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LY 135305

" in MedChemExpress (MCE) Product Catalog:
Cat. No. Product Name Target Research Areas Chemical Structure
  • HY-120563
    LY135305

    		Thrombin Cardiovascular Disease
    LY 135305 is a thrombin activation inhibitor. LY 135305 inhibits spontaneous metastasis and increases animal survival .
    LY135305
  • HY-117019
    LY150310 free base

    		Others Cancer
    LY150310 is able to inhibit thromboxane synthase, cyclooxygenase, and thrombin activation, biochemical processes that have been proposed in the literature as targets for anti-metastatic agents. The objectives of this study were twofold: (a) to compare the anti-metastatic activity of Eli Lilly compounds with reference anti-metastatic compounds nafazatrom and RA233; and (b) to examine the correlation between inhibition of spontaneous lung metastasis and survival. The anti-metastatic activity of the compounds was evaluated using the Lewis lung squamous cell carcinoma cell model. In this model, 5×10^5 tumor cells were implanted into the gastrocnemius muscle, the primary tumor was resected on day 14, and lung metastatic lesions were counted on day 25. The compounds were administered every 12 hours from day 5 to day 19. Nafazatrom, LY150310, LY189332, and LY135305 were found to inhibit spontaneous lung metastasis in a dose-dependent manner. The ED50 values ??of these compounds were 50, 0.5, 2, and 0.35 mg/kg/day, respectively; the corresponding therapeutic indices (LD50/ED50) were 7, 180, 255, and 511, respectively. To evaluate the effects of nafazatrom, LY150310, LY189332, and LY135305 on animal survival, these compounds were given at the maximum anti-metastatic dose of 200, 60, 20, and 6 mg/kg/day, respectively. Two dosing schedules were used: (a) from day 5 to 19; (b) from day 5 to death. These compounds did not significantly alter median survival times or the number of long-term survivors at any dosing schedule. RA233 did not inhibit lung metastasis or increase median survival time at a schedule in which the maximum tolerated dose of 200 mg/kg/day was given until death on day 5. Postmortem examination of animals given nafazatrom, LY150310, LY189332, and LY1350310 revealed complete suppression of lung lesions, whereas lesions developed in the liver, kidney, spleen, and brain. The results of this study suggest that the effects of a compound on the number of metastatic lesions in target organs may not be predictive of its effects on survival. To successfully translate laboratory data into clinical applications, survival should be considered a predictor of the potential clinical utility of a compound.
    LY150310 free base

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