Structural and functional regulation of lactate dehydrogenase-A in cancer.


:Dysregulated metabolism is one of the hallmarks of cancer. Under normal physiological conditions, ATP is primarily generated by oxidative phosphorylation. Cancers commonly undergo a dramatic shift toward glycolysis, despite the presence of oxygen. This phenomenon is known as the Warburg effect, and requires the activity of LDHA. LDHA converts pyruvate to lactate in the final step of glycolysis and is often upregulated in cancer. LDHA inhibitors present a promising therapeutic option, as LDHA blockade leads to apoptosis in cancer cells. Despite this, existing LDHA inhibitors have shown limited clinical efficacy. Here, we review recent progress in LDHA structure, function and regulation as well as strategies to target this critical enzyme.


Future Med Chem


Woodford MR,Chen VZ,Backe SJ,Bratslavsky G,Mollapour M




Has Abstract


2020-03-01 00:00:00












  • Selective and potent small-molecule inhibitors of PI3Ks.

    abstract::Class I PI3Ks are composed of four catalytic subunit variants (p110α, p110β, p110δ and p110γ). The PI3K pathway is among the most frequently activated pathways in many diseases, and has emerged as an attractive target for drug development, in particular for the treatment of many human cancers including breast, prostat...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Jeong Y,Kwon D,Hong S

    更新日期:2014-05-01 00:00:00

  • The critical role of epigallocatechin gallate in regulating mitochondrial metabolism.

    abstract::Epigallocatechin gallate (EGCG), one of polyphenols isolated from green tea, exhibits biology-benefiting effects with minimum severe adverse. EGCG is known to be a mitochondrion-targeting medicinal agent, regulating mitochondrial metabolism, including mitochondrial biogenesis, mitochondrial bioenergetics, and mitochon...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Shi W,Li L,Ding Y,Yang K,Chen Z,Fan X,Jiang S,Guan Y,Liu Z,Xu D,Wu L

    更新日期:2018-04-01 00:00:00

  • Proteolysis-targeting chimeras mediate the degradation of bromodomain and extra-terminal domain proteins.

    abstract::Bromodomain and extra-terminal domain (BET) protein family plays an important role in regulating gene transcription preferentially at super-enhancer regions and has been involved with several types of cancers as a candidate. Up to now, there are 16 pan-BET inhibitors in clinical trials, however, most of them have unde...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Yang Y,Wu Z,Chen P,Zheng P,Zhang H,Zhou J

    更新日期:2020-09-01 00:00:00

  • Prodrugs in combination with nanocarriers as a strategy for promoting antitumoral efficiency.

    abstract::Prodrug entrapment into nanocarriers for tumor delivery is a strategy to achieve a valid therapy with high efficiency. The prodrug contains anticancer agents conjugating with functional moieties or ligands so that the active component is released after metabolism in the body or tumor. The advantages of nanosystems for...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Lin MH,Hung CF,Hsu CY,Lin ZC,Fang JY

    更新日期:2019-08-01 00:00:00

  • Replacing sulfa drugs with novel DHPS inhibitors.

    abstract::More research effort needs to be invested in antimicrobial drug development to address the increasing threat of multidrug-resistant organisms. The enzyme DHPS has been a validated drug target for over 70 years as the target for the highly successful sulfa drugs. The use of sulfa drugs has been compromised by the wides...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Hammoudeh DI,Zhao Y,White SW,Lee RE

    更新日期:2013-07-01 00:00:00

  • New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane: facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes.

    abstract:BACKGROUND:Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Shimizu M,Higashi M,Takeda Y,Murai M,Jiang G,Asai Y,Nakao Y,Shirakawa E,Hiyama T

    更新日期:2009-08-01 00:00:00

  • The synthesis and biological evaluation of a new bioactive metabolite of mosapride as a potential gastroprokinetic agent.

    abstract:AIM:To synthesize the new bioactive metabolites of mosapride (R)-N-[2-hydroxy-3-(4-fluorobenzyl)amino]-propyl-5-chlorine-4-amino-2-ethoxyben-zamide (R-isomer) and (S)-N-[2-hydroxy-3-(4-fluorobenzyl)amino]-propyl-5-chlorine-4-amino-2-ethoxybenzamide (S-isomer) and evaluate their in vitro and in vivo pharmacological and ...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Yao J,Li K,Song Y,He Z,Liu Z,Zhao L,Wang S

    更新日期:2019-01-01 00:00:00

  • Dynorphin A analogs for the treatment of chronic neuropathic pain.

    abstract::Chronic pain is one of the most ubiquitous diseases in the world, but treatment is difficult with conventional methods, due to undesirable side effects of treatments and unknown mechanisms of pathological pain states. The endogenous peptide, dynorphin A has long been established as a target for the treatment of pain. ...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Hall SM,Lee YS,Hruby VJ

    更新日期:2016-01-01 00:00:00

  • Computer tools in the discovery of HIV-1 integrase inhibitors.

    abstract::Computer-aided drug design (CADD) methodologies have made great advances and contributed significantly to the discovery and/or optimization of many clinically used drugs in recent years. CADD tools have likewise been applied to the discovery of inhibitors of HIV-1 integrase, a difficult and worthwhile target for the d...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Liao C,Nicklaus MC

    更新日期:2010-07-01 00:00:00

  • Illuminating the lipidome to advance biomedical research: peptide-based probes of membrane lipids.

    abstract::Systematic investigation of the lipidome will reveal new opportunities for disease diagnosis and intervention. However, lipidomic research has been hampered by the lack of molecular tools to track specific lipids of interest. Accumulating reports indicate lipid recognition can be achieved with properly constructed sho...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Gao J,Zheng H

    更新日期:2013-05-01 00:00:00

  • 'Energy expenditure genes' or 'energy absorption genes': a new target for the treatment of obesity and Type II diabetes.

    abstract::Several hundred genes associated or linked to obesity have been described in the scientific literature. Whereas many of these genes are potential targets for the treatment of obesity and associated conditions, none of them have permitted the developement of an efficient drug therapy. As proposed by the 'thrifty genoty...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Braud S,Ciufolini M,Harosh I

    更新日期:2010-12-01 00:00:00

  • Novel RNA polymerase inhibitor found in soil extracts provides hope for future antibacterial drugs.

    abstract::Richard H Ebright talks to Rachel Coleby, Commissioning Editor: Ebright is at Rutgers University (New Brunswick, NJ, USA), where he performs research on the structure, mechanism, and regulation of bacterial transcription and on antibacterial drug discovery targeting bacterial transcription. He has received research aw...

    journal_title:Future medicinal chemistry

    pub_type: 面试


    authors: Ebright RH

    更新日期:2017-10-01 00:00:00

  • Fatty acid and mineral receptors as drug targets for gastrointestinal disorders.

    abstract::Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca2+-sensing receptors and Zn2+-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review prov...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Pongkorpsakol P,Moonwiriyakit A,Muanprasat C

    更新日期:2017-03-01 00:00:00

  • Discovery of 1,4-pentadien-3-one derivatives containing quinoxaline scaffolds as potential apoptosis inducers.

    abstract::Aim: To synthesize novel antiproliferative agents. Results & methodology: A variety of 1,4-pentadien-3-one derivatives bearing quinoxaline scaffolds was designed and synthesized and their antiproliferative activities were evaluated. Notably, compounds N3 and N4 exhibited markedly greater antiproliferative activities a...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Tang X,He J,Li Q,Tang X,Chen M,Hao G,Huai Z,Huang Y,Xue W

    更新日期:2020-08-01 00:00:00

  • Advances in antibiotic drug discovery: reducing the barriers for antibiotic development.

    abstract::Antibiotic drug discovery has been an essential field of research since the early 1900s, but the threat from infectious bacteria has only increased over the decades because of the emergence of widespread multidrug resistance. In this review, we discuss the recent advances in natural product, computational and medicina...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Murphy KE,Sloan GF,Lawhern GV,Volk GE,Shumate JT,Wolfe AL

    更新日期:2020-11-01 00:00:00

  • N3-substituted thymidine bioconjugates for cancer therapy and imaging.

    abstract::The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistri...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Khalil A,Ishita K,Ali T,Tjarks W

    更新日期:2013-04-01 00:00:00

  • Structure-activity relationship of natural and synthetic coumarin derivatives against Mycobacterium tuberculosis.

    abstract::Aim: Eight coumarin derivatives (1a-h) obtained from natural (-)-mammea A/BB (1) and 13 synthetic coumarins (2-14) had their cytotoxicity and biological activity evaluated against Mycobacterium tuberculosis H37Rv reference strain and multidrug-resistant clinical isolates. Materials & methods: Anti-M. tuberculosis acti...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Pires CT,Scodro RB,Cortez DA,Brenzan MA,Siqueira VL,Caleffi-Ferracioli KR,Vieira LC,Monteiro JL,Corrêa AG,Cardoso RF

    更新日期:2020-09-01 00:00:00

  • A small cytotoxic peptide from frog elicits potent antitumor immunity to prevent local tumor growth and metastases.

    abstract::Aim: Anticancer immunochemotherapy represents an attractive paradigm to improve therapeutic responses and reduce side effects. Results & methodology: Here, we show that a naturally occurring host defense peptide, HN-1 inhibited multiple malignant cells proliferation and tumor growth in a xenografted human breast tumor...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Qiao X,Yang H,Gao J,Cai S,Shi N,Wang M,Wang Y,Yu H

    更新日期:2019-10-01 00:00:00

  • The nitroimidazooxazines (PA-824 and analogs): structure-activity relationship and mechanistic studies.

    abstract::PA-824 is an experimental anti-tubercular agent that has a novel mechanism of action. It is effective against both active and persistent forms of the disease and has recently shown early bactericidal activity in a Phase II clinical trial. This review summarizes recent studies on the mode of action of PA-824 and outlin...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Denny WA,Palmer BD

    更新日期:2010-08-01 00:00:00

  • Auranofin is an effective agent against clinical isolates of Staphylococcus aureus.

    abstract::Aim: The orphan drug auranofin was recently found to exhibit antimicrobial properties. Materials & methods: We explored the efficacy of auranofin by evaluating the minimal inhibitory concentration against a collection of over 500 clinical isolates derived from multiple institutions, inclusive of drug resistant strains...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Tharmalingam N,Ribeiro NQ,da Silva DL,Naik MT,Cruz LI,Kim W,Shen S,Dos Santos JD,Ezikovich K,D'Agata EM,Mylonakis E,Fuchs BB

    更新日期:2019-06-01 00:00:00

  • Azide-alkyne cycloaddition en route to 4-aminoquinoline-ferrocenylchalcone conjugates: synthesis and anti-TB evaluation.

    abstract:AIM:Tuberculosis is responsible for 9.6 million infections and 1.5 million deaths in 2015. The development of multidrug-resistant and extensively drug-resistant strains has impeded the development of effective antitubercular therapy. Results/methodology: The present manuscript describes the synthesis of a series of 4-a...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Singh A,Viljoen A,Kremer L,Kumar V

    更新日期:2017-10-01 00:00:00

  • Plant dipeptidyl peptidase-IV inhibitors as antidiabetic agents: a brief review.

    abstract::Diabetes mellitus is an increasing public health problem in the world. Type 2 diabetes is the most common type of diabetes whose complications contribute to its high death rate. It seriously impacts healthcare systems and patients' quality of life. Therefore, effective measures and new treatment strategies are needed ...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Turdu G,Gao H,Jiang Y,Kabas M

    更新日期:2018-05-01 00:00:00

  • Pharmacokinetic strategies for treatment of drug overdose and addiction.

    abstract::The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa contro...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Gorelick DA

    更新日期:2012-02-01 00:00:00

  • Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

    abstract:BACKGROUND:Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. RESULTS:We report t...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Keenan M,Alexander PW,Chaplin JH,Abbott MJ,Diao H,Wang Z,Best WM,Perez CJ,Cornwall SM,Keatley SK,Thompson RC,Charman SA,White KL,Ryan E,Chen G,Ioset JR,von Geldern TW,Chatelain E

    更新日期:2013-10-01 00:00:00

  • Indole molecules as inhibitors of tubulin polymerization: potential new anticancer agents.

    abstract::Agents that interfere with tubulin function have a broad anti-tumor spectrum and they represent one of the most significant classes of anticancer agents. In the past few years, several small synthetic molecules that have an indole nucleus as a core structure have been identified as tubulin inhibitors. Among these, sev...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Patil SA,Patil R,Miller DD

    更新日期:2012-10-01 00:00:00

  • Label-free screening assays: a strategy for finding better drug candidates.

    abstract::The last 10 years have seen advances in automation and high-throughput biochemistry in the drug-discovery arena. However, these advances have not led to improvements in drug-discovery success. Drug programs must find new ways to identify superior compounds. Advances in label-free assay technologies may provide advanta...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Lunn CA

    更新日期:2010-11-01 00:00:00

  • Therapeutic strategies for the treatment of spinal muscular atrophy.

    abstract::Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease that results in progressive dysfunction of motor neurons of the anterior horn of the spinal cord. SMA is caused by the loss of full-length protein expression from the survival of motor neuron 1 (SMN1) gene. The disease has a unique genetic profile...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Cherry JJ,Androphy EJ

    更新日期:2012-09-01 00:00:00

  • Interview with Chi-Chao Chan. Interview by Isaac Bruce.

    abstract::Chi-Chao Chan, an American board certified ophthalmologist, is the Chief of Immunopathology Section, Laboratory of Immunology and the Head of Histology Core at the National Eye Institute at National Institutes of Health (USA). In 1967, Dr Chan graduated from Chungzhan Medical College in Guangzhou, China and then earne...

    journal_title:Future medicinal chemistry

    pub_type: 历史文章,面试


    authors: Chan CC

    更新日期:2012-11-01 00:00:00

  • Design, synthesis and cellular metabolism study of 4'-selenonucleosides.

    abstract:BACKGROUND:4'-seleno-homonucleosides were synthesized as next-generation nucleosides, and their cellular phosphorylation was studied to confirm the hypothesis that bulky selenium atom can sterically hinder the approach of cellular nucleoside kinase to the 5'-OH for phosphorylation. RESULTS:4'-seleno-homonucleosides (n...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Yu J,Sahu PK,Kim G,Qu S,Choi Y,Song J,Lee SK,Noh M,Park S,Jeong LS

    更新日期:2015-01-01 00:00:00

  • Computational insight into the anticholinesterase activities and electronic properties of physostigmine analogs.

    abstract::Aim: Alzheimer's disease (AD) is known to be themajor cause of dementia among the elderly. The structural properties and binding interactions of the AD drug physostigmine (-)-phy, and its analogues (-)-hex and (-)-phe and (+)-phe, were examined, as well as their impact on the conformational changes of two different AD...

    journal_title:Future medicinal chemistry

    pub_type: 杂志文章


    authors: Adeniyi AA,Conradie J

    更新日期:2019-08-01 00:00:00