Pharmacophore-based 3D-QSAR modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold.

In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was applied on these hits, and 840 compounds were obtained through high-throughput virtual screening (HTVS). Standard precision (SP), extra precision (XP) and rule of five were also used in virtual screening protocol. Finally, six candidates were identified as potential MERTK inhibitors, with the docking mode in MERTK analyzed. PMID: 26673902 [PubMed - as supplied by publisher]
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research

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CONCLUSION Pediatric patients with SARS–CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDING Financial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex’s Lemonade Stand Foundation for Childhood Cancer; Children’s Oncology Group; Stand UP 2 Cancer; Team Connor;...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: October 2020Source: Clinical Lymphoma Myeloma and Leukemia, Volume 20, Issue 10Author(s): Prajwal Dhakal, Elizabeth Lyden, Kate-Lynn E. Muir, Zaid S. Al-Kadhimi, Lori J. Maness, Krishna Gundabolu, Vijaya Raj Bhatt
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
AbstractAimsDiabetes mellitus (DM) is widely recognized as a risk factor for diverse cancers in adults. However, the association between maternal diabetes and risk of childhood cancer in the offspring has so far not been well studied. We thus conducted a meta-analysis to evaluate the role of maternal diabetes on the risk of childhood cancer.MethodsWe performed a comprehensive literature search to identify eligible studies published up to June 20, 2020, including the PubMed, Web of science and Embase databases. Summary odds ratios (OR) and 95% confidence intervals (CI) were computed using a random-effects model (I2 &...
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
esco Albano Immunomodulatory drugs (IMiDs) are analogs of thalidomide. They have immunomodulatory, antiangiogenic and proapoptotic properties and exert a role in regulating the tumor microenvironment. Recently IMiDs have been investigated for their pleiotropic properties and their therapeutic applications in both solid tumors (melanoma, prostate carcinoma and differentiated thyroid cancer) and hematological malignancies. Nowadays, they are applied in de novo and relapsed/refractory multiple myeloma, in myelodysplastic syndrome, in del5q syndrome with specific use of lenalidomide and B-cell lymphoma. Several studies hav...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Immunotherapy is a very promising therapeutic approach against cancer that is particularly effective when combined with gene therapy. Immuno-gene therapy approaches have led to the approval of four advanced therapy medicinal products (ATMPs) for the treatment of p53-deficient tumors (Gendicine and Imlygic), refractory acute lymphoblastic leukemia (Kymriah) and large B-cell lymphomas (Yescarta). In spite of these remarkable successes, immunotherapy is still associated with severe side effects for CD19+ malignancies and is inefficient for solid tumors. Controlling transgene expression through an externally administered induc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSIONS: There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses. PMID: 32818321 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
CD20 is a protein expressed by wide ranges of lymphoid malignancies originating from B cells but not by indispensable normal tissues, making it an attractive target for therapies such as T-cell receptor (TCR) therapy. Current anti-CD20 therapeutics face a number of limitations. The most important limitation to current anti-CD20 therapies include cancer cells becoming resistant to the therapy. Resistance mechanisms to the existing CD20 therapies include loss of target antigen expression from the cell surface, loss of antibody epitope, or modulation of antibody epitope – all of which make the malignant cells “inv...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
This article is protected by copyright. All rights reserved.
Source: Biotechnology Progress - Category: Biotechnology Authors: Tags: REVIEW Source Type: research
This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL. PMID: 32755987 [PubMed - in process]
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
Abstract Adoptive transfer of T cells modified with chimeric antigen receptors (CAR-T cells) has changed the therapeutic landscape of hematological malignancies, particularly for acute lymphoblastic leukemia and large B cell lymphoma, where two different CAR-T products are now considered standard of care. Furthermore, intense research efforts are under way to expand the clinical application of CAR-T cell therapy for the benefit of patients suffering from other types of cancers. Nevertheless, CAR-T cell treatment is associated with toxicities such as cytokine release syndrome, which can range in severity from mild ...
Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
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