Publications by authors named "Sameer Nikhar"

Article Synopsis
  • Researchers have identified calcium-dependent protein kinase 1 (CDPK1) in the protozoan responsible for cryptosporidiosis as a promising target for new therapies.
  • A specific compound, a pyridopyrimidinone, was found to effectively inhibit CdPK1 and prevent the growth of various strains of the parasite in host cells.
  • Although the compound showed low systemic exposure after oral dosing, it achieved high concentrations in the gastrointestinal tract and demonstrated some effectiveness in animal models of the disease.
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Article Synopsis
  • Severe influenza A virus can cause serious issues like lung damage and breathing problems, and there are currently no good medicines to treat it.
  • A new drug called UH15-38 has been created to stop a harmful process (called necroptosis) that makes the lung problems worse during severe infections.
  • Tests showed that UH15-38 helped reduce lung inflammation and saved lives in infected patients, even when given later in the illness, making it a promising option for treating severe influenza and related conditions.
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Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain (NOD) cell signaling, a pathway implicated in numerous chronic inflammatory conditions. Herein, a pyrido[2,3-d]pyrimidin-7-one based class of RIPK2 kinase and NOD2 cell signaling inhibitors is described. For example, 33 (e.

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The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis.

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RIPK2 mediates inflammatory signaling by the bacteria-sensing receptors NOD1 and NOD2. Kinase inhibitors targeting RIPK2 are a proposed strategy to ameliorate NOD-mediated pathologies. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP-binding and XIAP-mediated ubiquitination of RIPK2.

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Key residues and binding mechanisms of PGE and PGE on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE and PGE docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site.

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A synthesis of gombamide A (1) using N-terminal peptide extension, oxidative disulfide bond formation, and late-stage 4-hydroxystyrylamide installation has been achieved. This divergent method was also utilized to synthesize several gombamide A derivatives with modification to the 4-hydroxystyrylamide via cyclic peptide 2. The natural product and four derivatives were found to be devoid of Na(+)/K(+)-ATPase activity at 10 μM.

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Cancer continues to be one of the biggest threats to the human civilization because there is no cure of it. Small heterocyclic molecule with low molecular weight and novel structural feature is therapeutically highly demanding. These molecules have the capability to disrupt signaling pathways leading to anticancer activities.

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