Chemistry:H3B-8800
From HandWiki
H3B-8800 is an experimental drug which acts as an inhibitor of the SF3B1 protein, which forms part of the splicing factor 3b protein complex. This is commonly mutated in some forms of cancer, principally leukemia but also some subtypes of breast cancer and melanoma. H3B-8800 has reached early stage human clinical trials in patients whose cancers express mutations that make them susceptible to inhibition of SF3B1.[1][2][3][4][5][6][7][8][9]
References
- ↑ "The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action". Genes & Development 32 (3–4): 309–320. February 2018. doi:10.1101/gad.311043.117. PMID 29491137.
- ↑ "H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers". Nature Medicine 24 (4): 497–504. May 2018. doi:10.1038/nm.4493. PMID 29457796.
- ↑ "Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia". Cancer Discovery 10 (9): 1388–1409. September 2020. doi:10.1158/2159-8290.CD-19-1436. PMID 32444465.
- ↑ "A Comprehensive Overview of Structure-Activity Relationships of Small-Molecule Splicing Modulators Targeting SF3B1 as Anticancer Agents". ChemMedChem 15 (22): 2098–2120. November 2020. doi:10.1002/cmdc.202000642. PMID 33037739.
- ↑ "Total Syntheses of Pladienolide-Derived Spliceosome Modulators". Molecules 26 (19): 5938. September 2021. doi:10.3390/molecules26195938. PMID 34641481.
- ↑ "Targeting the spliceosome machinery: A new therapeutic axis in cancer?". Biochemical Pharmacology 189. July 2021. doi:10.1016/j.bcp.2020.114039. PMID 32417188. https://inserm.hal.science/inserm-05172877.
- ↑ "Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers". International Journal of Molecular Sciences 22 (20). October 2021. doi:10.3390/ijms222011222. PMID 34681880.
- ↑ "Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms". Leukemia 35 (12): 3542–3550. December 2021. doi:10.1038/s41375-021-01328-9. PMID 34172893.
- ↑ "Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML". Science Translational Medicine 16 (728). January 2024. doi:10.1126/scitranslmed.ade2774. PMID 38170787.
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