Disease relevance of Fblim1

• To examine the CTL response to the influenza virus A/Ty/Ont/7732/66[H5N9], particularly the H5 hemagglutinin, a long term CTL line was generated from spleen cells of A/Ty/Ont-immune Balb/c [H-2d] mice secondarily stimulated in vitro with A/Ty/Cal/Hurst-2/71[H5N2] [1].
• Both (+)-calanolide A (Cal A; NSC 675451) and (+)-dihydrocalanolide A (DHCal A; NSC 678323) are currently under development for the treatment of HIV infections [2].
• Cal gamma1 may represent a potential therapeutic agent to eliminate self-reactive T cells in autoimmune diseases, providing that is delivered by antigen-specific T-cell ligands [3].

High impact information on Fblim1

• Cal contained a functional nuclear export signal and shuttled from the cytoplasm into the nucleus in response to calcium [4].
• The total heat evolved in the interval 10--37 degrees C scanned at 1 degree C min-1 ranged from 300 to 2500 X 10(-12) cal (1 Cal = 4.184 J) per cell, depending on cell density, glucose concentration, and the presence or absence of various drugs [5].
• The assays were used to compare the intravenous pharmacokinetics of the dihydro analogue relative to the parent compound, Cal A, and to determine the relative oral bioavailability of each drug in CD2F1 mice [2].
• The thymic precursors and mature T cells incubated with Cal gamma1 for only 30 min showed a drastic decrease or loss of cytokine production and proliferation following stimulation with the immunogenic peptide, or with CD3 and CD28 antibodies [3].
• Calicheamicin gamma1 (Cal gamma1) is a hydrophobic enediyne antibiotic known to cleave the DNA and lead to apoptosis in a variety of cells [3].

Anatomical context of Fblim1

• Targeting of highly suppressogenic drugs such as Cal gamma1 to autoreactive T cells may reduce considerable the therapeutic dose and the drug-related side effects [3].

Associations of Fblim1 with chemical compounds

• Cal A increases the Michaelis-Menten constant for binding of taurine to the transporter from 31+/-6 to 45+/-4 microM and reduces the taurine transport capacity from 210+/-20 to 170+/-10 nmol x g dry wt(-1) x min(-1) [corrected] [6].
• Herein, we show that Cal gamma1 exhibits a 1000-times stronger suppressogenic effect on antigen-specific (diabetogenic), and naïve CD4 T cells than Doxorubicin (Dox), another strong apoptotic drug [3].

References