Dolastatin 15

Names

[ Name ]:
Dolastatin 15

[Synonym ]:
(5S)-1-[(2S)-O-(N,N-DIMETHYL-VAL-VAL-N-ME-VAL-PRO-PRO)-2-HYDROXYISOVALERYL]-2-OXO-4-METHOXY-5-BENZYL-3-PYRROLINE
(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-{(2S)-O-[(N,N-dimethyl-L-valyl)-L-valyl-(N-methyl-L-valyl)-L-prolyl-L-prolyl]-2-hydroxy-isovaleryl}-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
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*))
dolastatin-15
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*))

Biological Activity

[Description]:

Dolastatin 15 (DLS 15), a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent Dolastatin 10. Dolastatin 15 induces cell cycle arrest and apoptosis in multiple myeloma cells. Dolastatin 15 can be used as an ADC cytotoxin[1][2][3].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

[Target]

Auristatin

[In Vitro]

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[2]. Dolastatin 15 (DLS 15) displays growth inhibitory activity against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) with IC50 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[4].

[In Vivo]

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[3].

[References]

[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.

Chemical & Physical Properties

[ Density]:
1.2g/cm3

[ Boiling Point ]:
943.2ºC at 760mmHg

[ Molecular Formula ]:
C₄₅H₆₈N₆O₉

[ Molecular Weight ]:
837.05600

[ Flash Point ]:
524.2ºC

[ Exact Mass ]:
836.50500

[ PSA ]:
166.18000

[ LogP ]:
3.46120

[ Vapour Pressure ]:
0mmHg at 25°C

[ Index of Refraction ]:
1.572

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

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) ...

Related Compounds

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