Design, synthesis, and biological evaluation of phenyl thiazole-based AR-V7 degraders.

Multiple Splice variants of AR have been reported in the past few years. These splice variants are upregulated in most cases of CRPC resulting in poor prognosis. Most of these variants lack the ligand binding domain (LBD) but still bind to DNA resulting in constitutive activation of downstream targets.

Discovery of CA-4948, an Orally Bioavailable IRAK4 Inhibitor for Treatment of Hematologic Malignancies.

Small molecule potent IRAK4 inhibitors from a novel bicyclic heterocycle class were designed and synthesized based on hits identified from Aurigene's compound library. The advanced lead compound, CA-4948, demonstrated good cellular activity in ABC DLBCL and AML cell lines. Inhibition of TLR signaling leading to decreased IL-6 levels was also observed in whole blood assays.

Anticancer activity of methanolic extracts.

(water mimosa) is an edible medicinal plant used in treating various diseases. According to Phytochemical and Ethnobotanical Databases, is used in curing earaches, dysentery, syphilis, and tumour. The present study was aimed at demonstrating the anticancer activity of the methanolic extract.

Dihydroorotate Dehydrogenase Inhibitors Promote Cell Cycle Arrest and Disrupt Mitochondria Bioenergetics in Ramos Cells.

Background: The re-emerging of targeting Dihydroorotate Dehydrogenase (DHODH) in cancer treatment particularly Acute Myelogenous Leukemia (AML) has corroborated the substantial role of DHODH in cancer and received the attention of many pharmaceutical industries.

Objective: The effects of Brequinar Sodium (BQR) and 4SC-101 on lymphoblastoid cell lines were investigated.

Methods: DHODH expression and cell proliferation inhibition of lymphoblastoid and lymphoma cell lines were analyzed using Western blot analysis and XTT assay, respectively.

Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin.

Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells.

Dihydroorotate dehydrogenase Inhibitors Target c-Myc and Arrest Melanoma, Myeloma and Lymphoma cells at S-phase.

Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase.

Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH.

Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design.

Changes in the carbon dioxide expirogram in response to ozone exposure.

The objectives of this study were to quantify pulmonary responses to ozone (O3) exposure by parameters computed from the carbon dioxide expirogram and to compare these responses to decrements in forced expired spirometry. Anatomical dead space (VD) was determined from the pure dead space and transition regions of the expirogram. Four alternative parameters were computed from the alveolar plateau: slope (S), normalized slope (NS), peripheral cross-sectional area (AP) and well-mixed peripheral volume (VMP).

Inhibition of leukocyte adherence enables venular control of capillary perfusion in streptozotocin-induced diabetic rats.

Objective: Vasoactive molecules can diffuse from venules to dilate closely paired arterioles and enhance capillary perfusion. Venular control of capillary flow has been found to be dependent on nitric oxide (NO), which might be scavenged rapidly in diabetic microvasculature due to the presence of activated leukocytes. This study attempts to improve venular control of capillary flow using fucoidan, which inhibits venular leukocvte adhesion.

Nitric oxide measurements in rat mesentery reveal disrupted venulo-arteriolar communication in diabetes.

Objective: Arteriolar tone is partially controlled by diffusing mediators released by closely paired venules and is reported to depend on venular shear and venular leukocyte adherence. In healthy rat mesentery, venule-initiated arteriolar dilation and consequent enhanced capillary flow appear to be tightly regulated by nitric oxide (NO). In contrast, diabetes inhibits NO-dependent vasodilation and is associated with dysfunctional microcirculation.

L-arginine and antineutrophil serum enable venular control of capillary perfusion in hypercholesterolemic rats.

Objective: The purpose of this study was to investigate and counteract dysfunctional control of capillary flow in hypercholesterolemia. Capillary flow is controlled by arteriolar tone, which in turn is influenced by mediators released from closely paired venules in a mechanism that involves nitric oxide (NO). However, venular control of capillary flow is altered with hypercholesterolemia.