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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Molecular docking,acute myeloid leukemia,Virtual screening,IDH2
- چکیده:
- چکیده انگلیسی: Acute myeloid leukemia (AML) is symbolized by an increase in the number of myeloid cells in the bone marrow and
an arrest in their maturation, frequently resulting in hematopoietic insufficiency (granulocytopenia, thrombocytopenia,
or anemia) with or without leukocytosis either by a predominance of immature forms or a loss of normal hematopoiesis.
IDH2 gene encodes for isocitrate dehydrogenase enzyme which is involved in the TCA cycle domino effect and
converts isocitrate to alpha-ketoglutarate. In the U.S, the annual incidence of AML progressively increases with age
to a peak of 12.6 per 100,000 adults of 65 years or older. Mutations in isocitrate dehydrogenase 2 (arginine 132) have
been demonstrated to be recurrent gene alterations in acute myeloid leukemia (AML) by forming 2-Hydroxy alpha
ketoglutarate which, instead of participating in TCA cycle, accumulates to form AML. The current study approaches
by molecular docking and virtual screening to elucidate inhibitor with superior affinity against IDH2 and achieve a
pharmacological profile. To obtain the best established drug Molegro Virtual Docker algorithm was executed. The
compound AG-221 (Pub CID 71299339) having the high affinity score was subjected to similarity search to retrieve
the drugs with similar properties. The virtual screened compound SCHEMBL16391748 (PubChem CID-117816179)
shows high affinity for the protein. Comparative study and ADMET study for both the above compounds resulted in
equivalent chemical properties. Virtual screened compound SCHEMBL16391748 (PubChem CID-117816179) shows
the lowest re-rank score. These drugs are identified as high potential IDH2 inhibitors and can halt AML when validated
through further In vitro screening.- انتشار مقاله: 28-07-1397
- نویسندگان: Jajoriya Sweta,Ravina Khandelwal,Sivaraj Srinitha,Rashi Pancholi,Ritu Adhikary,Meer Asif Ali,Anuraj Nayarisseri,Sugunakar Vuree,Sanjeev Kumar Singh
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Molecular docking,mTOR,MM-GBSA,Virtual screening
- چکیده:
- چکیده انگلیسی: Breast cancer is the most frequent malignancy among women. It is a heterogeneous disease with different subtypes
defined by its hormone receptor. A hormone receptor is mainly concerned with the progression of the PI3K/AKT/
mTOR pathway which is often dysregulated in breast cancer. This is a major signaling pathway that controls the
activities such as cell growth, cell division, and cell proliferation. The present study aims to suppress mTOR protein
by its various inhibitors and to select one with the highest binding affinity to the receptor protein. Out of 40 inhibitors
of mTOR against breast cancer, SF1126 was identified to have the best docking score of -8.705, using Schrodinger
Suite which was further subjected for high throughput screening to obtain best similar compound using Lipinski’s
filters. The compound obtained after virtual screening, ID: ZINC85569445 is seen to have the highest affinity with
the target protein mTOR. The same result based on the binding free energy analysis using MM-GBSA showed that
the compound ZINC85569445 to have the the highest binding free energy. The next study of interaction between the
ligand and receptor protein with the pharmacophore mapping showed the best conjugates, and the ZINC85569445 can
be further studied for future benefits of treatment of breast cancer.- انتشار مقاله: 06-09-1397
- نویسندگان: Khushboo Patidar,Umesh Panwar,Sugunakar Vuree,Jajoriya Sweta,Manpreet Kaur Sandhu,Anuraj Nayarisseri,Sanjeev Kumar Singh
- مشاهده