PD 0332991 HCl
Synonym(s):6-Acetyl-8-cyclopentyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one, HCl, Cdk4/Cdk6 Inhibitor V, PD-0332991, HCl, PF-332991, HCl;StemSelect PD 0332991 - CAS 827022-32-2 - Calbiochem
- CAS NO.:827022-32-2
- Empirical Formula: C24H30ClN7O2
- Molecular Weight: 484
- MDL number: MFCD22420809
- EINECS: 1592732-453-0
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-07-02 08:55:03
What is PD 0332991 HCl?
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.
Properties of PD 0332991 HCl
storage temp. | = -70C |
solubility | ≥14.48 mg/mL in H2O; ≥2.42 mg/mL in DMSO; ≥2.79 mg/mL in EtOH with gentle warming and ultrasonic |
form | Yellow liquid |
color | Light yellow to yellow |
Safety information for PD 0332991 HCl
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation |
Precautionary Statement Codes |
P280:Wear protective gloves/protective clothing/eye protection/face protection. P302+P352:IF ON SKIN: wash with plenty of soap and water. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. P332+P313:IF SKIN irritation occurs: Get medical advice/attention. P337+P313:IF eye irritation persists: Get medical advice/attention. |
Computed Descriptors for PD 0332991 HCl
New Products
Tubulysin A Tubulysin G 2,2-diethoxyethanethioamide Potassium HMDS (1.0 M in THF) 2,2-Difluoropropanol 4-Methylenepiperidine HCl 4,4-DIFLUOROPIPERIDINE Isoxazole, 3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]thio]-4,5-dihydro-5,5-dimethyl- Cyclobutanamine, 3,3-difluoro- (9CI) (S)-(+)-3-HYDROXYTETRAHYDROFURAN (1S,4S)-4- (3,4-dichlorophenyl) -N-methyl-1,2,3,4- tetrahydrona phthalen -1-amine .D-Mandelate 3-(S)-(+)- (-1-carbamoyl-1, 1-diphenylmethyl)- pyrrolidine-L- tartarate 1-tosyl-3-(R)-(-)- hydroxypyrrolidine Magnesium Trisilicate Latanoprostene Bunod Lubiprostone 7-Methoxyquinoline-4-carboxylic acid 1H-Imidazole-4-carbonitrile 7-Methoxyquinoline-4-carbonitrile (2S)-3-Methyl-2-(methylamino)-1-butanol (R)-methyl 2-formamido-3-(tritylthio)propanoate Methyl (2R)-2-amino-3-[(triphenylmethyl)sulfanyl]propanoate Methylprednisolone EP Impurity D FUSIDIC ACID EP IMPURITY I / FUSIDIC ACID BP IMPURITY I / FUS 16-EPI-DEACETYL FUSIDIC ACIDRelated products of tetrahydrofuran
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