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 and CDK6 with IC50 of ~ 40 nM. It is 7.5-fold more selective for CDK1, 2, 4, 6 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Phase 1/2.

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  • (C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50 μM) or 0.2% DMSO as control from 18 to 40 hpf. One hundred to one hundred fifty embryos were treated with each compound. Representative images of live embryos are shown with gross morphology (Right) and pituitary Pomc-GFP-positive cells at higher magnification (Left) at 40 hpf. Embryos exposed to flavopiridol developed early developmental defect before pituitary POMC cell ontogeny occurs. (D) Relative expression of pituitary Pomc-eGFP fluorescence analyzed using Volocity 5.2 software (Improvision; mean ±SE of relative expression, n = 7). (E) R-roscovitine specifically suppresses expansion of pituitary POMC cells overexpressing zPttg from 18 to 48 hpf. Double transgenic Tg:Pomc-Pttg;Prl-RFP embryos were generated by breeding Tg:Pomc-Pttg fish with a previously generated PRL-RFP transgenic line, in which RFP was targeted to pituitary lactotrophs by a zebrafish Prolactin promoter (34). Representative fluorescent microscopy of pituitary POMC-eGFP (a and b) and PRL-RFP (c and d) expression in live Tg:Pomc-Pttg; Pomc-eGFP and Tg:Pomc-Pttg;Prl-RFP embryos treated with 0.2% DMSO (a and c) or 50 μM R-roscovitine (b and d). (F) Relative expression of pituitary POMC-eGFP or PRL-RFP fluorescence were analyzed (mean ±SE of relative expression; n = 10). Results represent one of three similar experiments;*P < 0.02 and **P < 0.000005. (Scale bar, 50 μm.)

    PNAS 2011 108, 8417. Flavopiridol (Alvocidib) purchased from Selleck.

