Category: 41270-96-6

de Azevedo, Ricardo A. published the artcileMIF inhibition as a strategy for overcoming resistance to immune checkpoint blockade therapy in melanoma, Recommanded Product: 4-Iodo-6-phenylpyrimidine, the publication is OncoImmunology (2020), 9(1), 1846915/1, database is CAplus and MEDLINE.

Immune checkpoint blockade (ICB) has demonstrated an impressive outcome in patients with metastatic melanoma, yet, durable complete response; even with Ipilimumab/Nivolumab combo are under 30%. Primary and acquired resistance in response to ICB is commonly due to a tumor immune escape mechanism dictated by the tumor microenvironment (TME). Macrophage Migratory Inhibition Factor (MIF) has emerged as an immunosuppressive factor secreted in the TME. We have previously demonstrated that blockade of the MIF-CD74 signaling on macrophages and dendritic cells restored the anti-tumor immune response against melanoma. Here, we report that inhibition of the MIF-CD74 axis combined with ipilimumab could render resistant melanoma to better respond to anti-CTLA-4 treatment. We provide evidence that blocking the MIF-CD74 signaling potentiates CD8+ T-cells infiltration and drives pro-inflammatory M1 conversion of macrophages in the TME. Furthermore, MIF inhibition resulted in reprogramming the metabolic pathway by reducing lactate production, HIF-1αand PD-L1 expression in the resistant melanoma cells. Melanoma patient data extracted from the TCGA database supports the hypothesis that high MIF expression strongly correlates with poor response to ICB therapy. Our findings provide a rationale for combining anti-CTLA-4 with MIF inhibitors as a potential strategy to overcome resistance to ICB therapy in melanoma, turning a “cold” tumor into a “hot” one mediated by the activation of innate immunity and reprogramming of tumor metabolism and reduced PD-L1 expression in melanoma cells.

OncoImmunology published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Recommanded Product: 4-Iodo-6-phenylpyrimidine.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Dickerhof, Nina published the artcileMacrophage migration inhibitory factor (MIF) is rendered enzymatically inactive by myeloperoxidase-derived oxidants but retains its immunomodulatory function, SDS of cas: 41270-96-6, the publication is Free Radical Biology & Medicine (2015), 498-511, database is CAplus and MEDLINE.

Macrophage migration inhibitory factor (MIF) is an important player in the regulation of the inflammatory response. Elevated plasma MIF is found in sepsis, arthritis, cystic fibrosis and atherosclerosis. Immunomodulatory activities of MIF include the ability to promote survival and recruitment of inflammatory cells and to amplify pro-inflammatory cytokine production MIF has an unusual nucleophilic N-terminal proline with catalytic tautomerase activity. It remains unclear whether tautomerase activity is required for MIF function, but small mols. that inhibit tautomerase activity also inhibit the pro-inflammatory activities of MIF. A prominent feature of the acute inflammatory response is neutrophil activation and production of reactive oxygen species, including myeloperoxidase (MPO)-derived hypochlorous acid and hypothiocyanous acid. We hypothesized that MPO-derived oxidants would oxidize the N-terminal proline of MIF and alter its biol. activity. MIF was exposed to hypochlorous acid and hypothiocyanous acid and the oxidative modifications on MIF were examined by LC-MS/MS. Imine formation and carbamylation was observed on the N-terminal proline in response to MPO-dependent generation of hypochlorous and hypothiocyanous acid, resp. These modifications led to a complete loss of tautomerase activity. However, modified MIF still increased CXCL-8/IL-8 production by peripheral blood mononuclear cells (PBMCs) and blocked neutrophil apoptosis, indicating that tautomerase activity is not essential for these biol. functions. Pre-treatment of MIF with hypochlorous acid protected the protein from covalent modification by the MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP). Therefore, oxidant generation at inflammatory sites may protect MIF from inactivation by more disruptive electrophiles, including drugs designed to target the tautomerase activity of MIF.

