Abstract:
:The Pathogen Box is a 400-strong collection of drug-like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition to malaria and tuberculosis. This library represents an ensemble of numerous successful drug discovery programmes from around the globe, aimed at providing a powerful resource to stimulate open source drug discovery for diseases threatening the most vulnerable communities in the world. This review seeks to provide an in-depth analysis of the literature pertaining to the compounds in the Pathogen Box, including structure-activity relationship highlights, mechanisms of action, related compounds with reported activity against different diseases, and, where appropriate, discussion on the known and putative targets of compounds, thereby providing context and increasing the accessibility of the Pathogen Box to the drug discovery community.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Veale CGLdoi
10.1002/cmdc.201800755subject
Has Abstractpub_date
2019-02-19 00:00:00pages
386-453issue
4eissn
1860-7179issn
1860-7187journal_volume
14pub_type
杂志文章,评审相关文献
ChemMedChem文献大全abstract::The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily that affects immune response, development, and metabolism in target tissues. Glucocorticoids are widely used to treat diverse pathophysiological conditions, but their clinical applicability is limited by side effects. A prediction of the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800274
更新日期:2009-01-01 00:00:00
abstract::We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moie...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000305
更新日期:2010-12-03 00:00:00
abstract::A series of water-soluble (benzoyloxy)methyl esters of acetylsalicylic acid (ASA), commonly known as aspirin, are described. The new derivatives each have alkyl chains containing a nitric oxide (NO)-releasing nitrooxy group and a solubilizing moiety bonded to the benzoyl ring. The compounds were synthesized and evalua...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300105
更新日期:2013-07-01 00:00:00
abstract::Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300144
更新日期:2013-07-01 00:00:00
abstract::Selectivity is a central aspect of lead optimization in the drug discovery process. Medicinal chemists often try to decrease molecular flexibility to improve selectivity, given the common belief that the two are interdependent. To investigate the relationship between polypharmacology and conformational flexibility, we...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402389
更新日期:2015-02-01 00:00:00
abstract::Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substitu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200307
更新日期:2012-11-01 00:00:00
abstract::Greater than the sum of its parts: Artemisinins are currently in phase I-II clinical trials against breast, colorectal and non-small-cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin-polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies an...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200536
更新日期:2013-05-01 00:00:00
abstract::Recently we reported on aryl-fluorosulfates as possible stable and effective electrophiles for the design of lysine covalent, cell permeable antagonists of protein-protein interactions (PPIs). Here we revisit the use of aryl-sulfonyl fluorides as Lys-targeting moieties, incorporating these electrophiles in XIAP (X-lin...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000355
更新日期:2020-11-18 00:00:00
abstract::An efficient stereocontrolled synthesis afforded alkoxymethylenephosphonate (MP) analogues of lysophosphatidic acid (LPA) and phosphatidic acid (PA). The pharmacological properties of MP-LPA and MP-PA analogues were characterized for LPA receptor subtype-specific agonist and antagonist activity using Ca(2+)-mobilizati...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700111
更新日期:2007-12-01 00:00:00
abstract::A series of cis-configured epoxides and aziridines containing hydrophobic moieties and amino acid esters were synthesized as new potential inhibitors of the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays revealed the N-benzyl-3-phenyl-substituted aziridines 11 and 17 as the most potent inhibito...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700101
更新日期:2008-02-01 00:00:00
abstract::Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impairments of the NO-sGC signaling pathway have been implicated in the pathogenesis of cardiovascular and other diseases. Direct stimulation of sGC represents a promising therapeutic strategy particularly for the treat...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900014
更新日期:2009-05-01 00:00:00
abstract::Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many c...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100027
更新日期:2011-07-04 00:00:00
abstract::Indolicidin (IR13), a 13-residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402215
更新日期:2014-09-01 00:00:00
abstract::Efavirenz (EFV), an antiretroviral that interacts clinically with co-administered drugs via activation of the pregnane X receptor (PXR), is extensively metabolized by the cytochromes P450. We tested whether its primary metabolite, 8-hydroxyEFV (8-OHEFV) can activate PXR and potentially contribute to PXR-mediated drug-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700730
更新日期:2018-04-06 00:00:00
abstract::Various structurally modified analogues of FR235222 (1), a natural tetrapeptide inhibitor of mammalian histone deacetylases, were prepared in a convergent approach. The design of the compounds was aimed to investigate the effect of structural modifications of the tetrapeptide core involved in enzyme binding in order t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700095
更新日期:2007-10-01 00:00:00
abstract::The development of more selective chemotherapeutic agents for benign treatments of malicious diseases is highly desirable. In recent years model systems for the release of small molecule drugs from nucleic acid conjugates by templated chemical or photochemical reactions have been designed. Common for these systems is ...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.200700013
更新日期:2007-06-01 00:00:00
abstract::Unraveling the mechanisms involved in castration- and therapy-resistant prostate cancer has led to a renewed interest in androgen receptor (AR)-targeted therapeutics. Anti-androgens that block the activity of the AR therefore remain a valid therapeutic option. However, they must be more effective than, or display a di...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200549
更新日期:2013-04-01 00:00:00
abstract::The CXCR3 receptor, a class A G protein-coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure-b...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500573
更新日期:2016-03-17 00:00:00
abstract::The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recen...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402278
更新日期:2014-12-01 00:00:00
abstract::Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders. A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme. Most of the compounds were found to be potent inhibitors of MAO-B, with ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200484
更新日期:2013-03-01 00:00:00
abstract::β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the or...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100042
更新日期:2011-07-04 00:00:00
abstract::Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential thera...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000839
更新日期:2020-12-04 00:00:00
abstract::P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402463
更新日期:2015-02-01 00:00:00
abstract::There has been significant interest in spleen tyrosine kinase (Syk) owing to its role in a number of disease states, including autoimmunity, inflammation, and cancer. Ongoing therapeutic programs have resulted in several compounds that are now in clinical use. Herein we report our optimization of the imidazopyrazine c...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500333
更新日期:2016-01-19 00:00:00
abstract::Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has li...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700220
更新日期:2017-08-22 00:00:00
abstract::We report the synthesis of trifluoromethylated metallocenes (M=Fe, Ru) and related metal-free compounds for comparison of their biological properties with the aim to establish structure-activity relationships toward the anti-proliferative activity of this compound class. All new compounds were comprehensively characte...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402001
更新日期:2014-06-01 00:00:00
abstract::The cytotoxic activity of a series of 23 new isoerianin derivatives with modifications on both the A and B rings was studied. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. The most cytotoxic compound, isoerianin (3), strongly in...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000456
更新日期:2011-03-07 00:00:00
abstract::In the present review the crucial role of the guanidinium functional group in facilitating the transport of dendritic polymers through liposomal and cell membranes is discussed, along with other structural features of guanidinylated dendritic polymers that fine-tune their transport properties, and even determine their...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.200800190
更新日期:2008-11-01 00:00:00
abstract::Based on the crystal structures of human alpha-GalCer-CD1d and iNKT-alpha-GalCer-CD1d complexes, nonglycosidic analogues of alpha-GalCer were synthesized. They activate iNKT cells resulting in dendritic cell maturation and the priming of antigen-specific T and B cells. Therefore, they are attractive adjuvants in vacci...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800354
更新日期:2009-02-01 00:00:00
abstract::Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N-terminal side chain (1), C-terminal side chain (2), or the C-terminus (3) to a...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000280
更新日期:2020-08-19 00:00:00