PD 0332991 HCl

Bezeichnung:PD 0332991 HCl

CAS-Nr827022-32-2

Englisch Name:PD 0332991 HCl

CBNumberCB22593007

SummenformelC24H30ClN7O2

Molgewicht484

MOL-Datei827022-32-2.mol

PD 0332991 HCl physikalisch-chemischer Eigenschaften

storage temp.	= -70C
Löslichkeit	≥14.48 mg/mL in H2O; ≥2.42 mg/mL in DMSO; ≥2.79 mg/mL in EtOH with gentle warming and ultrasonic
Aggregatzustand	Yellow liquid

Sicherheit

HS Code

29399990

Gefahreninformationscode (GHS)

PD 0332991 HCl Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Allgemeine Beschreibung
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
target
CDK4/cyclin D1
Einzelnachweise
[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.

PD 0332991 HCl Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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