3 research outputs found
Additional file 1: of Assessment of reverse remodeling predicted by myocardial deformation on tissue tracking in patients with severe aortic stenosis: a cardiovascular magnetic resonance imaging study
Figure S1. Bland-Altman plot with LVMI values of the baseline Echo and CMR. There was a positive correlation between LVMI values of the baseline Echo and CMR images (r = 0.73, p < 0.001), and ICC was 0.723 (95% confidence interval: 0.580â0.823, p < 0.001). Figure S2. The median time duration from AVR to follow-up Echo (median days [interquartile range]: 833[372â1183] days) (PPTX 82 kb
Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors
Lysyl hydroxylase 2 (LH2) catalyzes the formation of
highly stable
hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus
promoting lung cancer metastasis through its capacity to modulate
specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening
(HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1â18, and identified 12 and 13 that inhibit LH2 with IC50âs of approximately
300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum
mechanics/molecular mechanics (QM/MM) modeling indicates that the
selectivity of 12 and 13 may stem from noncovalent
interactions like hydrogen bonding between the morpholine/piperazine
rings with the LH2-specific Arg661. Treatment of 344SQ WT cells with 13 resulted in a dose-dependent reduction in their migration
potential, whereas the compound did not impede the migration of the
same cell line with an LH2 knockout (LH2KO)
Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors
Lysyl hydroxylase 2 (LH2) catalyzes the formation of
highly stable
hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus
promoting lung cancer metastasis through its capacity to modulate
specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening
(HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1â18, and identified 12 and 13 that inhibit LH2 with IC50âs of approximately
300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum
mechanics/molecular mechanics (QM/MM) modeling indicates that the
selectivity of 12 and 13 may stem from noncovalent
interactions like hydrogen bonding between the morpholine/piperazine
rings with the LH2-specific Arg661. Treatment of 344SQ WT cells with 13 resulted in a dose-dependent reduction in their migration
potential, whereas the compound did not impede the migration of the
same cell line with an LH2 knockout (LH2KO)