A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay.

A Novel High-Throughput 1536-well Notch1 γ-Secretase AlphaLISA Assay. Comb Chem High Throughput Screen. 2013 Feb 27; Authors: Chau DM, Shum D, Radu C, Bhinder B, Gin D, Gilchrist ML, Djaballah H, Li YM Abstract The Notch pathway plays a crucial role in cell fate decisions through controlling various cellular processes. Overactive Notch signal contributes to cancer development from leukemias to solid tumor. γ-Secretase is an intramembrane protease responsible for the final proteolytic step of Notch that releases the membrane-tethered Notch fragment for signaling. Therefore, γ-Secretase is an attractive drug target in treating Notch-mediated cancers. However, the absence of high-throughput γ-Secretase assay using Notch substrate has limited the identification and development of γ-Secretase inhibitors that specifically target the Notch signaling pathway. Here, we report on the development of a 1536-well γ-Secretase assay using a biotinylated recombinant Notch1 substrate. We effectively assimilated and miniaturized this newly developed Notch1 substrate with the AlphaLISA detection technology and demonstrated its robustness with a calculated Z score of 0.66. We further validated this optimized assay by performing a pilot screening against a chemical library consisting of ~5,600 chemicals and identified known γ-secretase inhibitors e.g. DAPT, and Calpeptin; as well as a novel γ-secretase inhibitor referred to as KD-I-...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research

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Conditions:   Acute Myeloid Leukemia;   Acute Lymphoblastic Leukemia;   Biphenotypic Acute Leukemia;   Undifferentiated Leukemia;   Prolymphocytic Leukemia;   Myelodysplastic Syndromes;   Chronic Myelogenous Leukemia;   Myeloproliferative Neoplasm;   Relapsed Large Cell Lymphoma;   Man tle Cell Lymphoma;   Hodgkin Lymphoma;   Burkitt Lymphoma;   Relapsed T-Cell Lymphoma;   Relapsed Chronic Lymphocytic Leukemia;   Relapsed Smal...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Drug giant Merck&Co. announced Monday that it will spend billions to buy a 26-year old biotech company that's struggled to bring a cancer drug to market.   Merck (NYSE: MRK) will spend approximately $2.7 billion to acquire Burlington-based ArQule Inc. (Nasdaq: ARQL). The biotech's drug that's furthest along in clinical trials is in the mid-stage tests against relapsed or refractory chronic lymphocytic leukemia. ArQule is expected to disclose more clinical data at an industry conference Monday. ArQule,…
Source: bizjournals.com Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
(University of Texas M. D. Anderson Cancer Center) A Phase II study pairing azacitidine with enasidenib boosts complete remission in patients with AML with IDH2 mutations.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Conclusions: CD200 has a great impact in diagnosing B- chronic lymphoproliferative disorders, especially when we want to determine the origin of a CD19, CD5 positive population and distinguish between CLL and MCL. CD 23 is a reliable marker in those cases, but, as we showed, CD23 might have a lower specificity than CD200 for CLL. We added CD200 in our panels in order to diagnose chronic lymphoproliferative disorders, not to replace CD 23, but to improve and save time in our diagnostic process. The high expression of CD200 in CLL and HCL could open the option for new- targeted therapy (anti-CD200). PMID: 31803290 [PubMed]
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Authors: Malhotra H, Radich J, Garcia-Gonzalez P Abstract Subsequent to the development and global availability of BCR/ABL-targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various pu...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Winters A, Gore L Abstract Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse a...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
This article reviews the current landscape of antibody-based and cellular immunotherapies under current clinical evaluation with an emphasis on active or soon-to-open phase 1 trials for children with relapsed/refractory AML. PMID: 31808843 [PubMed - in process]
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers’ instructions, once the components—sterile water and cytarabine powder—are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC an...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Clinical Report Source Type: research
(ECOG-ACRIN Cancer Research Group) The ECOG-ACRIN Cancer Research Group today announced results from extended follow-up of patients in its randomized Phase 3 clinical trial, E1912. Previously untreated patients (aged 70 or younger) with chronic lymphocytic leukemia (CLL) who received ibrutinib-based therapy lived longer and with sustained benefit, compared to standard FCR chemoimmunotherapy. The updated analysis supports the earlier trial findings (Shanafelt, New England Journal of Medicine, August 2019).
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
i Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-ΣMMHX) translocation product respectively, disrupt the essential hematopoie...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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