Structure–activity relationship studies of SETD8 inhibitors

Small-Molecule Inhibitors of SETD8 with Cellular Activity

SETD8/SET8/Pr-SET7/KMT5A is the sole protein lysine methyltransferase (PKMT) known to monomethylate lysine 20 of histone H4 in vivo. SETD8's methyltransferase activity has been implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. Developing SETD8 inhibitors with cellular activity is a key step toward...

Structure–Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors

EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functional groups. The most potent EPAC inhibitor 12a exists as a mixture of insepara...

postnatal studies of bats (pipistrellus kuhlii and miniopterus schreibersii) & histomorphology and histochemistry studies of organs and diseases of (neurergus microspilotus and n. kaiseri)

1. to determine whether difference in birth body mass influenced growth performance in pipistrellus kuhlii we studied a total of 12 captive-born neonates. bats were assigned to two body mass groups: light birth body mass (lbw: 0.89 ± 0.05, n=8) and heavy birth body mass (hbw: 1.35 ± 0.08, n=4). heavier body mass at birth was associated with rapid postnatal growth (body mass and forearm length) ...

High-SETD8 inactivates p53 in neuroblastoma

Epigenetics and differentiation are intimately related in Neuroblastoma (NB), the most common extracranial solid tumor of childhood. NB originates from neural crest and primary tumors have a sympathoadrenal progenitor phenotype. High-risk NB is considered a failure of sympathoadrenal terminal differentiation. Despite intense multimodal treatment, high-risk NB is also one of the most aggressive ...

quantitative structure activity relationship and docking studies on imidazole derivatives as p-glycoprotein inhibitors