Preferred Label : Zelebrudomide, (S)-;
NCIt synonyms : 2-Pyrazinecarboxamide, 3-((4-(1-(((3S)-1-(2-(2,6-Dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl)-3-pyrrolidinyl)methyl)-4-piperidinyl)phenyl)amino)-5-(1-piperidinyl)-;
NCIt definition : The S-enantiomer of zelebrudomide, an orally bioavailable chimeric targeting molecule
(CTM) and targeted degrader of Bruton's tyrosine kinase (BTK), with potential immunomodulatory
drug (IMiD) and antineoplastic activities. Zelebrudomide is comprised of a cereblon
(CRBN)-binding moiety conjugated, via a linker, to a BTK-binding moiety. Upon administration,
zelebrudomide targets and binds to BTK with its BTK-targeting moiety. Upon binding,
the CRBN-binding moiety recruits CRBN, a component of the CRL4-CRBN E3 ubiquitin ligase
complex. This catalyzes ubiquitination and proteasome-mediated degradation of BTK,
and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway.
This prevents both B-cell activation and BTK-mediated activation of downstream survival
pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress
BTK. In addition, zelebrudomide catalyzes the degradation of CRBN neosubstrates Aiolos
(IKZF3) and Ikaros (IKZF1), two transcription factors regulating T-cell function.
This modulates the activity of the immune system and increases the activation of T-lymphocytes,
thereby increasing T-cell-mediated anti-tumor effects. BTK, a member of the src-related
BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies;
it plays an important role in B-lymphocyte development, activation, signaling, proliferation
and survival. CRBN, the substrate recognition component of the CRL4-CRBN E3 ubiquitin
ligase complex, plays a key role in the ubiquitination of certain proteins. Compared
to BTK inhibitors, zelebrudomide may overcome tumor resistance associated with BTK
inhibitor-induced resistance mutations.;
UNII : LSC67HA8DE;
CAS number : 2416131-46-7;
Origin ID : C213361;
chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
