Medicinal Chemistry

When does chemical elaboration induce a ligand to change its binding mode? Malhotra S et al. J Med Chem, 2016, 60(1):128-145.

Application of off-rate screening in the identification of novel pan-isoform inhibitors of pyruvate dehydrogenase kinase. Brough PA et al. J Med Chem, 2017, 60(6):2271-2286.Non-coding RNAs as drug targets. Matsui M et al. Nat Rev Drug Discov, 2017, 16(3):167-179.

Drugging RAS: know the enemy. Papke B et al. Science, 2017, 355(6330):1158-1163.

RON kinase: a target for treatment of cancer-induced bone destruction and osteoporosis. Andrade K et al. Sci Transl Med, 2017, 9(374).

Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis. Andrews FH et al. Proc Natl Acad Sci USA, 2017, 114(7):E1072-E1080.

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies. Kariolis MS et al. J Clin Invest. 2017, 127(1):183-198.

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Kotschy A et al. Nature, 2016, 538(7626):477-482.

Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties. Brust TF et al. Sci Signal, 2017, 10(467).

Synthesis and pharmacological characterization of novel trans-cyclopropylmethyl-linked bivalent ligands that exhibit selectivity and allosteric pharmacology at the dopamine D3 receptor (D3R). Kumar V et al. J Med Chem, 2017, 60(4):1478-1494.

Recent advances in drug discovery of GPCR allosteric modulators for neurodegenerative disorders. Lutjens R  et al. Curr Opin Pharmacol, 2017, 32:91-95.

The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo. Liu C et al. Sci Signal, 2017, 10 (467).

Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists.Zheng Y et al. Nature, 2016, 540(7633):458-461. 

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Tran AT et al. Nat Commun, 2017, 8:14414.

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Oliver JD et al. Proc Natl Acad Sci USA, 2016, Epub ahead of print.

DNA-encoded chemistry: enabling the deeper sampling of chemical space. Goodnow RA Jr et al. Nat Rev Drug Discov, 2017, 16(2):131-147. 

Expanding the cancer arsenal with targeted therapies: disarmament of the antiapoptotic Bcl-2 proteins by small molecules. Yap JL et al. J Med Chem, 2017, 60(3):821-838.

Displacement of drugs from human serum albumin: from molecular interactions to clinical significance. Rimac H et al. Curr Med Chem, 2017, Epub ahead of print.

PDE7-selective and dual inhibitors: advances in chemical and biological research. Jankowska A et al. Curr Med Chem, 2017, Epub ahead of print.

 

Synthetic Chemistry

Unique physicochemical and catalytic properties dictated by the B3NO2 ring system. Noda H et al. Nature Chemistry, 2017, 1-7.

Decarbonylative diaryl ether synthesis by Pd and Ni catalysis. Takise R et al. J Am Chem Soc, 2017, 139(9):3340-3343.

Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group. Yongbing L et al. Nature Chemistry, 2017, 9, 26-32.

Ligand-Enabled beta-C-H arylation of alpha-amino acids without installing exogenous directing groups. Gang C et al. Angewandte Chemie, 2017, 56:1506-1509.

Direct C-H cyanation of arenes via organic photoredox catalysis. Joshua BM et al. J Am Chem Soc, 2017, 139(8):2880-2883.

Strain-release heteroatom functionalization: development, scope, and stereospecificity. Justin ML et al. J Am Chem Soc, 2017, 139(8):3209-3226.

Highly efficient C-H hydroxylation of carbonyl compounds with oxygen under mild conditions. Yu-Feng L et al. Angewandte Chemie, 2014, 53, 548.

Applications of palladium-catalyzed C-N cross-coupling reactions. Paula RC et al. Chemical Reviews, 2016, 116(19):12564-12649.

Aryl amination using ligand-free Ni(II) salts and photoredox catalysis. Corcoran EB et al. Science, 2016, 353(6296):279-283.

Site-selective and stereoselective functionalization of unactivated C-H bonds. kuangbiao L et al. Nature, 2016, 533:230-234.

Formation of a-chiral centers by asymmetric b-C(sp3)-H arylation, alkenylation, and alkynylation. Qing-Feng W et al. Science, 2017, 355(6324):499-503.

Medicinal Chemistry

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models (Source: NCBI)

PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression (Source: NCBI)

Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition (Source: NCBI)

Targeting BRK-positive breast cancers with small molecule kinase inhibitors (Source: NCBI)

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models (Source: NCBI)

XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer (Source: NCBI) 

Imaging approaches to optimize molecular therapies (Source: NCBI)

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth (Source: NCBI)

TNIK inhibition abrogates colorectal cancer stemness (Source: NCBI)

Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2(+) Breast Cancer (Source: NCBI)

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients (Source: NCBI)

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease (Source: NCBI)

Structural insights into HDAC6 tubulin deacetylation and its selective inhibition (Source: NCBI) 

Histone deacetylase 6 structure and molecular basis of catalysis and inhibition (Source: NCBI)

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease (Source: NCBI)

The next generation of therapeutics for chronic kidney disease (Source: NCBI)

Methanobactin reverses acute liver failure in a rat model of Wilson disease (Source: NCBI)

IL-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization (Source: NCBI)

Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen (Source: NCBI)

Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice (Source: NCBI)

Twenty years on: the impact of fragments on drug discovery (Source: NCBI)

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities (Source: NCBI)

Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates (Source: NCBI)

Epithelial-mesenchymal transition: a new target in anticancer drug discovery (Source: NCBI)

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. (Source: ACS Publications)

From the RNA world to the clinic. (Source: Science Magazine)

The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target (Source: NCBI)

The role of myeloid cells in cancer therapies. (Source: NCBI)

NLRC5/MHC class I transactivator is a target for immune evasion in cancer. (Source: NCBI) 

Suppression of microRNA activity amplifies IFN-y-induced macrophage activation and promotes anti-tumour immunity (Source: NCBI)

Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ. (Source: NCBI)

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. (Source: NCBI)

Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. (Source: NCBI)

Repurposing an HIV drug for melanoma. (Source: Science Magazine)

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. (Source: NCBI)

sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. (Source: NCBI) 

 Emerging concepts of T cell metabolism as a target of immunotherapy. (Source: Nature.com)

Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. (Source: NCBI)

Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. (Source: NCBI)

Synthetic Chemistry

 

 

Medicinal Chemistry

G protein-coupled receptors as targets for anti-diabetic therapeutics. (Nature Review Drug Discovery)

Late-stage diversification of biologically active molecules via chemoenzymatic  C-H functionalization. (ACS Catalysis)

Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.(Nature Medicine)

Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. (Science Translational Medicine)

Silence of the GUCY2C tumor suppressor. (Science Translational Medicine) 

Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. (Proceedings of the National Academy of Sciences)

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. (Nature)

Discovery of Novel Blood-Brain Barrier Targets to Enhance Brain Uptake of Therapeutic Antibodies. (Neuron)

PPAR-δ is repressed in Huntington’s disease, is required for normal neuronal function and can be targeted therapeutically. (Nature Medicine)

A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. (Neuron)

The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling. (Science Transnational Medicine)

Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area. (Addiction Biology)

Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. (Science Signalling)

Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1. (Science Translational Medicine)

De Novo design at the edge of chaos. (Journal of Medicinal Chemistry)

Synthetic Chemistry

Dual C-F, C-H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls. (Journal of the American Chemical Society)

Network Analysis Guided Synthesis of Weisaconitine D and Liljestrandinine. (Nature)

Practical Ni-Catalyzed Aryl-Alkyl Cross-Coupling of Secondary Redox-Active Esters. (Journal of the American Chemical Society)

Strain-release amination. (Science)

