Displaying publications 1 - 20 of 40 in total

  1. Hassan MZ, Osman H, Ali MA, Ahsan MJ
    Eur J Med Chem, 2016 Nov 10;123:236-255.
    PMID: 27484512 DOI: 10.1016/j.ejmech.2016.07.056
    Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure-activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.
    Matched MeSH terms: Molecular Targeted Therapy
  2. Abdullah B
    Biomed Imaging Interv J, 2006 Oct;2(4):e28.
    PMID: 21614327 MyJurnal DOI: 10.2349/biij.2.4.e28
    Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas.
    Matched MeSH terms: Molecular Targeted Therapy
  3. Abdullah JM, Mustafa Z, Ideris A
    Biomed Res Int, 2014;2014:386470.
    PMID: 25243137 DOI: 10.1155/2014/386470
    Glioblastoma multiforme (GBM), or grade IV glioma, is one of the most lethal forms of human brain cancer. Current bioscience has begun to depict more clearly the signalling pathways that are responsible for high-grade glioma initiation, migration, and invasion, opening the door for molecular-based targeted therapy. As such, the application of viruses such as Newcastle disease virus (NDV) as a novel biological bullet to specifically target aberrant signalling in GBM has brought new hope. The abnormal proliferation and aggressive invasion behaviour of GBM is reported to be associated with aberrant Rac1 protein signalling. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process. Ultimately, intracellular stress leads the infected glioma cell to undergo cell death. In this review, we describe the characteristics of malignant glioma and the aberrant genetics that drive its aggressive phenotype, and we focus on the use of oncolytic NDV in GBM-targeted therapy and the interaction of NDV in GBM signalling that leads to inhibition of GBM proliferation and invasion, and subsequently, cell death.
    Matched MeSH terms: Molecular Targeted Therapy*
  4. Lim SH, Wu L, Kiew LV, Chung LY, Burgess K, Lee HB
    PLoS ONE, 2014;9(3):e82934.
    PMID: 24622277 DOI: 10.1371/journal.pone.0082934
    Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = -7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.
    Matched MeSH terms: Molecular Targeted Therapy*
  5. Pandurangan AK, Esa NM
    Asian Pac. J. Cancer Prev., 2014;15(2):551-60.
    PMID: 24568457
    Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)- κB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, Wnt/β-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.
    Matched MeSH terms: Molecular Targeted Therapy*
  6. Warrier S, Marimuthu R, Sekhar S, Bhuvanalakshmi G, Arfuso F, Das AK, et al.
    Int. J. Biochem. Cell Biol., 2016 06;75:104-11.
    PMID: 27063405 DOI: 10.1016/j.biocel.2016.04.002
    The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated. A wide acting family of Wnt mediators, secreted frizzled-related proteins (sFRPs), has not been probed so far as molecular indicators of disease occurrence and progression of Alzheimer's. Unlike the effect of the Dickkopf (DKK) family of Wnt antagonists on AD, the sFRP molecules have a more pleiotropic impact on the Wnt signaling cascade and probably have a far-reaching involvement in neurodegeneration. The role of sFRPs has been poorly described in AD, and in this review, we analyze the present status of the role of sFRPs on neurodegeneration, their likely involvement, and potential implications in treatment modalities of AD. This information would provide valuable clues for the development of potential therapeutic targets for aberrant neurodegenerative disorders.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  7. Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ
    Eur. J. Pharmacol., 2015 Sep 15;763(Pt A):104-14.
    PMID: 25987420 DOI: 10.1016/j.ejphar.2015.04.056
    The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  8. Yeong CH, Cheng MH, Ng KH
    J Zhejiang Univ Sci B, 2014 Oct;15(10):845-63.
    PMID: 25294374 DOI: 10.1631/jzus.B1400131
    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.
    Matched MeSH terms: Molecular Targeted Therapy/trends*
  9. Sabetian S, Shamsir MS
    BMC Syst Biol, 2015;9:37.
    PMID: 26187737 DOI: 10.1186/s12918-015-0186-7
    Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process. The main purpose of this study is to identify putative drug targets for human sperm-egg interaction deficiency and consider if the detected essential proteins are targets for any known drugs using protein-protein interaction network and ingenuity pathway analysis.
    Matched MeSH terms: Molecular Targeted Therapy*
  10. Jalil MA, Suwanpayak N, Kulsirirat K, Suttirak S, Ali J, Yupapin PP
    Int J Nanomedicine, 2011;6:2925-32.
    PMID: 22131837 DOI: 10.2147/IJN.S26266
    A novel nanomicro syringe system was proposed for drug storage and delivery using a PANDA ring resonator and atomic buffer. A PANDA ring is a modified optical add/drop filter, named after the well known Chinese bear. In principle, the molecule/drug is trapped by the force generated by different combinations of gradient fields and scattering photons within the PANDA ring. A nanomicro needle system can be formed by optical vortices in the liquid core waveguide which can be embedded on a chip, and can be used for long-term treatment. By using intense optical vortices, the required genes/molecules can be trapped and transported dynamically to the intended destinations via the nanomicro syringe, which is available for drug delivery to target tissues, in particular tumors. The advantage of the proposed system is that by confining the treatment area, the effect can be decreased. The use of different optical vortices for therapeutic efficiency is also discussed.
    Matched MeSH terms: Molecular Targeted Therapy/instrumentation*
  11. Lee JJ, Saiful Yazan L, Che Abdullah CA
    Int J Nanomedicine, 2017;12:2373-2384.
    PMID: 28392694 DOI: 10.2147/IJN.S127329
    Breast cancer is the most common malignancy worldwide, especially among women, with substantial after-treatment effects. The survival rates of breast cancer have decreased over the years even with the existence of various therapeutic strategies, specifically, chemotherapy. Clinical drugs administered for breast cancer appear to be non-targeting to specific cancer sites leading to severe side effects and potentially harming healthy cells instead of just killing cancer cells. This leads to the need for designing a targeted drug delivery system. Nanomaterials, both organic and inorganic, are potential drug nanocarriers with the ability of targeting, imaging and tracking. Various types of nanomaterials have been actively researched together with their drug conjugate. In this review, we focus on selected nanomaterials, namely solid-lipid, liposomal, polymeric, magnetic nanoparticles, quantum dots, and carbon nanotubes and their drug conjugates, for breast cancer studies. Their advantages, disadvantages and previously conducted studies were highlighted.
    Matched MeSH terms: Molecular Targeted Therapy*
  12. Lee YT, Tan YJ, Oon CE
    Eur. J. Pharmacol., 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
    Matched MeSH terms: Molecular Targeted Therapy/methods*
  13. Ingle PV, Samsudin SZ, Chan PQ, Ng MK, Heng LX, Yap SC, et al.
    Ther Clin Risk Manag, 2016;12:445-55.
    PMID: 27042086 DOI: 10.2147/TCRM.S92377
    This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions.
    Matched MeSH terms: Molecular Targeted Therapy
  14. Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.
    Curr. Pharm. Des., 2014;20(21):3428-44.
    PMID: 24001228
    Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.
    Matched MeSH terms: Molecular Targeted Therapy/methods
  15. Fatemian T, Chowdhury EH
    Curr Cancer Drug Targets, 2014;14(7):599-609.
    PMID: 25308718
    Malfunctions in membrane transporters or disruptions in signaling cascades induce resistance to chemotherapy in cancer cells resulting in treatment failure. To adjust the genetic alterations leading to these cellular protective measures, dissection and verification of the contributing routes would be required. In justification of knockdown of the key genes, RNA interference provides a reliable probing tool, enabling exploration of phenotypic manifestation of targeted genes. Investigation of the non-transporter targets, predominantly oncogenes and tumor suppressor genes, by means of small interfering RNA with the aim to re-sensitize cancer cells to therapeutics will be discussed in this review.
    Matched MeSH terms: Molecular Targeted Therapy*
  16. Ong SB, Katwadi K, Kwek XY, Ismail NI, Chinda K, Ong SG, et al.
    Expert Opin. Ther. Targets, 2018 03;22(3):247-261.
    PMID: 29417868 DOI: 10.1080/14728222.2018.1439015
    INTRODUCTION: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI. Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI. Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.
    Matched MeSH terms: Molecular Targeted Therapy*
  17. Rapalli VK, Singhvi G, Dubey SK, Gupta G, Chellappan DK, Dua K
    Biomed. Pharmacother., 2018 Oct;106:707-713.
