123884-00-4

中文名称 DOLASTATIN 15

CAS 123884-00-4

分子式 C45H68N6O9

分子量 837.06

MOL 文件 123884-00-4.mol

123884-00-4 结构式

基本信息物理化学性质安全数据常见问题列表

基本信息

英文别名

DLS 15
Nsc 617668
DOLASTATIN 15
(5S)-1-[(2S)-O-(N,N-VAL-VAL-N-ME-VAL-PRO-PRO)-2-HYDROXYISOVALERYL]-2-OXO-4-METHOXY-5-BENZYL-3-PYRROLINE
(5S)-1-[N,N-Dimethyl-L-Val-L-Val-N-methyl-L-Val-L-Pro-L-Pro-L-Hyiv-]-5-benzyl-4-methoxy-1H-pyrrol-2(5H)-one
(5S)-1-[(2S)-O-(N,N-DIMETHYL-VAL-VAL-N-ME-VAL-PRO-PRO)-2-HYDROXYISOVALERYL]-2-OXO-4-METHOXY-5-BENZYL-3-PYRROLINE
Dolastatin 15 (5S)-1-[(2S)-O-(N,N-Dimethyl-Val-Val-N-Me-Val-Pro-Pro)-2-hydroxyisovaleryl]-2-oxo-4-methoxy-5-benzyl-3-pyrroline
L-Proline, 1-(1-(N-(N-(N,N-dimethyl-L-valyl)-L-valyl)-N-methyl-L-valyl)-L-propyl)-, 1-((2,5-dihydro-3-methoxy-5-oxo-2-(phenylmethyl)-1H-pyrrol-1-yl)carbonyl)-2-methylpropyl ester, (S-(R*,R*))-
L-Proline, 1-(1-(N-(N-(N,N-dimethyl-L-valyl)-L-valyl)-N-methyl-L-valyl)-L-prolyl)-, 1-((2,5-dihydro-3-methoxy-5-oxo-2-(phenylmethyl)-1H-pyrrol-1-yl)carbonyl)-2-methylpropyl ester, (S-(R*,R*))-

物理化学性质

储存条件−20°C

形态白色固体。

安全数据

安全说明22-24/25

WGK Germany3

常见问题列表

生物活性

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。

靶点

Auristatin

体外研究

Dolastatin 15 (DLS 15) induces cell cycle arrest at the G2/M phase followed by apoptosis in various human myeloma cell lines (RPMI8226, U266, and IM9). Dolastatin 15 induces apoptosis of myeloma cells via activation of both mitochondrial- and Fas (CD95)/Fas-L (CD95-L)-mediated pathways. Dolastatin 15 (DLS 15) displays growth inhibitory activity against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) with IC ₅₀ values ranging from 0.039-28.8 nM, which were 2.7-9.2-fold higher than the values for dolastatin 10. All four SCLC cell lines underwent G2/M arrest within 24 hours of exposure to dolastatin 15.

体内研究

Dolastatin 15 conjugates to Trastuzumab via lysine residues at the drug C-terminus using a non-cleavable linker (Trastuzumab-amide-C-term-Dol15) produced target-dependent growth inhibition of cells endogenously expressing high HER2 levels (i.e., SK-BR-3, SK-OV-3) in vitro. This ADC was effective at varying doses (i.e., 10 and 20 mg/kg) in the SK-OV-3 human ovarian cancer xenograft.