ret-in-3

RET-IN-3 is a RETV804M kinase inhibitor with potential anticancer activity for the study of non-small cell lung cancer.

Vandetanib Fumarate is an orally available tyrosine kinase inhibitor. Vandetanib Fumarate works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a

QZ2135 (compound 20) is a PROTAC degrader that specifically targets RET and exhibits antitumor activity in vivo within a Ba F3-KIF5B-RET-G810C xenograft mouse model. The compound demonstrates degradation activity with DC50 values of 4.7 nM (WT), 17.2 nM (V804M), and 73.8 nM (G810C) when targeting KIF5B-RET. QZ2135 is composed of the target protein ligand (red part) RETligand-3, the E3 ligase ligand (blue part) Lenalidomide-F, and the PROTAC Linker (black part) 7-Iodohept-1-yne, wherein the target protein ligand combined with the linker forms the conjugate RETLigand-Linker Conjugate-1.

Ganglioside GM1is a monosialylated ganglioside and the prototypic ganglioside for those containing one sialic acid residue.1,2It is found in a large variety of cells, including immune cells and neurons, and is enriched in lipid rafts in the cell membrane.3It associates with growth factor receptors, including TrkA, TrkB, and the GDNF receptor complex containing Ret and GFRα, and is required for TrkA expression on the cell surface. Ganglioside GM1interacts with other proteins to increase calcium influx, affecting various calcium-dependent processes, including inducing neuronal outgrowth during differentiation. Ganglioside GM1acts as a receptor for cholera toxin, which binds to its oligosaccharide group, facilitating toxin cell entry into epithelial cells of the jejunum.4,5Similarly, it is bound by the heat-labile enterotoxin fromE. coliin the pathogenesis of traveler's diarrhea.6Ganglioside GM1gangliosidosis, characterized by a deficiency in GM1-β-galactosidase, the enzyme that degrades ganglioside GM1, leads to accumulation of the gangliosides GM1and GA1in neurons and can be fatal in infants.1Levels of ganglioside GM1are decreased in the substantia nigra pars compacta in postmortem brain from patients with Parkinson's disease.3Ganglioside GM1mixture contains a mixture of ovine ganglioside GM1molecular species with primarily C18:0 fatty acyl chain lengths, among various others. [Matreya, LLC. Catalog No. 1544] 1.Kolter, T.Ganglioside biochemistryISRN Biochem.506160(2012) 2.Mocchetti, I.Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophinsCell Mol. Life Sci.62(19-20)2283-2294(2005) 3.Ledeen, R.W., and Wu, G.The multi-tasked life of GM1 ganglioside, a true factotum of natureTrends Biochem. Sci.40(7)407-418(2015) 4.Turnbull, W.B., Precious, B.L., and Homans, S.W.Dissecting the cholera toxin-ganglioside GM1 interaction by isothermal titration calorimetryJ. Am. Chem. Soc.126(4)1047-1054(2004) 5.Blank, N., Schiller, M., Krienke, S., et al.Cholera toxin binds to lipid rafts but has a limited specificity for ganglioside GM1Immunol. Cell Biol.85(5)378-382(2007) 6.Minke, W.E., Roach, C., Hol, W.G., et al.Structure-based exploration of the ganglioside GM1 binding sites of Escherichia coli heat-labile enterotoxin and cholera toxin for the discovery of receptor antagonistsBiochemistry38(18)5684-5692(1999)

PLM-101 is an anticancer compound orally active against acute myeloid leukemia by targeting FLT3 and RET. It impedes RET function, promoting autophagic breakdown of FLT3, and suppresses the PI3K and Ras ERK pathways, contributing to its anti-leukemic effects. The compound's antitumor efficacy is demonstrated in both a mouse MV4-11 flank xenograft model (doses of 3 and 10 mg kg; po) and an allogeneic xenograft mouse model (dose of 40 mg kg; po) [1].

RET-IN-25 (compound 6b) is an anticancer RET kinase inhibitor effective against medullary thyroid carcinoma (MTC), with half-maximal inhibitory concentrations (IC50s) of 3.6 μM at 3 days and 3.0 μM at 6 days in TT(C634R) MTC [1].

Sulforhodamine 101 DHPE, a fluorescent probe, results from the conjugation of sulforhodamine 101, a red fluorescent dye with excitation emission spectra of 586 605 nm, to the phospholipid 1,2-dipalmitoyl-sn-glycero-3-PE. It effectively integrates into phospholipid bilayers and is utilized for imaging solid supported lipid bilayers, detecting protein-ligand interactions on bilayers, and monitoring lipid probe colocalization in liposomes through resonance energy transfer (RET).