Alvocidib
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Alvocidib (INN; also known as Flavopiridol) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute myeloid leukemia, by Tolero Pharmaceuticals, Inc. It has been studied also for the treatment of arthritis[1] and atherosclerotic plaque formation[2] The target of Flavopiridol is the positive transcription elongation factor P-TEFb.[3][4] Treatment of cells with Flavopiridol leads to inhibition of P-TEFb and the loss of mRNA production.[5][6]
The compound is a synthetic analog of natural product rohitukine which was initially extracted from Amoora rohituka [syn. Aphanamixis polystachya] and later from Dysoxylum binectariferum.[7][8]
Orphan drug[edit | edit source]
| “ | Tolero Pharmaceuticals Inc. announced that the FDA has granted orphan drug designation for Alvocidib, its cyclin-dependent kinase small molecule inhibitor, for the treatment of patients with acute myeloid leukemia.[9] | ” |
References[edit | edit source]
- ↑ , Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors, J. Immunol., 2008, Vol. 180(Issue: 3), pp. 1954–61, DOI: 10.4049/jimmunol.180.3.1954, PMID: 18209094,
- ↑ , Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat, Circulation, 1999, Vol. 100(Issue: 6), pp. 659–65, DOI: 10.1161/01.cir.100.6.659, PMID: 10441105,
- ↑ , Flavopiridol inhibits P-TEFb and blocks HIV-1 replication, J. Biol. Chem., 2000, Vol. 275(Issue: 37), pp. 28345–8, DOI: 10.1074/jbc.C000446200, PMID: 10906320,
- ↑ , Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo, J. Biol. Chem., 2001, Vol. 276(Issue: 34), pp. 31793–9, DOI: 10.1074/jbc.M102306200, PMID: 11431468,
- ↑ , Functional association of Gdown1 with RNA polymerase II poised on human genes, Mol. Cell, 2012, Vol. 45(Issue: 1), pp. 38–50, DOI: 10.1016/j.molcel.2011.10.022, PMID: 22244331, PMC: 3259526,
- ↑ , c-Myc regulates transcriptional pause release, Cell, 2010, Vol. 141(Issue: 3), pp. 432–45, DOI: 10.1016/j.cell.2010.03.030, PMID: 20434984, PMC: 2864022,
- ↑ , The structure of rohitukine, the main alkaloid of Amoora rohituka (syn.Aphanamixis polystachya) (Meliaceae), Tetrahedron Lett., Vol. 20(Issue: 1), pp. 721–724, DOI: 10.1016/S0040-4039(01)93556-7,
- ↑ , Immunopharmacological potential of rohitukine: a novel compound isolated from the plant Dysoxylum binectariferum, Asia Pac J Pharmcol., Vol. 3(Issue: 1), pp. 91–98,
- ↑ http://www.healio.com/hematology-oncology/hematologic-malignancies/news/online/%7B74c6a69e-4529-400d-98e9-d5ee6c602122%7D/fda-grants-orphan-drug-status-to-alvocidib-for-aml
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