PD 0332991 (Palbociclib) HCl | Licensed by Pfizer

Validation & Quality Control

Product Citations(5)

Proc Natl Acad Sci U S A, 2011, 108(20), 8414-8419

Pigment Cell Melanoma Res, 2012, ahead of print

Am J Cancer Res, 2012, 2(6), 726-735

PLoS One, 2012, 7(12), e51847

Submitted to the Graduate Faculty of the School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy;, 2011,

Customer Reviews(7) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

PD 0332991 (Palbociclib) HCl is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Pfizer Licensed Library

Product Information

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Research Area
Research Area
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1116	PD 0332991 (Palbociclib) HCl	30 mg/mL	3 mg/mL	<1 mg/mL
S2768	Dinaciclib (SCH727965)	<1 mg/mL	79 mg/mL	26 mg/mL
S1524	AT7519	<1 mg/mL	10 mg/mL	<1 mg/mL
S2679	Flavopiridol (Alvocidib) HCl	37 mg/mL	88 mg/mL	<1 mg/mL
S1153	Roscovitine (Seliciclib, CYC202)	<1 mg/mL	71 mg/mL	6 mg/mL
S1145	SNS-032 (BMS-387032)	<1 mg/mL	76 mg/mL	<1 mg/mL
S1249	JNJ-7706621	<1 mg/mL	79 mg/mL	<1 mg/mL
S1572	BS-181 HCl	3 mg/mL	83 mg/mL	27 mg/mL
S2735	SCH 900776	<1 mg/mL	60 mg/mL	3 mg/mL
S1487	PHA-793887	<1 mg/mL	72 mg/mL	72 mg/mL
S2621	AZD5438	<1 mg/mL	74 mg/mL	74 mg/mL
S2742	PHA-767491	<1 mg/mL	24 mg/mL	<1 mg/mL
S2751	Milciclib (PHA-848125)	<1 mg/mL	92 mg/mL	<1 mg/mL
S2670	A-674563	72 mg/mL	72 mg/mL	18 mg/mL
S1230	Flavopiridol (Alvocidib)	<1 mg/mL	15 mg/mL	8 mg/mL
S2688	R547	<1 mg/mL	60 mg/mL	<1 mg/mL
S2014	BMS-265246	<1 mg/mL	20 mg/mL	<1 mg/mL
S1579	PD 0332991 (Palbociclib) Isethionate	100 mg/mL	<1 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	PD 0332991 is a highly selective inhibitor of CDK4/cyclin D1 and CDK6/cyclin D2 with IC50 of 11 nM and 16 nM, respectively.
Targets	CDK4/cyclin D1	CDK6/cyclin D2
IC50	11 nM	16 nM ^[1]
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 μM. 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]
Clinical Trials	PD 0332991 is currently under Phase II clinical trial for advanced or metastatic liposarcoma.
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.

Protocol(Only for Reference)

Kinase Assay: ^[1]

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 792–928) of pRb fused to GST (GST·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 μM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) or 12 μM ATP (for CDK2-cyclin E, CDK2-cyclin A, and CDC2-cyclin B) containing 0.25 μCi of [γ-³²P]ATP, 20 ng of enzyme, 1 μg of GST·RB-Cterm, and PD 0332991 (0.001-0.1μM). All components except the [γ-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 [γ-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 is kept 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 β plate counter.

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 792–928) of pRb fused to GST (GST·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 μM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) or 12 μM ATP (for CDK2-cyclin E, CDK2-cyclin A, and CDC2-cyclin B) containing 0.25 μCi of [γ-³²P]ATP, 20 ng of enzyme, 1 μg of GST·RB-Cterm, and PD 0332991 (0.001-0.1μM). All components except the [γ-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 [γ-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 is kept 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 β plate counter.

Cell Assay: ^[1]

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
Concentrations	0.01-1 μM
Incubation Time	24 hours
Method	Cells are seeded at 2 × 10⁴ per well in a 96-well plate and incubated overnight. PD 0332991 (0.01-1 μM) is added to the wells and incubated at 37 °C for another 24 hours. [¹⁴C]Thymidine (0.1 μCi) is added to each well and incorporation of the radiolabel is allowed to proceed for 72 hours. Incorporated radioactivity is determined with a β plate counter.

