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123884-00-4

中文名稱 DOLASTATIN 15
英文名稱 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 結(jié)構(gòu)式 123884-00-4 結(jié)構(gòu)式

基本信息

中文別名
多拉司他汀 15
英文別名
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*))-

物理化學(xué)性質(zhì)

沸點(diǎn)954.0±65.0 °C(Predicted)
密度1.20±0.1 g/cm3(Predicted)
儲(chǔ)存條件−20°C
溶解度Methanol: soluble
酸度系數(shù)(pKa)13.88±0.46(Predicted)
形態(tài)白色固體。

安全數(shù)據(jù)

安全說(shuō)明22-24/25
WGK Germany3

常見(jiàn)問(wèn)題列表

生物活性
Dolastatin 15 (DLS 15),一種從 Dolabella auricularia 中提取的去甲肽,是一種有效的抗有絲分裂劑 (antimitotic),在結(jié)構(gòu)上與抗微管蛋白劑 Dolastatin 10 有關(guān)。Dolastatin 15 誘導(dǎo)多發(fā)性骨髓瘤細(xì)胞周期阻滯和凋亡。Dolastatin 15 可作為 ADC 細(xì)胞毒素。
靶點(diǎn)

Auristatin

體外研究

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.

體內(nèi)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.

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