Ppc-1 is a chemical compound known for its inhibitory effects on the Gram-negative periodontopathogen Porphyromonas gingivalis. It acts as a mitochondrial uncoupler, enhancing mitochondrial oxygen consumption without affecting ATP production. Additionally, Ppc-1 serves as a cell-permeate inhibitor of interleukin-2 (IL-2). This compound exhibits various beneficial activities, including anti-obesity, antibacterial, and anti-inflammatory properties.
Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.
JC-171 is a selective NLRP3 inflammasome inhibitor, with an IC50 of 8.45 μM for inhibiting LPS ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages[1]. JC-171 (0-100 μM) blocks NLRP3 inflammasome activation and IL-1β production in primary macrophages dose dependently[1]. Cell Viability Assay[1] Cell Line: J774A.1 murine macrophage cells JC-171 treatment delays the progression and reduces the severity of experimental autoimmune encephalomyelitis (EAE) in mouse[1]. Animal Model: Mice immunized subcutaneously with 200 μg Myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide emulsified in Complete Freund's Adjuvant (CFA) on day 0 followed by injection of 200 ng of pertussis toxin. [1]. Chunqing Guo, et al. Development and Characterization of a Hydroxyl-Sulfonamide Analogue, 5-Chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a Novel NLRP3 Inflammasome Inhibitor for Potential Treatment of Multiple Sclerosis. ACS Chem Neurosci. 2017 Oct 18;8(10):2194-2201.
BMSpep-57, a potent macrocyclic peptide inhibitor, competitively disrupts the PD-1 PD-L1 interaction, demonstrating a significant inhibitory concentration (IC50) of 7.68 nM. It exhibits binding affinity towards PD-L1 with dissociation constants (Kd) of 19 nM and 19.88 nM in MicroScale Thermophoresis (MST) and Surface Plasmon Resonance (SPR) assays, respectively. This compound enhances T cell functionality by promoting Interleukin-2 (IL-2) production within Peripheral Blood Mononuclear Cells (PBMCs).
INCB16562 is a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. Treatment of myeloma cells with INCB16562 potently inhibited interleukin-6 (IL-6)-induced phosphorylation of STAT3. INCB16562 abrogated the protective effects of recombinant cytokines or bone marrow stromal cells and sensitized myeloma cells to cell death by exposure to dexamethasone, melphalan, or bortezomib. Oral administration of INCB16562 antagonized the growth of myeloma xenografts in mice and enhanced the antitumor activity of relevant agents in combination studies. INCB16562 is a potent JAK1 2 inhibitor and that mitigation of JAK STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents. ( source: Neoplasia. 2010 Jan;12(1):28-38. ).
PCC0208018 is a novel activator of effector T cells, enhancing T cell proliferation and activation to release interferon gamma (IFN-γ) and interleukin-2 (IL-2) without blocking the programmed cell death 1 (PD-1) programmed cell death-ligand 1 (PD-L1) binding and not directly affecting tumor cell viability in vitro.