Disease relevance of LM-975

• Immune thrombocytopenia caused by flavone-8-acetic acid [1].
• Flavone-8-acetic acid plus recombinant human interleukin 2 is a successful antitumor therapy in mice bearing the Renca murine renal cell carcinoma [2].
• Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer [3].
• Response to flavone acetic acid (NSC 347512) of primary and metastatic human colorectal carcinoma xenografts [4].
• Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma [5].

High impact information on LM-975

• Renal cell carcinoma-bearing mice, successfully treated with flavone-8-acetic acid and recombinant human IL-2, showed a reversion to a Th1-like pattern [6].
• Flavone-8-acetic acid inhibits ristocetin-induced platelet agglutination and prolongs bleeding time [7].
• Initial experiments examining T-cell signal transduction proteins demonstrated that T cells from Renca-bearing mice had undetectable levels of p56lck and zeta-chain of the T-cell receptor and that flavone-8-acetic acid and recombinant human interleukin 2 therapy could be used as a model for reversal of these alterations [2].
• In mice successfully treated with flavone 8-acetic acid and recombinant human interleukin 2, the T-cells expressed normal levels of all three nuclear NF kappa B/Rel proteins [8].
• Activated peritoneal macrophages, obtained from mice pretreated with Bacillus Calmette-Guérin, after exposure in vitro to flavone-8-acetic acid (FAA; NSC 347512) at a concentration of 890 microM, produce nitrite (3.7 nmol/10(6) cells), as measured 20 h later by the Griess reaction [9].

Chemical compound and disease context of LM-975

• Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer [10].

Biological context of LM-975

• As was found previously with analogues of flavone-8-acetic acid (FAA) (Atwell et al. Anti-Cancer Drug Des. 1989, 4, 161), all electronic modifications of the XAA nucleus led to severe decreases or complete abolition of activity, suggesting narrow structure-activity relationships [11].
• Although the antitumour agent flavone-8-acetic acid (FAA) exhibits remarkable activity against murine solid tumours, its clinical use has a number of pharmacological drawbacks, including low dose potency and dose-dependent pharmacokinetics [12].
• Decarboxylation of the antitumour drugs flavone-8-acetic acid and xanthenone-4-acetic acid by nitrogen dioxide [13].
• DNA fragmentation was increased by 1 mM/1 FAA, 1 mM/l novobiocin and 50 microM/l RS-61443 within 3 h of incubation [14].
• The structure of flavone-8-acetic acid, a chemotherapeutic agent, and its application to drug design [15].

Anatomical context of LM-975

• The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration [3].
• A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A [16].
• Hyporesponsiveness of macrophages from C3H/HeJ (endotoxin-resistant) mice to the antitumour agent flavone acetic acid (NSC 347512) [17].

Associations of LM-975 with other chemical compounds

• Interaction between flavone acetic acid (LM-975, NSC 349512) and radiation in Glasgow's osteogenic sarcoma in vivo [18].
• The antitumor agents flavone-8-acetic acid (FAA) and its dose-potent analogue 5,6-dimethylxanthenone-4-acetic acid (DMXAA), currently in clinical trials, have a novel mechanism of action that is mediated through their ability to induce a spectrum of cytokines [19].
• The stability of solutions of the antitumour antimetabolites, vinca alkaloids, podophyllotoxins, interferons, steroids and platinum drugs as well as maytansine, asparaginase, amsacrine, flavone-8-acetic acid, mitoguazone, and N-phosphonoacetyl-L-aspartate (PALA) is reviewed [20].
• The effect of flavone (CAS 525-82-6, 2-phenylbenzopyran-4-one, 1), flavone-8-acetic acid (CSA 87626-55-9, FAA, 2) and 10 substituted flavones on the luminol-dependent chemiluminescence of murine macrophages was studied in vitro [21].

Gene context of LM-975

• Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase N/CD13 [22].
• Flavone acetic acid (FAA, NSC 347512) is a new anticancer drug currently undergoing clinical investigation [23].
• The production of nitric oxide in endotoxin-resistant C3H/HeJ mice in response to flavone-8-acetic acid (FAA), derivatives of xanthenone-4-acetic (XAA), endotoxin and recombinant human tumour necrosis factor-alpha (TNF-alpha) was investigated and compared with the induction of haemorrhagic necrosis in subcutaneous M16/C tumours [24].
• Inhibition of DT-diaphorase (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone-8-acetic acid (FAA): implications for bioreductive drug development [25].
• Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid (FAA). Part 4: Variation of the basic structure [26].

Analytical, diagnostic and therapeutic context of LM-975

• Stability of flavone-8-acetic acid (LM975) in aqueous solutions by high-performance liquid chromatography [27].

References