CAS 114899-77-3|Trabectedin

Introduction：Basic information about CAS 114899-77-3|Trabectedin, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Trabectedin BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	Trabectedin
CAS Number	114899-77-3	Molecular Weight	761.837
Density	1.6±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₃₉H₄₃N₃O₁₁S	Melting Point	/
MSDS	/	Flash Point	/

Names

Name	trabectedin
Synonym	More Synonyms

Trabectedin BiologicalActivity

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.IC50 Value: 0.1-3.7 nM (breast cancer cell lines) [1]Target: Apoptosis inducer; Anticancerin 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].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
Related Catalog	Signaling Pathways >>Apoptosis >>ApoptosisNatural Products >>AlkaloidResearch Areas >>Cancer
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.

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.IC50 Value: 0.1-3.7 nM (breast cancer cell lines) [1]Target: Apoptosis inducer; Anticancerin 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].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

Related Catalog

Signaling Pathways >>Apoptosis >>ApoptosisNatural Products >>AlkaloidResearch Areas >>Cancer

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.

Chemical & Physical Properties

Density	1.6±0.1 g/cm3
Molecular Formula	C₃₉H₄₃N₃O₁₁S
Molecular Weight	761.837
Exact Mass	761.261841
PSA	194.02000
LogP	3.10
Index of Refraction	1.732
InChIKey	PKVRCIRHQMSYJX-XHKCZRNKSA-N
SMILES	COc1cc2c(cc1O)CCNC21CSC2c3c(OC(C)=O)c(C)c4c(c3C(COC1=O)N1C(O)C3Cc5cc(C)c(OC)c(O)c5C(C21)N3C)OCO4
Storage condition	-20°C

Synonyms

ecteinascidin-743

(1R,1'R,2'R,3'R,11'S,12'S,14'R)-5',6,12'-Trihydroxy-6',7-dimethoxy-7',21',30'-trimethyl-27'-oxo-3,4-dihydro-2H-spiro[isoquinoline-1,26'-[17,19,28]trioxa[24]thia[13,30]diazaheptacyclo[12.9.6.1.0.0.0.0]triaconta[4,6,8,15,20,22]hexaen]-22'-yl acetate

ET-743

Trabectedin

ecteinascidin 743

(1'R,6R,6aR,7R,13S,14S,16R)

Ecteinascidine 743

Ecteinascidin

ET743

Yondelis(R)

UNII-ID0YZQ2TCP

5-(acetyloxy)-3',4',6,6a,7,13,14,16-octahydro-6',8,14-trihydroxy-7',9-dimethoxy-4,10,23-trimethyl-,[6R-(6a,6a3,73,133,143,16a,20R*)]

Yondelis

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