1613293-05-2

Upstream product

• 82944-18-1 2,2,7-trimethyl-4H-benzo[d][1,3]dioxin-4-one 
• 691857-35-9 7-(bromomethyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one 
• 50-85-1 2-hydroxy-p-toluic acid 
• 83908-06-9 4-bromomethylsalicylic acid methyl ester 
• 4670-56-8 methyl 2-hydroxy-4-methylbenzoate 

Downstream Products

• 1613293-06-3 N-((S)-1-(((R)-1-(7-((hexadecylamino)methyl)-4-oxo-4H-benzo-[d][1,3,2]dioxaborinin-2-yl)-3-methylbutyl)amino)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide 

Relevant academic research and scientific papers

Identification of lipid-like salicylic acid-based derivatives as potent and membrane-permeable PTP1B inhibitors

Developing protein tyrosine phosphatase-1B (PTP1B) inhibitors is an important strategy to treat type 2 diabetes mellitus (T2DM). Most existing ionic PTP1B inhibitors aren't of clinical useful due to their low cell-permeability, however. Herein, we introduced a series of lipid-like acid-based (salicylic acid) modules to prepare PTP1B inhibitors, and demonstrated a marked improvement of cell-permeability while maintaining excellent PTP1B inhibitory activity (e.g. compound B12D, IC50 = 0.37 μM against PTP1B and Papp = 1.5 × 10?6 cm/s). We believe that this strategy can be widely utilized to modify potent lead compounds with low cell-permeability.

Liposomal bortezomib nanoparticles via boronic ester prodrug formulation for improved therapeutic efficacy in vivo

In this study, we describe the development of liposomal bortezomib nanoparticles, which was accomplished by synthesizing bortezomib prodrugs with reversible boronic ester bonds and then incorporating the resulting prodrugs into the nanoparticles via surface conjugation. Initially, several prodrug candidates were screened based upon boronic ester stability using isobutylboronic acid as a model boronic acid compound. The two most stable candidates were then selected to create surface conjugated bortezomib prodrugs on the liposomes. Our strategy yielded stable liposomal bortezomib nanoparticles with a narrow size range of 100 nm and with high reproducibility. These liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity against multiple myeloma cell lines in vitro and remarkable tumor growth inhibition with reduced systemic toxicity compared to free bortezomib in vivo. Taken together, this study demonstrates the incorporation of bortezomib into liposomal nanoparticles via reversible boronic ester bond formation to enhance the therapeutic index for improved patient outcome.

NANOPARTICLE DRUG DELIVERY SYSTEMS

The invention provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes or micelles that contain one or more targeting peptides and/or anticancer drugs. In various embodiments, the components of the liposomes can include a) a phospholipid and optionally a lipid that is not a phospholipid; b) a pegylated lipid; c) a peptide-ethylene glycol (EG)-lipid conjugate wherein the peptide is a targeting ligand, and d) one or more drug-conjugated lipid, encapsulated drugs, or a combination thereof. The peptide- EG-lipid conjugate can be, for example, a compound of Formula (I) or Formula (II). The ethylene glycol (EG) segments of the peptide-EG-lipid conjugate can be, for example, EG6 to about EG36; and the EG segment can be conjugated to one or more lysine moieties.