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Narazaciclib is an orally bioavailable small molecule multi-kinase inhibitor under clinical investigation for the treatment of various solid tumors and hematologic malignancies. It potently inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), NUAK family SNF1-like kinase 1 (ARK5/NUAK1), colony stimulating factor 1 receptor (CSF1R), CDK2, and FLT3. By inhibiting these kinases, narazaciclib disrupts cell cycle progression—particularly by preventing phosphorylation of retinoblastoma protein (Rb) in early G1 phase—leading to G1 cell cycle arrest and suppression of DNA synthesis in cancer cells. It also interferes with ARK5-mediated signaling pathways associated with tumor growth and invasion. Narazaciclib has demonstrated the ability to cross the blood-brain barrier and shows antitumor activity in preclinical models. The drug is being developed primarily by Traws Pharma for indications including relapsed/refractory multiple myeloma, low-grade endometrioid endometrial cancer (LGEEC), HER2-negative metastatic breast cancer, glioma/glioblastoma multiforme, mantle cell lymphoma, hepatocellular carcinoma, colorectal cancer, ovarian cancer, acute myeloid leukemia (AML), among others[2][3][4][5][6][7].
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