Parthenolide prodrug LC-1 slows growth of intracranial glioma

Joseph K. Hexum; Chani M. Becker; Aaron M. Kempema; John R. Ohlfest; David A. Largaespada; Daniel A. Harki

doi:10.1016/j.bmcl.2015.04.058

Parthenolide prodrug LC-1 slows growth of intracranial glioma

Joseph K. Hexum, Chani M. Becker, Aaron M. Kempema, John R. Ohlfest, David A. Largaespada, Daniel A. Harki

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was found to have low micromolar cytotoxic activity against three glioma cell lines and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth kinetics and extended the survival time of tumor-bearing mice in comparison to the vehicle control. Consequently, LC-1 represents a promising lead compound for further development as a glioma therapy.

Original language	English (US)
Article number	22641
Pages (from-to)	2493-2495
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2015.04.058
State	Published - May 26 2015

Bibliographical note

Funding Information:
We gratefully acknowledge Hyundai Hope on Wheels (Hope Grant Award), The V Foundation for Cancer Research (V Scholar Award to DAH), and the Children’s Cancer Research Fund (Minneapolis, MN) for financial support.

Keywords

Blood-brain barrier
Glioblastoma
LC-1
Parthenolide
Pharmacokinetics

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10.1016/j.bmcl.2015.04.058

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@article{25604ebae4d24ab090ac1a653cb62c9a,

title = "Parthenolide prodrug LC-1 slows growth of intracranial glioma",

abstract = "LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was found to have low micromolar cytotoxic activity against three glioma cell lines and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth kinetics and extended the survival time of tumor-bearing mice in comparison to the vehicle control. Consequently, LC-1 represents a promising lead compound for further development as a glioma therapy.",

keywords = "Blood-brain barrier, Glioblastoma, LC-1, Parthenolide, Pharmacokinetics",

author = "Hexum, {Joseph K.} and Becker, {Chani M.} and Kempema, {Aaron M.} and Ohlfest, {John R.} and Largaespada, {David A.} and Harki, {Daniel A.}",

note = "Funding Information: We gratefully acknowledge Hyundai Hope on Wheels (Hope Grant Award), The V Foundation for Cancer Research (V Scholar Award to DAH), and the Children{\textquoteright}s Cancer Research Fund (Minneapolis, MN) for financial support. ",

year = "2015",

month = may,

day = "26",

doi = "10.1016/j.bmcl.2015.04.058",

language = "English (US)",

volume = "25",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Parthenolide prodrug LC-1 slows growth of intracranial glioma

AU - Hexum, Joseph K.

AU - Becker, Chani M.

AU - Kempema, Aaron M.

AU - Ohlfest, John R.

AU - Largaespada, David A.

AU - Harki, Daniel A.

N1 - Funding Information: We gratefully acknowledge Hyundai Hope on Wheels (Hope Grant Award), The V Foundation for Cancer Research (V Scholar Award to DAH), and the Children’s Cancer Research Fund (Minneapolis, MN) for financial support.

PY - 2015/5/26

Y1 - 2015/5/26

N2 - LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was found to have low micromolar cytotoxic activity against three glioma cell lines and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth kinetics and extended the survival time of tumor-bearing mice in comparison to the vehicle control. Consequently, LC-1 represents a promising lead compound for further development as a glioma therapy.

AB - LC-1 (also known as DMAPT or dimethylamino-parthenolide), a prodrug of parthenolide, was tested for anti-proliferative activity against glioma. LC-1 was found to have low micromolar cytotoxic activity against three glioma cell lines and was also found to be brain penetrant in healthy mice (2.1-3.0 brain-to-plasma ratio). In a syngeneic GL261 murine glioma model, LC-1 slowed tumor growth kinetics and extended the survival time of tumor-bearing mice in comparison to the vehicle control. Consequently, LC-1 represents a promising lead compound for further development as a glioma therapy.

KW - Blood-brain barrier

KW - Glioblastoma

KW - LC-1

KW - Parthenolide

KW - Pharmacokinetics

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DO - 10.1016/j.bmcl.2015.04.058

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SP - 2493

EP - 2495

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 12

M1 - 22641

ER -

Parthenolide prodrug LC-1 slows growth of intracranial glioma

Abstract

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Keywords

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