MedKoo product information:

  XMT-1107

Fumagillin-derived polymer conjugate XMT-1107 is a polymeric prodrug consisting of the fumagillol-derived small molecule XMT-1191 tethered to the hydrophilic, biodegradable70 kDa polymer poly[1- hydroxymethylethylene hydroxymethylformal] (PHF) with potential antiangiogenic and antineoplastic activities. Upon administration, fumagillin-derived polymer conjugate XMT-1107 releases XMT-1191, which may inhibit angiogenesis through the irreversible inhibition of the methionine aminopeptidase 2 (METAP2); although the exact mechanism of action has yet to be fully elucidated, this agent appears to induce cell cycle arrest in endothelial cells, inhibiting their proliferation and migration. Compared to an unconjugated fumagillin analog, XMT-1107 exhibits improved solubility and an extended half life due to its PHF backbone. METAP2, a member of the methionyl aminopeptidase family, binds two cobalt or manganese ions and protects the alpha subunit of eukaryotic initiation factor 2 (EIF2) from inhibitory phosphorylation by removing the amino-terminal methionine residue from nascent protein; this aminopeptidase may be overexpressed in a variety of tumor cell types. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

XMT-1107 is being evaluated in an ongoing Phase 1 clinical trial in refractory advanced solid tumors. The drug candidate is partnered with Teva for all indications worldwide, except for Japan, through a deal signed in April 2010. Japanese sales of the two top-selling angiogenesis inhibitors, Avastin® and Nexavar®, are expected to reach in excess of $1 billion per year.

Fumagillin is a complex biomolecule and used as an antimicrobial agent. It was isolated in 1949 from the microbial organism Aspergillus fumigatus. Fumagillin has been used in the treatment of microsporidiosis. It is also an amebicide. Fumagillin can block blood vessel formation by binding to an enzyme called methionine aminopeptidase and for this reason, the compound, together with semisynthetic derivatives, are investigated as a angiogenesis inhibitor  in the treatment of cancer. Preliminary clinical trials are being conducted by Zafgen into using the fumagillin analog beloranib for weight loss. (source: http://en.wikipedia.org/wiki/Fumagillin). 

Chemical structure of Fumagillin

((2E,4E,6E,8E)-10-{[(3R,4S,5S,6R)-5-methoxy- 4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1- oxaspiro[2.5]octan-6-yl]oxy}-10 -oxodeca-2,4,6,8-tetraenoic acid)

Current developer:    Mersana Therapeutics.