Purity & Quality Control

Choose Selective CDK Inhibitors

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Flavopiridol (Alvocidib) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM. It is 7.5-fold more selective for CDK1, 2, 4, 6 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
CDK1 [1] CDK2 [1] CDK4 [1] CDK6 [1] CDK7 [1]
40 nM 40 nM 40 nM 40 nM 300 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 Mk\vVJJwdGmoZYLheIlwdiCjc4PhfS=> NUi5UY5GSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBKTDhiY3XscJMtKEmFNUC9O{BvVQ>? NVvOOoQxOTdzMkO4NlE>
Sf9 cells NWPQTVcyTnWwY4Tpc44h[XO|YYm= M1HMPGlvcGmkaYTpc44hd2ZicnXjc41jcW6jboSgZ5lkdGmwIFGvR2RMOiCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzMEBKSzVyPUGyJI5O NUPwV4sxOTd7MESzOlY>
LNCaP human prostate carcinoma cell M2HIS3Bzd2yrZnXyZZRqd25iYYPzZZk> NYHiT4FUUW6qaXLpeIlwdiCxZjDMUmNiWCCqdX3hckBxem:|dHH0[UBk[XKlaX7vcYEh[2WubDDwdo9tcW[ncnH0bY9v NFnYbnMyOjF7MEOxNy=>
HCT116/VP35 human colon carcinoma cell MXnQdo9tcW[ncnH0bY9vKGG|c3H5 MWDJcohq[mm2aX;uJI9nKEiFVEGxOk9XWDN3IHj1cYFvKGOxbH;uJINiemOrbn;tZUBk\WyuIIDyc4xq\mW{YYTpc44tKEmFNUC9NVchdk1? NF76Z5QyOjF7MEOxNy=>
HCT116 human colon carcinoma cell NEPRV|JRem:uaX\ldoF1cW:wIHHzd4F6 NEPCO|hKdmirYnn0bY9vKG:oIFjDWFEyPiCqdX3hckBkd2yxbjDjZZJkcW6xbXGgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPUG4JI5O MXuxNlE6ODNzMx?=
HCT116/VM46 human colon carcinoma cell M3jxT3Bzd2yrZnXyZZRqd25iYYPzZZk> NFzsdYNKdmirYnn0bY9vKG:oIFjDWFEyPi:YTUS2JIh2dWGwIHPvcI9vKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:OjFibl2= Mm[1NVIyQTB|MUO=
human A2780 cells NWHVPGlxS3m2b4TvfIlkyqCjc4PhfS=> MWGyOEBp NHXvboxEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCOjd6MDDj[YxteyCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVI{KG6P NY\vdWhpOjN|MEG3Olc>
MCF7 cells M3HYUHBzd2yrZnXyZZRqd25iYYPzZZk> NGjWW2hCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JG1ETjdiY3XscJMtKEmFNUC9NlYhdk1? NGC2SYUyPzF{M{iyNS=>
human MRC5 cells MVfDfZRwfG:6aXRCpIF{e2G7 M4HTVlczKGh? Moi3R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUXJEPSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBIUTVyPUK4JI5O NGPwemgzOzNyMUe2Oy=>
human A2780 cells NV;1Spl2S3m2b4TvfIlkyqCjc4PhfS=> MonEO|IhcA>? MVvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBNlc5OCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBIUTVyPUK5JI5O MlTHNlM{ODF5Nke=
human A2780 cells MkXNR5l1d3SxeHnjxsBie3OjeR?= NF34cI01QCCq NUGxUG9HS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTJ5OECgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiR1m1NF0{OSCwTR?= M37SSlI{OzBzN{[3
A2780/DDP-R human ovarian carcinoma cell MUTQdo9tcW[ncnH0bY9vKGG|c3H5 NIDTPIFKdmirYnn0bY9vKG:oIFGyO|gxN0SGUD3SJIh2dWGwIH;2ZZJq[W5iY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD1|ODDuUS=> MVyxNlE6ODNzMx?=
human MRC5 cells NGTkWFBEgXSxdH;4bYPDqGG|c3H5 NF3wOng1QCCq NYLIe|I3S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVVKFNTDj[YxteyCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVM6KG6P MnnSNlM{ODF5Nke=
ABAE human fibroblast cell NV\5NIRMWHKxbHnm[ZJifGmxbjDhd5NigQ>? NEfFUWxKdmirYnn0bY9vKG:oIFHCRWUhcHWvYX6g[oljem:kbHHzeEBk\WyuIIDyc4xq\mW{YYTpc44tKEmFNUC9OFUhdk1? NFjlTpUyOjF7MEOxNy=>
