Dolastatin 15

Dolastatin 15用途

Dolastatin 15 (DLS 15),一种从 Dolabella auricularia 中提取的去甲肽,是一种有效的抗有丝分裂剂 (antimitotic),在结构上与抗微管蛋白剂 Dolastatin 10 有关。Dolastatin 15 诱导多发性骨髓瘤细胞周期阻滞和凋亡。Dolastatin 15 可作为 ADC 细胞毒素。

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Dolastatin 15名称

[ CAS 号 ]:
123884-00-4

[ 中文名 ]:
多拉司他汀 15

[ 英文名 ]:
Dolastatin 15

[英文别名 ]:

dolastatin-15

Dolastatin 15生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 抗体- 药物偶联物 >> ADC细胞毒素

信号通路 >> 细胞周期/DNA损伤 >> 微管/微管蛋白

信号通路 >> 细胞骨架 >> 微管/微管蛋白

[ 靶点 ]

Auristatin

[体外研究]

多拉司他丁15(DLS 15)诱导人骨髓瘤细胞系(RPMI8226、U266和IM9)G2/M期细胞周期阻滞,随后凋亡。多司他丁15通过激活线粒体和Fas(CD95)/Fas-L(CD95-L)介导的途径诱导骨髓瘤细胞凋亡[2]。多拉司他丁15(DLS 15)对4种SCLC细胞株(NCI-H69、NCI-H82、NCI-H345、NCI-H446)均有生长抑制作用,IC50值在0.039-28.8nm之间,比多拉司他丁10高2.7-9.2倍。所有四种SCLC细胞系在暴露于多拉司他丁15后24小时内均经历G2/M期阻滞[4]。

[体内研究]

多拉司他丁15通过药物C末端的赖氨酸残基与曲妥珠单抗结合,使用不可切割的连接物(曲妥珠单抗酰胺-C-末端-Dol15)在体外对内源性表达高HER2水平(即SK-BR-3、SK-OV-3)的细胞产生靶向生长抑制。这种ADC在不同剂量(即10和20 mg/kg)的SK-OV-3人卵巢癌异种移植中有效[3]。

[参考文献]

[1]. Bai R, et al. Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules. Biochem Pharmacol. 1992 Jun 23;43(12):2637-45.

[2]. Sato M, et al. A natural peptide, dolastatin 15, induces G2/M cell cycle arrest and apoptosis of human multiple myeloma cells. Int J Oncol. 2007 Jun;30(6):1453-9.

[3]. Gianolio DA, et al. Targeting HER2-positive cancer with dolastatin 15 derivatives conjugated to trastuzumab, novel antibody-drug conjugates. Cancer Chemother Pharmacol. 2012 Sep;70(3):439-49.

[4]. Ali MA, et al. Dolastatin 15 induces apoptosis and BCL-2 phosphorylation in small cell lung cancer cell lines. Anticancer Res. 1998 Mar-Apr;18(2A):1021-6.

Dolastatin 15物理化学性质

[ 密度 ]:
1.2g/cm3

[ 沸点 ]:
943.2ºC at 760mmHg

[ 分子式 ]:
C₄₅H₆₈N₆O₉

[ 分子量 ]:
837.05600

[ 闪点 ]:
524.2ºC

[ 精确质量 ]:
836.50500

[ PSA ]:
166.18000

[ LogP ]:
3.46120

[ 蒸汽压 ]:
0mmHg at 25°C

[ 折射率 ]:
1.572

[ 储存条件 ]:
-20°C

Dolastatin 15MSDS

详细MSDS(安全技术说明书)

Dolastatin 15安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危险品运输编码 ]:
NONH for all modes of transport

Dolastatin 15文献

End-binding proteins sensitize microtubules to the action of microtubule-targeting agents.

Proc. Natl. Acad. Sci. U. S. A. 110(22) , 8900-5, (2013)

Microtubule-targeting agents (MTAs) are widely used for treatment of cancer and other diseases, and a detailed understanding of the mechanism of their action is important for the development of improv...

The bcl-2 and p53 oncoproteins can be modulated by bryostatin 1 and dolastatins in human diffuse large cell lymphoma.

Anticancer Drugs 6(3) , 392-7, (1995)

The effects of dolastatin 10 (Dol10) and dolastatin 15 (Dol15) alone, and after treatment with bryostatin 1 (Bryo1), on human diffuse large cell lymphoma cell line (WSU-DLCL2) were studied. At a conce...

Effects of dolastatins on human B-lymphocytic leukemia cell lines.

Leuk. Res. 17(4) , 333-9, (1993)

Dolastatins are naturally occurring peptides isolated from marine animals and are known to be potent anti-neoplastic agents. Here, the three compounds dolastatin 10 (Dola 10), dolastatin 15 (Dola 15) ...

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