EC Number   |
Application |
Reference |
|---|
   2.5.1.46 | analysis |
DHS activity can be determined by coupling the first phase reaction with the NADH-Glo assay in which the generation of luminescence is dependent on NADH derived from the DHS partial reaction. The non-radioactive DHS/NADH-Glo coupled assay is highly specific, sensitive and reproducible and can be configured for high throughput screening of small molecule libraries |
758631 |
| 2.5.1.46 | drug development |
Cryptosporidium parvum DHS is a traget for drug development, as GC7 effectively inhibits parasite infection and growth in cultured host cells |
739026 |
| 2.5.1.46 | drug development |
fungal DHS is a target for the development of inhibitors, for which CNI-1493 may serve as a lead substance |
-, 723229 |
| 2.5.1.46 | medicine |
elevated mRNA levels of the target enzymes deoxyhypusine synthase (DHPS) and ornithine decarboxylase (ODC) correlate with poor prognosis in a large cohort of neuroblastoma tumors. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) and the ODC inhibitor alpha-difluoromethylornithine (DFMO) are target-specific and in combination induce synergistic effects in neuroblastomas at concentrations that are not individually cytotoxic. The drug combination induces caspase 3/7/9, but not caspase 8-mediated apoptosis, in neuroblastoma cells. Hypusinated eIF5A levels and intracellular spermidine levels correlate directly with drug treatments |
758759 |
| 2.5.1.46 | medicine |
in a transgenic mouse model of type 1 diabetes, in which human GAD65 is expressed in pancreatic beta-cells, and human MHC-II is expressed on antigen presenting cells, deoxyhypusine synthase inhibitor N''-guanyl-1,7-diaminoheptane, i.e. GC7, alters the pathophysiology by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. Inhibition of eIF5A resets the proinflammatory bias in the pancreatic microenvironment. There is reduction of Th1/Th17 response, an increase in Treg numbers, debase in IL17 and IL21 cytokines levels in serum, lowering of anti-GAD65 antibodies, and ablation of the ER stress that improves functionality of the beta-cells, but minimal effect on the cytotoxic CD8 T-cell mediated response |
760180 |
| 2.5.1.46 | medicine |
recurrent missense variant p.Asn173Ser is identified with likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del]), or c.1A>G [p.Met1?] in unrelated individuals having similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. The c.1014+1G>A variant causes aberrant splicing. Recombinant p.Asn173Ser or p.Tyr305_Ile306del protein show reduced (20%) or absent in vitro activity, respectively. The p.Tyr305_Ile306del and p.Asn173Ser variants result in reduced hypusination of eIF5A compared to wild-type DHPS enzyme |
758622 |
