Melanoma Cells Inhibit iNKT Cell Functions via PGE2 and IDO1.

Invariant natural killer T (iNKT) cells are a distinct group of immune cells known for their immunoregulatory and cytotoxic activities, which are crucial in immune surveillance against tumors. They have been extensively investigated as a potential target for adoptive cell immunotherapy. Despite the initial promise of iNKT cell-based immunotherapy as a treatment for melanoma patients, its effective utilization has unfortunately yielded inconsistent outcomes.

A Pilot Study on Clinical Scores, Immune Cell Modulation, and Microbiota Composition in Allergic Patients with Rhinitis and Asthma Treated with a Probiotic Preparation.

Background: Specific drugs and/or immunotherapies are widely used to treat allergies, but drug-induced adverse effects recently led to explore new additional strategies. We studied whether a probiotic preparation (iPROB®; Anallergo SpA, Florence, Italy) is effective in allergic patients and the mechanisms underlying clinical outcomes.

Methods: Eligible patients (n = 28), all suffering from allergic rhinitis with/without bronchial asthma, were consecutively recruited at the Allergology Medical Unit (Novara, Italy) and treated with this probiotic.

The [1,2,4]Triazolo[4,3-a]pyridine as a New Player in the Field of IDO1 Catalytic Holo-Inhibitors.

Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) are considered a promising strategy in cancer immunotherapy as they are able to boost the immune response and to work in synergy with other immunotherapeutic agents. Despite the fact that no IDO1 inhibitor has been approved so far, recent studies have shed light on the additional roles that IDO1 mediates beyond its catalytic activity, conferring new life to the field. Here we present a novel class of compounds originated from a structure-based virtual screening made on IDO1 active site.

Recurrent N209* ABHD5 mutation in two unreported families with Chanarin Dorfman Syndrome.

ABHD5 protein is widely involved in lipid and energy homeostasis. Mutations in the ABHD5 gene are associated with the onset of Neutral Lipid Storage Disease with Ichthyosis (NLSDI), historically known as Chanarin Dorfman Syndrome (CDS). CDS is a rare autosomal recessive lipid storage disease, characterized by non-bullous congenital ichthyosiform eritrhoderma (NCIE), hepatomegaly and liver steatosis.

Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to Pharmacodynamic Activity.

In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs.

Exploring calixarene-based clusters for efficient functional presentation of Streptococcus pneumoniae saccharides.

Calixarenes are promising scaffolds for an efficient clustered exposition of multiple saccharide antigenic units. Herein we report the synthesis and biological evaluation of a calix[6]arene functionalized with six copies of the trisaccharide repeating unit of Streptococcus pneumoniae (SP) serotype 19F. This system has demonstrated its ability to efficiently inhibit the binding between the native 19F capsular polysaccharide and anti-19F antibodies, despite a low number of exposed saccharide antigens, well mimicking the epitope presentations in the polysaccharide.

Synthesis, Docking and Biological Evaluation of a Novel Class of Imidazothiazoles as IDO1 Inhibitors.

IDO1, a key dioxygenase in tryptophan-kynurenine metabolism, appeared in the last 10 years at the vanguard of druggable targets in cancer therapy due to its well-established role both in immune escape and inflammatory neovascularization. Among the pool of IDO1 inhibitors that have entered clinical trials, none have reached approval. The identification of novel inhibitors endowed with better clinical profile, together with the further comprehension of the interactions with residues in IDO1 active site, are still a need.

A multicomponent approach in the discovery of indoleamine 2,3-dioxygenase 1 inhibitors: Synthesis, biological investigation and docking studies.

Indoleamine 2,3-dioxygenase plays a crucial role in immune tolerance and has emerged as an attractive target for cancer immunotherapy. In this study, the Passerini and Ugi multicomponent reactions have been employed to assemble a small library of imidazothiazoles that target IDO1. While the p-bromophenyl and the imidazothiazole moieties have been kept fixed, a full SAR study has been performed on the side-chain, leading to the discovery of nine compounds with sub-micromolar IC values in the enzyme-based assay.

Transition-Metal-Free Synthesis of 2-Arylimidazolones via Cascade Reaction between Arynes and α,α'-Disubstituted α-Isocyanoacetamides.

The reaction between arynes and secondary α,α'-disubstituted α-isocyanoacetamides was developed to access 2-arylimidazolones of structural diversity and complexity in a straightforward manner.