Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer

Wojtowicz‐Praga, Slawomir; Low, Jennifer A.; Marshall, John L.; Ness, Elizabeth; Dickson, Robert B.; Barter, James F.; Sale, Mark; McCann, Peter P.; Moore, Jonathan M.; Cole, A. F. D.; Hawkins, Michael

doi:10.1007/bf00210790

Cited by 118 publications

(48 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This clearly suggests that expression of matrix metalloproteinase -9 is an early event in melanoma progression (Kerkela & Saarialho-Kere, 2003). Several studies using either cell lines or animal models have demonstrated that the balance between matrix metalloproteinases and their inhibitors finally determines melanoma progression (Hofmann et al, 2000b;Wojtowicz-Praga et al, 1998;Rudek et al, 2001;Jin et al, 2006;Wojtowicz-Praga et al, 1996;Bodey et al, 2001;Airola et al, 1999). Overexpression of TIMP-1, -2, and -3 significantly reduces melanoma tumour cell invasion, migration, growth and metastasis, and significantly reduces tumour neovascularization in several tumour models (Anand-Apte et al, 1996).…”

Section: Integrin Signalling and Extracellular Matrix Enzymesmentioning

confidence: 98%

Role of Angiogenesis and Microenvironment in Melanoma Progression

Ria¹,

Reale²,

Vacca³

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

View full text Add to dashboard Cite

Section: Integrin Signalling and Extracellular Matrix Enzymesmentioning

confidence: 98%

Role of Angiogenesis and Microenvironment in Melanoma Progression

Ria¹,

Reale²,

Vacca³

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

View full text Add to dashboard Cite

“…These are pseudopeptide derivatives that mimic the cleavage site of MMP substrates (Wojtowicz-praga et al,1996). They act as competitive inhibitors which inhibit the MMP activity by interacting with the Zn 2+ in catalytic sites and then chelating it (Gialeli et al, 2011).…”

Section: Peptidomimetic Mmpimentioning

confidence: 99%

“…Batimastat is the first MMPI which was tested in humans, (Wojtowicz-praga et al, 1996) but it has broad spectrum of inhibition and low water solubility because of which its intraperitoneal administration is required. To overcome these drawbacks Marimastat was introduced which can be orally administered but associated with the side effects of musculoskeletal pain (Steward and Thomas, 2000).…”

Section: Peptidomimetic Mmpimentioning

confidence: 99%

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Yadav¹,

Puri²,

Rastogi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

187

131

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

show abstract

“…Batimastat showed a poor oral bioavailability and also could not be given intravenously due to its limited solubility. Therefore clinical studies were performed using intraperitoneal or intrapleural administration [35][36][37][38]. Following intraperitoneal administration, rapid systemic absorption was seen with serum levels exceeding concentrations causing 50% inhibition (IC 50 ) of major MMPs for prolonged periods of time.…”

Section: Phase I Studiesmentioning

confidence: 99%

Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives

2001

View full text Add to dashboard Cite

The Oncologist 2001;6:415-427 www.TheOncologist.com Correspondence: Ronald Hoekstra, M.D., Department of Medical Oncology, University Hospital Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Fax: 31-10-463-4627; e-mail: hoekstra@oncd.azr.nl Received May 25, 2001; accepted for publication August 7, 2001. ©AlphaMed Press 1083-7159/2001 INTRODUCTIONThe importance of proteinases in tumor invasion was first recognized in 1925 when Fischer found that a lytic substance from sarcoma cells could degrade the fibrin stroma. Later it was found that the serine proteinase plasminogen activator (PA) played an important role in activating plasminogen to plasmin. Apart from PAs, proteinases such as serine, cysteine, and metalloproteinases have been associated with cancer [1]. It is important to realize that high levels of extracellular proteolytic activity are not restricted to the malignant phenotype, but are also seen in a number of physiological processes such as embryo implantation, wound healing, and angiogenesis. A common feature in these processes is the breaching of histological barriers with the degradation of the extracellular matrix (ECM) composed of basement membrane and extracellular stroma.Matrix metalloproteinases (MMPs) are enzymes able to degrade most components of the ECM such as collagens, laminins, fibronectins, elastins, and the protein core of proteoglycans. At this moment more than 20 different MMPs have been identified and classified. They show a consistent sequence homology and in general share a pre-domain, which is a signal peptide for secretion, a pro-domain, important for maintaining latency, a catalytic domain with a highly

show abstract

Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer

Cited by 118 publications

References 11 publications

Role of Angiogenesis and Microenvironment in Melanoma Progression

Role of Angiogenesis and Microenvironment in Melanoma Progression

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives

Contact Info

Product

Resources

About