픽산트론

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Warning

• 유해·위험 문구

  H302：삼키면 유해함

  H315：피부에 자극을 일으킴

  H319：눈에 심한 자극을 일으킴

  H335：호흡 자극성을 일으킬 수 있음

• 예방조치문구

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

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

픽산트론 화학적 특성, 용도, 생산

• 개요

  In May 2012, pixantrone was approved by the European Commission as a single agent for the treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) in adult patients who have failed on at least two previous therapies. Pixantrone (also known as BBR- 2778) is an anthracycline analogue that was specifically designed to address the cardiotoxicity seen in earlier agents by replacement of a 1,4- dihydroxyanthracene-9,10-dione core with a benzoisoquinoline-5,10-dione ring system. Pixantrone inhibits topoisomerase II by intercalation with DNA and is also believed to form covalent adducts with the N-2 amino group of guanine via a formaldehyde aminal formed with the primary amino groups. Pixantrone is less cytotoxic than other anthracycline derivatives, but shows good antitumor activity in vivo in a variety of preclinical tumor models, including leukemia and lymphoma models. Pixantrone also demonstrated significantly reduced cardiotoxicity in preclinical models compared with the anthracyclines doxorubicin and mitroxantrone. Pixantrone was synthesized by Friedel–Crafts reaction of pyridine-3,4-dicarboxylic acid anhydride with 1,4-difluorobenzene to give a ketoacid that was cyclized to the tricyclic core by treatment with fuming sulfuric acid at 140℃. Reaction of the resulting 6,9-difluorobenzoisoquinoline-5-10-dione with ethylenediamine followed by careful pH adjustment and treatment with maleic acid gave pixantrone in good overall yield and purity.

• 용도

  Pixantrone is an antineoplastic drug belonging to group of antitumor antibiotics. Pixantrone is an anlogue of Mitoxantrone (M373425) and is just as potent in the treatment of multiple sclerosis with fewer toxic effects on cardiac tissue. Studies suggest that Pixantrone significantly reduces amyloid beta (A beta(1-42)) neurotoxicity, a mechanism implicated in Alzheimer's disease.

• Clinical Use

  Pixuvri (Pixantrone dimaleate) is a novel aza-anthracenedione derivative approved in Europe for the treatment of adult patients with non-Hodgkin B-cell lymphoma. It is also being pursued as a treatment for various cancers, and specifically as an alternative to other structurally-related drugs like mitoxantrone, employed for treatment of breast cancer, acute myeloid leukemia (AML), and non- Hodgkins lymphoma.Pixantrone dimaleate has been designed to maintain antitumor efficacy while decreasing highly cardiotoxic side effects observed during treatment with other related anti-tumor anthracenedione derivatives. Like many anthracenedione drugs, the mechanism of action for pixantrone dimaleate likely includes a number of pathways and processes, with studies suggesting intercalation into DNA and/or interference with DNA –Topoisomerase II activity, leading to subsequent protein associated-DNA strand breaks and eventually to cell death.

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