플리티뎁신플리티뎁신

플리티뎁신플리티뎁신 속성

플리티뎁신플리티뎁신 C화학적 특성, 용도, 생산

개요

Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin?. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents.

생물학적 활성

Plitidepsin is a cytotoxic peptide originally found in the sea squirt Aplidium albicans. It interacts with a protein (eEF1A2) which is overexpressed in some cancers. This interaction leads to apoptosis. Synthetically produced plitidepsin has been found to have antiproliferative effects on cancer cells. Phase II trials have investigated its activity in tumours such as lung cancer, melanoma and multiple myeloma.

Mechanism of action

Plitidepsin induces apoptosis in multiple myeloma cells, which involves activation of p38 and c-jun NH(2)-terminal kinase signaling, Fas/CD95 translocation to lipid rafts, and ultimately caspase activation. The investigational agent also decreases the proliferation of multiple myeloma cells, an effect mediated by the suppression of several proliferative genes.In a pivotal phase III trial of patients with relapsed or refractory multiple myeloma, plitidepsin in combination with dexamethasone (Dex) significantly reduced the risk of progression or death compared to Dex alone.Plitidepsin has been approved by TGA in Australia for the treatment of multiple myeloma in combination with dexamethasone for patients that relapse after three lines of treatment, including proteasome inhibitors or immunomodulators.

Clinical Use

Plitidepsin is a cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. Plitidepsin displays a broad spectrum of antitumor activities, inducing apoptosis by triggering mitochondrial cytochrome c release, initiating the Fas/ DC95, JNK pathway and activating caspase 3 activation. This agent also inhibits elongation factor 1-a, thereby interfering with protein synthesis, and induces G1 arrest and G2 blockade, thereby inhibiting tumor cell growth.A phase II prospective open-label study (Ferme et al. 2008 ) to evaluate its activity in patients with relapsed/ refractory non-cutaneous PTCL was conducted in 14 patients. They were treated with plitidepsin 3.2 mg/m 2 IV infusion over 1-h on days 1, 8 and 15 every 4 weeks. Eleven patients were evaluable when preliminary results were reported, one was too early and two were non-evaluable. One con fi rmed CR and 3 PR’s were observed with a 36% objective response rate. Median overall survival was 11 months.
Plitidepsin was tolerable in this heavily pretreated population with low hematological toxicity. Transient but reversible ALT elevation was noticed in 7 patients.
Future trials will establish its role in T-cell lymphoma.

Safety Profile

Plitidepsin's safety profile has been extensively studied over both phase I and II/III trials, with the drug presenting mostly transient and tolerated adverse events. Myalgia, alanine aminotransferase/aspartate aminotransferase, creatine phosphokinase increase, fatigue, nausea, and vomiting constituted the most common dose-limiting toxicities in phase I studies. The same adverse events were reported regarding phase II/III studies, along with mild to moderate hematologic abnormalities, such as anaemia and thrombocytopenia. A hypersensitivity reaction was also observed; the event was well-tolerated, except one patient was withdrawn from a trial due to a grade 4 hypersensitivity reaction and hypotension. Notably, plitidepsin with dexamethasone was related to less hepatic enzyme abnormalities compared to plitidepsin alone, while a study assessing the combination of plitidepsin with dexamethasone and bortezomib reported no dose-limiting adverse events[1].

플리티뎁신플리티뎁신 준비 용품 및 원자재

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플리티뎁신플리티뎁신 공급 업체

공급자	전화	이메일	국가	제품 수	이점
Fuxin Pharmaceutical	+86-021-021-50872116 +8613122107989	contact@fuxinpharm.com	China	10297	58
BOC Sciences	16314854226; +16314854226	inquiry@bocsci.com	United States	19743	58
Henan Fengda Chemical Co., Ltd	+86-371-86557731 +86-13613820652	info@fdachem.com	China	20314	58
Alpha Biopharmaceuticals Co., Ltd	+86-15542445688	sales@alabiochem.com	China	888	58
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32760	60
SHANGHAI T&W PHARMACEUTICAL CO., LTD.	+86-021-61551413 +8618813727289	contact@trustwe.com	China	5738	58
Zhejiang Huida Biotech Co., LTD	008613515763466 8615669048680	wendy@huidabiotech.com	CHINA	87	58
Shanghai Minbiotech Co., Ltd.	+8617315815539	sales@minbiotech.com	CHINA	129	58
AFINE CHEMICALS LIMITED	+86-0571-85134551	info@afinechem.com	China	15395	58
Shenzhen Shengda Pharma Limited	755-85269922 +8613424394241	sales@shengdapharm.com	CHINA	310	58

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