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Drug intelligence / Profile preview
GSK3326595 + 5-azacitidine
- Development stage
- Discontinued
- Lead developer
- GSK
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
GSK3326595 + 5-azacitidine is an investigational combination therapy being studied primarily for relapsed, refractory, or treatment-naïve myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). GSK3326595 is a potent, selective, reversible small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), a key epigenetic regulator implicated in abnormal hematopoiesis and tumorigenesis. 5-azacitidine is a DNA methyltransferase inhibitor (hypomethylating agent) that incorporates into DNA and RNA, causing DNA hypomethylation and cytotoxicity in abnormal hematopoietic cells. The rationale for combining these agents is to inhibit distinct yet complementary epigenetic and cellular pathways to enhance anti-leukemic efficacy. This combination has been tested within a phase I/II clinical study in a dose escalation and dose expansion format in myeloid malignancies[1][4][5].
- Other names
- 5-azacitidine
02
Targets
PRMT5 (Protein arginine N-methyltransferase 5)DNMT1 (DNA (cytosine-5)-methyltransferase 1)
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