Disease relevance of NSC 617668

• PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic profile of the dolastatin 15 analog LU103793 when administered daily for 5 days every 3 weeks [1].
• At toxic concentrations dolastatin 15 caused the leukemia and lymphoma cells to arrest in mitosis [2].
• LU103793, a synthetic analogue of dolastatin 15, showed interesting pre-clinical activity in melanoma xenografts [3].
• The IC50 values for cell growth were obtained for dolastatin 15 with L1210 murine leukemia cells, human Burkitt lymphoma cells, and Chinese hamster ovary (CHO) cells (3, 3, and 5 nM with the three cell lines, respectively) [2].
• Dolastatin 15 induces apoptosis and BCL-2 phosphorylation in small cell lung cancer cell lines [4].

High impact information on NSC 617668

• SR cells were more sensitive to dolastatin 15 than to dolastatin 10 (IC50 = .00013-.0013 nM versus .0013-.013 nM) [5].
• Values for concentrations required for inhibition of proliferation by 50% (IC50) were .00013-.0013 nM for dolastatin 10 in each cell line; values for dolastatin 15 were approximately .13 nM in DB and HT cells and .0013-.013 nM in RL cells [5].
• Dolastatins 10 and 15 both inhibited human and murine bone marrow cell colony formation in a concentration-dependent manner, with the concentration required for half maximal inhibition ranging from 0.1 to 1 pg/mL for dolastatin 10 and from 10 to 100 pg/mL for dolastatin 15 [6].
• PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of the dolastatin-15 analogue, tasidotin (ILX651), when administered i.v. daily for 5 days every 3 weeks [7].
• PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors [8].

Biological context of NSC 617668

• Cemadotin (LU103793) (NSC D-669356) is a water-soluble synthetic analogue of dolastatin 15 that inhibits cell proliferation in vitro and the growth of human tumor xenografts [9].
• Antineoplastic agents 360. Synthesis and cancer cell growth inhibitory studies of dolastatin 15 structural modifications [10].
• We attempted to gain insight into the binding site for dolastatin 15 on tubulin by studying inhibitory effects of other drugs when the gel filtration column was equilibrated with both [3H]dolastatin 15 and a second, nonradiolabeled drug [11].
• Bryo1, Dol10 and Dol15 induced apoptosis which was seen on morphological examination, by flow cytometry and DNA fragmentation on agarose gel electrophoresis [12].
• Immunoblot analysis of dolastatin 15-treated cells which overexpressed bcl-2 revealed a pattern consistent with bcl-2 phosphorylation [4].

Anatomical context of NSC 617668

• Both diazonamide A and the oxygen analog are potent inhibitors of microtubule assembly, equivalent in activity to dolastatin 10 and therefore far more potent than dolastatin 15 [13].

Gene context of NSC 617668

• Despite its potency and the loss of microtubules in treated cells, the interaction of dolastatin 15 with tubulin in vitro was weak [2].
• All four SCLC cell lines underwent G2/M arrest within 24 hours of exposure to dolastatin 15, and three had morphologic evidence of apoptosis after 48 hours [4].
• Following extraction from plasma, using a solid-phase C18 cartridge, capillary zone electrophoresis was used to separate, detect and quantitate dolastatin-10 using the structurally related compound dolastatin-15 as the internal standard [14].

Analytical, diagnostic and therapeutic context of NSC 617668

• Among all these metabolites, dolastatin 10 and dolastatin 15 exhibit the most promising antiproliferative properties and are currently under evaluation in clinical trials [15].

References