Perpustakaan Universitas Padjajaran
Pencarian Spesifik

Detail Cantuman

No image available for this title

Text  

T267- Synergistic Antitumor Effect of a NAMPT Inhibitor and a NAD Kinase Inhibitor in Mutant IDHI Cancers (Alvinsyah Adhityo Pramono; Joseph R. Bertino; Keri Lestari; Herry Herman; Debabrata Baneriee; Sharon R. Pine; Anas Subarnas; Tri Hanggono Achmad; Rizky Abdulah)

NAD(H) and NADPH are important cofactors in cellular metabolism. These molecules protect cancer cells from detrimental effect of ROS generated in ...

  • CodeCallNoLokasiKetersediaan
    FFUP20230041T267Tersedia
  • Perpustakaan
    Fakultas Farmasi
    Judul Seri
    -
    No. Panggil
    T267
    Penerbit Fakultas Farmasi Universitas Padjadjaran : Jatinangor.,
    Deskripsi Fisik
    -
    Bahasa
    Indonesia
    ISBN/ISSN
    -
    Klasifikasi
    T267
    Tipe Isi
    -
    Tipe Media
    -
    Tipe Pembawa
    -
    Edisi
    -
    Subyek
    -
    Info Detil Spesifik
    -
    Pernyataan Tanggungjawab
  • NAD(H) and NADPH are important cofactors in cellular metabolism. These molecules protect cancer cells from detrimental effect of ROS generated in actively proliferating cancer cells. NAD is generated through three biosynthetic pathways, i.e., nicotinic acid pathway, de novo synthesis pathway, and NAD salvage pathway. In order to efficiently reduce NAD pools and to avoid redundancy, we investigated mutant isocitrate dehydrogenase 1/2 (mIDH1/2) cancers that lack the nicotinic acid pathway. Mutant IDH1/2 protein converts α-ketoglutarate into D-2-hydroxyglutarate (D-2HG), an oncometabolite that accelerates the tumorigenesis process and inhibits NAPRT in the nicotinic acid pathway. STF-118804, a NAMPT inhibitor, and Thionicotinamide (ThioNa), a NADK inhibitor, were tested for cytotoxicity in mIDH1 cancer cell lines C85, HCT16, HCT8, and HT1080. Results showed that STF-118804 sensitized all cell lines with the highest and the lowest IC50= 70 μM and 150nM. ThioNa also exhibited cytotoxicity ranging from 25μM-150μM. the combination of both drugs achieved appreciable synergistic activity in mIDH1 cancers with combination index (CI) value at ED50 ranging from 0.30-0.53. Metabolomics study has showed that the drug combination significantly decreases 2-HG, NAD, NADPH, ATP, isocitrate, and α-ketoglutarate compared to the control group. Thus, the (iii)
    combination of both NAMPT inhibitor and NADK inhibitor might be a novel strategy in ameliorating proliferative disease like cancers.

  • Tidak tersedia versi lain

  • Silakan login dahulu untuk melihat atau memberi komentar.


//

Informasi