当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > Identification of oxadiazoles as new drug leads for the control of schistosomiasis.

Identification of oxadiazoles as new drug leads for the control of schistosomiasis.

Abstract：

:Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends almost exclusively on praziquantel. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a quantitative high-throughput screen, were shown to inhibit a parasite enzyme, thioredoxin glutathione reductase (TGR), with activities in the low micromolar to low nanomolar range. Incubation of parasites with these compounds led to rapid inhibition of TGR activity and parasite death. The activity of the oxadiazole 2-oxides was associated with a donation of nitric oxide. Treatment of schistosome-infected mice with 4-phenyl-1,2,5-oxadiazole-3-carbonitrile-2-oxide led to marked reductions in worm burdens from treatments against multiple parasite stages and egg-associated pathologies. The compound was active against the three major schistosome species infecting humans. These protective effects exceed benchmark activity criteria set by the World Health Organization for lead compound development for schistosomiasis.

journal_name

Nat Med

journal_title

Nature medicine

authors

Sayed AA,Simeonov A,Thomas CJ,Inglese J,Austin CP,Williams DL

doi

10.1038/nm1737

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

407-12

issue

4

eissn

1078-8956

issn

1546-170X

pii

nm1737

journal_volume

14

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury.

    abstract：:Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/11387

    authors： Springer JE,Azbill RD,Knapp PE

    更新日期：1999-08-01 00:00:00

  • A framework for understanding and targeting residual disease in oncogene-driven solid cancers.

    abstract：:Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, res...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4091

    authors： Bivona TG,Doebele RC

    更新日期：2016-05-05 00:00:00

  • A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.

    abstract：:Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3665

    authors： Herranz D,Ambesi-Impiombato A,Palomero T,Schnell SA,Belver L,Wendorff AA,Xu L,Castillo-Martin M,Llobet-Navás D,Cordon-Cardo C,Clappier E,Soulier J,Ferrando AA

    更新日期：2014-10-01 00:00:00

  • Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection.

    abstract：:Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (term...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1192

    authors： Morizono K,Xie Y,Ringpis GE,Johnson M,Nassanian H,Lee B,Wu L,Chen IS

    更新日期：2005-03-01 00:00:00

  • Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.

    abstract：:Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4421

    authors： Huot N,Jacquelin B,Garcia-Tellez T,Rascle P,Ploquin MJ,Madec Y,Reeves RK,Derreudre-Bosquet N,Müller-Trutwin M

    更新日期：2017-11-01 00:00:00

  • The effects of tobacco control policies on global smoking prevalence.

    abstract：:Substantial global effort has been devoted to curtailing the tobacco epidemic over the past two decades, especially after the adoption of the Framework Convention on Tobacco Control1 by the World Health Organization in 2003. In 2015, in recognition of the burden resulting from tobacco use, strengthened tobacco control...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-01210-8

    authors： Flor LS,Reitsma MB,Gupta V,Ng M,Gakidou E

    更新日期：2021-01-21 00:00:00

  • Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma.

    abstract：:Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an o...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0827-2

    authors： Donovan LK,Delaidelli A,Joseph SK,Bielamowicz K,Fousek K,Holgado BL,Manno A,Srikanthan D,Gad AZ,Van Ommeren R,Przelicki D,Richman C,Ramaswamy V,Daniels C,Pallota JG,Douglas T,Joynt ACM,Haapasalo J,Nor C,Vladoiu MC,

    更新日期：2020-05-01 00:00:00

  • Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis.

    abstract：:Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1945

    authors： Binder NB,Niederreiter B,Hoffmann O,Stange R,Pap T,Stulnig TM,Mack M,Erben RG,Smolen JS,Redlich K

    更新日期：2009-04-01 00:00:00

  • Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis.

    abstract：:Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of ser...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/76216

    authors： Yan SD,Zhu H,Zhu A,Golabek A,Du H,Roher A,Yu J,Soto C,Schmidt AM,Stern D,Kindy M

    更新日期：2000-06-01 00:00:00

  • Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells.

    abstract：:Angiogenic tumor vessels are promising targets for the activity and the selective delivery of cancer therapeutics. The bone marrow contributes different cell types to the tumor stroma, including hematopoietic cells and, as recently suggested, vascular endothelial cells (ECs). Thus, transplantation of genetically modif...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm871

    authors： De Palma M,Venneri MA,Roca C,Naldini L

    更新日期：2003-06-01 00:00:00

  • Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy.

    abstract：:Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by toxic gain of function of the androgen receptor (AR). Previously, we found that co-regulator binding through the activation function-2 (AF2) domain of AR is essential for pathogenesis, suggesting that AF2 may be a potential drug target for selec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4500

    authors： Badders NM,Korff A,Miranda HC,Vuppala PK,Smith RB,Winborn BJ,Quemin ER,Sopher BL,Dearman J,Messing J,Kim NC,Moore J,Freibaum BD,Kanagaraj AP,Fan B,Tillman H,Chen PC,Wang Y,Freeman BB III,Li Y,Kim HJ,La Spada AR