HL60 human leukemia cell NXfpW4FiWHKxbHnm[ZJifGmxbjDhd5NigQ>? NYLXeIs4UW6qaXLpeIlwdiCxZjDIUFYxKGi3bXHuJIxmfWunbXnhJINmdGxicILvcIln\XKjdHnvckwhUUN3ME20OkBvVQ>? Ml:1NVIyQTB|MUO=
human MRC5 cells M1G0TWN6fG:2b4jpZ:Kh[XO|YYm= MkeyNlQhcA>? NIO5[WlEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOWkN3IHPlcIx{KGGodHXyJFI1KGi{czDifUBOXFRiYYPzZZktKEeLNUC9OFkhdk1? NYL1VWpTOjN|MEG3Olc>
Hs 27 human fibroblast cell NUfGbYZ1WHKxbHnm[ZJifGmxbjDhd5NigQ>? NYjOb4VDUW6qaXLpeIlwdiCxZjDId{AzPyCqdX3hckBncWK{b3LsZZN1KGOnbHygdJJwdGmoZYLheIlwdixiSVO1NF02OSCwTR?= M4f0clEzOTlyM{Gz
CCRF-CEM human leukemia cell M4LObXBzd2yrZnXyZZRqd25iYYPzZZk> MWfJcohq[mm2aX;uJI9nKEOFUl[tR2VOKGi3bXHuJIxmfWunbXnhJINmdGxicILvcIln\XKjdHnvckwhUUN3ME21NkBvVQ>? MoDiNVIyQTB|MUO=
OVCAR-3 human ovarian carcinoma cell Mo\mVJJwdGmoZYLheIlwdiCjc4PhfS=> MXHJcohq[mm2aX;uJI9nKE:YQ1HSMVMhcHWvYX6gc5ZiemmjbjDjZZJkcW6xbXGgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyPUW0JI5O M4HoTFEzOTlyM{Gz
A2780/DDP-S human ovarian carcinoma cell M3LwWnBzd2yrZnXyZZRqd25iYYPzZZk> MoP5TY5pcWKrdHnvckBw\iCDMke4NE9FTFBvUzDoeY1idiCxdnHybYFvKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:PTZibl2= Ml;yNVIyQTB|MUO=
human HMEC1 cells M17WR2N6fG:2b4jpZ:Kh[XO|YYm= NV60epZ1OjRiaB?= NFzBOnlEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJVUWFMTDj[YxteyCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6NCCJSUWwQVYyKG6P MkizNlM{ODF5Nke=
human HMEC1 cells M{\YSmN6fG:2b4jpZ:Kh[XO|YYm= NIG0UGk1QCCq M3LDPGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhOTUNzIHPlcIx{KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKEeLNUC9OlIhdk1? NGPIT4kzOzNyMUe2Oy=>
A2780/TAX-S human ovarian carcinoma cell MlO3VJJwdGmoZYLheIlwdiCjc4PhfS=> MkLZTY5pcWKrdHnvckBw\iCDMke4NE9VSVhvUzDoeY1idiCxdnHybYFvKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:PjVibl2= MYmxNlE6ODNzMx?=
LS174T human colon carcinoma cell NYDXc4NjWHKxbHnm[ZJifGmxbjDhd5NigQ>? M{S1T2lvcGmkaYTpc44hd2ZiTGOxO|RVKGi3bXHuJINwdG:wIHPhdoNqdm:vYTDj[YxtKHC{b3zp[oVz[XSrb36sJGlEPTB;NkWgcm0> MX6xNlE6ODNzMx?=
MCF-7 human breast carcinoma cell MV7Qdo9tcW[ncnH0bY9vKGG|c3H5 MX;Jcohq[mm2aX;uJI9nKE2FRj23JIh2dWGwIHLy[YF{fCClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTZ4IH7N M2raXlEzOTlyM{Gz
human HMEC1 cells Mn\iR5l1d3SxeHnjxsBie3OjeR?= NWPTNWtLPzJiaB?= NULKcmN{S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUE2HQ{GgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiR1m1NF03PiCwTR?= M3TINFI{OzBzN{[3
PC3 human prostate carcinoma cell MlLYVJJwdGmoZYLheIlwdiCjc4PhfS=> M{PZNWlvcGmkaYTpc44hd2ZiUFOzJIh2dWGwIIDyc5N1[XSnIHPhdoNqdm:vYTDj[YxtKHC{b3zp[oVz[XSrb36sJGlEPTB;Nk[gcm0> M1Xk[VEzOTlyM{Gz
human A2780 cell line MVHQdo9tcW[ncnH0bY9vKGG|c3H5 MnLZO|IhcA>? NFLOPG5CdnSrcILvcIln\XKjdHn2[UBm\m[nY4SgZYdicW6|dDDoeY1idiCDMke4NEBk\WyuIHzpcoUhf2G|IHTleIVzdWmwZXSgbY4h[SC5aH;s[UBk\WyuIEeyJIhzKGO7dH;0c5hq[2m2eTDhd5NigSxiSVO1NF04OSCwTR?= MUKxOVAzPzh4Mx?=
human ovarian (A2780) cancer cell M125S2N6fG:2b4jpZ:Kh[XO|YYm= MoTjR5l1d3SxeHnjJIVn\mWldDDvckBpfW2jbjDveoFzcWGwIDjBNlc5OCliY3HuZ4VzKGOnbHygcIlv\SxiSVO1NF04OSCwTR?= M1fH[lE2OTJ3OUex
MLF mouse lung fibroblast cell NEDXblhRem:uaX\ldoF1cW:wIHHzd4F6 M4DxSmlvcGmkaYTpc44hd2ZiTVzGJI1wfXOnIHz1coch\mmkcn;icIF{fCClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:PzJibl2= NVrQeldlOTJzOUCzNVM>
