Flavopiridol (Alvocidib)

Catalog No.S1230 Synonyms: NSC 649890 HCl,HMR-1275

Flavopiridol (Alvocidib) Chemical Structure

Molecular Weight(MW): 401.84

Flavopiridol (Alvocidib) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Phase 1/2.

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Cited by 29 Publications

Purity & Quality Control

Choose Selective CDK Inhibitors

Biological Activity

Description Flavopiridol (Alvocidib) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Phase 1/2.
Features First CDK inhibitor to be used in human clinical trials.
Targets
CDK9 [8]
(Cell-free assay)
CDK1 [8]
(Cell-free assay)
CDK4 [9]
(Cell-free assay)
CDK2 [8]
(Cell-free assay)
CDK6 [9]
(Cell-free assay)
20 nM 30 nM 20-40 nM 40 nM 60 nM
In vitro

Flavopiridol displays less activity against unrelated kinases such as MAP, PAK, PKC, and EGFR with IC50 of >14 μM. Flavopiridol significantly inhibits the colony growth of HCT116, A2780, PC3, and Mia PaCa-2 cells with IC50 of 13 nM, 15 nM, 10 nM and 36 nM, respecitively. [1] Flavopiridol also potently inhibits the activity of Glycogen synthase kinase-3 (GSK-3) with an IC50 of 280 nm. [2] Compared with other CDKs, Flavopiridol inhibits the activity of CDK7 less potently with IC50 of 875 nM. Flavopiridol (0.5 μM) inhibits both pSer807/811 Rb and pThr199 NPM, whereas mild changes are observed at pThr821 Rb. Flavopiridol also decreases the overall RNA polymerase II level, as well as the phosphorylation of RNA polymerase II on the CTD repeats at Ser2 Ser5. [3] As a broad spectrum CDK inhibitor, Flavopiridol can inhibit cell cycle progression in either G1 or G2. Flavopiridol (0.3 μM) induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. [4] Flavopiridol exhibits potent cytotoxicity against a wide variety of tumor cell lines with IC50 values ranging form 16 nM for LNCAP to 130 nM for K562. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ID8 cells NYP6RpR3WHKxbHnm[ZJifGmxbjDhd5NigQ>? NFjQUINCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGlFQCClZXzsd{whUUN3ME23JI5O MWixO|EzOzh{MR?=
Sf9 cells M1XRdmZ2dmO2aX;uJIF{e2G7 NFzq[lBKdmirYnn0bY9vKG:oIILlZ49u[mmwYX70JIN6[2yrbjDBM2NFUzJiZYjwdoV{e2WmIHnuJHNnQSClZXzsd{whUUN3ME2xNkBvVQ>? NGizd3AyPzlyNEO2Oi=>
LNCaP human prostate carcinoma cell NWnrb3V3WHKxbHnm[ZJifGmxbjDhd5NigQ>? MXHJcohq[mm2aX;uJI9nKEyQQ3HQJIh2dWGwIIDyc5N1[XSnIHPhdoNqdm:vYTDj[YxtKHC{b3zp[oVz[XSrb36= M3m0S|EzOTlyM{Gz
HCT116/VP35 human colon carcinoma cell MUHQdo9tcW[ncnH0bY9vKGG|c3H5 NVHkOIdCUW6qaXLpeIlwdiCxZjDIR3QyOTZxVmCzOUBpfW2jbjDjc4xwdiClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTF5IH7N NWPscZRkOTJzOUCzNVM>
HCT116 human colon carcinoma cell MXTQdo9tcW[ncnH0bY9vKGG|c3H5 M37PWGlvcGmkaYTpc44hd2ZiSFPUNVE3KGi3bXHuJINwdG:wIHPhdoNqdm:vYTDj[YxtKHC{b3zp[oVz[XSrb36sJGlEPTB;MUigcm0> NVLzV|VzOTJzOUCzNVM>