    更新日期：2018-05-01 00:00:00

  • Real-time quantitative RT-PCR after laser-assisted cell picking.

    abstract：:The present study describes a technique for quantitation of mRNA in a few isotypic cells obtained from an intact organ structure by combining laser-assisted cell picking and real-time PCR. The microscopically controlled lasering of selected cells in stained tissue sections was applied to lung alveolar macrophages, whi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/3327

    authors： Fink L,Seeger W,Ermert L,Hänze J,Stahl U,Grimminger F,Kummer W,Bohle RM

    更新日期：1998-11-01 00:00:00

  • Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia.

    abstract：:Systemic inflammation induces various adaptive responses including tachycardia. Although inflammation-associated tachycardia has been thought to result from increased sympathetic discharge caused by inflammatory signals of the immune system, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1231

    authors： Takayama K,Yuhki K,Ono K,Fujino T,Hara A,Yamada T,Kuriyama S,Karibe H,Okada Y,Takahata O,Taniguchi T,Iijima T,Iwasaki H,Narumiya S,Ushikubi F

    更新日期：2005-05-01 00:00:00

  • Interstitial cells of Cajal generate a rhythmic pacemaker current.

    abstract：:Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagat...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0798-848

    authors： Thomsen L,Robinson TL,Lee JC,Farraway LA,Hughes MJ,Andrews DW,Huizinga JD

    更新日期：1998-07-01 00:00:00

  • Development of universal antidotes to control aptamer activity.

    abstract：:With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1990

    authors： Oney S,Lam RT,Bompiani KM,Blake CM,Quick G,Heidel JD,Liu JY,Mack BC,Davis ME,Leong KW,Sullenger BA

    更新日期：2009-10-01 00:00:00

  • On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

    abstract：:Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threate...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4146

    authors： Theurl I,Hilgendorf I,Nairz M,Tymoszuk P,Haschka D,Asshoff M,He S,Gerhardt LM,Holderried TA,Seifert M,Sopper S,Fenn AM,Anzai A,Rattik S,McAlpine C,Theurl M,Wieghofer P,Iwamoto Y,Weber GF,Harder NK,Chousterman BG,

    更新日期：2016-08-01 00:00:00

  • Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

    abstract：:Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs)...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0116-5

    authors： Cañadas I,Thummalapalli R,Kim JW,Kitajima S,Jenkins RW,Christensen CL,Campisi M,Kuang Y,Zhang Y,Gjini E,Zhang G,Tian T,Sen DR,Miao D,Imamura Y,Thai T,Piel B,Terai H,Aref AR,Hagan T,Koyama S,Watanabe M,Baba H,

    更新日期：2018-08-01 00:00:00

  • Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy.

    abstract：:Peripheral nerve injuries represent a significant problem in public health, constituting 2-5% of all trauma cases1. For severe nerve injuries, even advanced forms of clinical intervention often lead to incomplete and unsatisfactory motor and/or sensory function2. Numerous studies report the potential of pharmacologica...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0196-2

    authors： Koo J,MacEwan MR,Kang SK,Won SM,Stephen M,Gamble P,Xie Z,Yan Y,Chen YY,Shin J,Birenbaum N,Chung S,Kim SB,Khalifeh J,Harburg DV,Bean K,Paskett M,Kim J,Zohny ZS,Lee SM,Zhang R,Luo K,Ji B,Banks A,Lee HM,Hua

    更新日期：2018-12-01 00:00:00

  • Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: implications for antiviral therapy.

    abstract：:Evolutionary patterns of virus replication and distribution in lymphoid tissue during the early phases of HIV infection have not been delineated. Lymph node (LN) biopsies were excised from patients at different times after the estimated time of primary infection. Within 3 months of the acute viral syndrome, HIV was mo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0398-341

    authors： Pantaleo G,Cohen OJ,Schacker T,Vaccarezza M,Graziosi C,Rizzardi GP,Kahn J,Fox CH,Schnittman SM,Schwartz DH,Corey L,Fauci AS

    更新日期：1998-03-01 00:00:00

  • Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.

    abstract：:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase (NOS) that blocks MPTP neurotoxi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0996-1017

    authors： Hantraye P,Brouillet E,Ferrante R,Palfi S,Dolan R,Matthews RT,Beal MF

    更新日期：1996-09-01 00:00:00

  • Developing neoantigen-targeted T cell-based treatments for solid tumors.

    abstract：:Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting 'neoantigens'-the somatic mutations expressed only by tumor cells-might...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-019-0596-y

    authors： Yamamoto TN,Kishton RJ,Restifo NP

    更新日期：2019-10-01 00:00:00

  • Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition.

    abstract：:Cells that are deficient in homologous recombination, such as those that lack functional breast cancer-associated 1 (BRCA1) or BRCA2, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, BRCA-deficient tumors represent only a small fraction of adult cancers, which might restrict the therape...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2377

    authors： Johnson N,Li YC,Walton ZE,Cheng KA,Li D,Rodig SJ,Moreau LA,Unitt C,Bronson RT,Thomas HD,Newell DR,D'Andrea AD,Curtin NJ,Wong KK,Shapiro GI

    更新日期：2011-06-26 00:00:00

  • G-CSF induces E-selectin ligand expression on human myeloid cells.

    abstract：:Clinical use of G-CSF can result in vascular and inflammatory complications. To investigate the molecular basis of these effects, we analyzed the adherence of G-CSF-mobilized human peripheral blood leukocytes (ML) to inflamed (TNF-alpha-stimulated) vascular endothelium. Studies using parallel plate assays under physio...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1470

    authors： Dagia NM,Gadhoum SZ,Knoblauch CA,Spencer JA,Zamiri P,Lin CP,Sackstein R

    更新日期：2006-10-01 00:00:00

  • Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.

    abstract：:Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) wit...

    journal_title：Nature medicine

    pub_type： 临床试验,杂志文章

    doi：10.1038/s41591-018-0295-0

    authors： Cideciyan AV,Jacobson SG,Drack AV,Ho AC,Charng J,Garafalo AV,Roman AJ,Sumaroka A,Han IC,Hochstedler MD,Pfeifer WL,Sohn EH,Taiel M,Schwartz MR,Biasutto P,Wit W,Cheetham ME,Adamson P,Rodman DM,Platenburg G,Tome MD,

    更新日期：2019-02-01 00:00:00

  • Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.

    abstract：:The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies ex...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3362

    authors： Falzarano D,de Wit E,Rasmussen AL,Feldmann F,Okumura A,Scott DP,Brining D,Bushmaker T,Martellaro C,Baseler L,Benecke AG,Katze MG,Munster VJ,Feldmann H

    更新日期：2013-10-01 00:00:00

  • Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.

    abstract：:This corrects the article DOI: 10.1038/nm.4439. ...

    journal_title：Nature medicine

    pub_type： 已发布勘误

    doi：10.1038/nm0418-526b

    authors： Bolouri H,Farrar JE,Triche T Jr,Ries RE,Lim EL,Alonzo TA,Ma Y,Moore R,Mungall AJ,Marra MA,Zhang J,Ma X,Liu Y,Liu Y,Auvil JMG,Davidsen TM,Gesuwan P,Hermida LC,Salhia B,Capone S,Ramsingh G,Zwaan CM,Noort S,Pic

    更新日期：2018-04-10 00:00:00

  • Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.

    abstract：:Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a singl...

    journal_title：Nature medicine

    pub_type： 杂志文章,随机对照试验

    doi：10.1038/nm1310

    authors： Rapoport AP,Stadtmauer EA,Aqui N,Badros A,Cotte J,Chrisley L,Veloso E,Zheng Z,Westphal S,Mair R,Chi N,Ratterree B,Pochran MF,Natt S,Hinkle J,Sickles C,Sohal A,Ruehle K,Lynch C,Zhang L,Porter DL,Luger S,Guo C,

    更新日期：2005-11-01 00:00:00

  • Inducible nitric oxide synthase gene expression in the brain during systemic inflammation.

    abstract：:Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escheri...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0596-581

    authors： Wong ML,Rettori V,al-Shekhlee A,Bongiorno PB,Canteros G,McCann SM,Gold PW,Licinio J

    更新日期：1996-05-01 00:00:00

  • A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis.

    abstract：:We report the involvement of an evolutionarily conserved set of mycobacterial genes, the esx-3 region, in evasion of bacterial killing by innate immunity. Whereas high-dose intravenous infections of mice with the rapidly growing mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were rapidly l...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2420

    authors： Sweeney KA,Dao DN,Goldberg MF,Hsu T,Venkataswamy MM,Henao-Tamayo M,Ordway D,Sellers RS,Jain P,Chen B,Chen M,Kim J,Lukose R,Chan J,Orme IM,Porcelli SA,Jacobs WR Jr

    更新日期：2011-09-04 00:00:00

  • v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation.

    abstract：:Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1514

    authors： Lee SH,Rho J,Jeong D,Sul JY,Kim T,Kim N,Kang JS,Miyamoto T,Suda T,Lee SK,Pignolo RJ,Koczon-Jaremko B,Lorenzo J,Choi Y

    更新日期：2006-12-01 00:00:00