Free Radical Biology & Medicine published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, SDS of cas: 41270-96-6.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Qian, Yong published the artcileActivity-Based Proteome Profiling Probes Based on Woodward’s Reagent K with Distinct Target Selectivity, COA of Formula: C10H7IN2, the publication is Angewandte Chemie, International Edition (2016), 55(27), 7766-7771, database is CAplus and MEDLINE.

Woodward’s reagent K (WRK) is a reactive heterocyclic compound that has been employed in protein chem. to covalently and unspecifically label proteins at nucleophilic amino acids, notably at histidine and cysteine. The authors have developed a panel of WRK-derived activity-based probes and show that surprisingly and unexpectedly, these probes are fairly selective for a few proteins in the human proteome. The WRK-derived probes show unique reactivity towards the catalytic N-terminal proline in the macrophage migration inhibitory factor (MIF) and can be used to label and, if equipped with a fluorophore, to image MIF activities in living cells.

Angewandte Chemie, International Edition published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, COA of Formula: C10H7IN2.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Cisneros, Jose A. published the artcileA Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors, Computed Properties of 41270-96-6, the publication is Journal of the American Chemical Society (2016), 138(27), 8630-8638, database is CAplus and MEDLINE.

Human macrophage migration inhibitory factor (MIF) is both a keto-enol tautomerase and a cytokine associated with numerous inflammatory diseases and cancer. Consistent with observed correlations between inhibition of the enzymic and biol. activities, discovery of MIF inhibitors has focused on monitoring the tautomerase activity using L-dopachrome Me ester or 4-hydroxyphenyl pyruvic acid as substrates. The accuracy of these assays is compromised by several issues including substrate instability, spectral interference, and short linear periods for product formation. In this work, we report the syntheses of fluorescently labeled MIF inhibitors and their use in the first fluorescence polarization-based assay to measure the direct binding of inhibitors to the active site. The assay allows the accurate and efficient identification of competitive, noncompetitive, and covalent inhibitors of MIF in a manner that can be scaled for high-throughput screening. The results for 22 compounds show that the most potent MIF inhibitors bind with K_d values of ca. 50 nM; two are from our laboratory, and the other is a compound from the patent literature. X-ray crystal structures for two of the most potent compounds bound to MIF are also reported here. Striking combinations of protein-ligand hydrogen bonding, aryl-aryl, and cation-π interactions are responsible for the high affinities. A new chem. series was then designed using this knowledge to yield two more strong MIF inhibitors/binders.

Journal of the American Chemical Society published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Computed Properties of 41270-96-6.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Yaddanapudi, Kavitha published the artcileControl of Tumor-Associated Macrophage Alternative Activation by Macrophage Migration Inhibitory Factor, SDS of cas: 41270-96-6, the publication is Journal of Immunology (2013), 190(6), 2984-2993, database is CAplus and MEDLINE.

Tumor stromal alternatively activated macrophages are important determinants of antitumor T lymphocyte responses, intratumoral neovascularization, and metastatic dissemination. Our recent efforts to investigate the mechanism of macrophage migration inhibitory factor (MIF) in antagonizing antimelanoma immune responses reveal that macrophage-derived MIF participates in macrophage alternative activation in melanoma-bearing mice. Both peripheral and tumor-associated macrophages (TAMs) isolated from melanoma bearing MIF-deficient mice display elevated proinflammatory cytokine expression and reduced anti-inflammatory, immunosuppressive, and proangiogenic gene products compared with macrophages from tumor-bearing MIF wild-type mice. Moreover, TAMs and myeloid-derived suppressor cells from MIF-deficient mice exhibit reduced T lymphocyte immunosuppressive activities compared with those from their wild-type littermates. Corresponding with reduced tumor immunosuppression and neo-angiogenic potential by TAMs, MIF deficiency confers protection against transplantable s.c. melanoma outgrowth and melanoma lung metastatic colonization. Finally, we report for the first time, to our knowledge, that our previously discovered MIF small mol. antagonist, 4-iodo-6-phenylpyrimidine, recapitulates MIF deficiency in vitro and in vivo, and attenuates tumor-polarized macrophage alternative activation, immunosuppression, neoangiogenesis, and melanoma tumor outgrowth. These studies describe an important functional contribution by MIF to TAM alternative activation and provide justification for immunotherapeutic targeting of MIF in melanoma patients.

