Preferred Label : Sirpiglenastat;
NCIt synonyms : Glutamine Antagonist DRP-104; (S)-Isopropyl 2-((S)-2-acetamido-3-(1h-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate;
NCIt definition : A broad acting glutamine antagonist, with potential immunomodulatory and antineoplastic
activities. Upon administration, DON (6-Diazo-5-oxo-L-norleucine), the active moiety
of sirpiglenastat, irreversibly inhibits multiple enzymes involved in glutamine metabolism.
Blocking glutamine metabolism inhibits proliferation in rapidly growing tumor cells
and leads to an induction of cell death. Unlike normal healthy cells, glutamine-dependent
tumors rely heavily on the intracellular conversion of exogenous glutamine into glutamate
and glutamate metabolites to both provide energy and generate building blocks for
the production of macromolecules, which are needed for cellular growth and survival.
In addition, blocking glutamine metabolism leads to the accumulation of glutamine
in tumor cells and increases glutamine concentration in the tumor microenvironment
(TME) upon tumor cell death. As glutamine is essential for T-cell generation, DON
may also enhance T-cell proliferation and activation in the TME, which may lead to
further killing of tumor cells. The conversion of sirpiglenastat to the active moiety
DON occurs primarily in tumor cells, allowing glutamine metabolism in healthy cells
which may lessen adverse effects.;
UNII : 9GGE6A0ZMK;
CAS number : 2079939-05-0;
Molecule name : DRP-104; DRP 104;
NCI Metathesaurus CUI : CL1407906;
Origin ID : C174038;
UMLS CUI : C5554580;
Semantic type(s)
- UMLS correspondences (same concept)
- concept_is_in_subset
