Palbociclib HCl
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202173

CAS#: 827022-32-2 (HCl)

Description: Palbociclib, also known as PD0332991, 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.


Chemical Structure

img
Palbociclib HCl
CAS# 827022-32-2 (HCl)

Theoretical Analysis

MedKoo Cat#: 202173
Name: Palbociclib HCl
CAS#: 827022-32-2 (HCl)
Chemical Formula: C24H29N7O2
Exact Mass: 0.00
Molecular Weight: 483.990
Elemental Analysis: C, 59.56; H, 6.25; Cl, 7.33; N, 20.26; O, 6.61

Price and Availability

Size Price Availability Quantity
100mg USD 90 Ready to ship
200mg USD 150 Ready to ship
500mg USD 250 Ready to ship
1g USD 450 Ready to ship
2g USD 750 Ready to ship
5g USD 1650 Ready to ship
Bulk inquiry

Related CAS #: 571190-30-2 (free base)   827022-32-2 (HCl)   827022-33-3 (isethionate)   Unknown (Palbociclib-SMCC)   Unknown (Succinic)  

Synonym: PD 0332991; PD-0332991; PD0332991; PD0332991; PD332991; PD-332991; PD 332991; Palbociclib, brand name: Ibrance

IUPAC/Chemical Name: 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride

InChi Key: STEQOHNDWONVIF-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H29N7O2.ClH/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32;/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29);1H

SMILES Code: O=C1C(C(C)=O)=C(C)C2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5.[H]Cl

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in water and ethanol; slightly soluble in DMSO with warm.

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in water or DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Palbociclib is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. In the G1 phase of the cell cycle, mammalian cells must pass a checkpoint, known as the restriction point “R”, in order to complete the cell cycle and divide. CDK4 and CDK6 complex with cyclin D drive the phosphorylation of the retinoblastoma protein, Rb, which allows the cell to pass R and commit to division. Regulation of one or more proteins involved in this checkpoint is lost in many cancers. However, by inhibiting CDK4/6, palbociclib ensures that the cyclin D-CDK4/6 complex cannot aid in phosphorylating Rb. This prevents the cell from passing R and exiting G1, and in turn from proceeding through the cell cycle.  

Biological target: Palbociclib (PD 0332991) monohydrochloride is a CDK4/6 inhibitor with IC50s of 11 nM and 16 nM, respectively.
In vitro activity: In the current study, activation of RB via treatment with the CDK4/6 inhibitor palbociclib in A549 lung adenocarcinoma cells results in a metabolic shift wherein palbociclib alters aspects of glucose and glutamine utilization. Specifically, palbociclib decreases glucose metabolism through the PPP via inhibition of G6PD activity (Fig. 3a–c), while increasing glutaminolysis to maintain basal mitochondrial function (Fig. 6c, f). Moreover, both changes observed were rescued upon knockdown of RB, suggesting the metabolic consequences of CDK4/6 inhibition in A549 cells are RB-dependent. Reference: Cancer Cell Int. 2020; 20: 280. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329430/
In vivo activity: Mice were sensitized by repeated administration of OVA (ovalbumin) with alum adjuvant, and anaphylaxis was induced with an intraperitoneal OVA challenge, as shown in Fig. 5a. Ketotifen treatment was as positive control. OVA mice exhibited decreasing rectal temperatures 30–50 min after the OVA challenge injection, and these temperature reductions were attenuated by palbociclib (Fig. 5b). Concomitantly, total serum IL-4 and IL-10 levels reflective of inflammation were increased after the OVA challenge and those increases were suppressed by palbociclib (Fig. 5c, d). Reference: J Transl Med. 2019; 17: 276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702723/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 1.0 2.10
H2O 20.0 41.30