Journal of Immunology published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C18H20N2O12, SDS of cas: 41270-96-6.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Rajasekaran, Deepa published the artcileTargeting distinct tautomerase sites of D-DT and MIF with a single molecule for inhibition of neutrophil lung recruitment, Application of 4-Iodo-6-phenylpyrimidine, the publication is FASEB Journal (2014), 28(11), 4961-4971, database is CAplus and MEDLINE.

We report a new inflammatory activity for extracellular D-dopachrome tautomerase (D-DT), the recruitment of neutrophils to the lung on D-DT intratracheal installation of C57BL/6J mice with an EC₅₀ of 5.6 μg. We also find that D-DT and macrophage migration inhibitory factor (MIF) have additive effects in neutrophil recruitment. Although the tautomerase site of D-DT and its homolog MIF are biophys. very different, 4-iodo-6-phenylpyrimidine (4-IPP) forms a covalent bond with Pro-1 of both proteins, resulting in a 6-phenylpyrimidine (6-PP) adduct. Recruitment of neutrophils to the lung for the 6-PP adducts of D-DT and MIF are reduced by ∼50% relative to the apo proteins, demonstrating that an unmodified Pro-1 is important for this activity, but there is no cooperativity in inhibition of the proteins together. The differences in the binding mode of the 6-PP adduct for D-DT was determined by crystallog. studies at 1.13 Å resolution and compared to the structure of the MIF-6-PP complex. There are major differences in the location of the 6-PP adduct to the D-DT and MIF active sites that provide insight into the lack of cooperativity by 4-IPP and into tuning the properties of the covalent inhibitors of D-DT and MIF that are necessary for the development of therapeutic small mols. against neutrophil damage from lung infections such as Pseudomonas aeruginosa in cystic fibrosis and immunocompromised patients.

FASEB Journal published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Application of 4-Iodo-6-phenylpyrimidine.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Schindler, Lisa published the artcileMacrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells, Category: iodides-buliding-blocks, the publication is Journal of Leukocyte Biology (2021), 110(5), 893-905, database is CAplus and MEDLINE.

The chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) is a pivotal driver of acute and chronic inflammatory conditions, cardiovascular disease, autoimmunity, and cancer. MIF modulates the early inflammatory response through various mechanisms, including regulation of neutrophil recruitment and fate, but the mechanisms and the role of the more recently described MIF homolog MIF-2 (D-dopachrome tautomerase; D-DT) are incompletely understood. Here, we show that both MIF and MIF-2/D-DT inhibit neutrophil apoptosis. This is not a direct effect, but involves the activation of mononuclear cells, which secrete CXCL8 and other prosurvival mediators to promote neutrophil survival. Individually, CXCL8 and MIF (or MIF-2) did not significantly inhibit neutrophil apoptosis, but in combination they elicited a synergistic response, promoting neutrophil survival even in the absence of mononuclear cells. The use of receptor-specific inhibitors provided evidence for a causal role of the noncognate MIF receptor CXCR2 expressed on both monocytes and neutrophils in MIF-mediated neutrophil survival. We suggest that the ability to inhibit neutrophil apoptosis contributes to the proinflammatory role ascribed to MIF, and propose that blocking the interaction between MIF and CXCR2 could be an important anti-inflammatory strategy in the early inflammatory response.

Journal of Leukocyte Biology published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Category: iodides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Gu, Yu-lei published the artcileGene knockout or inhibition of macrophage migration inhibitory factor alleviates lipopolysaccharide-induced liver injury via inhibiting inflammatory response, Application of 4-Iodo-6-phenylpyrimidine, the publication is Hepatobiliary & Pancreatic Diseases International (2021), 20(5), 469-477, database is CAplus and MEDLINE.

Background: Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains. Methods: The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured. Liver histopathol. was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S, R)-3-(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid Me ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury. Results: Compared with wild-type mice, the liver function indexes and inflammation factors presented no significant difference in the Mif^-/- mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1β were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, m RNA levels of TNF-α, IL-1β and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice. Conclusions: In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis.

