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

13 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

Keywords

Blood-brain barrier
Glioblastoma
LC-1
Parthenolide
Pharmacokinetics

Access

10.1016/j.bmcl.2015.04.058

Fingerprint Dive into the research topics of 'Parthenolide prodrug LC-1 slows growth of intracranial glioma'. Together they form a unique fingerprint.

Cite this

Hexum, J. K., Becker, C. M., Kempema, A. M., Ohlfest, J. R., Largaespada, D. A., & Harki, D. A. (2015). Parthenolide prodrug LC-1 slows growth of intracranial glioma. Bioorganic and Medicinal Chemistry Letters, 25(12), 2493-2495. [22641]. https://doi.org/10.1016/j.bmcl.2015.04.058

@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.}",

year = "2015",

month = may,

day = "26",

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

language = "English (US)",

volume = "25",

pages = "2493--2495",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "12",

}

TY - JOUR

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.

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

UR - http://www.scopus.com/inward/record.url?scp=84929706402&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929706402&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2015.04.058

DO - 10.1016/j.bmcl.2015.04.058

M3 - Article

C2 - 25978958

AN - SCOPUS:84929706402

VL - 25

SP - 2493

EP - 2495

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 12

M1 - 22641

ER -