human NCI60 cells NEfDXmtRem:uaX\ldoF1cW:wIHHzd4F6 M{fsWFczKGh? MWHBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE6FSU[wJINmdGy|IHHmeIVzKDd{IHjyd{BjgSC|dXzmc5Jpd2SjbXnu[UBDKGG|c3H5MEBIUTVyPUe0Mlchdk1? MV6yNVA5ODdyMx?=
LX-1 human lung carcinoma NXzHUGpOWHKxbHnm[ZJifGmxbjDhd5NigQ>? MYHJcohq[mm2aX;uJI9nKEy[LUGgbJVu[W5ibIXu[{Bk[XKlaX7vcYEheHKxbHnm[ZJifGmxbjygTWM2OD15NTDuUS=> NG\lOpIyOjF7MEOxNy=>
A431 human squamous cell M3j3R3Bzd2yrZnXyZZRqd25iYYPzZZk> NVrVXJZnUW6qaXLpeIlwdiCxZjDBOFMyKGi3bXHuJJNyfWGvb4XzJINmdGxiY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD15NTDuUS=> M3z6[VEzOTlyM{Gz
SKBR-3 human breast carcinoma cell M1jGfHBzd2yrZnXyZZRqd25iYYPzZZk> NVjqTJdTUW6qaXLpeIlwdiCxZjDTT2JTNTNiaIXtZY4h[nKnYYP0JINiemOrbn;tZUBk\WyuIIDyc4xq\mW{YYTpc44tKEmFNUC9O|chdk1? MmjKNVIyQTB|MUO=
A2780/TAX-R human ovarian carcinoma cell NYGzNGtlWHKxbHnm[ZJifGmxbjDhd5NigQ>? Ml3STY5pcWKrdHnvckBw\iCDMke4NE9VSVhvUjDoeY1idiCxdnHybYFvKGOjcnPpco9u[SClZXzsJJBzd2yrZnXyZZRqd25uIFnDOVA:Pzhibl2= M{DQOFEzOTlyM{Gz
M109 mouse lung carcinoma cell Mlv0VJJwdGmoZYLheIlwdiCjc4PhfS=> NH7uUWdKdmirYnn0bY9vKG:oIF2xNFkhdW:3c3WgcJVv\yClYYLjbY5wdWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRThyIH7N NUC0XYp3OTJzOUCzNVM>
CACO-2 human colon carcinoma cell NFXYfGRRem:uaX\ldoF1cW:wIHHzd4F6 MknXTY5pcWKrdHnvckBw\iCFQVPPMVIhcHWvYX6gZ49td25iY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD16NjDuUS=> MUWxNlE6ODNzMx?=
A549 human lung carcinoma cell NVfHVI83WHKxbHnm[ZJifGmxbjDhd5NigQ>? NV:0fmdUUW6qaXLpeIlwdiCxZjDBOVQ6KGi3bXHuJIx2dmdiY3HyZ4lvd22jIHPlcIwheHKxbHnm[ZJifGmxbjygTWM2OD17NjDuUS=> MlLGNVIyQTB|MUO=
MIP human colon carcinoma cell M1TvV2Z2dmO2aX;uJIF{e2G7 NGfabVRKdmirYnn0bY9vKG:oIF3JVEBpfW2jbjDjc4xwdiClYYLjbY5wdWFiY3XscEBtcW6nLDDJR|UxRTBwMUKg{txO NXjzSI9xOTJzOUCzNVM>
K562 human leukemia cell MXLQdo9tcW[ncnH0bY9vKGG|c3H5 MYrJcohq[mm2aX;uJI9nKEt3NkKgbJVu[W5ibHX1b4VucWFiY3XscEBxem:uaX\ldoF1cW:wLDDJR|UxRTBwMUOg{txO NH7NbGsyOjF7MEOxNy=>
MCF-7 tumor cell MVfQdo9tcW[ncnH0bY9vKGG|c3H5 MV3Jcohq[mm2aX;uJI9nKE2FRj23JJR2dW:{IHPlcIwheHKxbHnm[ZJifGmxbh?= NY[xXW9UOTB6NEOyNVE>
human NCI60 cells NITwUYpRem:uaX\ldoF1cW:wIHHzd4F6 Ml\rO|IhcA>? NWXEZ2trSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2k3OCClZXzsd{Bie3Onc4Pl[EBieyCuZYToZYwh\W[oZXP0JIFnfGW{IEeyJIhzeyCkeTDzeYxnd3Kqb3ThcYlv\SCEIHHzd4F6NCCOQ{WwQVAvQTB2IN88US=> NIHWWnYzOTB6MEewNy=>
PC3 cell MnfjSpVv[3Srb36gZZN{[Xl? M1rDNmlvcGmkaYTpc44hd2ZiUFOzJINmdGxiY3zvco9o\W6rYzDhd5NigSxiSVO1NF0yOCEQvF2= M4rTelEyODZ|NkC5
HCT116 cell MlfXSpVv[3Srb36gZZN{[Xl? M{nmS2lvcGmkaYTpc44hd2ZiSFPUNVE3KGOnbHygZ4xwdm:pZX7pZ{Bie3OjeTygTWM2OD1zMzFOwG0> NW[3SlZvOTFyNkO2NFk>
A2780 cell NXG5S49VTnWwY4Tpc44h[XO|YYm= NY\nfZVFUW6qaXLpeIlwdiCxZjDBNlc5OCClZXzsJINtd26xZ3XubYMh[XO|YYpvwKwhUUN3ME2xOUDPxE1? M2LZO|EyODZ|NkC5
Mia PaCa-2 cell MULGeY5kfGmxbjDhd5NigQ>? M3\oW2lvcGmkaYTpc44hd2ZiTXnhJHBiS2FvMjDj[YxtKGOub37v[4VvcWNiYYPzZZktKEmFNUC9N|Yh|ryP NIXBZpUyOTB4M{[wPS=>
human A2780 cells MoTqSpVv[3Srb36gZZN{[Xl? NVHhV41UUW6qaXLpeIlwdiCxZjDj[IsudWWmaXH0[YQhVlCPIIDoc5NxcG:{eXzheIlwdiCjdDD0bJIyQTliaX6gbJVu[W5iQUK3PFAh[2WubIO= NVToN45QOTh2Nkm4NFk>
human A2780 cells NGHw[XVHfW6ldHnvckBie3OjeR?= Ml;kNlQhcA>? MV\Jcohq[mm2aX;uJI9nKGOmaz3t[YRq[XSnZDDSZkBxcG:|cHjvdplt[XSrb36gZZQhfGi{OEKxJIlvKGi3bXHuJGEzPzhyIHPlcIx{KGGodHXyJFI1KGi{cx?= MUSxPFQ3QThyOR?=

... Click to View More Cell Line Experimental Data

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 <1 mg/mL
In vivo 5% DMSO+30% PEG 300+ddH2O 2.5mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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 (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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*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 )

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    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 Conditions Sponsor/Collaborators Start Date Phases
NCT00094978 Terminated Carcinoma, Small Cell|Carcinoma, Non-Small-Cell Lung|Esophageal Neoplasms|Mesothelioma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) October 25, 2004 Phase 1
NCT02520011 Recruiting Acute Myeloid Leukemia Tolero Pharmaceuticals, Inc. December 2015 Phase 2
NCT01349972 Completed Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)|Adult Acute Monoblastic Leukemia (M5a)|Adult Acute Monocytic Leukemia (M5b)|Adult Acute Myeloblastic Leukemia With Maturation (M2)|Adult Acute Myeloblastic Leukemia Without Maturation (M1)|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Del(5q)|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Adult Acute Myelomonocytic Leukemia (M4)|Adult Erythroleukemia (M6a)|Adult Pure Erythroid Leukemia (M6b)|Secondary Acute Myeloid Leukemia|Untreated Adult Acute Myeloid Leukemia National Cancer Institute (NCI) April 2011 Phase 2
NCT01076556 Terminated Chronic Lymphocytic Leukemia|Prolymphocytic Leukemia|Recurrent Small Lymphocytic Lymphoma|Refractory Chronic Lymphocytic Leukemia|Stage I Chronic Lymphocytic Leukemia|Stage I Small Lymphocytic Lymphoma|Stage II Chronic Lymphocytic Leukemia|Stage II Small Lymphocytic Lymphoma|Stage III Chronic Lymphocytic Leukemia|Stage III Small Lymphocytic Lymphoma|Stage IV Chronic Lymphocytic Leukemia|Stage IV Small Lymphocytic Lymphoma National Cancer Institute (NCI) April 2010 Phase 1
NCT00991952 Completed Adenocarcinoma of the Gastroesophageal Junction|Diffuse Adenocarcinoma of the Stomach|Intestinal Adenocarcinoma of the Stomach|Mixed Adenocarcinoma of the Stomach|Recurrent Gastric Cancer|Stage IIIA Gastric Cancer|Stage IIIB Gastric Cancer|Stage IIIC Gastric Cancer|Stage IV Gastric Cancer National Cancer Institute (NCI) September 2009 Phase 2
NCT00957905 Completed Recurrent Extragonadal Seminoma|Recurrent Malignant Extragonadal Germ Cell Tumor|Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor|Recurrent Malignant Testicular Germ Cell Tumor|Recurrent Ovarian Germ Cell Tumor|Stage III Testicular Cancer|Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor|Stage IV Extragonadal Seminoma|Stage IV Ovarian Germ Cell Tumor National Cancer Institute (NCI) June 2009 Phase 2

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

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CDK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID