Trabectedin

Cas No.:	114899-77-3
Synonyms:	Ecteinascidin 743; ET-743; Ecteinascidin
SMILES:	CC1=C(OC)C(O)=C2C3[C@@H]4[C@@H]5C6=C(C7=C(OCO7)C(C)=C6OC(C)=O)[C@@H](COC(C8(C9=CC(OC)=C(O)C=C9CCN8)CS5)=O)N4C(O)C(CC2=C1)N3C
Formula:	C39H43N3O11S
M.Wt:	761.91
Purity:	>99%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Trabectedin (Ecteinascidin-743 or ET-743) is a novel antitumour agent of marine origin with potent antitumour activity both in vitro and in vivo.
Target:	IC50 Value: 0.1-3.7 nM (breast cancer cell lines) [1]Target: Apoptosis inducer; Anticanceri
In Vivo:	A xenograft mouse model of human MLS showed marked reduction of CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels, and partial decrease of PTX3 after trabectedin treatment [3]. The MTD of trabectedin was 700 microg/m(2) due to dose-limiting neutropaenia and the RDs in the previously treated/untreated patients were 500 and 600 microg/m(2), respectively. Most common toxicities were nausea/vomiting (67%), asthenia/fatigue (55%) and reversible ASAT/ALAT elevation (51%) [4]. Toxicity: Most common toxicities were nausea/vomiting (67%), asthenia/fatigue (55%) and reversible ASAT/ALAT elevation (51%) [4].Clinical trial: A Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies. Phase 1/2
In Vitro:	Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells [2]. In vitro treatment with noncytotoxic concentrations of trabectedin selectively inhibited the production of CCL2, CXCL8, IL-6, VEGF, and PTX3 by MLS primary tumor cultures and/or cell lines [3].
References:	[1]. Takahashi N, et al. Sequence-dependent synergistic cytotoxicity of ecteinascidin-743 and paclitaxel in human breast cancer cell linesin vitro and in vivo. Cancer Res. 2002 Dec 1;62(23):6909-15. [2]. Atmaca H, et al. A diverse induction of apoptosis by trabectedin in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) breast cancer cells. Toxicol Lett. 2013 Jun 20;221(2):128-136. [3]. Germano G, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res. 2010 Mar 15;70(6):2235-44. [4]. Sessa C, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. Eur J Cancer. 2009 Aug;45(12):2116-22.