Aryl Nitriles from Alkynes Using tert-Butyl Nitrite: Metal-Free Approach to C≡C Bond Cleavage. (ACS Organic Letters)

An Improved System for the Aqueous Lipshutz-Negishi Cross-Coupling of Alkyl Halides with Aryl Electrophiles.(Angewandte Chemie)

Access to Difluoromethylated Arenes by Pd-Catalyzed Reaction of Arylboronic Acids with Bromodifluoroacetate. (ACS Organic Letters)

Direct Difluoromethylation of Aryl Halides via Base Metal Catalysis at Room Temperature. (Journal of the American Chemical Society)

 

Medicinal Chemistry

 

Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic mastocytosis with eosinophilia and chronic myelomonocytic leukemia. T L Lasho et. al. Blood Cancer Journal 2015 5(e275).

 

A new family of choline kinase inhibitors with antiproliferative and antitumor activity derived from natural products. A. Estvez-Braun, et. al.,Clinical Translational Oncology. 2015, 7(1) pp. 74-84.

 

Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Ho PC, et. al., Cell, 2015, 162(6), pp.1217-28.

 

Broad anti-tumor activity of a small molecule that selectively targets the Warburg effect and lipogenesis. Colin. A. Flaveny et al. Cancer Cell (2015) 28, pp. 42-56. 

 

Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy. Jerome Chal, et. al., Nature Biotechnology, 2015, 33, pp. 962-969.

 

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease, Jilu Zhang et. al., Science Translational Medicine, 2015, 7 (308)

 

Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Qian Zhang, et. al., Nature, 2015, 525, pp. 389-393.

 

Identification of the first inverse agonist of retinoid-related orphan receptor (ROR) with dual selectivity for RORB and RORyT. Christian Gege, et. al. Bioorganic & Medicinal Chem Letters. 2014, 24(22), pp. 5265-7. 

 

Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Shangyu Hong et. al. Nature Medicine, 2015, 21(8), pp. 887-94.

 

A small-molecule antivirulence agent for treating Clostridium difficile infection, Kristina Oresic Bender et. al., Science Translational Medicine, 2015, 7 (306).

 

GPR3, a therapeutic target for AD? Orla Smith. Science Signalling, 2015, 8 (399), pp. ec305.

 

Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models. Yunhong Huang, et. al., Science Translational Medicine, 2015, 7 (309) pp. 309ra164.

 

Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Chun-Hyung Kim et. al., Proceedings of the National Academy of Sciences of the United States of America. 2015, 112(28) pp.8756-61.

 

Combination cancer immunotherapy and new immunomodulatory targets. Kathleen M. Mahoney et. al. Nature Reviews Drug Discovery, 2015, 14, pp. 561-584.

 

Big opportunities for small molecules in immuno-oncology. Jerry L. Adams, etc. al. Nature Reviews Drug Discovery, 2015, 14, 603-622.

 

Inhibiting one kinase to kill them all, Leslie K. Ferrarelli. Science Signaling, 2015, 8 (397) pp. ec284.

 

Targeting human cancer by a glycosaminoglycan binding malaria protein. Ali Salanti et al. Cancer Cell, 2015, 28 (4), pp. 500-514. 

 

Finding the good in malaria. Leslie K. Ferrarelli. Science Signaling, 2015, 8 (397), pp. ec297.

 

BET inhibitor resistance emerges from leukaemia stem cells. Chun Yew Fong, et al. Nature, 2015, 525, pp. 538-542.

 

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Philipp Rathert, et al. Nature, 2015, 525, pp. 543-547.

 

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Pawel Mazur, et al. Nature Medicine, 2015, 21, pp.1163-1171.

 

PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2. Timothy Witney, et. al. Science Translational Medicine, 2015, 7(310) pp. 310ra169.

 

The proinflammatory role of HECTD2 in innate immunity and experimental lung injury. Tiffany Coon et.al. Science Translational Medicine, 2015, 7(295). pp. 295ra109.

