Preferred Label : DTRMWXHS-12/Everolimus/Pomalidomide Combination Agent DTRM-555;
NCIt synonyms : DTRMWXHS-12/Everolimus/Pomalidomide; DTRMWXHS-12-Everolimus-Pomalidomide;
NCIt definition : An orally bioavailable combination of DTRMWXHS-12, a Bruton's tyrosine kinase (BTK)
inhibitor, everolimus, a mammalian Target of Rapamycin (mTOR) inhibitor, and pomalidomide,
an immunomodulatory drug (IMiD), that may be used for the treatment of B-cell malignancies.
Upon oral administration of DTRM-555, the DTRMWXHS-12 component inhibits the activity
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, and leads to an inhibition of the growth of malignant B-cells that
overexpress BTK. BTK plays an important role in the development, activation, signaling,
proliferation and survival of B-lymphocytes. The everolimus component binds to the
immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and
inhibits the activation of mTOR, a key regulatory kinase. Upregulated in some tumors,
mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility,
and survival that is located downstream of the PI3K/Akt signaling pathway. The pomalidomide
component may inhibit TNF-alpha production, enhance the activity of T cells and natural
killer (NK) cells and enhance antibody-dependent cellular cytotoxicity (ADCC). In
addition, pomalidomide may inhibit tumor angiogenesis, promote cell cycle arrest in
susceptible tumor cell populations, and stimulate erythropoiesis. The combination
of a BTK inhibitor, an mTOR inhibitor and an IMiD may work synergistically to kill
malignant B-cells and prevent drug resistance.;
Molecule name : DTRM 555; DTRM-555;
NCI Metathesaurus CUI : CL1407876;
Origin ID : C173999;
UMLS CUI : C5418050;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
