Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using an Enabled Drug Discovery Platform.

Despite the success of first, second, and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer with classical EGFR mutations (L858R or Exon 19 deletions), disease progression occurs due to the acquisition of T790M and C797S resistance. Herein, we report a physics-based computationally driven lead identification approach that identified structurally unique imidazo[3.2-]pyrazoles as reversible and wild-type-sparing EGFR TKIs of classical mutations bearing both T790M and C797S.

Utilization of Low Cost Biofertilizers for Adsorptive Removal of Congo Red Dye.

Presence of colors, organic surface finishing agents and surfactants in textile industry effluent makes it highly detrimental for surrounding environment. Hence the effluent from textile industry needs treatment for removal of these colors, organic and inorganic components before its disposal. Hence applicability of low cost and environmental friendly biosorbents, Azospirillium biofertilizer and Rhizobium biofertilizer were investigated for removal of Congo red dye.

Lectin Drug Conjugates Targeting High Mannose N-Glycans.

Cancer-associated alterations to glycosylation have been shown to aid cancer development and progression. An increased abundance of high mannose N-glycans has been observed in several cancers. Here, we describe the preparation of lectin drug conjugates (LDCs) that permit toxin delivery to cancer cells presenting high mannose N-glycans.

Design and synthesis of novel spirocyclic carboxylic acids as potent and orally bioavailable DGAT1 inhibitors and their biological evaluation.

A series of novel spirocyclic DGAT1 inhibitors containing the oxadiazole motif were designed and synthesized for biological evaluation. Several compounds exhibited potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity. Optimization of the series led to the identification of five lead compounds 8, 9, 10, 11 and 12 that showed excellent in-vitro activity with IC values ranging from 7 to 20 nM against human DGAT1.