Navigation Links
Agios research demonstrates the effects of mutant IDH1 and IDH2 inhibitors in primary tumor models
Date:4/4/2013

Cambridge, Mass. April 4, 2013 Agios Pharmaceuticals, Inc., the leading biopharmaceutical company focused on discovering and developing novel drugs in the fields of cancer metabolism and rare metabolic genetic diseases, announced today the publication of two articles in the journal Science by Agios scientists and their collaborators demonstrating the effects of the company's small molecule isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutant specific inhibitors in primary human tumor models. These data add to a growing body of scientific research demonstrating the significant promise of targeting mutant IDH1 and IDH2 enzymes as novel approaches to treating cancer.

"These papers represent the first publications to show the effects of inhibiting mutant IDH1 and IDH2 enzymes in patient-derived tumor samples, extending Agios' record of scientific leadership in cancer metabolism," said David Schenkein, M.D., chief executive officer at Agios. "While IDH mutations are genetically validated cancer targets, these findings provide further preclinical support that these mutations are driving disease, and appropriately targeted therapeutics can reverse the effects. Our IDH programs continue to produce promising results, and we are excited to advance toward clinical studies that will bring a potentially transformative treatment option to patients."

Tumors carrying IDH mutations are known to produce high levels of 2-HG, as shown originally by Agios scientists in Nature in 2009. In the first Science article, titled "Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation," Agios scientists show that cancer-associated IDH mutations may cause a block in cellular differentiation to promote tumorigenesis. To elucidate the relationship between mutant enzyme activity, 2-HG levels and oncogenic state, Agios developed a mutant-selective IDH2 inhibitor. Primary samples of acute myeloid leukemia (AML) cells were derived from four patients with AML carrying the IDH2 mutation. Upon treatment with the inhibitor, differentiation of blast (leukemic) cells was observed. In a separate experiment in TF-1 cells, the inhibitor was able to restore the ability of the cells to differentiate upon stimulation with erythropoeitin. Each of these observations was correlated with dose-dependent reductions in the oncometabolite 2-HG, which is thought to block differentiation in leukemia cells harboring IDH mutations.

In the second article, "An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells," Agios researchers, Ingo K. Mellinghoff, M.D., of Memorial Sloan-Kettering Cancer Center, and colleagues from several institutions report that a selective mutant IDH1 inhibitor discovered at Agios blocked the ability of mutant IDH1 to produce 2-HG in an in vivo primary xenograft model, impairing the growth of patient-derived IDH1-mutant glioma (brain cancer) cells. Furthermore, reduction of 2-HG to near basal levels induced expression of genes involved in both astroctyic and oligodendrocyte differentiation.

These data suggest that targeted therapy with IDH mutant inhibitors could induce tumor cell differentiation and support clinical study of IDH1 and IDH2 mutant targeted agents for the treatment of AML and other cancers. Both articles were published online in the journal Science on April 4, 2013.


'/>"/>

Contact: Dan Budwick
dan@purecommunicationsinc.com
973-271-6085
Pure Communications Inc.
Source:Eurekalert

Related medicine news :

1. Vygone Presents a Revolutionary Electro Waveform Device to Help Treat Molluscum Contagiosum Lesions
2. UCLA Brain Injury Research Center gets NCAA funding for research on sports concussions
3. NIH awards $20 million over 5 years to train next generation of global health researchers
4. Researchers develop a new cell and animal model of inflammatory breast cancer
5. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
6. Sexually abused boys at risk for more unsafe sex: UBC research
7. Researchers Find Gene Mutations That May Be a Key to Autism
8. LSUHSC research finds HPV-related head & neck cancers rising, highest in middle-aged white men
9. Researchers find evidence of banned antibiotics in poultry products
10. Presidential keynote address and new research highlights from the American Society of Pediatric Otolaryngology meeting
11. Scientific session and new research highlights
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... (PRWEB) , ... June 27, 2016 , ... Quality metrics ... yet in many ways they remain in the eye of the beholder, according to ... a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... ... ... legally blind and certified personal trainer is helping to develop a weight loss fitness plan ... fix the two major problems leading the fitness industry today:, , ... They don’t eliminate all the reasons people quit their exercise program ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library ... City Observer , brings up a new, often overlooked aspect of head lice: the parasite’s ... for fumigation is not a common occurrence, but a necessary one in the event that ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as a method ... —Johnson is one of the first doctors to perform the treatment. Orthobiologics are ...
(Date:6/24/2016)... ... June 24, 2016 , ... Those who have experienced traumatic events may suffer ... unhealthy avenues, such as drug or alcohol abuse, as a coping mechanism. To avoid ... healthy coping following a traumatic event. , Trauma sufferers tend to feel a range ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 Research and ... Market for Companion Diagnostic Tests" report to their offering. ... for Companion Diagnostics The World Market for ... personalized medicine diagnostics. Market analysis in the report includes the ... Market (In Vitro Diagnostic Kits) by Region (N. America, EU, ...
(Date:6/24/2016)... , Belgium , June 24, ... VNRX), today announced the appointment of Dr. ... Directors as a Non-Executive Director, effective June 23, ... Audit, Compensation and Nominations and Governance Committees.  As ... Futcher will provide independent expertise and strategic counsel ...
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Market - Forecast to 2022" report to their offering. ... method for the patients with kidney failure, it replaces the ... from the patient,s blood and thus the treatment helps to ... chloride in balance. Increasing number of ESRD ...
Breaking Medicine Technology: