Bioorg Med Chem Lett. 2010 Feb 1;20(3):853-6. Epub 2010 Jan 4.

Discovery of matrix metalloproteases selective and activated peptide-doxorubicin prodrugs as anti-tumor agents.

Hu Z, Jiang X, Albright CF, Graciani N, Yue E, Zhang M, Zhang SY, Bruckner R, Diamond M, Dowling R, Rafalski M, Yeleswaram S, Trainor GL, Seitz SP, Han W.

Source

Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543, USA. zilun.hu@bms.com

Abstract

To selectively target doxorubicin (Dox) to tumor tissue and thereby improve the therapeutic index and/or efficacy of Dox, matrix metalloproteinases (MMP) activated peptide-Dox prodrugs were designed and synthesized by coupling MMP-cleavable peptides to Dox. Preferred conjugates were good substrates for MMPs, poor substrates for neprilysin, an off-target proteinase, and stable in blood ex vivo. When administered to mice with HT1080 xenografts, conjugates, such as 19, preferentially released Dox in tumor relative to heart tissue and prevented tumor growth with less marrow toxicity than Dox.

PMID:: 20060717; [PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

Labome Researcher Resource - ExactAntigen/Labome

Molecular Biology Databases

DOXORUBICIN - HSDB

Supplemental Content

Save items

Related citations in PubMed

Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity. [Mol Cancer Ther. 2005]
Matrix metalloproteinase-activated doxorubicin prodrugs inhibit HT1080 xenograft growth better than doxorubicin with less toxicity.
Albright CF, Graciani N, Han W, Yue E, Stein R, Lai Z, Diamond M, Dowling R, Grimminger L, Zhang SY, et al. Mol Cancer Ther. 2005 May; 4(5):751-60.
The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy. [J Med Chem. 2001]
The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy.
Garsky VM, Lumma PK, Feng DM, Wai J, Ramjit HG, Sardana MK, Oliff A, Jones RE, DeFeo-Jones D, Freidinger RM. J Med Chem. 2001 Nov 22; 44(24):4216-24.
A doxorubicin-CNGRC-peptide conjugate with prodrug properties. [Biochem Pharmacol. 2002]
A doxorubicin-CNGRC-peptide conjugate with prodrug properties.
van Hensbergen Y, Broxterman HJ, Elderkamp YW, Lankelma J, Beers JC, Heijn M, Boven E, Hoekman K, Pinedo HM. Biochem Pharmacol. 2002 Mar 1; 63(5):897-908.
CD10 is a key enzyme involved in the activation of tumor-activated peptide prodrug CPI-0004Na and novel analogues: implications for the design of novel peptide prodrugs for the therapy of CD10+ tumors. [Cancer Res. 2003]
CD10 is a key enzyme involved in the activation of tumor-activated peptide prodrug CPI-0004Na and novel analogues: implications for the design of novel peptide prodrugs for the therapy of CD10+ tumors.
Pan C, Cardarelli PM, Nieder MH, Pickford LB, Gangwar S, King DJ, Yarranton GT, Buckman D, Roscoe W, Zhou F, et al. Cancer Res. 2003 Sep 1; 63(17):5526-31.
Review Matrix metalloproteases: underutilized targets for drug delivery. [J Drug Target. 2007]
Review Matrix metalloproteases: underutilized targets for drug delivery.
Vartak DG, Gemeinhart RA. J Drug Target. 2007 Jan; 15(1):1-20.

See reviews... See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioAssay
PubChem BioAssay experiments on the biological activities of small molecules that cite the current articles. The depositors of BioAssay data provide these references.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.

Recent activity

Clear Turn Off Turn On

Discovery of matrix metalloproteases selective and activated peptide-doxorubicin...
Discovery of matrix metalloproteases selective and activated peptide-doxorubicin prodrugs as anti-tumor agents.
Bioorg Med Chem Lett. 2010 Feb 1 ;20(3):853-6. Epub 2010 Jan 4 .

PubMed
17ss-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in p...
17ss-Hydroxysteroid dehydrogenase type 1 as predictor of tamoxifen response in premenopausal breast cancer.
Eur J Cancer. 2010 Mar ;46(5):892-900. Epub 2010 Jan 8 .

PubMed
Large conformational changes in proteins: signaling and other functions.
Large conformational changes in proteins: signaling and other functions.
Curr Opin Struct Biol. 2010 Apr ;20(2):142-7. Epub 2010 Jan 8 .

PubMed
The serotonin transporter gene and risk for alcohol dependence: a meta-analytic ...
The serotonin transporter gene and risk for alcohol dependence: a meta-analytic review.
Drug Alcohol Depend. 2010 Apr 1 ;108(1-2):1-6. Epub 2010 Jan 8 .

PubMed
Imovane and narcotic addiction.
Imovane and narcotic addiction.
N Z Med J. 1991 Mar 13 ;104(907):103.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to:

Discovery of matrix metalloproteases selective and activated peptide-doxorubicin prodrugs as anti-tumor agents.

Source

Abstract

Publication Types, MeSH Terms, Substances

Publication Types

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Supplemental Content

Save items

Related citations in PubMed

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information