Flavopiridol HCl

Names

[ Name ]:
Flavopiridol HCl

[Synonym ]:
Alvocidib hydrochloride
HL-275
4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methyl-4-piperidinyl]-, hydrochloride (1:1)
2-(2-Chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methyl-4-piperidinyl]-4H-chromen-4-one hydrochloride (1:1)
(-)-2-(2-Chlorophenyl)-5,7-dihydroxy-8-[(3s,4r)-3-hydroxy-1-methyl-4-piperidinyl]-4h-1-benzopyran-4-one hydrochloride
Flavopiridol HCl
Flavopiridol (Alvocidib) HCl
Flavopiridol (Hydrochloride)
HMR-1275
Flavopiridol Hydrochloride
L 86-8275
Flavopiridol HCI

Biological Activity

[Description]:

Flavopiridol Hydrochloride is a broad inhibitor of CDK, competing with ATP to inhibit CDKs including CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
603.6ºC at 760 mmHg

[ Melting Point ]:
169.5-170ºC

[ Molecular Formula ]:
C₂₁H₂₁Cl₂NO₅

[ Molecular Weight ]:
438.301

[ Flash Point ]:
318.8ºC

[ Exact Mass ]:
437.079681

[ PSA ]:
94.14000

[ LogP ]:
4.04450

[ Vapour Pressure ]:
2.03E-15mmHg at 25°C

[ Storage condition ]:
-20℃

Safety Information

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22

[ RTECS ]:
DJ2978830

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.