 

TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. David Choy, et. al. Science Translational Medicine, 2015, 7 (301), pp. 301ra129.

 

Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2. Rocio Vila-Bedmar, et. al. Science Signaling, 2015 8 (386), pp. ra73.

 

PCSK6-mediated corin activation is essential for normal blood pressure, Shenghan Chen, et. al. Nature Medicine, 2015, 21, pp. 1048-1053.

 

Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination. P. Robert Beatty, et. al. Science Translational Medicine. 2015, 7 (304), pp. 304ra141.

 

Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders. S. A. Barnes et. al. Molecular Psychiatry. 2015, 20, pp. 1161-1172.

 

UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo. Heather Mortiboys, et. al. Neurology. 2015, 85 (10), pp. 846-852.

 

Human Acid B-Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease. Camilla Parmeggiani, et. al. Chembiochem, 2015, 16 (14), pp. 2054-64.

 

Speedy repair with stabilized B-catenin. Tanya J Shaw, Science Translational. 2015, 7 (297), pp. 297ec125.

 

The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. Soung H. Lee et al., JEM, 2015, 7 (297), pp. 297ec125.

 

Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine. Simon Akerman, et. al. Science Translational Medicine, 2015, 7 (308), pp. 308ra157.

 

FTO obesity variant circuitry and adipocyte browning in humans. Melina Claussnitzer, et. al. New England Journal of Medicine, 2015, 373, pp. 895-907.
Remote control of therapeutic T cells through a small molecule-gated chimeric receptor Chia-Yung Wu, et. al. Science, 2015, 8 (399), pp. ec300.

 

Synthetic Chemistry

A fluorinated ligand enables room-temperature and regioselective pd-catalyzed fluorination of aryl triflates and bromides. Aaron C. Sather et. al. Journal of the American Chemical Society, 2015.  

 

Phthalimide conjugation as a strategy for in vivo target protein degradation. Georg E. Winter et. al. Science, 2015, 348 (6241), pp. 1376-1381. 

 

Dosage delivery of sensitive reagents enables glove-box-free synthesis. Stephen L. Buchwald et. al. Nature, 2015, 524, pp. 208-211.  

 

Medicinal Chemistry

Emerging Formats for Next-Generation Antibody Drug Conjugates. Mahendra P. Deonarain et. al. Expert Opinion on Drug Discovery, 2015, 10 (5) pp. 463-481.

Identification of Small-Molecule Inhibitors of Calcineurin-NFATc Signaling That Mimic the PxIxIT Motif of Calcineurin Binding Partners. Minos-Timotheos Matsoukas et. al. Science Signal. 2015, 8(382), pp. ra63.

Pharmacological Repression of PPARγ Promotes Osteogenesis. David P. Marciano et. al. Nature Communications, 2015, 6 (7443).

Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Daniel Egan et. al. Molecular Cell, 2015.

The Support of Human Genetic Evidence for Approved Drug Indications. Matthew R. Nelson et. al., Nature Genetics, 2015.

The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity. Cathy Slack et. al. Cell, 2015, 162, pp. 1–12.

Synthetic Chemistry

Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization, Song Song et. al. ACS Organic Letters, 2015, 17 (12), pp 2886–2889.

Practical Olefin Hydroamination with Nitroarenes. Jinghan Gui et. al. Science, 2015, 348 (6237), pp. 886-891.

Regioselective Metal-Free Cross-Coupling of Quinoline N-Oxides with Boronic Acids. Luis Bering et. al. ACS Organic Letters, 2015, 17 (12), pp 3134–3137.

Shelf-Stable Electrophilic Reagents for Trifluoromethylthiolation. Xinxin Shao et. al. Accounts of Chemical Research, 2015, 48 (5), pp 1227–1236.

Practical Olefin Hydroamination with Nitroarenes. Phil S. Baran et. al. Science. 2015, 348(6237), pp. 886-891.