Preferred Label : Pan-KRAS Inhibitor BI 1701963;
NCIt synonyms : SOS1:KRAS Interaction Inhibitor BI 1701963; Protein-protein Interaction Inhibitor BI 1701963; PPI Inhibitor BI 1701963;
NCIt definition : An orally available protein-protein interaction (PPI) inhibitor that targets the guanine
nucleotide exchange factor Son of sevenless homolog 1 (SOS1), with potential antineoplastic
activity. Upon oral administration, pan-KRAS inhibitor BI 1701963 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.;
Molecule name : BI-1701963; BI 1701963;
NCI Metathesaurus CUI : CL979206;
Origin ID : C166138;
UMLS CUI : C5237725;
Semantic type(s)
- concept_is_in_subset
- has_target