Hepatobiliary & Pancreatic Diseases International published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Application of 4-Iodo-6-phenylpyrimidine.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Zheng, Yuhuan published the artcileRole of myeloma-derived MIF in myeloma cell adhesion to bone marrow and chemotherapy response, Recommanded Product: 4-Iodo-6-phenylpyrimidine, the publication is Journal of the National Cancer Institute (2016), 108(11), djw131/1-djw131/11, database is CAplus and MEDLINE.

Multiple myeloma (MM) remains an incurable cancer characterized by accumulation of malignant plasma cells in the bone marrow (BM). The mechanism underlying MM homing to BM is poorly elucidated. The clin. significance of migration inhibitory factor (MIF) expression was examined by analyzing six independent gene expression profile databases of primary MM cells using the Student’s t test and Kaplan-Meier test. ELISA was used to examine MIF expression. In vivo bioluminescent imaging was used to determine MM cell localization and treatment efficacy in human MM xenograft mouse models, with three to four mice per group. MM cell attachment to BM stromal cells (BMSCs) was monitored by cell adhesion assay. MIF regulation of the expression of adhesion mols. was determined by chromatin immunoprecipitation (ChIP) assay. Statistical tests were two-sided. High levels of MIF were detected in MM BM (MIF level in BM plasma: healthy = 10.72 ± 5.788 ng/mL, n = 5; MM = 1811 ± 248.7 ng/mL, n = 10; P < .001) and associated with poor survival of patients (Kaplan-Meier test for MM OS: 87 MIF high patients, 86 MIFlow patients, P = .02). Knocking down MIF impaired MM cell adhesion to BMSCs in vitro and led to formation of extramedullary tumors in SCID mice. MIF acted through surface receptor CXCR4 and adaptor COPS5 to regulate the expression of adhesion mols. ALCAM, ITGAV, and ITGB5 on MM cells. More importantly, MIF-deficient MM cells were sensitive to chemotherapy in vitro when cocultured with BMSCs and in vivo. MIF inhibitor 4-IPP sensitized MM cells to chemotherapy. MIF is an important player and a novel therapeutic target in MM. Inhibiting MIF activity will sensitize MM cells to chemotherapy.

Journal of the National Cancer Institute published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C9H6BrNO, Recommanded Product: 4-Iodo-6-phenylpyrimidine.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

De Valk, J. published the artcilePyrimidines from this laboratory. XXXI. ANRORC [addition nucleophile ring opening ring closing] mechanism. V. Occurrence of the ANRORC [addition nucleophile ring opening ring closing] mechanism in aminations of substituted haloaza-aromatics with potassium amide in liquid ammonia, Formula: C10H7IN2, the publication is Recueil des Travaux Chimiques des Pays-Bas (1973), 92(3), 442-8, database is CAplus.

Evidence is presented that the amination of 4-chloro-2,6-diphenylpyrimidine with KNH2 in liquid ammonia into the corresponding 4-amino compound occurs to the extent of about 45% by the ANRORC mechanism. In the amination of the 4-iodo- and 4-fluoro derivatives of 2,6-diphenylpyrimidine however, the ANRORC mechanism is not operative at all. The amination of 5-bromo-4-chloro-2,6-diphenylpyrimidine into 4-amino-5-bromo-2,6-diphenylpyrimidine occurs to the extent of about 18% by the ANRORC mechanism. The synthesis of 5-bromo-4-chloro-2,6-diphenylpyrimidine-1(3)-15N and of the 4-fluoro, 4-chloro and 4-iodo derivatives of 2,6-diphenylpyrimidine-1(3)-15N is described.

Recueil des Travaux Chimiques des Pays-Bas published new progress about 41270-96-6. 41270-96-6 belongs to iodides-buliding-blocks, auxiliary class Pyrimidine,Iodide,Benzene,Immunology/Inflammation,MIF, name is 4-Iodo-6-phenylpyrimidine, and the molecular formula is C10H7IN2, Formula: C10H7IN2.

Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com