Accession Number : ADA474983


Title :   New Drugs for CML


Descriptive Note : Final rept. 1 Feb 2006-31 Jan 2007


Corporate Author : SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA


Personal Author(s) : Deisseroth, Albert B


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a474983.pdf


Report Date : 01 Feb 2007


Pagination or Media Count : 26


Abstract : The goal of the experiments was to test if the acetylenes could be used to suppress the in vivo growth of P210Bcr-Abl dependent cell lines. The work completed during the funding showed that the acetylene compound K1P which had been shown to suppress the in vitro growth of CML cells which are resistant to imatinib and to inhibit p210Bcr-Abl dependent in vitro CML cell growth at the nanomolar concentrations when combined with imatinib could also suppress the in vivo growth of a P210Bcr-Abl dependent cell line (Baf-1P210Bcr-Abl). These studies also showed that the medium in which the drugs were dissolved must contain 0.1% ethanol to increase the solubility sufficiently to suppress in vivo P210Bcr-Abl dependent cell growth. Finally the presence of serum in the medium used to expose the drugs to the P210Bcr-Abl dependent cells blocked the suppressive activity of the drugs despite the presence of 0.1% ethanol. These data suggested that chemical functionalities which could improve the bioavailability of the drugs in the presence of serum needed to be added to the ester side chain of the acetylene compounds. This work once completed will enable further in vivo toxicity and efficacy studies to proceed.


Descriptors :   *GLYCOPROTEINS , *DRUGS , *BREAST CANCER , *CELLS(BIOLOGY) , TOXICITY , MUTATIONS , SOLUBILITY , SUPPRESSION , PHOSPHORUS TRANSFERASES , ACETYLENES , IN VIVO ANALYSIS , ESTERS , IN VITRO ANALYSIS , CHEMICAL BONDS , PATIENTS


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE