Identifying cancer targets based on machine learning methods via Chou's 5-steps rule and general pseudo components.
Abstract In recent years, the successful implementation of human genome project has made people realize that genetic, environmental and lifestyle factors should be combined together to study cancer due to the complexity and various forms of the disease. The increasing availability and growth rate of 'big data' derived from various omics, opens a new window for study and therapy of cancer. In this paper, we will introduce the application of machine learning methods in handling cancer big data including the use of artificial neural networks, support vector machines, ensemble learning and naïve Bayes classifiers...
Source: Current Topics in Medicinal Chemistry - October 16, 2019 Category: Chemistry Authors: Liang R, Xie J, Zhang C, Zhang M, Huang H, Huo H, Cao X, Niu B Tags: Curr Top Med Chem Source Type: research

Current Topics in Medicinal Chemistry: The Six Most Cited Publications 2016-2019.
Abstract PMID: 31592749 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - October 10, 2019 Category: Chemistry Authors: Reitz AB Tags: Curr Top Med Chem Source Type: research

Precision Tumor Medicine and Drug Targets.
Abstract PMID: 31592750 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - October 10, 2019 Category: Chemistry Authors: Liu W, Wang X, Zhu H, Duan Y Tags: Curr Top Med Chem Source Type: research

Anti-Cancer Drug Discovery: Structure, Function and Novel Strategy - Part-II.
Abstract PMID: 31592751 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - October 10, 2019 Category: Chemistry Authors: Thakur SS Tags: Curr Top Med Chem Source Type: research

Advances in Dopamine D1 Receptor Ligands for Neurotherapeutics.
Abstract The dopamine D1 receptor (D1R) is essential for neurotransmission in various brain pathways where it modulates key functions including voluntary movement, memory, attention and reward. Not surprisingly, the D1R has been validated as a promising drug target for over 40 years and selective activation of this receptor may provide novel neurotherapeutics for neurodegenerative and neuropsychiatric disorders. Several pharmacokinetic challenges with previously identified small molecule D1R agonists have been recently overcome with the discovery and advancement of new ligands, including drug-like non-catechol D1R...
Source: Current Topics in Medicinal Chemistry - September 27, 2019 Category: Chemistry Authors: Felsing DE, Jain MK, Allen JA Tags: Curr Top Med Chem Source Type: research

The Advance in Important Target Proteins.
Abstract PMID: 31526338 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - September 20, 2019 Category: Chemistry Authors: Duan Y, Zhu H Tags: Curr Top Med Chem Source Type: research

Recent Progress in the Development of Small Molecule c-Met Inhibitors.
Abstract C-Met, also referred to as Hepatocyte Growth Factor Receptor (HGFR), is a heterodimeric receptor tyrosine kinase. It has been determined that c-Met gene mutations, overexpression, and amplification also occur in a variety of human tumor types, and these events are closely related to the aberrant activation of the HGF/c-Met signaling pathway. Meanwhile, high c-Met expression is closely associated with poor prognosis in cancer patients. The c-Met kinase has emerged as an attractive target for developing antitumor agents. In this review, we cover the recent advances on the small molecule c-Met inhibitors dis...
Source: Current Topics in Medicinal Chemistry - September 20, 2019 Category: Chemistry Authors: Lv PC, Yang YS, Wang ZC Tags: Curr Top Med Chem Source Type: research

Recent Advances in Medicinal Chemistry to Treat Filariasis and Helminthiasis.
Abstract PMID: 31509098 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - September 13, 2019 Category: Chemistry Authors: Srivastava SK Tags: Curr Top Med Chem Source Type: research

Bioactive Natural and Synthetic Peroxides for the Treatment of Helminth and Protozoan Pathogens: Synthesis and Properties.
Abstract The significant spread of helminth and protozoan infections, the uncontrolled intake of the known drugs by a large population, the emergence of resistant forms of pathogens have prompted people to search for alternative drugs. In this review, we have focused attention on structures and synthesis of peroxides active against parasites causing neglected tropical diseases and toxoplasmosis. To date, promising active natural, semi-synthetic and synthetic peroxides compounds have been found. PMID: 31509099 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - September 13, 2019 Category: Chemistry Authors: Vil' VA, Terent'ev AO, Mulina OM Tags: Curr Top Med Chem Source Type: research

Prospects of Utilizing Computational Techniques for the Treatment of Human Diseases.
Abstract PMID: 31490742 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - September 8, 2019 Category: Chemistry Authors: Nayarisseri A Tags: Curr Top Med Chem Source Type: research

Epigenetic Regulation and Drug Discovery for Cancer Therapy.
Abstract PMID: 31486748 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - September 7, 2019 Category: Chemistry Authors: Yu B, Ouyang L Tags: Curr Top Med Chem Source Type: research

KRAS: A promising therapeutic target for cancer treatment.
Abstract Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the most commonly mutated oncogene in human cancer. The developments of many cancers depend on sustained expression and signaling of KRAS, which makes KRAS a high-priority therapeutic target. Scientists have not successfully developed drugs that target KRAS, although efforts have been made last three decades. In this review, we highlight the emerging experimental strategies of impairing KRAS membrane localization and the direct targeting of KRAS. We also conclude the combinatorial therapies and RNA interference technology for treatment of KRAS mutant ...
Source: Current Topics in Medicinal Chemistry - September 5, 2019 Category: Chemistry Authors: Wu HZ, Xiao JQ, Xiao SS, Cheng Y Tags: Curr Top Med Chem Source Type: research

Overview of Current Immunotherapies Targeting Mutated KRAS Cancers.
Abstract The occurrence of somatic substitution mutations of the KRAS proto-oncogene are highly prevalent in certain cancer types, which often leads to constant activation of proliferative pathways and subsequent neoplastic transformation. It is often seen as a gateway mutation in carcinogenesis, and has been commonly deemed as a predictive biomarker for poor prognosis and relapse when conventional chemotherapeutics are employed. Additionally, its mutational status also renders EGFR targeted therapies ineffective owing to its downstream location. Efforts to discover new approaches targeting this menacing culprit h...
Source: Current Topics in Medicinal Chemistry - September 4, 2019 Category: Chemistry Authors: Hoo WPY, Siak PY, In LLA Tags: Curr Top Med Chem Source Type: research

Targeting Mutant KRAS for Anticancer Therapy.
Abstract Over the past decades, designing therapeutic strategies to target KRAS-mutant cancers, which is one of the most frequent mutant oncogenes among all cancer types, have proven unsuccessful regardless of many concerted attempts. There are key challenges for KRAS-mutant anticancer therapy, as the complex cellular processes involved in KRAS signaling has present. Herein we highlight the emerging therapeutic approaches for inhibiting KRAS signaling and blocking KRAS functions, in hope to serve as a more effective guideline for future development of therapeutics. PMID: 31475898 [PubMed - as supplied by publ...
Source: Current Topics in Medicinal Chemistry - September 2, 2019 Category: Chemistry Authors: Chen F, Alphonse MP, Liu Y, Liu Q Tags: Curr Top Med Chem Source Type: research

Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors.
Abstract The Ras proteins play an important role in cell growth, differentiation, proliferation and survival by regulating diverse signaling pathways. Oncogenic mutant K-Ras is the most frequently mutated class of Ras superfamily and highly prevalent in many human cancers. Despite intensive efforts to combat various K-Ras-mutant-driven cancers, no effective K-Ras-specific inhibitors have yet been approved for clinical use to date. Since K-Ras proteins must be associated to the plasma membrane for their function, targeting K-Ras plasma membrane localization represents a logical and potentially tractable therapeutic...
Source: Current Topics in Medicinal Chemistry - September 2, 2019 Category: Chemistry Authors: Ye N, Xu Q, Li W, Wang P, Zhou J Tags: Curr Top Med Chem Source Type: research

Drug Combinatorial Therapies for Treatment of KRAS Mutated Lung Cancers.
Abstract KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS has proven to be challenging. The mutations of KRAS are associated with poor prognosis, resistance to both adjuvant therapy and targeted EGFR TKI. The EGFR TKI provide significant clinical benefit for patients whose tumors bear EGFR mutations. However, tumors with KRAS mutations rarely respond to EGFR TKI therapy. Thus, the combination therapy is essential for the treatment of lung cancers with KRAS mutations. EGFR TKI combined with inhibitors of MAPKs, PI3K/mTOR, HDAC, Wee1, PARP, CDK and Hsp90, even m...
Source: Current Topics in Medicinal Chemistry - September 2, 2019 Category: Chemistry Authors: He H, Xu C, Cheng Z, Qian X, Zheng L Tags: Curr Top Med Chem Source Type: research

Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) mutations in the occurrence and treatment of pancreatic cancer.
Kirsten Rat Sarcoma Viral Oncogene Homologue(KRAS) mutations in the occurrence and treatment of pancreatic cancer. Curr Top Med Chem. 2019 Aug 28;: Authors: Zhu Z, Xiao S, Hao H, Hou Q, Fu X Abstract Pancreatic cancer is a highly malignant tumor with a 5-year survival rate of less than 6% and incidence increasing year by year in global. Pancreatic cancer has a poor prognosis and a high recurrence rate almost same as the death rate. However, the effective available prevention and treatment measures for pancreatic cancer were still limited. The genome variation is one of the main reasons for the occ...
Source: Current Topics in Medicinal Chemistry - August 28, 2019 Category: Chemistry Authors: Zhu Z, Xiao S, Hao H, Hou Q, Fu X Tags: Curr Top Med Chem Source Type: research

Mechanisms of protective effects of SGLT2 inhibitors in cardiovascular disease and renal dysfunction.
Abstract Type 2 diabetes mellitus is one of the most common form of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160g daily of glucose in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes lead to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular uptake glucose as a fundamental process for homeostasis, growth, and metabolism. In human, three families of glucose transport...
Source: Current Topics in Medicinal Chemistry - August 28, 2019 Category: Chemistry Authors: Liu B, Wang Y, Zhang Y, Yan B Tags: Curr Top Med Chem Source Type: research

The Application of the RNA Interference Technologies for KRAS: Current Status, Future Perspective and Associated Challenges.
Abstract KRAS is a member of the murine sarcoma virus oncogene-RAS gene family. It plays an important role in the prevention, diagnosis and treatment of tumors during tumor cell growth and angiogenesis. KRAS is the most commonly mutated oncogene in human cancers, such as the pancreatic cancers, colon cancers, and lung cancers. Detection of KRAS gene mutation is an important indicator for tracking the status of oncogenes, illuminating the developmental prognosis of various cancers, and the efficacy of radiotherapy and chemotherapy. However, the efficacy of different patients in clinical treatment is not the same. S...
Source: Current Topics in Medicinal Chemistry - August 28, 2019 Category: Chemistry Authors: Shao YT, Ma L, Zhang TH, Xu TR, Ye YC, Liu Y Tags: Curr Top Med Chem Source Type: research

Therapeutic progress and knowledge basis about natriuretic peptide system in heart failure.
Abstract Notwithstanding substantial improvements in diagnosis and treatment, heart failure (HF) remains a major disease burden with high prevalence and poor outcomes worldwide. Natriuretic peptides (NPs) modulate whole cardiovascular system and exhibit multiple cardio-protective effects, including the counteraction of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), promotion of vasodilatation and natriuresis, and inhibition of hypertrophy and fibrosis. Novel pharmacological therapies based on NPs may achieve a valuable shift in managing patients with HF from inhibiting RAAS and S...
Source: Current Topics in Medicinal Chemistry - August 26, 2019 Category: Chemistry Authors: Fu S, Chang Z, Luo L, Deng J Tags: Curr Top Med Chem Source Type: research

Virtual Screening Techniques in Drug Discovery: Review and Recent Applications.
Abstract The discovery of bioactive molecules is an expensive and time-consuming process and new strategies are continuously searched for in order to optimize this process. Virtual screening (VS) is one of the recent strategies that has been explored for the identification of candidate bioactive molecules. The number of new techniques and software that employ this strategy has grown considerably in recent years, so, before their use, it is necessary to understand the basics an also the limitations behind each one to get the most out of them. It is also necessary to assess the real contributions of this strategy so...
Source: Current Topics in Medicinal Chemistry - August 15, 2019 Category: Chemistry Authors: da Silva Rocha SFL, Olanda CG, Fokoue HH, Sant Anna CMR Tags: Curr Top Med Chem Source Type: research

Targeting Histone Lysine Demethylase LSD1/KDM1A as a New Avenue for Cancer Therapy.
Abstract PMID: 31389779 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - August 9, 2019 Category: Chemistry Authors: Fang Y, Liao G, Yu B Tags: Curr Top Med Chem Source Type: research

New Experimental and Computational Tools for Drug Discovery. - Part-VII.
iacute;az H Abstract PMID: 31389780 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - August 9, 2019 Category: Chemistry Authors: Scotti MT, Muratov EN, González-Díaz H Tags: Curr Top Med Chem Source Type: research

Fragment Based Approaches for Allosteric Metabotropic Glutamate Receptor (mGluR) Modulators.
ű GM Abstract Metabotropic glutamate receptors (mGluR) are members of the class C G-protein coupled receptors (GPCR-s) and have eight subtypes. These receptors are responsible for a variety of functions in the central and peripheral nervous systems and their modulation has therapeutic utility in neurological and psychiatric disorders. It was previously established that selective orthosteric modulation of these receptors is challenging, and this stimulated the search for allosteric modulators. Fragment Based Drug Discovery (FBDD) is a viable approach to find ligands binding at allosteric sites owing to their limit...
Source: Current Topics in Medicinal Chemistry - August 8, 2019 Category: Chemistry Authors: Orgován Z, Ferenczy GG, Keserű GM Tags: Curr Top Med Chem Source Type: research

microRNAs in Cardiovascular Disease: Small Molecules but Big Roles.
Abstract microRNAs (miRNAs) are an evolutionarily conserved class of small single-stranded noncoding RNAs. The aberrant expression of specific miRNAs has been implicated in the development and progression of diverse cardiovascular diseases. For many decades, miRNA therapeutics has flourished, taking advantage of the fact that miRNAs can modulate gene expression and control cellular phenotypes at the posttranscriptional level. Genetic replacement or knockdown of target miRNAs by chemical molecules, referred to as miRNA mimics or inhibitors, has been used to reverse their abnormal expression as well as their adverse...
Source: Current Topics in Medicinal Chemistry - August 8, 2019 Category: Chemistry Authors: Yan B, Wang H, Tan Y, Fu W Tags: Curr Top Med Chem Source Type: research

Homologation: A versatile molecular modification strategy to drug discovery.
Abstract Homologation is a concept introduced by Gerhard in 1853 to describe homologous series into organic chemistry. Since then the concept has been adapted and used in Medicinal Chemistry as one of the most important strategies for molecular modification. The homologation types, their influence on physico-chemical properties and molecular conformation will be presented and discussed. Its application in lead-identification and lead optimization steps, as well as its impact on pharmacodynamics and pharmacokinetic properties will be highlighted from selected examples. PMID: 31393250 [PubMed - as supplied by p...
Source: Current Topics in Medicinal Chemistry - August 8, 2019 Category: Chemistry Authors: Lima LM, Alves MA, do Amaral DN Tags: Curr Top Med Chem Source Type: research

Role of Botanicals/Endophytic Compounds in Modulation of Multidrug Transporters.
Abstract PMID: 31362649 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - August 2, 2019 Category: Chemistry Authors: Dwivedi GR Tags: Curr Top Med Chem Source Type: research

Renal Alterations Induced by the Venom of Colombian Scorpion Centruroides margaritatus.
CONCLUSION: Our results suggest that C. margaritatus venom can trigger renal impairment, mainly in the proximal kidney tubule. PMID: 31364515 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 31, 2019 Category: Chemistry Authors: Galíndez-Cerón JD, Jorge RJB, Chavez-Acosta MH, Jorge ARC, Alves NTQ, Prata MMG, de Paulo Rodrigues FA, Havt A, Sampaio TL, Martins AMC, Guerrero-Vargas JA, Monteiro HSA, Vidal JTB Tags: Curr Top Med Chem Source Type: research

Untangling the Metabolic Reprogramming in Brain Cancer: Discovering Key Molecular Players Using Mass Spectrometry.
Abstract Cells metabolism alteration is the new hallmark of cancer as well as the way for carcinogenesis investigation. It is well known that malignant cells switch to aerobic glycolysis pathway occurring also in healthy proliferating cells. Recently, it was shown that in malignant cells, intracellular fatty acids synthesis replace dietary fatty acids which change cancer cells lipid composition noticeably. These alterations in energy metabolism and structural lipid production explain the high proliferation rate of malignant tissues. However, metabolic reprogramming affects not only lipid metabolism but many of the...
Source: Current Topics in Medicinal Chemistry - July 29, 2019 Category: Chemistry Authors: Sorokin A, Shurkhay V, Pekov S, Zhvansky E, Ivanov D, Kulikov EE, Popov I, Potapov A, Nikolaev E Tags: Curr Top Med Chem Source Type: research

Achievement in cancer research and its therapeutics in hundred years.
Abstract Cancer research has progressed leaps and bounds over the years. This review is a brief overview of the cancer research, milestone achievements and its therapeutic studies over the one hundred ten years which would give us an insight of how far we have come to understand and combat this fatal disease leading to millions of deaths worldwide. Modern biology has proved cancer is very complex process still we do not know precisely how it triggers. It involves several factors such as proto-oncogene, oncogene, kinase, tumor suppressor gene, growth factor, signalling cascade, micro RNA, SiRNA, immunity, environme...
Source: Current Topics in Medicinal Chemistry - July 29, 2019 Category: Chemistry Authors: Shastri S, Chatterjee B, Thakur SS Tags: Curr Top Med Chem Source Type: research

Venoms and isolated toxins from snakes of medical impact in the Northeast Argentina: State of the art. Potential pharmacological applications.
usco L, Leiva LCA Abstract Among the ophidians that inhabit the Northeast of Argentina, the genus Bothrops such as B. alternatus and B. diporus species (also known as yararás) and Crotalus durisus terrificus (named cascabel), represent the most studied snake venom for more than thirty years. These two genera of venomous snakes account for the majority of poisonous snake envenomations and therefore constitute a medical emergency in this region. This review presents a broad description of the compiled knowledge about venomous snakebite: its pathophysiological action, protein composition, isolated toxins, toxi...
Source: Current Topics in Medicinal Chemistry - July 24, 2019 Category: Chemistry Authors: Garcia Denegri ME, Bustillo S, Gay CC, Van De Velde A, Gomez G, Echeverría S, Gauna Pereira MDC, Maruñak S, Nuñez S, Bogado F, Sanchez M, Teibler GP, Fusco L, Leiva LCA Tags: Curr Top Med Chem Source Type: research

Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening.
CONCLUSION: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA PLA2s. PMID: 31345152 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 24, 2019 Category: Chemistry Authors: Sobrinho JC, Francisco AF, Simões-Silva R, Kayano AM, Alfonso JJ, Gomez AF, Arruda A, Ferreira AS, Santos APA, Luiz MB, Teles CBG, Pereira SS, Zanchi FB, Calderon LA, Zuliani JP, Soares AM Tags: Curr Top Med Chem Source Type: research

Utilization of the Plant Clusia fluminensis Planch & Triana Against Some Toxic Activities of the Venom of Bothrops jararaca and B. jararacussu Snake Venom Toxic activities.
CONCLUSION: Antivenom properties of C. fluminensis extracts deserve further investigation in order to gain detailed knowledge regarding the neutralization profile of these extracts. PMID: 31339072 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 24, 2019 Category: Chemistry Authors: da Silva AR, Anholeti MC, Pietroluongo M, Sanchez EF, Valverde AL, de Paiva SR, Figueiredo MR, Kaplan MAC, Fuly AL Tags: Curr Top Med Chem Source Type: research

Plants and phytocompounds active against Bothrops venoms.
es RM Abstract Snakebite envenomation is an important health problem in tropical countries, with severe human and social consequences. In Latin America, the Bothrops species constitutes the main threat to humans, and the envenomation caused by these species quickly develop into severe local tissue damage, including swelling, hemorrhaging, myonecrosis, skin ulceration, and pain. The systemic effects of envenomation are usually neutralized by antivenom serum therapy, despite its intrinsic risks. However, neutralization of local tissue damage remains a challenge. To improve actual therapy, two major alternatives are ...
Source: Current Topics in Medicinal Chemistry - July 23, 2019 Category: Chemistry Authors: Jorge RJB, Martins RD, Araújo RM, da Silva MA, Monteiro HSA, Ximenes RM Tags: Curr Top Med Chem Source Type: research

Isolation, biochemical characterization and antiparasitic activity of BmatTX-IV, a basic Lys49-phospholipase A2 from the venom of Bothrops mattogrossensis from Paraguay.
CONCLUSION: Physicochemical and biological characterization of snake venoms components is critically important, since these complex mixtures provide a source of molecules with antiparasitic potential, making further studies necessary to identify and characterize components with higher efficacy and selectivity. PMID: 31340737 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 23, 2019 Category: Chemistry Authors: Alfonso JJ, Kayanoa AM, Garay AFG, Simões-Silva R, Sobrinho JC, Vourliotis S, Soares AM, Calderon LA, Gómez MCV Tags: Curr Top Med Chem Source Type: research

The Anthelmintic effect on Strongyloides venezuelensis induced by BnSP-6, a Lys49-phospholipase A2 homologue from Bothrops pauloensis venom.
CONCLUSION: Altogether, our results shed light on the potential of BNSP-6 as an anthelmintic agent, which can lead to further investigations as a tool for pharmaceutical discoveries. PMID: 31340738 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 23, 2019 Category: Chemistry Authors: Rodrigues JP, Vasconcelos Azevedo FVP, Zoia MAP, Maia LP, Correia LIV, Costa-Cruz JM, de Melo Rodrigues V, Goulart LR Tags: Curr Top Med Chem Source Type: research

Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.
Abstract The serotonin (5-HT) 5-HT2C receptor (5-HT2CR) is recognized as a critical mediator of disease-related pathways and behaviors based upon actions in the central nervous system (CNS). Since the 5-HT2CR is a class A G protein-coupled receptor (GPCR), drug discovery efforts have traditionally pursued activation of the receptor through synthetic ligands with agonists proposed for treatment of obesity, substance use disorders and impulse control disorders while antagonists may add value in the treatment of anxiety, depression and schizophrenia. The most significant agonist discovery to date is the FDA-approved ...
Source: Current Topics in Medicinal Chemistry - July 8, 2019 Category: Chemistry Authors: Wold EA, Wild CT, Cunningham KA, Zhou J Tags: Curr Top Med Chem Source Type: research

PET Imaging of Adenosine Receptors in Diseases.
Abstract Adenosine receptors (ARs) are a class of purinergic G-protein-coupled receptors (GPCRs). Extracellular adenosine is a pivotal regulation molecule that adjusts physiological function through the interaction with four ARs: A1R, A2AR, A2BR, and A3R. Alterations of ARs function and expression have been studied in neurological diseases (epilepsy, Alzheimer's disease, and Parkinson's disease), cardiovascular diseases, cancer, and inflammation and autoimmune diseases. A series of positron emission tomography (PET) probes for imaging ARs have been developed. The PET imaging probes have provided valuable informati...
Source: Current Topics in Medicinal Chemistry - July 8, 2019 Category: Chemistry Authors: Li J, Hong X, Li G, Conti PS, Zhang X, Chen K Tags: Curr Top Med Chem Source Type: research

Targeting the PAC1 Receptor for Neurological and Metabolic Disorders.
Abstract The pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor (PAC1R, ADCYAP1R1) is a member of the vasoactive intestinal peptide (VIP)/secretin/glucagon family of G protein-coupled receptors (GPCRs). PAC1R has been shown to play crucial roles in the central and peripheral nervous systems. The activation of PAC1R initiates diverse downstream signal transduction pathways, including adenylyl cyclase, phospholipase C, MEK/ERK and Akt pathways that regulate a number of physiological systems to maintain functional homeostasis. Accordingly, at times of tissue injury or insult, PACAP/PAC...
Source: Current Topics in Medicinal Chemistry - July 8, 2019 Category: Chemistry Authors: Liao C, de Molliens MP, Schneebeli ST, Brewer M, Song G, Chatenet D, Braas KM, May V, Li J Tags: Curr Top Med Chem Source Type: research

Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: Current approaches for therapeutics development.
Abstract The cannabinoid receptor 1 (CBR1) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eve...
Source: Current Topics in Medicinal Chemistry - July 8, 2019 Category: Chemistry Authors: Nguyen T, Thomas BF, Zhang Y Tags: Curr Top Med Chem Source Type: research

Recent Advances in Medicinal Chemistry to Treat Tuberculosis - Part-II.
Abstract PMID: 31274062 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 6, 2019 Category: Chemistry Authors: Srivastava SK Tags: Curr Top Med Chem Source Type: research

DNA Damaging Agents in Cancer Therapy.
Abstract PMID: 31274063 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - July 6, 2019 Category: Chemistry Authors: You F, Gao C Tags: Curr Top Med Chem Source Type: research

Recent Advances of Small Molecular Regulators Targeting G Protein-Coupled Receptors Family for Oncology Immunotherapy.
Abstract The great clinical successes of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggest the draw of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms that exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G protein-coupled receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, histamine...
Source: Current Topics in Medicinal Chemistry - June 28, 2019 Category: Chemistry Authors: He P, Zhou W, Liu M, Chen Y Tags: Curr Top Med Chem Source Type: research

5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation.
CONCLUSION: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies. PMID: 31223089 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - June 21, 2019 Category: Chemistry Authors: Roque Marques KM, do Desterro MR, de Arruda SM, de-Araújo Neto LN, de Lima MDCA, de Almeida SMV, Silva ECDD, Aquino TM, Júnior EFDS, Júnior JXD, Silva MM, de A Dantas MD, C Santos JC, Figueiredo IM, Bazin MA, Marchand P, da Silva TG, Mendonça Junior F Tags: Curr Top Med Chem Source Type: research

Vanillin-Related N-Acylhydrazones: Synthesis, Antischistosomal Properties and Target Fishing Studies.
CONCLUSION: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials. PMID: 31223088 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - June 20, 2019 Category: Chemistry Authors: Moraes J, Rando DGG, da Costa MOL, Pavani TFA, Oliveira T, Santos PFD, Amorim CR, Pinto PLS, Brito MG, Silva MPN, Roquini DB Tags: Curr Top Med Chem Source Type: research

In Vitro And In Vivo Antifilarial Activity Of Standardized Extract Of Calotropis procera Flowers Against Brugia malayi.
CONCLUSION: Flowers of C. procera have definite microfilaricidal and macrofilaricidal activity. Whether this activity is due to lupeol, β-sitosterol and triacontanol found in the hexane fraction remains to be investigated. This is the first report on antifilarial efficacy of flowers of the plant C. procera. PMID: 31218959 [PubMed - as supplied by publisher] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - June 20, 2019 Category: Chemistry Authors: Murthy PK, Kushwaha V, Rastogi S, Pandey MM, Saxena K, Khatoon S, Rawat AKS Tags: Curr Top Med Chem Source Type: research

STAT3: A Potential Drug Target for Tumor and Inflammation.
Abstract STAT (Signal transducers and activators of transcription) is a cellular signal transcription factor involved in the regulation of many cellular activities, such as cell differentiation, proliferation, angiogenesis in normal cells. During the study of the STAT family, STAT3 was found to be involved in many diseases, such as high expression and sustained activation of STAT3 in tumor cells, promoting tumor growth and proliferation. In the study of inflammation, it was found that it plays an important role in anti-inflammatory and repairing damage tissue. Because of the important role of STAT3, a large number...
Source: Current Topics in Medicinal Chemistry - June 20, 2019 Category: Chemistry Authors: Hu YS, Han X, Liu XH Tags: Curr Top Med Chem Source Type: research

Research progress of Axl inhibitors.
Abstract Axl, a receptor tyrosine kinase (RTK) belonging to the TAM (Axl, Mer, Tyro3) family, participates in many signal transduction cascades after mostly stimulated by Growth arrest-specific 6(Gas6). Axl is widely expressed in many organs, such as macrophages, endothelial cells, heart, liver and skeletal muscle. Over-expression and activation of Axl are associated with promoting chemotherapy resistance, cell proliferation, invasion and metastasis in many human cancers, such as breast, lung, and pancreatic cancers. Therefore, the research and development of Axl inhibitors is of great significance to strengthen t...
Source: Current Topics in Medicinal Chemistry - June 20, 2019 Category: Chemistry Authors: Sun ZG, Zhang JM, Qian Y Tags: Curr Top Med Chem Source Type: research

Current Challenges and Updates on the Therapy of Fungal Infections.
Abstract PMID: 31210103 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - June 19, 2019 Category: Chemistry Authors: Silva LN, de Mello TP, de Souza Ramos L, Branquinha MH, Dos Santos ALS Tags: Curr Top Med Chem Source Type: research

Design and Development of Drugs Targeting Protein-Protein Interactions - Part-II.
Abstract PMID: 31210104 [PubMed - in process] (Source: Current Topics in Medicinal Chemistry)
Source: Current Topics in Medicinal Chemistry - June 19, 2019 Category: Chemistry Authors: Gupta SP Tags: Curr Top Med Chem Source Type: research