Corrigendum to "Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitor...
Published in Bioorganic & medicinal chemistry
Design, synthesis and biological evaluation of anthranilamide derivatives as potent SMO inhibitors.
Published in Bioorganic & medicinal chemistry
A series of anthranilamide derivatives were designed and synthesized as novel smoothened (SMO) inhibitors based on the SMO inhibitor taladegib (LY2940680), which can also inhibit the SMO-D473H mutant, via a ring-opening strategy. The phthalazine core in LY2940680 was replaced with anthranilamide, which retained the inhibitory activity towards the h...
Pyrimethamine conjugated histone deacetylase inhibitors: Design, synthesis and evidence for triple negative breast cance...
Published in Bioorganic & medicinal chemistry
Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which has been recognized as a promising cancer therapeutic target. Small molecule pyrimethamine (PYM) is a known direct inhibitor of activated STAT3 and it is currently under clinical trial. Also, histone deacetylase (HDAC) inhibition has been shown to ...
CT2-3, a novel magnolol analogue suppresses NSCLC cells through triggering cell cycle arrest and apoptosis.
Published in Bioorganic & medicinal chemistry
Magnolol, a major bioactive component found in Magnolia officinalis with anti-inflammation and anti-oxidation activities as well as minimized cytotoxic effects. Although magnolol has a wide range of clinical applications, the anti-tumor activity of magnolol is not efficient. Herein, we reported the synthesis and anti-cancer activities of three nove...
An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4.
Published in Bioorganic & medicinal chemistry
Identification of structural determinants required for potent inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) could help develop safer drugs and more effective pharmacoenhancers. We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent CYP3A4 inhibitor marketed as ph...
Unexpected small molecules as novel SIRT2 suicide inhibitors.
Published in Bioorganic & medicinal chemistry
A series of sirtuin inhibitor candidates were assembled based on an intermediate ester (1a) our accidently discovered. After screening and evaluation, several SIRT2 selective inhibitors were identified, which can inhibit all the deacetylation, defatty-acylation and debenzoylation of SIRT2. Among these inhibitors, compound 1e was the best SIRT2 sele...
Discovery and structure-activity relationships of spiroindolines as novel inducers of oligodendrocyte progenitor cell di...
...Published in Bioorganic & medicinal chemistry
A novel series of spiroindoline derivatives was discovered for use as inducers of oligodendrocyte progenitor cell (OPC) differentiation, resulting from optimization of screening hit 1. Exploration of structure-activity relationships led to compound 18, which showed improved potency (rOPC EC50 = 0.0032 μM). Furthermore, oral administration of compou...
Discovery of disubstituted xylylene derivatives as small molecule direct inhibitors of Keap1-Nrf2 protein-protein intera...
Published in Bioorganic & medicinal chemistry
The Keap1-Nrf2-ARE system represents a crucial antioxidant defense mechanism that protects cells against reactive oxygen species. Targeting Keap1-Nrf2 protein-protein interaction (PPI) has become a promising drug target for several oxidative stress-related and inflammatory diseases including pulmonary fibrosis, chronic obstructive pulmonary disorde...
STAT3 inhibitory activity of naphthoquinones isolated from Tabebuia avellanedae.
...Published in Bioorganic & medicinal chemistry
The extract of Tabebuia avellanedae has been used as a folk medicine, and the various biological activities of T. avellanedae have been extensively studied. However, few studies have reported which natural products play a role in their biological effects. In this study, we evaluated representative naphthoquinones isolated from T. avellanedae and fo...
A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding g...
...Published in Bioorganic & medicinal chemistry
Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a ...
