Palbociclib Isethionate | PD0332991 | CAS#571190-30-2 | CAS#827022-32-2 | 827022-33-3 | CDK inhibitor

MedKoo Cat#: 106610 | Name: Palbociclib Isethionate

Description:

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

Palbociclib, also known as PD0332991, is an orally available pyridopyrimidine-derived cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. PD-0332991 selectively inhibits cyclin-dependent kinases (particularly Cdk4/cyclin D1 kinase), which may inhibit retinoblastoma (Rb) protein phosphorylation; inhibition of Rb phosphorylation prevents Rb-positive tumor cells from entering the S phase of the cell cycle (arrest in the G1 phase), resulting in suppression of DNA replication and decreased tumor cell proliferation. PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50 = 0.011 μmol/L) and Cdk6 (IC50 = 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. Isethionate was approved on 2/3/2015 for treatment of advanced (metastatic) breast cancer.

Chemical Structure

Palbociclib Isethionate

CAS#827022-33-3 (isethionate)

Theoretical Analysis

MedKoo Cat#: 106610

Name: Palbociclib Isethionate

CAS#: 827022-33-3 (isethionate)

Chemical Formula: C26H35N7O6S

Exact Mass: 0.0000

Molecular Weight: 573.67

Elemental Analysis: C, 54.44; H, 6.15; N, 17.09; O, 16.73; S, 5.59

Price and Availability

Size	Price	Availability
100mg	USD 90.00	Ready to ship
200mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 450.00	Ready to ship
2g	USD 750.00	Ready to ship
5g	USD 1,650.00	Ready to ship

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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 Isethionate, 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 2-hydroxyethane-1-sulfonate

InChi Key

LYYVFHRFIJKPOV-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H29N7O2.C2H6O4S/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;3-1-2-7(4,5)6/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29);3H,1-2H2,(H,4,5,6)

SMILES Code

O=C1C(C(C)=O)=C(C)C2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5.OCCS(=O)(O)=O

Appearance

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 DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in 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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T04K10

QC Data

View QC data: current batch, Lot#A8T04K10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	17.40
	H2O	50.0	87.20

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 573.67 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.

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:

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.

