Disease relevance of Lavendustin A

• In the gerbil hippocampus, genistein and lavendustin A, tyrosine kinase inhibitors, were administered 30 min before initiation of 5-min ischemia and reperfusion [1].
• Lavendustin A and CGP 47778A showed neither focus inhibition nor toxicity [2].
• Administration of the Src PTK inhibitor lavendustin A (LD-A; 1 mg/kg iv) before the PC ischemia on day 1 (group III, n = 7) failed to block the delayed protective effect against myocardial infarction 24 h later [3].
• We show here that two different PTK inhibitors, herbimycin A and lavendustin A, both selectively downregulate a subpopulation of nicotinic acetylcholine receptors (AChRs) on chick ciliary ganglion neurons in culture [4].
• Co-administration of 1.0 microg lavendustin A with NMDA significantly reduced the duration of spontaneous pain behaviour and inhibited NMDA-induced hyperalgesia [5].

High impact information on Lavendustin A

• Whereas genistein (100 microM), lavendustin A (20 microM), and tyrphostins 34 and 47 (both at 150 microM) had no effect on integrin dependent or CAM stimulated neurite outgrowth, the erbstatin analogue (10-15 micrograms/ml) and tyrphostins 23 and 25 (both at 150 microM) specifically inhibited the response stimulated by all three CAMs [6].
• In agreement, coronary muscle MaxiK currents were enhanced by Lavendustin A [7].
• The HOX-11 gene expression was also suppressed by the tyrosine kinase inhibitors tryphostin and lavendustin A [8].
• Other PTK inhibitors, such as lavendustin A and tyrphostin RG50864, also inhibited the Ag-induced activation of PTK and histamine release [9].
• An analogue of Lavendustin-A (RG 14467) showed similar inhibition kinetics to that of Lavendustin-A [10].

Chemical compound and disease context of Lavendustin A

• However, when present at the onset of the 30-min ischemia both genistein and lavendustin A completely aborted protection (31.4+/-2.0 and 28.1+/-1.5%, respectively) [11].

Biological context of Lavendustin A

• Similar to rod CNG channels, lavendustin A prevented this regulation, suggesting the involvement of a tyrosine phosphorylation event [12].
• Confocal imaging of eggs coinjected with lavendustin A and Oregon Green-dextran showed that the Ca2+ wave was inhibited under normal insemination conditions but that the block of the Ca2+ wave could be overcome with very high sperm densities [13].
• Whereas the lavendustin A partial structure is ineffective in inhibiting cell proliferation, esterification of its carboxylic acid function leads to measurable antiproliferative activity [14].
• Pretreatment of THP-1 cells with lavendustin A and PP1 upregulated the uptake of virulent C. burnetii but had no effect on the phagocytosis of avirulent organisms [15].
• After the same preincubation period, the IC50 of the lavendustin-A blockade was 30 +/- 15 nM [16].

Anatomical context of Lavendustin A

• Lavendustin A produced a dose-dependent decrease in the proportion of XR1 cells displaying focal adhesions [17].
• Acute and chronic effects of genistein, tyrphostin and lavendustin A on steroid synthesis in luteinized human granulosa cells [18].
• Lavendustin A enhances axon elongation in VHL gene-transfected neural stem cells [19].
• We studied the effect of insulin and lavendustin-A (a tyrosine kinase inhibitor) on the short-circuit current (ISC) of primary cultures of fetal distal rat lung epithelium (FDLE) [20].
• Chloride efflux during the progesterone-initiated human sperm acrosome reaction is inhibited by lavendustin A, a tyrosine kinase inhibitor [21].

Associations of Lavendustin A with other chemical compounds

• The protein tyrosine kinase (PTK) inhibitors lavendustin A and genistein were used to determine the possible role of tyrosine kinase activity during retinal development in vivo and in vitro [17].
• These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and -ethenes bearing a salicyl moiety appear to be valuable structural motifs for the construction of extremely potent PTK inhibitors [22].
• Of the four receptor subtypes, only epsilon1/zeta1 receptor currents were affected by basal PTK inhibition via lavendustin A, whereas PTP inhibition by phenylarsine oxide or orthovanadate enhanced currents from epsilon1/zeta1 and epsilon2/zeta1 receptors [23].
• Further, the differentiation induced by cPrG * HCl was blocked by tyrosine kinase inhibitors (lavendustin A and HMA) but unaffected by the inhibitors of A-kinase (H-89) or C-kinase (H-7) [24].
• Furthermore, both tyrosine and serine phosphorylation of I kappa B-alpha were blocked by pretreatment with either the nonreceptor tyrosine kinase inhibitor lavendustin-A (LD-A) or the PKC inhibitor chelerythrine (Che) (both given at doses previously shown to block ischemic PC) [25].

Gene context of Lavendustin A

• Verapamil inhibited neither [3H]thymidine incorporation nor JAK2 phosphorylation stimulated by hGH, whereas a tyrosine kinase inhibitor, lavendustin A, blocked the mitogenic effect [26].
• Various protein kinase inhibitors, including lavendustin A, tyrphostin, H7, and staurosporine, which may affect the PTB domain function, could not abolish the FE65L-mediated TNF resistance [27].
• Similarly ineffective were PD 169316, an inhibitor for p38 MAP kinase, other inhibitors for protein kinases as lavendustin A, Gö 6983, wortmannin, rapamycin, as well as the protein tyrosine kinase inhibitors herbimycin A and genistein [28].
• Another two tyrosine kinase inhibitors, Lavendustin A (LA) and genistein (GEN), had no effect on CYP1A1 induction by benzimidazoles and 3-MC [29].
• Design, synthesis, and biological evaluation of a series of lavendustin A analogues that inhibit EGFR and Syk tyrosine kinases, as well as tubulin polymerization [30].

Analytical, diagnostic and therapeutic context of Lavendustin A

• A series of conformationally restricted analogues were synthesized in order to elucidate the possible effects of different amide conformations of lavendustin A derivatives on cytotoxicity in cancer cell cultures and on inhibition of tubulin polymerization [31].
• Lavendustin A itself did not cause any sedation, motor impairment or analgesia [5].
• The inhibition of EGF and HGF receptor tyrosine kinase activity by lavendustin A was confirmed by Western blotting [32].
• The conductance, activated in response to endogenous signaling pathways in BIB-expressing oocytes, is decreased after treatment with 20 microm insulin and is enhanced with 10 microm lavendustin A, a tyrosine kinase inhibitor [33].

References