And the inhibition of LacCer levels due to a decrease in LCS activity and LCS mass upon feeding D-PDMP contributes to the inhibition of angiogenesis and decreased renal tumor volume. In sum, these studies suggest that D-PDMP may be well suited to effectively and safely mitigate tumor growth and also neo-intimal proliferation following balloon angioplasty in rabbits and eventually in man. And this is substantiated from the works conducted in other laboratories wherein D-PDMP was shown to target LCS to mitigate various phenotypes in vitro and in vivo. Clearly, D-PDMP is not a specific inhibitor of UGCG. Never the less, it is commercially available and its kinetics and bioavailability are known. It is not toxic and is well tolerated by experimental animals. It has been used widely and has increased our knowledge of the inter relationship between glycosphingolipid metabolism and various phenotypes in vitro and in vivo. On the other hand, the rapid turnover of DPDMP requires that some derivative of this compound and/or an alternative approach of its delivery may be relatively more efficacious in mitigating tumor growth and angiogenesis. In addition to the catalytic ARTD domain located at the C-terminus, they contain a sterile alpha motif next to the catalytic domain, which is responsible for the multimerization of the tankyrases. The target proteins are recognized by five ankyrin repeat clusters and the interactions of the ARCs link tankyrases to various cellular pathways. Human tankyrases are highly conserved with 89% sequence identity and share overlapping functions. TNKS1 contains an additional N-terminal region with repeats of histidine, proline, and serine residues, but the function of this motif is so far unknown. TNKS1 was discovered as an enzyme controlling the length of human telomeres and this was the first implication that tankyrase inhibitors could be useful as therapeutic agents against cancer. Later, TNKS2 was discovered and multiple roles of tankyrases in various cellular signaling pathways have Torin 1 mTOR inhibitor implied that tankyrase inhibitors could be potential drugs especially towards different forms of cancer. The rationale for using tankyrase inhibitors in cancer therapy comes from its various functions within the cell. Tankyrases PARsylate TRF1, a shelterin complex protein protecting telomeres. The modification causes dissociation of TRF1 from the telomeres allowing extension of the WZ4002 telomere by a telomerase enzyme. Due to high telomerase activity, tumor cells escape cellular senescence by uncontrolled telomere extension. Inhibition of tankyrase catalytic activity in tumor cells prevents uncontrolled telomere extension, triggering cellular senescence. Tankyrase 1 is also involved in mitosis as the protein is localized to spindle poles and its catalytic activity is essential for normal bipolar spindle structure. TNKS1 depletion leads to mitotic arrest without DNA damage in HeLa cells, while some other cell lines undergo mitosis with subsequent DNA damage and arrest with a senescence-like phenotype. The cellular factors behind these events are poorly understood and remain to be elucidated before the therapeutical potential of tankyrase inhibition in this setting is evaluated. Wnt signaling pathway is often overactivated in cancers. The identification of tankyrases as part of the b-catenin destruction complex has put tankyrases as one of the promising drug targets regulating Wnt signaling.