1: Wu J, Wang J, O'Connor TN, Tzetzo SL, Gurova KV, Knudsen ES, Witkiewicz AK. Separable cell cycle arrest and immune response elicited through pharmacological CDK4/6 and MEK inhibition in RASmut disease models. Mol Cancer Ther. 2024 Aug 16. doi: 10.1158/1535-7163.MCT-24-0369. Epub ahead of print. PMID: 39148328. 2: Fu JF, Hsu CL, Hsu PC. The antitumor activity of osimertinib plus palbociclib in non-small cell lung cancer patient-derived xenograft (PDX)/2D/3D culture models harboring EGFR amplification and CDKN2A/2B homozygous deletions. Neoplasia. 2024 Aug 14;57:101039. doi: 10.1016/j.neo.2024.101039. Epub ahead of print. PMID: 39146623. 3: Wen Y, Sun X, Zeng L, Liang S, Li D, Chen X, Zeng F, Zhang C, Wang Q, Zhong Q, Deng L, Guo L. CDK4/6 Inhibitors Impede Chemoresistance and Inhibit Tumor Growth of Small Cell Lung Cancer. Adv Sci (Weinh). 2024 Aug 13:e2400666. doi: 10.1002/advs.202400666. Epub ahead of print. PMID: 39136283. 4: Chen BF, Tsai YF, Chao TC, Lien PJ, Lin YS, Feng CJ, Chen YJ, Cheng HF, Liu CY, Lai JI, Tseng LM, Huang CC. Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population. Clin Exp Med. 2024 Aug 12;24(1):185. doi: 10.1007/s10238-024-01458-1. PMID: 39133334; PMCID: PMC11319386. 5: Lin W, Zeng Y, Weng L, Yang J, Zhuang W. Comparative analysis of adverse events associated with CDK4/6 inhibitors based on FDA's adverse event reporting system: a case control pharmacovigilance study. BMC Pharmacol Toxicol. 2024 Aug 9;25(1):47. doi: 10.1186/s40360-024-00770-6. PMID: 39123221; PMCID: PMC11312934. 6: Beypınar İ, Demir H, Yaslıkaya Ş, Köşeci T, Demir B, Çolak G, Ağaoğlu AB, Şahbazlar M, Şancı PC, Çabuk D, Işık U, Şahin E, Coşkun A, Caner B, Aykut T, Artaç M, Duygulu ME, Sever N, Öksüz S, Turan N, Aykan MB, Tüzün EK, Uysal M, Uğurlu İ, Sakin A, Acar C, Özaşkın D, Şakalar T, Keskinkılıç M, Yavuzşen T, Köse N, Ertürk İ, Yıldırım N, Balçık OY, Alkan A, Selvi O, Erçin E, Ünal OÜ, Karaçin C. Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study. Breast Cancer Res Treat. 2024 Aug 9. doi: 10.1007/s10549-024-07456-x. Epub ahead of print. PMID: 39123071. 7: Patil PH, Desai MP, Rao RR, Mutalik S, Puralae Channabasavaiah J. Strategy to Improve the Oral Pharmacokinetics of Cyclin-Dependent Kinase 4/6 Inhibitors: Enhancing Permeability and CYP450 Inhibition by a Natural Bioenhancer. AAPS PharmSciTech. 2024 Aug 8;25(6):181. doi: 10.1208/s12249-024-02899-3. PMID: 39117933. 8: Baziyar MA, Hosseini A, Jandel F. The role of palbociclib on the alterations in CDKN2, CCNE1, E2F3, MDM2 expressions as target genes of miR-141. PLoS One. 2024 Aug 8;19(8):e0306545. doi: 10.1371/journal.pone.0306545. PMID: 39116089; PMCID: PMC11309483. 9: Mehata AK, Bonlawar J, Tamang R, Malik AK, Setia A, Kumar S, Challa RR, Vallamkonda B, Koch B, Muthu MS. PLGA Nanoplatform for the Hypoxic Tumor Delivery: Folate Targeting, Therapy, and Ultrasound/Photoacoustic Imaging. ACS Appl Bio Mater. 2024 Aug 8. doi: 10.1021/acsabm.4c00853. Epub ahead of print. PMID: 39115968. 10: Tzoumpa S, Bejar C, Villette B, Louveau B, Zelek L, Martin A, Briard O, Bitout D, Caux F, Battistella M, Mourah S, Maubec E. Clinical benefit from palbociclib, letrozole and goserelin combination therapy for sweat gland carcinoma with neuroendocrine differentiation (SCAND). J Eur Acad Dermatol Venereol. 2024 Aug 8. doi: 10.1111/jdv.20276. Epub ahead of print. PMID: 39115046. 11: Elazzazy S, Al-Ziftawi NH, Mohamed Ibrahim MI, Bujassoum S, Hamad A. Comparative cost-effectiveness analysis of CDK4/6 inhibitors in the first-line treatment of HR-positive and HER2-negative advanced breast cancer: a Markov's model-based evaluation. Front Oncol. 2024 Jul 24;14:1413676. doi: 10.3389/fonc.2024.1413676. PMID: 39114308; PMCID: PMC11303311. 12: Yang H, Zhang X, Xu L, Zhou Y, Ma R, Chen H, Zhao S, Baatar M, Chen L, Deng X, Gu H, Wang X. Palbociclib-derived multifunctional molecules for lysosomal targeting and diagnostic-therapeutic integration. Future Med Chem. 2024 Jul 2;16(13):1287-1298. doi: 10.1080/17568919.2024.2347072. Epub 2024 May 22. PMID: 39109433; PMCID: PMC11318731. 13: Patil PH, Desai M, Birangal S, Gurupur GS, Rao M, Yadav A, Kurawattimath V, Chaudhari A, Sharma T, Pinjari J, Channabasavaiah JP. The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter- Mediated Drug-Drug Interactions. Eur J Drug Metab Pharmacokinet. 2024 Aug 6. doi: 10.1007/s13318-024-00909-0. Epub ahead of print. PMID: 39105991. 14: Vanni S, Miserocchi G, Gallo G, Fausti V, Gabellone S, Liverani C, Spadazzi C, Cocchi C, Calabrese C, De Luca G, Bassi M, Gessaroli M, Tomasetti N, Campobassi A, Pieri F, Ercolani G, Cavaliere D, Gurrieri L, Riva N, Recine F, Ibrahim T, Mercatali L, Jones R, De Vita A. Role of CDK4 as prognostic biomarker in Soft Tissue Sarcoma and synergistic effect of its inhibition in dedifferentiated liposarcoma sequential treatment. Exp Hematol Oncol. 2024 Aug 5;13(1):74. doi: 10.1186/s40164-024-00540-4. PMID: 39103896; PMCID: PMC11299298. 15: Rauthan A, Jain A, Singh M, Sendur MAN. Palbociclib in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer: A Systematic Scoping Review of Real-World Evidence from Countries Outside of Western Regions that Are Underrepresented in Clinical Trials. Oncol Ther. 2024 Aug 2. doi: 10.1007/s40487-024-00295-2. Epub ahead of print. PMID: 39095679. 16: Álvarez Criado J, Zamora Auñon P, Martínez Marín V, GarcíaTrevijano Cabetas M, Collada Sánchez VL, Espinosa Arranz E, Romero-Garrido JA, Benedi-González J, Díaz Almirón M, Herrero Ambrosio A. Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast. J Oncol Pharm Pract. 2024 Aug 2:10781552241269677. doi: 10.1177/10781552241269677. Epub ahead of print. PMID: 39095042. 17: Sen A, Khan S, Rossetti S, Broege A, MacNeil I, DeLaForest A, Molden J, Davis L, Iversrud C, Seibel M, Kopher R, Schulz S, Laing L. Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway. Mol Oncol. 2024 Aug 2. doi: 10.1002/1878-0261.13703. Epub ahead of print. PMID: 39092562. 18: Wang C, Hwang M, Paulson B, Mhandire D, Ozair S, O'Connor TL, Gandhi S, Attwood KM, Hertz DL, Goey AK. Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity. Pharmacogenomics. 2024 Aug 2:1-9. doi: 10.1080/14622416.2024.2380240. Epub ahead of print. PMID: 39092502. 19: Chen SH, Chen CH, Lin HC, Yeh SA, Hwang TL, Chen PJ. Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis. J Adv Res. 2024 Jul 31:S2090-1232(24)00310-2. doi: 10.1016/j.jare.2024.07.026. Epub ahead of print. PMID: 39089617. 20: Attwa MW, Abdelhameed AS, Kadi AA. An ultra-fast ultra-high-performance liquid chromatography-tandem mass spectrometry method for estimating the in vitro metabolic stability of palbociclib in human liver microsomes: In silico study for metabolic lability, absorption, distribution, metabolism, and excretion features, and DEREK alerts screening. J Sep Sci. 2024 Aug;47(15):e2400346. doi: 10.1002/jssc.202400346. PMID: 39087624.