HCT116/VM46 human colon carcinoma cell NGDMPYtRem:uaX\ldoF1cW:wIHHzd4F6 MoXJTY5pcWKrdHnvckBw\iCKQ2SxNVYwXk12NjDoeY1idiClb3zvckBk[XKlaX7vcYEh[2WubDDwdo9tcW[ncnH0bY9vNCCLQ{WwQVIyKG6P MYmxNlE6ODNzMx?=
human A2780 cells MV7DfZRwfG:6aXRCpIF{e2G7 MY[yOEBp NHHp[FFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCOjd6MDDj[YxteyCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVI{KG6P MYeyN|MxOTd4Nx?=
MCF7 cells M1;W[XBzd2yrZnXyZZRqd25iYYPzZZk> NYLZTHhMSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBOS0Z5IHPlcIx{NCCLQ{WwQVI3KG6P MnLBNVcyOjN6MkG=
human MRC5 cells NWGyOWpKS3m2b4TvfIlkyqCjc4PhfS=> MUO3NkBp MnjCR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUXJEPSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBIUTVyPUK4JI5O NI\abHgzOzNyMUe2Oy=>
human A2780 cells NXzu[W1{S3m2b4TvfIlkyqCjc4PhfS=> NVPCdI5DPzJiaB?= NFj6cG1EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCOjd6MDDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVI6KG6P MnvyNlM{ODF5Nke=
human A2780 cells NF7Dd2FEgXSxdH;4bYPDqGG|c3H5 M3z2fFQ5KGh? NHLWVnFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCOjd6MDDj[YxteyCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVMyKG6P NEPEVGgzOzNyMUe2Oy=>
A2780/DDP-R human ovarian carcinoma cell MoT6VJJwdGmoZYLheIlwdiCjc4PhfS=> M3rvWmlvcGmkaYTpc44hd2ZiQUK3PFAwTESSLWKgbJVu[W5ib4\hdolidiClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTN6IH7N NXn4dGJ7OTJzOUCzNVM>
human MRC5 cells MVXDfZRwfG:6aXRCpIF{e2G7 NGTpfmw1QCCq NHvXXpdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOWkN3IHPlcIx{KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKEeLNUC9N|khdk1? NF3uWIczOzNyMUe2Oy=>
ABAE human fibroblast cell M{TzfXBzd2yrZnXyZZRqd25iYYPzZZk> Mn;GTY5pcWKrdHnvckBw\iCDQlHFJIh2dWGwIH\pZpJw[myjc4SgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPUS1JI5O M13MOlEzOTlyM{Gz
HL60 human leukemia cell NVu4[JNXWHKxbHnm[ZJifGmxbjDhd5NigQ>? MoPRTY5pcWKrdHnvckBw\iCKTE[wJIh2dWGwIHzleYtmdWmjIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD12NjDuUS=> MnT3NVIyQTB|MUO=
human MRC5 cells NFS0W2dEgXSxdH;4bYPDqGG|c3H5 MoPlNlQhcA>? M4rTdmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1TSzViY3XscJMh[W[2ZYKgNlQhcHK|IHL5JG1VXCCjc4PhfUwhT0l3ME20PUBvVQ>? M{LxdlI{OzBzN{[3
Hs 27 human fibroblast cell M4HGdnBzd2yrZnXyZZRqd25iYYPzZZk> MXTJcohq[mm2aX;uJI9nKEi|IEK3JIh2dWGwIH\pZpJw[myjc4SgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPUWxJI5O NEnGd5kyOjF7MEOxNy=>
CCRF-CEM human leukemia cell NFyzXHdRem:uaX\ldoF1cW:wIHHzd4F6 MlHLTY5pcWKrdHnvckBw\iCFQ2LGMWNGVSCqdX3hckBt\XWtZX3pZUBk\WyuIIDyc4xq\mW{YYTpc44tKEmFNUC9OVIhdk1? NFHGUoEyOjF7MEOxNy=>
OVCAR-3 human ovarian carcinoma cell NH2wUYFRem:uaX\ldoF1cW:wIHHzd4F6 NFv2[XZKdmirYnn0bY9vKG:oIF;WR2FTNTNiaIXtZY4hd3[jcnnhckBk[XKlaX7vcYEh[2WubDDwdo9tcW[ncnH0bY9vNCCLQ{WwQVU1KG6P M1jWUlEzOTlyM{Gz
