Flavopiridol

Cas No.:	146426-40-6
Chemical Name:	2-(2-chlorophenyl)-5,7-dihydroxy-8-((3R,4S)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one
Synonyms:	L 86-8275; L-868275; L 868275; L868275; HMR 1274; HMR-1274; HMR1274; Flavoperidol; Alvocidib;
SMILES:	O=C1C=C(C2=CC=CC=C2Cl)OC3=C([C@H]4[C@@H](O)CN(C)CC4)C(O)=CC(O)=C13
Formula:	C21H20ClNO5
M.Wt:	401.84
Purity:	99%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Flavopiridol is a broad spectrum and competitive inhibitor of CDKs, inhibiting CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.
Target:	CDK1/Cyc B1:30 nM (IC50) CDK2/Cyc E:170 nM (IC50) CDK4/Cyc D1:100 nM (IC50) MAP:19000 nM (IC50) PKC:14000 nM (IC50) EGFR:22000 nM (IC50)
In Vitro:	Flavopiridol (2 μM) robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases[1]. Flavopiridol results in potent upregulation of a number of PRGs in treatments lasting 4-24 h. Flavopiridol has and immediate and long-term effect on the expression of several PRGs. In serum starved cells re-stimulated with serum, flavopiridol also inhibits the expression of these genes, but subsequently, JUNB, GADD45B and EGR1 are upregulated in the presence of flavopiridol[2].
Kinase Assay:	Briefly, lysates containing approximately 3×106 cells are incubated with 50 μM LEVD-AFC (caspase 4 substrate) or LETD-AFC (caspase 8 substrate) containing 10 mM dithiothretiol (DTT). caspase 4 activity is measured one hour after addition of substrate and caspase 8 activity is measured 30 minutes after addition of substrate. Release of free AFC is measured with a Beckman-Coulter DTX 880 multimode detector.
Cell Assay:	The cells treated with flavopiridol are washed after 4 hours with PBS and resuspended in regular growth medium (RPMI 1640) supplemented with 10% human serum and antibiotics for the remainder of the incubation time. In the case of flavopiridol/chloroquine samples, chloroquine is re-added in the fresh media after flavopiridol is washed at 4 hours. For all the other conditions, cells are incubated with the respective drugs for 24 hours continuously.
References:	[1]. Mahoney E, et al. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.Blood. 2012 Aug 9;120(6):1262-1273. [2]. Keskin H, et al. Complex effects of flavopiridol on the expression of primary response genes. Cell Div. 2012 Mar 29;7:11. [3]. Kim KS, et al.Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects. J Med Chem. 2000 Nov 2;43(22):4126-34.