Preparing Stock Solutions

The following data is based on the product molecular weight 483.99 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Conroy LR, Lorkiewicz P, He L, Yin X, Zhang X, Rai SN, Clem BF. Palbociclib treatment alters nucleotide biosynthesis and glutamine dependency in A549 cells. Cancer Cell Int. 2020 Jul 1;20:280. doi: 10.1186/s12935-020-01357-x. PMID: 32624705; PMCID: PMC7329430. 2. Sun Y, Sun Y, Yan K, Li Z, Xu C, Geng Y, Pan C, Chen X, Zhang L, Xi Q. Potent anti-tumor efficacy of palbociclib in treatment-naïve H3.3K27M-mutant diffuse intrinsic pontine glioma. EBioMedicine. 2019 May;43:171-179. doi: 10.1016/j.ebiom.2019.04.043. Epub 2019 May 3. PMID: 31060906; PMCID: PMC6558223. 3. Wang TH, Chen CC, Leu YL, Lee YS, Lian JH, Hsieh HL, Chen CY. Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma. J Formos Med Assoc. 2020 Dec 18:S0929-6646(20)30609-4. doi: 10.1016/j.jfma.2020.12.009. Epub ahead of print. PMID: 33342707. 4. Hou YB, Ji K, Sun YT, Zhang LN, Chen JJ. CDK4/6 inhibitor palbociclib suppresses IgE-mediated mast cell activation. J Transl Med. 2019 Aug 20;17(1):276. doi: 10.1186/s12967-019-2026-9. PMID: 31429774; PMCID: PMC6702723.
In vitro protocol: 1. Conroy LR, Lorkiewicz P, He L, Yin X, Zhang X, Rai SN, Clem BF. Palbociclib treatment alters nucleotide biosynthesis and glutamine dependency in A549 cells. Cancer Cell Int. 2020 Jul 1;20:280. doi: 10.1186/s12935-020-01357-x. PMID: 32624705; PMCID: PMC7329430. 2. Sun Y, Sun Y, Yan K, Li Z, Xu C, Geng Y, Pan C, Chen X, Zhang L, Xi Q. Potent anti-tumor efficacy of palbociclib in treatment-naïve H3.3K27M-mutant diffuse intrinsic pontine glioma. EBioMedicine. 2019 May;43:171-179. doi: 10.1016/j.ebiom.2019.04.043. Epub 2019 May 3. PMID: 31060906; PMCID: PMC6558223.
In vivo protocol: 1. Wang TH, Chen CC, Leu YL, Lee YS, Lian JH, Hsieh HL, Chen CY. Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma. J Formos Med Assoc. 2020 Dec 18:S0929-6646(20)30609-4. doi: 10.1016/j.jfma.2020.12.009. Epub ahead of print. PMID: 33342707. 2. Hou YB, Ji K, Sun YT, Zhang LN, Chen JJ. CDK4/6 inhibitor palbociclib suppresses IgE-mediated mast cell activation. J Transl Med. 2019 Aug 20;17(1):276. doi: 10.1186/s12967-019-2026-9. PMID: 31429774; PMCID: PMC6702723.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK547882/ PubMed PMID: 31643218.

2: Serra F, Lapidari P, Quaquarini E, Tagliaferri B, Sottotetti F, Palumbo R. Palbociclib in metastatic breast cancer: current evidence and real-life data. Drugs Context. 2019 Jul 16;8:212579. doi: 10.7573/dic.212579. eCollection 2019. Review. PubMed PMID: 31391852; PubMed Central PMCID: PMC6668507.

3: Bellet M, Ahmad F, Villanueva R, Valdivia C, Palomino-Doza J, Ruiz A, Gonzàlez X, Adrover E, Azaro A, Valls-Margarit M, Parra JL, Aguilar J, Vidal M, Martín A, Gavilá J, Escrivá-de-Romaní S, Perelló A, Hernando C, Lahuerta A, Zamora P, Reyes V, Alcalde M, Masanas H, Céliz P, Ruíz I, Gil M, Seguí MÀ, de la Peña L. Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication. Ther Adv Med Oncol. 2019 May 10;11:1758835919833867. doi: 10.1177/1758835919833867. eCollection 2019. Review. PubMed PMID: 31205497; PubMed Central PMCID: PMC6535716.

4: Poratti M, Marzaro G. Third-generation CDK inhibitors: A review on the synthesis and binding modes of Palbociclib, Ribociclib and Abemaciclib. Eur J Med Chem. 2019 Jun 15;172:143-153. doi: 10.1016/j.ejmech.2019.03.064. Epub 2019 Apr 4. Review. PubMed PMID: 30978559.

5: Eggersmann TK, Degenhardt T, Gluz O, Wuerstlein R, Harbeck N. CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. BioDrugs. 2019 Apr;33(2):125-135. doi: 10.1007/s40259-019-00337-6. Review. PubMed PMID: 30847853.

6: Petrelli F, Ghidini A, Pedersini R, Cabiddu M, Borgonovo K, Parati MC, Ghilardi M, Amoroso V, Berruti A, Barni S. Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials. Breast Cancer Res Treat. 2019 Apr;174(3):597-604. doi: 10.1007/s10549-019-05133-y. Epub 2019 Jan 18. Review. PubMed PMID: 30659432.

7: McShane TM, Wolfe TA, Ryan JC. Updates on managing advanced breast cancer with palbociclib combination therapy. Ther Adv Med Oncol. 2018 Sep 3;10:1758835918793849. doi: 10.1177/1758835918793849. eCollection 2018. Review. Erratum in: Ther Adv Med Oncol. 2018 Dec 03;10:1758835918810117. PubMed PMID: 30202448; PubMed Central PMCID: PMC6122240.

8: De Luca A, Maiello MR, D'Alessio A, Frezzetti D, Gallo M, Carotenuto M, Normanno N. Pharmacokinetic drug evaluation of palbociclib for the treatment of breast cancer. Expert Opin Drug Metab Toxicol. 2018 Sep;14(9):891-900. doi: 10.1080/17425255.2018.1514720. Epub 2018 Sep 3. Review. PubMed PMID: 30130984.

9: Palbociclib for breast cancer. Aust Prescr. 2018 Aug;41(4):127-128. doi: 10.18773/austprescr.2018.029. Epub 2018 Jun 12. Review. PubMed PMID: 30116084; PubMed Central PMCID: PMC6091774.

10: Schmidt M, Sebastian M. Palbociclib-The First of a New Class of Cell Cycle Inhibitors. Recent Results Cancer Res. 2018;211:153-175. doi: 10.1007/978-3-319-91442-8_11. Review. PubMed PMID: 30069766.

11: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500860/ PubMed PMID: 29999919.

12: Laderian B, Fojo T. CDK4/6 Inhibition as a therapeutic strategy in breast cancer: palbociclib, ribociclib, and abemaciclib. Semin Oncol. 2017 Dec;44(6):395-403. doi: 10.1053/j.seminoncol.2018.03.006. Epub 2018 Mar 26. Review. PubMed PMID: 29935901.

13: de Dueñas EM, Gavila-Gregori J, Olmos-Antón S, Santaballa-Bertrán A, Lluch-Hernández A, Espinal-Domínguez EJ, Rivero-Silva M, Llombart-Cussac A. Preclinical and clinical development of palbociclib and future perspectives. Clin Transl Oncol. 2018 Sep;20(9):1136-1144. doi: 10.1007/s12094-018-1850-3. Epub 2018 Mar 21. Review. PubMed PMID: 29564714.

14: Liu M, Liu H, Chen J. Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncol Rep. 2018 Mar;39(3):901-911. doi: 10.3892/or.2018.6221. Epub 2018 Jan 19. Review. PubMed PMID: 29399694.

15: Xu Y, Li X, Xu YF, Yang XM. Poorly Differentiated Esophageal Neuroendocrine Carcinoma Treated With the CDK4/6 Inhibitor, Palbociclib: A Case Report and Literature Review. Am J Ther. 2018 Sep/Oct;25(5):e595-e598. doi: 10.1097/MJT.0000000000000610. Review. PubMed PMID: 29232286.

16: Raiss H, Péron J, Tartas S, Trillet-Lenoir V, Freyer G, Errihani H. Palbociclib-Induced Thrombotic Microangiopathy in Metastatic Breast Cancer Patient Surviving for 18 Years: Case Report and Review of the Literature. Clin Breast Cancer. 2018 Jun;18(3):e263-e266. doi: 10.1016/j.clbc.2017.10.001. Epub 2017 Oct 7. Review. PubMed PMID: 29153774.

17: Wilson FR, Varu A, Mitra D, Cameron C, Iyer S. Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer. Breast Cancer Res Treat. 2017 Nov;166(1):167-177. doi: 10.1007/s10549-017-4404-4. Epub 2017 Jul 27. Review. PubMed PMID: 28752187; PubMed Central PMCID: PMC5645434.

18: Kwapisz D. Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib. Breast Cancer Res Treat. 2017 Nov;166(1):41-54. doi: 10.1007/s10549-017-4385-3. Epub 2017 Jul 24. Review. PubMed PMID: 28741274.

19: Ettl J, Harbeck N. The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Expert Rev Anticancer Ther. 2017 Aug;17(8):661-668. doi: 10.1080/14737140.2017.1347506. Epub 2017 Jul 12. Review. PubMed PMID: 28649895.

20: Costa R, Costa RB, Talamantes SM, Helenowski I, Peterson J, Kaplan J, Carneiro BA, Giles FJ, Gradishar WJ. Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib. Breast. 2017 Oct;35:1-7. doi: 10.1016/j.breast.2017.05.016. Epub 2017 Jun 12. Review. PubMed PMID: 28618307.