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Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival.
Data indicate that targeting XBP-1 has potential as a treatment strategy, not only for multiple myeloma, but also for mature B cell leukemia and lymphoma.
Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells.
It is shown that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis in normal and malignant B cells, implying that prolonged activation of STing can lead to apoptosis.
Synthesis of Novel Tricyclic Chromenone-Based Inhibitors of IRE-1 RNase Activity
- S. Ranatunga, C. Tang, J. D. Del Valle
- Biology, ChemistryJournal of medicinal chemistry
- 21 April 2014
The synthesis and biological evaluation of novel chromenone-based covalent inhibitors of IRE-1 led to the identification of 30 as a potent inhibitor of Ire-1 RNase activity and XBP-1s expression in wild type B cells and human mantle cell lymphoma cell lines.
β-Strand mimics based on tetrahydropyridazinedione (tpd) peptide stitching.
Analysis by NMR, molecular modeling and X-ray crystallography suggests both covalent and non-covalent stabilization of extended peptide conformations of tetrahydropyridazinedione backbone tether exhibit reduced conformational flexibility external to the heterocyclic constraint.
Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate.
Solid-Phase Synthesis of Tetrahydropyridazinedione-Constrained Peptides
- C. Kang, S. Ranatunga, M. Sarnowski, J. D. Del Valle
- Chemistry, BiologyOrganic letters
- 8 October 2014
The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported, and the scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues.
Total synthesis of the putative structure of lucentamycin A.
- Ujjwal Pal, S. Ranatunga, Yamuna Ariyarathna, J. D. Del Valle
- ChemistryOrganic letters
- 28 October 2009
A rapid and stereoselective enolate-Claisen rearrangement provides access to the 4-ethylidene-3-methylproline (Emp) subunit of lucentamycin A and suggests the need for structural revision.
Synthesis and conformational analysis of bicyclic extended dipeptide surrogates.
- S. Ranatunga, W. Liyanage, J. D. Del Valle
- Chemistry, BiologyThe Journal of organic chemistry
- 6 August 2010
Structural data suggest that ring size and relative stereochemistry have a profound effect on the ability of these scaffolds to act as beta-strand mimetics and should inform the design of related conformational probes.
An ester enolate-Claisen rearrangement route to substituted 4-alkylideneprolines. studies toward a definitive structural revision of lucentamycin A.
- S. Ranatunga, Jinsoo Kim, Ujjwal Pal, J. D. Del Valle
- ChemistryThe Journal of organic chemistry
- 5 October 2011
The studies indicate that the Emp stereogenic centers are not the source of structural misassignment, and the current strategy should find broad utility in the synthesis of additional natural product analogues and related 3-alkyl-4-alksylidene prolines.