« Back
Home /
Palbociclib (PD-0332991) HCl

Palbociclib (PD-0332991) HCl

Item no.	S1116-5000
Manufacturer	Selleckchem
CASRN	827022-32-2
Amount	5 g
Quantity options	10 mg 1 g 10 g 10 mM/1 ml 5 mg 50 mg 5 g 500 mg
Category	Oncology Neuroscience Neural Signaling Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Skin Cancer Bladder Cancer Colorectal Cancer Breast Cancer Heart & Blood Cancer
Type	Inhibitors
Specific against	other
Smiles	CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C.Cl
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	827022-32-2'
Similar products	PD
Available
Manufacturer - Targets	CDK6, CDK4
Storage Conditions	2 years -80 in solvent
Molecular Weight	483, 99
Administration	Given by gavage
Animal Models	Advanced stage human tumor xenografts including Colo-205, MDA-MB-435 breast, SF-295 glioblastoma, ZR-75-1 breast, PC-3 prostate, H125 lung, SW-620 colon, H23 lung and MDA-MB-468 breast (Rb negative) are established in severe combined immunodeficient mice.
Cell lines	Tumor cell lines including MDA-MB-435, ZR-75-1, T-47D, MCF-7, H1299, Colo-205, MDA-MB-468, H2009, CRRF-CEM and K562
Clinical Trials	PD 0332991 is currently under Phase II clinical trial for advanced or metastatic liposarcoma.
Concentrations	0.01-1 uM
Dosages	0-150 mg/kg
Formulation	Dissolved in sodium lactate buffer (50 mM, pH 4.0)
IC50	11 nM, 11 nM, 11 nM, 11 nM, 11 nM, 11 nM
In vitro	PD 0332991 has little effect on other protein kinases including EGFR, FGFR, PGFR, IR. PD 0332991 is a non-ATP competitive inhibitor of Cdk4. PD 0332991 inhibits MDA-MB-435 breast carcinoma cells with IC50 of 66 nM, which is due to reduced Rb phosphorylation at Ser780. PD 0332991 inhibits thymidine incorporation into the DNA of Rb-positive human breast, colon, and lung carcinomas as well as human leukemias, with IC50 values ranging from 0.04-0.17 uM. PD 0332991 shows no activity in Rb-negative cells. PD 0332991 causes an accumulation of cells in G1 in MDA-MB-453 breast and Colo-205 carcinoma cells. [1] PD 0332991 also shows activity in 5T33MM myeloma cells (immunocompetent model) and sensitizes the cells to killing by bortezomib. [2] PD 0332991 inhibits luminal ER-positive as well as HER2-amplified breast cancer cell lines including MDA-MB-175, ZR-75-30, CAMA-1, MDA-MB-134, HCC-202 and UACC-893. PD 0332991 enhances the activity of tamoxifen and trastuzumab in these cell lines. PD 0332991 enhances the sensitivity of tamoxifen in the MCF7 tamoxifen-resistant cells. [3] A recent study shows that PD 0332991 could suppress malignant rhabdoid tumor (MRT) cell lines including MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS and the sensitivity of the MRT cell lines to PD 0332991 is inversely correlated with expression of p16. [4]
In vivo	PD 0332991 indicates complete tumor stasis in a MDA-MB-435 xenograft at 150 mg/kg. PD 0332991 also shows broad-spectrum antitumor activity in multiple human tumor xenografts by eliminating phospho-Rb and the proliferative marker Ki-67 from tumor tissue and down-regulation of genes under the transcriptional control of E2F. [1]
Incubation Time	24 hours
Kinase Assay	Cdk Assays, A stock solution of PD0332991 is prepared in DMSO. CDK assays are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insect cells through baculovirus infection and purified. The substrate for the assays is a fragment (amino acids 792â€“928) of pRb fused to GST (GSTÂ·RB-Cterm). The total volume in each well is 0.1 mL containing a final concentration of 20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 25 uM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) or 12 uM ATP (for CDK2-cyclin E, CDK2-cyclin A, and CDC2-cyclin B) containing 0.25 uCi of [gamma-32P]ATP, 20 ng of enzyme, 1 ug of GSTÂ·RB-Cterm, and PD 0332991 (0.001-0.1uM). All components except the [gamma-32P]ATP are added to the wells, and the plate is placed on a plate mixer for 2 min. The reaction is started by adding the [gamma-32P]ATP and the plate is incubated at 25 C for 15 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid and the plate ipt at 4 C for at least 1 hour to allow the substrate to precipitate. The wells are then washed 5 times with 0.2 mL of 10% trichloroacetic acid and radioactive incorporation is determined with a beta plate counter.
Method	Cells are seeded at 2, 104 per well in a 96-well plate and incubated overnight. PD 0332991 (0.01-1 uM) is added to the wells and incubated at 37 C for another 24 hours. [14C]Thymidine (0.1 uCi) is added to each well and incorporation of the radiolabel is allowed to proceed for 72 hours. Incorporated radioactivity is determined with a beta plate counter.
Solubility (25C)	DMSO 3 mg/mL, Water 30 mg/mL, Ethanol <1 mg/mL
Information	Palbociclib (PD-0332991) HCl is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays, respectively. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.
Chemical Name	6-acetyl-8-cyclopentyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2, 3-d]pyrimidin-7(8H)-one hydrochloride
Features	PD 0332991 itself does not kill cancer cells - just halts their growth and could be used in which glioblastoma has come back after treatment with temozolomide, a chemotherapy used in many cancer patients.

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Request Data Sheet

S1116-5000-datasheet.pdf

S1116-5000-safety-datasheet.pdf