A2780/DDP-S human ovarian carcinoma cell MWTQdo9tcW[ncnH0bY9vKGG|c3H5 MWrJcohq[mm2aX;uJI9nKEF{N{iwM2RFWC2VIHj1cYFvKG:4YYLpZY4h[2G{Y3nuc41iKGOnbHygdJJwdGmoZYLheIlwdixiSVO1NF02PiCwTR?= M1j6NVEzOTlyM{Gz
human HMEC1 cells NILXbGVEgXSxdH;4bYPDqGG|c3H5 NV;mb2VUOjRiaB?= NVrDUG5VS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUE2HQ{GgZ4VtdHNiYX\0[ZIhOjRiaILzJIJ6KE2WVDDhd5NigSxiR1m1NF03OSCwTR?= NEizZ5kzOzNyMUe2Oy=>
human HMEC1 cells NH7kVHlEgXSxdH;4bYPDqGG|c3H5 NGXJb5g1QCCq MoDNR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTG1GSzFiY3XscJMh[W[2ZYKgOFghcHK|IHL5JG1VXCCjc4PhfUwhT0l3ME22NkBvVQ>? NHm5N2UzOzNyMUe2Oy=>
A2780/TAX-S human ovarian carcinoma cell MWHQdo9tcW[ncnH0bY9vKGG|c3H5 MXzJcohq[mm2aX;uJI9nKEF{N{iwM3RCYC2VIHj1cYFvKG:4YYLpZY4h[2G{Y3nuc41iKGOnbHygdJJwdGmoZYLheIlwdixiSVO1NF03PSCwTR?= NXLPS|ZOOTJzOUCzNVM>
LS174T human colon carcinoma cell MX3Qdo9tcW[ncnH0bY9vKGG|c3H5 MXHJcohq[mm2aX;uJI9nKEyVMUe0WEBpfW2jbjDjc4xwdiClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTZ3IH7N NWrmO3RqOTJzOUCzNVM>
MCF-7 human breast carcinoma cell NGPWblZRem:uaX\ldoF1cW:wIHHzd4F6 NILoOFFKdmirYnn0bY9vKG:oIF3DSk04KGi3bXHuJIJz\WG|dDDjZZJkcW6xbXGgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPU[2JI5O M2PRPVEzOTlyM{Gz
human HMEC1 cells MmjjR5l1d3SxeHnjxsBie3OjeR?= MU[3NkBp M3PwdWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhOTUNzIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEeLNUC9OlYhdk1? NXTOd25KOjN|MEG3Olc>
PC3 human prostate carcinoma cell NUPFcVc{WHKxbHnm[ZJifGmxbjDhd5NigQ>? MmD0TY5pcWKrdHnvckBw\iCSQ{OgbJVu[W5icILvd5RifGViY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD14NjDuUS=> NUThZWlCOTJzOUCzNVM>
human A2780 cell line NFG0VHBRem:uaX\ldoF1cW:wIHHzd4F6 MnrvO|IhcA>? NHnmWXlCdnSrcILvcIln\XKjdHn2[UBm\m[nY4SgZYdicW6|dDDoeY1idiCDMke4NEBk\WyuIHzpcoUhf2G|IHTleIVzdWmwZXSgbY4h[SC5aH;s[UBk\WyuIEeyJIhzKGO7dH;0c5hq[2m2eTDhd5NigSxiSVO1NF04OSCwTR?= M1X6S|E2ODJ5OE[z
human ovarian (A2780) cancer cell MXnDfZRwfG:6aXRCpIF{e2G7 NVXrSZdjS3m2b4TvfIlkKGWoZnXjeEBwdiCqdX3hckBwfmG{aXHuJEhCOjd6MDmgZ4Fv[2W{IHPlcIwhdGmwZTygTWM2OD15MTDuUS=> MYmxOVEzPTl5MR?=
MLF mouse lung fibroblast cell MXzQdo9tcW[ncnH0bY9vKGG|c3H5 M2LWV2lvcGmkaYTpc44hd2ZiTVzGJI1wfXOnIHz1coch\mmkcn;icIF{fCClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:PzJibl2= NFn6TVkyOjF7MEOxNy=>
human NCI60 cells MWXQdo9tcW[ncnH0bY9vKGG|c3H5 NGHiOZc4OiCq MU\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE6FSU[wJINmdGy|IHHmeIVzKDd{IHjyd{BjgSC|dXzmc5Jpd2SjbXnu[UBDKGG|c3H5MEBIUTVyPUe0Mlchdk1? Mo\jNlExQDB5MEO=
LX-1 human lung carcinoma MYjQdo9tcW[ncnH0bY9vKGG|c3H5 M3\HfGlvcGmkaYTpc44hd2ZiTGitNUBpfW2jbjDseY5oKGOjcnPpco9u[SCycn;sbYZmemG2aX;uMEBKSzVyPUe1JI5O NUK1UWZYOTJzOUCzNVM>
A431 human squamous cell Mnu2VJJwdGmoZYLheIlwdiCjc4PhfS=> NUiye2Q1UW6qaXLpeIlwdiCxZjDBOFMyKGi3bXHuJJNyfWGvb4XzJINmdGxiY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD15NTDuUS=> MoTtNVIyQTB|MUO=
SKBR-3 human breast carcinoma cell M3rmfXBzd2yrZnXyZZRqd25iYYPzZZk> MW\Jcohq[mm2aX;uJI9nKFONQmKtN{BpfW2jbjDidoVie3RiY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD15NzDuUS=> MYGxNlE6ODNzMx?=
A2780/TAX-R human ovarian carcinoma cell M{O2PXBzd2yrZnXyZZRqd25iYYPzZZk> MnnNTY5pcWKrdHnvckBw\iCDMke4NE9VSVhvUjDoeY1idiCxdnHybYFvKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:Pzhibl2= NHnVZmEyOjF7MEOxNy=>
M109 mouse lung carcinoma cell MkL0VJJwdGmoZYLheIlwdiCjc4PhfS=> M4LwNWlvcGmkaYTpc44hd2ZiTUGwPUBud3W|ZTDseY5oKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:QDBibl2= MlruNVIyQTB|MUO=
CACO-2 human colon carcinoma cell NWqwbmhDWHKxbHnm[ZJifGmxbjDhd5NigQ>? NGjiZ|RKdmirYnn0bY9vKG:oIFPBR28uOiCqdX3hckBkd2yxbjDjZZJkcW6xbXGgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPUi2JI5O NGfYSngyOjF7MEOxNy=>
A549 human lung carcinoma cell NFH5VnJRem:uaX\ldoF1cW:wIHHzd4F6 NHTwN|FKdmirYnn0bY9vKG:oIFG1OFkhcHWvYX6gcJVv\yClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTl4IH7N M13mbFEzOTlyM{Gz
MIP human colon carcinoma cell Mk\RSpVv[3Srb36gZZN{[Xl? MnvzTY5pcWKrdHnvckBw\iCPSWCgbJVu[W5iY3;sc44h[2G{Y3nuc41iKGOnbHygcIlv\SxiSVO1NF0xNjF{IN88US=> M1m2RVEzOTlyM{Gz
K562 human leukemia cell MX;Qdo9tcW[ncnH0bY9vKGG|c3H5 MnrPTY5pcWKrdHnvckBw\iCNNU[yJIh2dWGwIHzleYtmdWmjIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD1yLkGzJO69VQ>? NHfUfFIyOjF7MEOxNy=>
MCF-7 tumor cell NYixSWE6WHKxbHnm[ZJifGmxbjDhd5NigQ>? NYrMdIdlUW6qaXLpeIlwdiCxZjDNR2YuPyC2dX3vdkBk\WyuIIDyc4xq\mW{YYTpc44> NIHaRnkyODh2M{KxNS=>
human NCI60 cells M{j2fXBzd2yrZnXyZZRqd25iYYPzZZk> MX:3NkBp NHXoeGdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTVYxKGOnbHzzJIF{e2W|c3XkJIF{KGyndHjhcEBm\m[nY4SgZYZ1\XJiN{KgbJJ{KGK7IIP1cIZwemixZHHtbY5mKEJiYYPzZZktKEyFNUC9NE46ODRizszN NFvmTHMzOTB6MEewNy=>
PC3 cell NYLOR4V[TnWwY4Tpc44h[XO|YYm= MXfJcohq[mm2aX;uJI9nKFCFMzDj[YxtKGOub37v[4VvcWNiYYPzZZktKEmFNUC9NVAh|ryP NEH5PVkyOTB4M{[wPS=>
HCT116 cell NVmyVJlGTnWwY4Tpc44h[XO|YYm= NHPZWnhKdmirYnn0bY9vKG:oIFjDWFEyPiClZXzsJINtd26xZ3XubYMh[XO|YYmsJGlEPTB;MUOg{txO MnnmNVExPjN4MEm=
A2780 cell NIDrTlFHfW6ldHnvckBie3OjeR?= Mmf3TY5pcWKrdHnvckBw\iCDMke4NEBk\WyuIHPsc45w\2WwaXOgZZN{[XoxvJygTWM2OD1zNTFOwG0> NYrOc2liOTFyNkO2NFk>
Mia PaCa-2 cell NVXZ[YxQTnWwY4Tpc44h[XO|YYm= MU\Jcohq[mm2aX;uJI9nKE2rYTDQZWNiNTJiY3XscEBkdG:wb3flcolkKGG|c3H5MEBKSzVyPUO2JO69VQ>? MnvuNVExPjN4MEm=
human A2780 cells MnnhSpVv[3Srb36gZZN{[Xl? Ml;VTY5pcWKrdHnvckBw\iClZHutcYVlcWG2ZXSgUnBOKHCqb4PwbI9zgWyjdHnvckBifCC2aIKxPVkhcW5iaIXtZY4hSTJ5OECgZ4VtdHN? MnPTNVg1Pjl6MEm=
human A2780 cells NY\aTmJKTnWwY4Tpc44h[XO|YYm= NHmwboszPCCq MnfxTY5pcWKrdHnvckBw\iClZHutcYVlcWG2ZXSgVoIheGixc4Doc5J6dGG2aX;uJIF1KHSqckiyNUBqdiCqdX3hckBCOjd6MDDj[YxteyCjZoTldkAzPCCqcoO= NUTwdoRFOTh2Nkm4NFk>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Cleaved caspase-8 / Cleaved caspase-9 / Cleaved caspase-3; 