Animal Study: ^[1]

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.
Formulation	Dissolved in sodium lactate buffer (50 mM, pH 4.0)
Dosages	0-150 mg/kg
Administration	Given by gavage

1

References

Chemical Information

Download PD 0332991 (Palbociclib) HCl SDF

Molecular Weight (MW)	483.99
Formula	C₂₄H₂₉N₇O₂.HCl
CAS No.	827022-32-2, 571190-30-2 (free base)
Synonyms	N/A

Solubility (25°C) DMSO 3 mg/mL Water 30 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

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

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Research Area

Customer Reviews (7)

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Rating

Source

PNAS, 2011, 108, 8417. PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Fluorescent Microscopy and Confocal Imaging

Cell Lines

Tg:Pomc-Pttg embryo, Pomc-eGFP embryo

Concentrations

50 μM

Incubation Time

18-48 h

Results

Although ﬂavopiridol retarded early embryonic development before corticotroph ontogeny occurred, in vivo treatment of zebraﬁsh embryos with R-roscovitine, olomoucine, PD-0332991, and CAY10572 starting at 18 hpf caused no apparent growth defect by 40 hpf . Strikingly, R-roscovitine-treated embryos exhibited approximately 40% reduction in pituitary POMC-eGFP expression compared with controls. A modest, approximately 20%, reduction of POMC-eGFP expression was also observed in the olomoucine-treated group (1.0 ± 0.08 vs. 0.8 ± 0.07, mean ± SE; n = 7 for each group; P = 0.07), whereas PD-0332991 and CAY10572 caused no signiﬁcant change in pituitary POMC-eGFP expression compared with controls.

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Rating

Source

Clin Cancer Res, 17(13), 2011. PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Western Blot/Growth assay

Cell Lines

OE33/OE19/Flo1A cells

Concentrations

125 nM

Incubation Time

1/3/21 day

Results

PD-0332991 reduces expression of cyclinA in all 3 cell lines. PD-0332991 has no effect on the expression level of either total pRB or RB2 (p130) in EAC cells. PD-0332991 caused a significant reduction in colony formation in soft agar in all 3 cell lines tested, indicative of a reduction in anchorage independence.

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Rating

Source

The Pharmacogenomics Journal (2013) 13, 94–104 . PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Immunofluorescence

Cell Lines

Patient tumor cell

Concentrations

3 uM

Incubation Time

Results

Tumor organoids treated with VPA/ PD0332991 or SAHA/PD0332991 exhibited reduced structural integrity and increased cellular scatter with increasing concentrations of the drugs.

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Rating

Source

Clin Transl Oncol (2012) 14:197-206 . PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Immunofluorescence

Cell Lines

Murine MSCs cells

Concentrations

2 uM

Incubation Time

24-48 h

Results

We show that when cells are treated with PD332991 for 24–48 h there is a marked decrease in nuclear expression of cdk4 in PAX7- FKHR-expressing mMSCs. Further analysis by immunofluorescence showed that there is a minor upregulation in expression of MyoD1 in cells treated with cdk4 inhibitor for 48 h.

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Rating

Source

Dr Gao Zhang of University of Pennsylvania. PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Western blot

Cell Lines

WM3734 melanoma cells

Concentrations

0.25-4 μM

Incubation Time

36 h

Results

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Rating

Source

Dr Kun-Wei Liu from University of Pittsburgh. PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

IB analysis, Quantification of soft agar assays

Cell Lines

LN319 cells

Concentrations

Incubation Time

Results

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Rating

Source

Dr Sabine Paternot and Dr Pierre Roger of IRIBHM, ULB, Brussels. PD 0332991 (Palbociclib) HCl purchased from Selleck

Method

Western blot

Cell Lines

T98G glioma cells

Concentrations

1 μM

Incubation Time

Results

Product Citations (5)

Targeting zebraﬁsh and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor. [Liu NA, et al. Proc Natl Acad Sci U S A 2011;108(20), 8414-8419]
PubMed: 21536883
p16(INK) (4a) deficiency promotes DNA hyper-replication and genetic instability in melanocytes. [Fung C, et al. Pigment Cell Melanoma Res 2012;ahead of print]
PubMed: 23279822
Downregulation of Noxa by RAF/MEK inhibition counteracts cell death response in mutant B-RAF melanoma cells. [Kevin J Basile, et al. Am J Cancer Res 2012;2(6), 726-735]
PubMed: 23226618

Cyclin-Dependent Kinase 6 Phosphorylates NF-κB P65 at Serine 536 and Contributes to the Regulation of Inflammatory Gene Expression. [Buss H, et al. PLoS One 2012;7(12), e51847]
PubMed: 23300567
Platelet-derived growth factor receptor alpha overexpression cooperates with INK4A/ARF loss to promote gliomagenesis-roles of SHP-2 and PI3K pathways. [Liu KW. Submitted to the Graduate Faculty of the School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy; 2011;]

Tech Support & FAQs

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

Tel: +1-832-582-8158 Ext:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

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Related CDK Inhibitors

SNS-032 (BMS-387032)

SNS-032 is a novel, potent and selective CDK inhibitor of CDK2, CDK7 and CDK9 with IC50 of 38 nM, 62 nM and 4 nM, respectively.
Roscovitine (Seliciclib, CYC202)

Roscovitine (Seliciclib, CYC202, R-roscovitine) is a potent and selective CDK inhibitor for Cdc2/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p53 with IC50 of 0.65 μM, 0.7 μM, 0.7 μM and 0.16 μM, respectively.
Flavopiridol (Alvocidib)

Flavopiridol (Alvocidib, HMR-1275, L86-8275) is a pan-CDK inhibitor targeting CDK1, CDK2, CDK4, CDK5, CDK6 and CDK9 with IC50 of 30 nM, 170 nM, 100 nM, 170 nM, 80 nM and 20 nM, respectively.
JNJ-7706621

JNJ-7706621 is a potent and multi-target inhibitor for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, Aurora A and Aurora B with IC50 of 9 nM, 4 nM, 3 nM, 11 nM and 15 nM, respectively.
PHA-793887
PHA-793887 is a novel and potent inhibitor of CDK2, CDK5 and CDK7 with IC50 of 8 nM, 5 nM and 10 nM, respectively.
AT7519

AT7519 is a novel multi-CDK inhibitor for CDK1/cyclin B, CDK2/Cyclin A, CDK3/Cyclin E, CDK4/Cyclin D1, CDK5/p35 and CDK6/Cyclin D3 with IC50 of 210 nM, 47 nM, 360 nM, 100 nM, 13 nM and 170 nM, respectively.
BS-181 HCl

BS-181 is a highly selective CDK inhibitor for CDK7 with IC50 of 21 nM.
PD 0332991 (Palbociclib) Isethionate
PD 0332991 (Palbociclib) Isethionate is the isethionate of PD 0332991, a highly specific inhibitor of CDK4 and CDK6 with IC50 of 11 nM and 16 nM, respectively.
BMS-265246
BMS265246 is a potent and selective CDK inhibitor for CDK1/cyclin B and CDK2/cyclin E with IC50 of 6 nM and 9 nM, respectively.
AZD5438
AZD5438 is a potent inhibitor of CDK1, CDK2 and CDK9 with IC50 of 16 nM, 6 nM, and 20 nM, respectively.

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PD 0332991 (Palbociclib) HCl Licensed by Pfizer

Validation & Quality Control

Product Citations(5)

Customer Reviews(7) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

PD 0332991 (Palbociclib) HCl is available in the following compound libraries:

Product Information

Compare CDK Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]

References

Chemical Information

Research Area

Customer Reviews (7)

Product Citations (5)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related CDK Inhibitors

Cell Cycle and DNA Damage Related Products

Recently Viewed Items

Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1116	PD 0332991 (Palbociclib) HCl	30 mg/mL	3 mg/mL	<1 mg/mL
S2768	Dinaciclib (SCH727965)	<1 mg/mL	79 mg/mL	26 mg/mL
S1524	AT7519	<1 mg/mL	10 mg/mL	<1 mg/mL
S2679	Flavopiridol (Alvocidib) HCl	37 mg/mL	88 mg/mL	<1 mg/mL
S1153	Roscovitine (Seliciclib, CYC202)	<1 mg/mL	71 mg/mL	6 mg/mL
S1145	SNS-032 (BMS-387032)	<1 mg/mL	76 mg/mL	<1 mg/mL
S1249	JNJ-7706621	<1 mg/mL	79 mg/mL	<1 mg/mL
S1572	BS-181 HCl	3 mg/mL	83 mg/mL	27 mg/mL
S2735	SCH 900776	<1 mg/mL	60 mg/mL	3 mg/mL
S1487	PHA-793887	<1 mg/mL	72 mg/mL	72 mg/mL
S2621	AZD5438	<1 mg/mL	74 mg/mL	74 mg/mL
S2742	PHA-767491	<1 mg/mL	24 mg/mL	<1 mg/mL
S2751	Milciclib (PHA-848125)	<1 mg/mL	92 mg/mL	<1 mg/mL
S2670	A-674563	72 mg/mL	72 mg/mL	18 mg/mL
S1230	Flavopiridol (Alvocidib)	<1 mg/mL	15 mg/mL	8 mg/mL
S2688	R547	<1 mg/mL	60 mg/mL	<1 mg/mL
S2014	BMS-265246	<1 mg/mL	20 mg/mL	<1 mg/mL
S1579	PD 0332991 (Palbociclib) Isethionate	100 mg/mL	<1 mg/mL	<1 mg/mL

Choose Your Country or Region

Product Categories

PD 0332991 (Palbociclib) HCl Licensed by Pfizer

Validation & Quality Control

Product Citations(5)

Customer Reviews(7) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

PD 0332991 (Palbociclib) HCl is available in the following compound libraries:

Product Information

Compare CDK Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

Animal Study: [1]

References

Chemical Information

Research Area

Customer Reviews (7)

Product Citations (5)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related CDK Inhibitors

Cell Cycle and DNA Damage Related Products

Recently Viewed Items

E-newsletter

Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[1]