827022-32-2 Usage
Description
PD 0332991 is an orally active, selective inhibitor of the cyclin D kinases Cdk4 (IC50 = 11 nM) and Cdk6 (IC50= 16 nM) with no activity against a panel of 36 additional protein kinases. It has been reported to have antiproliferative activity against retinoblastoma-positive tumor cells, blocking retinoblastoma phosphorylation and inducing G1 arrest at nanomolar concentrations. PD 0332991 can inhibit the growth of certain ER-positive or HER2-amplified breast cancer cells (IC50s as low as 4 nM) and demonstrates synergy with tamoxifen and trastuzumab, respectively. PD 0332991 inhibition of Cdk4 activity has been used to demonstrate a role for insulin-activated cyclinD1-Cdk4 signaling in the control of glucose metabolism that is independent of cell cycle progression.
General Description
A cell-permeable, orally available and brain permeant, non-toxic pyridopyrimidinone compound that acts as a potent, selective, reversible, ATP competitive inhibitor of Cdk4 and Cdk6 (IC50 = 11, 9, and 15 nM for Cdk4/D1, Cdk4/D3 and Cdk6/D2, respectively). Hence, it reduces retinoblastoma protein phosphorylation at Ser780/Ser795 (IC50 = 66 nM in MDA-435 cells) and arrests cell cycle at G1 phase. Acts as a cytostatic agent, but does induce apoptotic cell death when used alone. However, it potentiates the cytotoxicity of dexamethasone (>Cat. No. 265005), bortezomib (>Cat. No. 504314), and tamoxifen (Cat. No. 579000) in estrogen receptor (ER)-positive cell lines. Exhibits only a trivial inhibitory activity towards Cdk2/E2, Cdk2/A, Cdk1/B and Cdk5/p25 in a 36-kinase panel (IC50 >10 μM). Improves endoderm differentiation of late G1-human embryonic stem cells expressing Smad2 or Smad3 (~ 750 nM) and further enhances endoderm differentiation into hepatic and pancreatic progenitor cells. Shown to regress the growth of human breast tumor xenografts in murine models (~150 mg/kg, p.o., daily).
Biochem/physiol Actions
Cell permeable: yes
references
[1] ivan diaz-padilla, lillian l. siu and ignacio duran. cyclin-dependent kinase inhibitors as potential targeted anticancer agents. invest new drugs. 2009, 27: 586–594.[2] richard s finn, judy dering, dylan conklin, ondrej kalous, david j cohen, amrita j desai, charles ginther, mohammad atefi, isan chen, camilla fowst, gerret los and dennis j slamon. pd 0332991, a selective cyclin d kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. breast cancer research. 2009, 11: r77.
Check Digit Verification of cas no
The CAS Registry Mumber 827022-32-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,2,7,0,2 and 2 respectively; the second part has 2 digits, 3 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 827022-32:
(8*8)+(7*2)+(6*7)+(5*0)+(4*2)+(3*2)+(2*3)+(1*2)=142
142 % 10 = 2
So 827022-32-2 is a valid CAS Registry Number.
827022-32-2Relevant articles and documents
Preparation method and process of palbociclib
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, (2021/03/30)
The invention relates to a preparation method of palbociclib. The preparation method comprises the steps of 1 reacting a compound I with a compound II to obtain an intermediate I; 2 carrying out a coupling reaction on the intermediate I and vinyl n-butyl ether to obtain an intermediate II; 3 removing a protecting group from the intermediate II under the action of an acid reagent to obtain palbociclib silicate; and 4 carrying out alkali replacement on the palbociclib silicate to obtain palbociclib.
PALBOCICLIB SALTS
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Page/Page column 44, (2017/07/01)
The subject of the invention relates to various new salts of palbociclib, furthermore to their hydrate and solvate forms, such as the palbociclib hydrogen bromide (1:1) salt, the palbociclib hydrogen bromide (1:2) dihydrate salt, the palbociclib hydrogen chloride (1:1) salt Form E, the palbociclib sulphate (2:1) dihydrate salt, the palbociclib camsylate (1:1) salt, the palbociclib napsylate (1:1) salt, the palbociclib napsylate (1:2) dihydrate salt, the palbociclib tosylate (1:1) salt, the palbociclib citrate (1:1) monohydrate salt, the palbociclib maleate (1:1) salt Form I, the palbociclib maleate (1:1) salt Form II and the palbociclib oxalate (1:1) salt. The subject of the invention also relates to the production of the above palbociclib salts, medicinal preparations containing these and the medical use of the above forms.
Preparation method for Palbociclib
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Paragraph 0042, (2017/01/02)
The invention relates to a preparation method for Palbociclib. The method comprises the following steps: taking 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyridino[2,3-d]pyridine-2-yl-amino)-pyridine-3-yl]-piperazine-1-carboxylic acid tert-butyl ester as a starting raw material; performing Heck reaction, rearrangement, deprotection and neutral reaction to obtain the Palbociclib, wherein the total yield is 70 to 80 percent. According to the preparation method disclosed by the invention, non-Pd-catalyzed heck reaction is investigated, such that a phosphorus-containing ligand which is high in cost and needs harsh reaction conditions is avoided, and the production cost and the technological operation risk are reduced; acetylchloride is used for rearrangement and deprotection reaction to obtain Palbociclib hydrochloride, and the Palbociclib hydrochloride is alkalized to obtain the high-purity Palbociclib.