PubMed: 31193061     


(C) Caspase activation was determined by western blotting. Flavopiridol treatment (300 nM) induced the expressions of cleaved caspase-8, -9 and -3 in a time-dependent manner. 

p-RNAPII / p-eIF4E / Mnk1 ; 

PubMed: 24572052     


After 24 h drug exposure, CDKI-73 or flavopiridol also abolished p-eIF4ES209 at 0.25 μM, indicating cellular inhibition of Mnk kinase activity. The same treatment with CDKI-73 or flavopiridol caused a loss in Mnk1 protein expression. CGP57380-treated cells abrogated p-RNAPIIS2 as well as p-eIF4E(S209) with a minimal effect on Mnk1 protein level.

p-ERK / ERK / p-p38 / p-4EBP1 / 4EBP1 / p-S6 ; 

PubMed: 24572052     


0.25 μM CDKI-73 or flavopiridol caused little changes in the phosphorylation of Erk and p38 MAPK; however, inhibited the 4E-BP1 phosphorylation (p-4E-BP1Thr70) by 24 h. CGP57380 had a minimal effect on these proteins.

CDK2 / CDK4 / Cyclin A / p21 / p27 / Rb; 

PubMed: 24572052     


Effect of flavopiridol on cell cycle-related protein expression in uterine leiomyoma cells. Twenty-four hours after treatment, cell extracts were prepared and subjected to immunoblotting analysis. β-Actin was used as an internal loading control.

31193061 24572052
Growth inhibition assay
Cell viability; 

PubMed: 31193061     


The antiproliferative effect of flavopiridol on CCA cell lines was determined using an MTT assay. KKU-055, KKU-100, KKU-213 and KKU-214 cells were treated with 50, 100, 200 or 300 nM of flavopiridol at 24, 48 or 72 h. The percentage of cell number in vehicle control was taken as 100%. Data are mean ± SD of three independent experiments. *P < 0.05 in all CCA cell lines, significantly different for each time point compared with vehicle control.

31193061
In vivo Administration of Flavopiridol at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, resulting in %T/C value of 110, and active against the human A2780 ovarian carcinoma implanted sc in nude mice, producing 1.5 log cell kill (LCK). [5] Flavopiridol treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. [6] In the p21-intact Hct116 xenografts in nude mice, administration of CPT-11 (100 mg/kg) followed by Flavopiridol (3 mg/kg) 7 and 16 hours later significantly inhibits tumor regression by 86% and 82%, respectively, displaying >2 fold inhibition compared with CPT-11 alone by 40 %. The combination produces ~30% complete response rate (CR) in contrast to CPT-11 alone where no CR is found. [7]

Protocol

Kinase Assay:

[1]

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CDK kinase assay:

For CDK1/cyclin B1 kinase assay, kinase reactions consist of 100 ng of baculovirus expressed GST-CDK1/cyclin B1 (human) complex, 1 μg histone HI, 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Tris, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 0.5 mM DTT). For CDK2/cyclin E kinase assay, kinase reactions consist of 5 ng of baculovirus expressed GST-CDK2/cyclin E (human) complex, 0.5 μg GST-RB fusion protein (amino acids 776-928 of retinoblastoma protein), 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). For CDK4/cyclin D1 kinase assay, kinase reactions consist of 150 ng of baculovirus expressed GST-CDK4/cyclin D1 (human), 280 ng of Stag-cyclin D1, 0.5 μg GST-RB fusion protein (amino acids 776-928 of retinoblastoma protein), 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Reactions are incubated for 45 minutes for CDK1 and CDK2, or 1 hour for CDK4 at 30 °C and stopped by the addition of cold trichloroacetic acid (TCA) to a final concentration 15%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester and the filters are quantitated using a TopCount 96-well liquid scintillation counter. Flavopiridol is dissolved at 10 mM in dimethylformamide (DMF) and evaluated at six concentrations, each in triplicate. The final concentration of DMF in the assay = 2%. IC50 values are derived by nonlinear regression analysis and have a coefficient of variance = 16%. To assay Flavopiridol activity on CDK6, a filter-binding assay is established. The following are combined in the reaction mixture: 2 μL of CDK6 (0.7 mg/μL), 5 μL of histone H1 (6 mg/mL), 14 μL of kinase buffer (60 mM β-glycerophosphate, 30 mM p-nitrophenyl phosphate, 25 mM MOPS (pH 7.0), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0.1 mM Na-vanadate), 3 μL of increasing concentrations of Flavopiridol diluted in 50% DMSO, and 6 μL of 33P-ATP (1 mCi/mL) in nonradioactive ATP at 90 μM concentration (final concentration: 15 μM). The assay is initiated by the addition of 33P-ATP. The reaction is incubated for 20 minutes at 30°C. A 25 μL aliquot of the supernatant is then spotted onto Whatman P81 phosphocellulose paper. Filters are washed 5 times with 1% phosphoric acid solution. Wet filters are counted in the presence of 1 mL of scintillation fluid. Cdk9 activity is measured using 50 nM of recombinant Cdk9/cyclin T in 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 3 μM Na3VO4, 150 μM RNA polymerase CDT peptide and 80 μM ATP. Cdk7 assay is performed in the same buffer using 37 nM of purified kinase in the presence of 200 μM ATP and 10 μM myelin binding protein as a substrate. The potency of Flavopiridol toward CDK9 and CDK7 is determined using either a strong anion exchanger (Dowex 1-X8 resin, formate form)-based assay or a scintillation proximity assay. IC50 values are calculated from the dose-response curves.
Cell Research:

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  • Cell lines: MCF-7, LNCAP, PC3, HCT116, CACO-2, A549, HL60, K562 cells and et al.
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 72 hours
  • Method:

    Cells are exposed to various concentrations of Flavopiridol for 72 hours at which time the tetrazolium dye, MTS in combination with phenazine methosulfate, is added. After 3 hours, the absorbency is measured at 492 nm, which is proportional to the number of viable cells. The results are expressed as IC50 values. For cell Cycle analysis, cells are fixed in paraformaldehyde and ethanol, washed, resuspended in staining solution of TdT enzyme and FITC-dUTP, washed, stained with PI following RNase treatment, and then analyzed by flow cytometry.


    (Only for Reference)
Animal Research:

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  • Animal Models: Female Balb/c×DBA/2J F1 mice inoculated ip with P388 ascites leukemic cells, and Balb/c nu/nu nude mice subcutaneous implanted with A2780, Br-cycE, or A431 cells
  • Formulation: Dissolved in a mixture of Cremophor/ethanol (50:50), and diluted in water
  • Dosages: ~7.5 mg/kg/day
  • Administration: Injection i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 15 mg/mL (37.32 mM)
Ethanol 8 mg/mL (19.9 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.
2.5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 401.84
Formula

C21H20ClNO5

CAS No. 146426-40-6
Storage powder
in solvent
Synonyms NSC 649890 HCl,HMR-1275

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03441555 Recruiting Drug: Venetoclax|Drug: Alvocidib Acute Myeloid Leukemia (AML) AbbVie|Tolero Pharmaceuticals Inc. May 30 2018 Phase 1
NCT03298984 Recruiting Drug: Alvocidib|Drug: Cytarabine|Drug: Daunorubicin Acute Myeloid Leukemia Tolero Pharmaceuticals Inc. September 25 2017 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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CDK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID