Insilico structure modeling and molecular docking analysis of phosphoribosyl pyrophosphate amidotransferase (PPAT) with antifolate inhibitors.

Insilico structure modeling and molecular docking analysis of phosphoribosyl pyrophosphate amidotransferase (PPAT) with antifolate inhibitors. Curr Cancer Drug Targets. 2018 Nov 26;: Authors: Bibi N, Parveen Z, Nawaz MS, Kamal MA Abstract Cancer remains the one most serious disease worldwide. Robust metabolism is hallmark of the cancer. PPAT (phosphoribosyl pyrophosphate amidotransferase) catalyzes the first committed step of de novo purine biosynthesis. Hence PPAT, the key regulatory spot in De novo purine nucleotide biosynthesis is an attractive and credible drug target for leukemia and other cancer therapeutics. In the present study detailed computational analysis has been performed for PPAT protein the key enzyme in de novo purine biosynthesis is inhibited by many folate derivatives, hence we aimed to investigate and gauge the inhibitory effect of antifolate derivatives; lomexterol (LTX) methotrexate (LTX), and pipretixin (PTX) with human PPAT to effectively capture and inhibit De novo purine biosynthesis pathway. Sequence to structure computational approaches followed by molecular docking experiments were performed to gain insight into the inhibitory mode, binding orientation and binding affinities of selected antifolate derivatives against important structural features of PPAT. Results indicated strong affinity of antifolate inhibitors for the conserved active site of PPAT molecule encompassing number of hydrophobic, hydrogen bonding, Vander waals ...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research

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Publication date: Available online 15 September 2019Source: Advances in Biological RegulationAuthor(s): Samuel Gusscott, Francesco Tamiro, Vincenzo Giambra, Andrew P. WengAbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and occupy the bone marrow compartment, thereby interfering with the production of normal blood cells. Pediatric T-ALL is curable with intensive chemotherapy, but there are significant, long-term side effects and ∼20% of patients suf...
Source: Advances in Biological Regulation - Category: Biology Source Type: research
Conditions:   Advanced Malignant Solid Neoplasm;   Caregiver;   Metastatic Malignant Solid Neoplasm;   Recurrent Leukemia;   Recurrent Lymphoma;   Recurrent Malignant Solid Neoplasm;   Recurrent Plasma Cell Myeloma Intervention:   Other: Questionnaire Administration Sponsors:   M.D. Anderson Cancer Center;   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
uilera Rivera-Luna Juárez-Méndez B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases t...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
BLOOD cancer symptoms are important to recognise with it being the fifth most common cancer in the UK and the third deadliest form of cancer. Acute leukaemia is one of the most common types of blood cancer, but what are the most commonly ignored signs?
Source: Daily Express - Health - Category: Consumer Health News Source Type: news
Authors: Mendoza-Almanza G, Ortíz-Sánchez E, Rocha-Zavaleta L, Rivas-Santiago C, Esparza-Ibarra E, Olmos J Abstract Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regressi...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Gui W, Li J, Zhang Z, Wang L, Zhao J, Ma L, Su L Abstract The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients develop...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Clinical Reports Source Type: research
In the past decade, tumour flare reaction (TFR) was considered as a new side effect associated with immunomodulatory agents (IMiDs) and as a condition of chronic lymphocytic leukaemia (CLL). However, this phenomenon is also observed with immune checkpoint inhibitors in solid tumours. It is still poorly understood and its incidence is underestimated. TFR has been associated with morbidity, therefore, early recognition and management of patients with TFR is critical. An exhaustive literature research between 1985 and 2016 was performed using PubMed; American Society of Clinical Oncology and American Society of Hematology abs...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Clinical Reports Source Type: research
Abstract Multiple myeloma is the cancer of plasma cells. Along with the development of new and effective therapies, improved outcomes in patients with multiple myeloma have increased the interest in minimal residual disease (MRD) monitoring. However, the considerable heterogeneity of immunophenotypic and molecular markers of myeloma cells has limited its clinical application. 5-Aminolevulinic acid (ALA) is a natural compound in the heme biosynthesis pathway. Following ALA treatment, tumor cells preferentially accumulate porphyrins because of the differential activities of aerobic glycolysis, known as Warburg effec...
Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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