From Wikipedia, the free encyclopedia
Alvocidib
Names
IUPAC name
2′-Chloro-5,7-dihydroxy-8-[(3S ,4R )-3-hydroxy-1-methylpiperidin-4-yl]flavone
Systematic IUPAC name
2-(2-Chlorophenyl)-5,7-dihydroxy-8-[(3S ,4R )-3-hydroxy-1-methylpiperidin-4-yl]-4H -1-benzopyran-4-one
Other names
Flavopiridol, HMR 1275, L-868275
Identifiers
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
MeSH
Flavopiridol
UNII
InChI=1S/C21H20ClNO5/c1-23-7-6-12(17(27)10-23)19-14(24)8-15(25)20-16(26)9-18(28-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,17,24-25,27H,6-7,10H2,1H3/t12-,17+/m0/s1
Y Key: BIIVYFLTOXDAOV-YVEFUNNKSA-N
Y
Clc4ccccc4C=2Oc1c(c(O)cc(O)c1C(=O)C=2)[C@H]3CCN(C)C[C@H]3O
Properties
C21 H20 ClNO5
Molar mass
401.8402
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Alvocidib (
INN ; also known as flavopiridol ) is a
flavonoid alkaloid
CDK9
kinase inhibitor under clinical development by Tolero Pharmaceuticals for the treatment of
acute myeloid leukemia . It has been studied also for the treatment of
arthritis
[1] and
atherosclerotic plaque formation.
[2] The target of alvocidib is the positive transcription elongation factor
P-TEFb .
[3]
[4] Treatment of cells with alvocidib 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
Aphanamixis polystachya (formerly Amoora rohituka , hence the name) and later from
Dysoxylum binectariferum .
[7]
[8]
Orphan drug
The FDA has granted
orphan drug designation to alvocidib for the treatment of patients with
acute myeloid leukemia .
[9]
References
^ Sekine C, Sugihara T, Miyake S, Hirai H, Yoshida M, Miyasaka N, Kohsaka H (2008).
"Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors" . J. Immunol . 180 (3): 1954–61.
doi :
10.4049/jimmunol.180.3.1954 .
PMID
18209094 .
^ Ruef J, Meshel AS, Hu Z, Horaist C, Ballinger CA, Thompson LJ, Subbarao VD, Dumont JA, Patterson C (1999).
"Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat" . Circulation . 100 (6): 659–65.
doi :
10.1161/01.cir.100.6.659 .
PMID
10441105 .
^ Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, Senderowicz AM, Peterlin BM, Price DH (2000).
"Flavopiridol inhibits P-TEFb and blocks HIV-1 replication" . J. Biol. Chem . 275 (37): 28345–8.
doi :
10.1074/jbc.C000446200 .
PMID
10906320 .
^ Chao SH, Price DH (2001).
"Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo" . J. Biol. Chem . 276 (34): 31793–9.
doi :
10.1074/jbc.M102306200 .
PMID
11431468 .
^ Cheng B, Li T, Rahl PB, Adamson TE, Loudas NB, Guo J, Varzavand K, Cooper JJ, Hu X, Gnatt A, Young RA, Price DH (2012).
"Functional association of Gdown1 with RNA polymerase II poised on human genes" . Mol. Cell . 45 (1): 38–50.
doi :
10.1016/j.molcel.2011.10.022 .
PMC
3259526 .
PMID
22244331 .
^ Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA (2010).
"c-Myc regulates transcriptional pause release" . Cell . 141 (3): 432–45.
doi :
10.1016/j.cell.2010.03.030 .
PMC
2864022 .
PMID
20434984 .
^ Harmon, AD; Weiss, U; Silverton, JV (1979). "The structure of rohitukine, the main alkaloid of Amoora rohituka (syn.Aphanamixis polystachya) (Meliaceae)". Tetrahedron Lett . 20 (1): 721–724.
doi :
10.1016/S0040-4039(01)93556-7 .
^ Lakdawala, AD; Shirole, MV; Mandrekar, SS; Dohadwalla, AN (1988). "Immunopharmacological potential of rohitukine: a novel compound isolated from the plant Dysoxylum binectariferum". Asia Pac J Pharmcol . 3 (1): 91–98.
^
"FDA grants orphan drug status to Alvocidib for AML" .