Antiviral drugs

Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection Lanford, E. R. et al. Science 327, 198–201 (2010)

This study investigated the potential of microRNA-122 (miR-122), a microRNA that is expressed in the liver and binds the hepatitis C virus (HCV) genome, as an antiviral target. Treatment of chimpanzees that were chronically infected with HCV with a locked nucleic acid–modified oligonucleotide complementary to miR-122 led to long-lasting suppression of HCV viraemia without the development of viral resistance to the therapy. Livers from treated chimpanzees showed normalization of the interferon pathway and improvement of HCV-induced pathology. So, targeting miR-122 could offer advantages over current HCV therapy.

Anticancer drugs

Tissue-penetrating delivery of compounds and nanoparticles into tumors Sugahara, K. N. et al. Cancer Cell 16, 510–520, (2009)

The poor penetration of drugs into tumours is an obstacle in cancer treatment. Sugahara and colleagues describe a method that enables compounds to be delivered into the tumour parenchyma. Conjugation of compounds to a peptide (termed iRGD) that contained the RGD integrin recognition motif and a consensus motif that mediates tissue penetration enabled injected compounds to spread into the extravascular tumour parenchyma. Furthermore, conjugating the peptide to albumin-embedded paclitaxel nanoparticles resulted in enhanced antitumour activity.

Protein–protein interactions

Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD Thorsen, T. S. et al. Proc. Natl Acad. Sci. USA 14 Dec 2009 (doi: 10.1073/pnas.0902225107)

This paper describes a small-molecule inhibitor (known as FSC231) of the PDZ domain in protein interacting with C kinase 1 (PICK1). In cell-cultured hippocampal neurons, FSC231 inhibited the interaction between the AMPA receptor GluR2 subunit and PICK1; accelerated GluR2 recycling following N-methyl-D-aspartate receptor-induced internalization; and blocked long-term depression and long-term potentiation. So, FSC231 might serve as a lead compound for therapeutics targeting the PDZ domain in PICK1.

Anticancer drugs

Novel mutant-selective EGFR kinase inhibitors against EGFR T790M Zhou, W. et al. Nature 462, 1070–1074 (2009)

The efficacy of current epidermal growth factor receptor (EGFR) kinase inhibitors — all of which contain a quinazoline-based core scaffold — is limited by the development of drug resistance. By screening a kinase inhibitor library against EGFRs that expressed T790M, a mutation that is present in 50% of patients demonstrating drug resistance, Zhou and colleagues identified a new class of pyrimidine EGFR inhibitors. In vitro, these compounds were more potent against EGFR T790M than quinazoline-based EGFR inhibitors, and, in vivo, a compound caused tumour regression in a model of lung cancer.