    PMID: 29990862 DOI: 10.1016/j.biopha.2018.06.136
    Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
    Matched MeSH terms: Molecular Targeted Therapy/adverse effects; Molecular Targeted Therapy/methods*
  18. Rasouli M, Ahmad Z, Omar AR, Allaudin ZN
    BMC Biotechnol., 2011 Nov 03;11:99.
    PMID: 22047106 DOI: 10.1186/1472-6750-11-99
    BACKGROUND: Diabetes mellitus is a complicated disease with a pathophysiology that includes hyperinsulinemia, hyperglycemia and other metabolic impairments leading to many clinical complications. It is necessary to develop appropriate treatments to manage the disease and reduce possible acute and chronic side effects. The advent of gene therapy has generated excitement in the medical world for the possible application of gene therapy in the treatment of diabetes. The glucagon-like peptide-1 (GLP-1) promoter, which is recognised by gut L-cells, is an appealing candidate for gene therapy purposes. The specific properties of L-cells suggest that L-cells and the GLP-1 promoter would be useful for diabetes therapy approaches.

    RESULTS: In this study, L-cells were isolated from a primary intestinal cell line to create suitable target cells for insulin expression studies. The isolated cells displayed L-cell properties and were therefore used as an L-cell surrogate. Next, the isolated L-cells were transfected with the recombinant plasmid consisting of an insulin gene located downstream of the GLP-1 promoter. The secretion tests revealed that an increase in glucose concentration from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold. Furthermore, L-cells quickly responded to the glucose stimulation; the amount of insulin protein increased 2-fold in the first 30 minutes and then reached a plateau after 90 minutes.

    CONCLUSION: Our data showed that L-cells efficiently produced the mature insulin protein. In addition, the insulin protein secretion was positively regulated with glucose induction. In conclusion, GLP-1 promoter and L-cell could be potential candidates for diabetes gene therapy agents.

    Matched MeSH terms: Molecular Targeted Therapy*
  19. Chaudhry GE, Jan R, Mohamad H, Tengku Muhammad TS
    Res Pharm Sci, 2019 Jun;14(3):273-285.
    PMID: 31160905 DOI: 10.4103/1735-5362.258496
    Breast cancer is amongst frequently diagnosed cancer type throughout the world. Due to reduced efficacy of current chemotherapeutics, several natural products have been screened for better alternatives. The cytotoxic activity of fractions prepared from leaves extract of Vitex rotundifolia (V. rotundifolia) on human breast cancer cell line, MCF-7 was studied. The fractions F1, F2, F3, and F5 of V. rotundifolia produced concentration-dependent cytotoxic effects on MCF-7 cell line. The relative potential of cytotoxicity of the fractions on MCF-7 cell line was found to be F3 > F2 > F5 > F1. The active fractions induce apoptosis in MCF-7 cell line determined by annexin V base assay. The phosphatidylserine externalization and the presence of DNA fragmentation in treated cells confirms the early and late apoptosis in treated cells. The V. rotundifolia fractions induced apoptosis by both pathways; extrinsic pathways via activation of caspase-8 and intrinsic pathways through enhanced bax/bcl-2 ratio and activation of caspase-3/7 and caspase-9 proapoptotic proteins. Furthermore, chemical profiling indicates various phenolic, flavonoids, and terpenoids compounds in the active fractions. Thus, V. rotundifolia might be a suitable candidate to investigate further and develop molecular targeted cancer therapeutics by understanding the fundamental mechanisms involved in the regulation of cell death in cancer cells.
    Matched MeSH terms: Molecular Targeted Therapy
  20. Yusuf M, Konc J, Sy Bing C, Trykowska Konc J, Ahmad Khairudin NB, Janezic D, et al.
    J Chem Inf Model, 2013 Sep 23;53(9):2423-36.
    PMID: 23980878 DOI: 10.1021/ci400421e
    ProBiS is a new method to identify the binding site of protein through local structural alignment against the nonredundant Protein Data Bank (PDB), which may result in unique findings compared to the energy-based, geometry-based, and sequence-based predictors. In this work, binding sites of Hemagglutinin (HA), which is an important target for drugs and vaccines in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2, which is located slightly above the TBHQ binding site, is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix A at the stem domain and recently targeted by cross-reactive antibodies, is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drug and vaccine development.
    Matched MeSH terms: Molecular Targeted Therapy*
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