Rociletinib hydrobromide is an orally delivered inhibitor of the mutant form of EGFR kinase (Kis: 21.5 nM and 303.3 nM for EGFR L858R T790M and EGFR WT).
Cyclo(L-Phe-L-Val) is a metabolite of the sponge bacterium Pseudoalteromonas sp. NJ6-3-1 that can autoinduce production of antibacterial substances active against S. aureus when co-cultured at a low cell density. It induces neurite outgrowth and branching of chick cortical neurons in vitro when used at concentrations of 16 and 32 μM. It increases phosphorylation of the PI3K substrate Akt, and neurite outgrowth induced by cyclo(L-Phe-L-Val) can be blocked by the PI3K inhibitor LY294002 . Cyclo(L-Phe-L-Val) enhances axon sprouting of calcitonin gene-related protein positive (CGRP+) primary afferents in the spinal cord following crush injury and of serotonin neurons in uninjured spinal cord. Cyclo(L-Phe-L-Val) is also a bitter taste component of cocoa and roasted coffee.
AGN 193109 is a potent antagonist of retinoic acid receptors (RARs; Kd= 2, 2, and 3 nM for RARα, β, and γ, respectively), exhibiting selectivity for RARs over retinoid X receptors (RXRs; Kd= >10,000 nM for human RXRα, β, and γ receptors). This compound effectively reverses cellular morphology changes and growth suppression induced by RAR agonists such as all-trans-RA, 13-cis-RA, and 9-cis-RA in ECE16-1 human endometrial ectocervical epithelial cells, particularly when used at a 10-fold molar excess. Furthermore, AGN 193109 downregulates the expression of cytokeratin K5-8, 13, 14, 16, 17, and 19 genes, indicating inhibition of retinoid action, specifically when co-administered with TTNPB but not as a standalone treatment. In vivo studies demonstrate teratogenic effects, including cleft palate, frontonasal dysplasia, and eye malformations in mouse fetuses following a single oral dose of 1 mg kg.
BODIPY-aminoacetaldehyde diethyl acetal (BAAA-DA) is a stable precursor to BODIPY-aminoacetaldehyde, a cell-permeable fluorescent substrate for aldehyde dehydrogenase (ALDH).1,2BODIPY-aminoacetaldehyde diethyl acetal is converted under acidic conditions to BODIPY-aminoacetaldehyde (BAAA).2BAAA is cell-permeant and is converted intracellularly by ALDH to BODIPY aminoacetate (BAA), which is retained by cells and can be used to identify cells with high ALDH activity.1BAA is a substrate for the efflux pump P-glycoprotein (P-gp) but co-application of BAAA with a P-gp inhibitor, such as verapamil , inhibits BAA efflux.2BAAA-DA has been used to isolate human hematopoietic progenitor cells, which have high ALDH activity, andviaflow cytometry to sort cancer stem cells that contain high levels of ALDH.1,3BAA used in cells can be excited at 488 nm and displays an emission maximum of 512 nm.4 1.Storms, R.W., Trujillo, A.P., Springer, J.B., et al.Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activityProceedings of the National Academy of Sciences of the United States of America96(16)9118-9123(1999) 2.Smith, C.A., Colvin, M., Storms, R.W., et al.BODIPY aminoacetaldehyde diethyl acetal08010501.81-15(2010) 3.Leng, Z., Yang, Z., Li, L., et al.A reliable method for the sorting and identification of ALDHhigh cancer stem cells by flow cytometryExp. Ther. Med.(2017) 4.Pomper, M.G., Wang, H., Minn, I., et al.Red fluorescent aldehyde dehydrogenase (ALDH) substrate(2015)
DTUN is a lipophilic hyponitrite radical initiator.1It initiates co-autoxidation of STY-BODIPY-embedded egg phosphatidylcholine liposomes when used at a concentration of 0.2 mM. DTUN has been used in fluorescence-enabled inhibited autoxidation (FENIX) assays for the development of ferroptosis inhibitors and the study of antioxidants in lipid membranes.1,2 1.Shah, R., Farmer, L.A., Zilka, O., et al.Beyond DPPH: Use of fluorescence-enabled inhibited autoxidation to predict oxidative cell death rescueCell Chem. Biol.26(11)1594-1607(2019) 2.Soula, M., Weber, R.A., Zilka, O., et al.Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducersNat. Chem. Biol.16(12)1351-1360(2020)