Publications by authors named "Shifali Shishodia"
Article Synopsis
- * Researchers are developing selective chemical probes for PBRM1's bromodomains to better understand its role in cancer and immunotherapy, as existing inhibitors also target other bromodomains (SMARCA2 and SMARCA4).
- * A study screened nearly 2,000 fragments identifying 17 potential inhibitors, leading to the creation of highly selective nanomolar inhibitors that block PBRM1’s ability to bind to acetylated histone peptides and stop the growth of PBR
Article Synopsis
- Carbapenems are essential antibiotics but are losing effectiveness due to metallo-β-lactamases (MBLs), which are enzymes that break them down.
- Researchers discovered indole-2-carboxylates (InCs) as new inhibitors that can effectively target MBLs, maintaining activity against all major clinically relevant classes of these enzymes.
- In laboratory tests, InCs not only restored the effectiveness of carbapenems against drug-resistant Gram-negative bacteria but also demonstrated a good safety profile and strong efficacy when combined with the antibiotic meropenem in animal models of infection.
Article Synopsis
- FTO is an enzyme that modifies nucleic acids and is involved in the demethylation of mRNA, making it a potential target for cancer treatments.
- Researchers used crystal structure data to create two series of FTO inhibitors, which were tested for their effectiveness and selectivity.
- A strong inhibitor was found that specifically targets FTO while avoiding interference with other similar enzymes, showcasing the importance of structure-based design in developing these compounds.
Article Synopsis
- * The authors present an improved five-step synthesis method for creating mA phosphoramidite, using a specific chemical reaction that enhances overall yield significantly.
- * This new synthesis approach not only improves mA production but is also applicable for other adenosine derivatives, including ethanoadenosine, which is relevant for research on the anticancer drug Carmustine.
Article Synopsis
- BRD4 is a part of the BET family, recognized as a potential target for treating cancer and inflammatory diseases by interfering with its interaction with acetylated chromatin.
- Researchers identified a unique ligandable site on BRD4, specifically near a cysteine residue (Cys356), which doesn't affect the usual acetyl-lysine binding sites, opening up a new pathway for drug development.
- The study shows that targeting this new site allows for the creation of bivalent and covalent inhibitors that can effectively displace BRD4 from chromatin, thus providing a promising approach for improving current treatments.
Article Synopsis
- A specific mutation in the FTO gene, previously linked to congenital malformations, was found in a family with nine affected members, showcasing lethal growth and developmental issues.
- A 21-month-old girl exhibited various severe health problems and a new homozygous missense mutation in the FTO gene, impacting crucial biochemical functions.
- This study reinforces the idea that mutations in FTO are significant contributors to serious developmental issues, particularly affecting the nervous and cardiovascular systems.
