mL
5 mM 0.6304 mL 3.1519 mL 6.3038 mL
10 mM 0.3152 mL 1.5759 mL 3.1519 mL
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Research Update

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Cell Death Dis 2021 May 31;12(6):562.PMID:34059639DOI:10.1038/s41419-021-03836-z.

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested Fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of Fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131).

Preclinical Pharmacokinetics of Fosciclopirox, a Novel Treatment of Urothelial Cancers, in Rats and Dogs

J Pharmacol Exp Ther 2019 Aug;370(2):148-159.PMID:31113837DOI:10.1124/jpet.119.257972.

Pharmacokinetic studies in rats and dogs were performed to characterize the in vivo performance of a novel prodrug, Fosciclopirox. Ciclopirox olamine (CPX-O) is a marketed topical antifungal agent with demonstrated in vitro and in vivo preclinical anticancer activity in several solid tumor and hematologic malignancies. The oral route of administration for CPX-O is not feasible due to low bioavailability and dose-limiting gastrointestinal toxicities. To enable parenteral administration, the phosphoryl-oxymethyl ester of ciclopirox (CPX), Fosciclopirox (CPX-POM), was synthesized and formulated as an injectable drug product. In rats and dogs, intravenous CPX-POM is rapidly and completely metabolized to its active metabolite, CPX. The bioavailability of the active metabolite is complete following CPX-POM administration. CPX and its inactive metabolite, ciclopirox glucuronide (CPX-G), are excreted in urine, resulting in delivery of drug to the entire urinary tract. The absolute bioavailability of CPX following subcutaneous administration of CPX-POM is excellent in rats and dogs, demonstrating the feasibility of this route of administration. These studies confirmed the oral bioavailability of CPX-O is quite low in rats and dogs compared with intravenous CPX-POM. Given its broad-spectrum anticancer activity in several solid tumor and hematologic cancers and renal elimination, CPX-POM is being developed for the treatment of urothelial cancer. The safety, dose tolerance, pharmacokinetics, and pharmacodynamics of intravenous CPX-POM are currently being characterized in a United States multicenter first-in-human Phase 1 clinical trial in patients with advanced solid tumors (NCT03348514).