Preferred Label : SOS1 Inhibitor ZG2001 Tosylate;
NCIt synonyms : ZG 2001 Tosylate; ZG2001 Tosylate; ZG-2001 Tosylate;
NCIt definition : The tosylate salt form of ZG2001, an orally available inhibitor of the guanine nucleotide
exchange factor (GEF) Son of sevenless homolog 1 (SOS1), with potential antineoplastic
activity. Upon oral administration, ZG2001 selectively targets and binds to SOS1,
thereby preventing the interaction of SOS1 with Kirsten rat sarcoma viral oncogene
homolog (KRAS) in the guanosine diphosphate (GDP)-bound 'off' state, which is the
inactivated state of KRAS. This abrogates the exchange of RAS-bound GDP for guanosine
triphosphate (GTP) and prevents the formation of GTP-loaded KRAS, which is the activated
'on' state of KRAS. This prevents activation of downstream RAF/mitogen-activated protein
kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway
by GTP-loaded KRAS. This inhibits mutant KRAS-dependent signaling and may inhibit
growth and survival of KRAS-expressing tumor cells. KRAS is a member of the RAS family
of oncogenes that is mutated in many cancer cell types. Mutations of KRAS may induce
constitutive signal transduction leading to tumor cell proliferation, survival, invasion,
and metastasis. SOS1 regulates the KRAS GDP-GTP cycle and promotes nucleotide exchange
and formation of 'active' KRAS-GTP.;
Origin ID : C208079;
concept_is_in_subset
- has_target
