플리티뎁신플리티뎁신

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Danger

• 유해·위험 문구

  H225：고인화성 액체 및 증기

  H319：눈에 심한 자극을 일으킴

• 예방조치문구

  P210：열·스파크·화염·고열로부터 멀리하시오 - 금연 하시오.

  P233：용기를 단단히 밀폐하시오. 용기는 환기가 잘 되는 곳에 단단히 밀폐하여 보관하시오.

  P240：용기와 수용설비를 접지 및 접합시키시오.

  P241：폭발 방지용 장비[전기적/환기/조명/...]을(를) 사용하시오.

  P242：스파크가 발생하지 않는 도구를 사용하시오

  P243：정전기 방지 조치를 취하시오.

  P261：분진·흄·가스·미스트·증기·...·스프레이의 흡입을 피하시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P270：이 제품을 사용할 때에는 먹거나, 마시거나 흡연하지 마시오.

  P271：옥외 또는 환기가 잘 되는 곳에서만 취급하시오.

  P280：보호장갑/보호의/보안경/안면보호구를 착용하시오.

  P301+P312：삼켜서 불편함을 느끼면 의료기관(의사)의 진찰을 받으시오.

  P303+P361+P353：피부(또는 머리카락)에 묻으면 오염된 모든 의복은 벗거나 제거하시오 피부를 물로 씻으시오/샤워하시오.

  P304+P340：흡입하면 신선한 공기가 있는 곳으로 옮기고 호흡하기 쉬운 자세로 안정을 취하시오.

  P305+P351+P338：눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.

  P321：(…) 처치를 하시오.

  P330：입을 씻어내시오.

  P337+P313：눈에 대한 자극이 지속되면 의학적인 조치· 조언를 구하시오.

  P370+P378：화재 시 불을 끄기 위해 (Section 5. 폭발, 화재시 대처방법의 적절한 소화제)을(를) 사용하시오.

  P403+P235：환기가 잘 되는 곳에 보관하고 저온으로 유지하시오.

  P501：...에 내용물 / 용기를 폐기 하시오.

플리티뎁신플리티뎁신 화학적 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 공급 업체

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