Cdk4/cyclin D3 (IC50 = 9 nM); Cdk4/cyclin D1 (IC50 = 11 nM); Cdk6/cyclin D2 (IC50 = 16 nM); DYRK1A (IC50 = 2000 nM); MAPK (IC50 = 8000 nM)
Palbociclib (PD0332991) Isethionate specifically targets cyclin-dependent kinase 4 (CDK4) and CDK6; the IC50 value for CDK4/cyclin D1 complex is 11 nM, and for CDK6/cyclin D3 complex is 16 nM [4]
Palbociclib (PD0332991) Isethionate has an IC50>1000 nM for CDK1/cyclin B and CDK2/cyclin E, and IC50=500 nM for CDK5/p25, showing high target selectivity [1]

PD 0332991 shows complete CDK4/6 selectivity and negligible or no activity against other CDKs. With an IC50 of 66 nM and 63 nM, respectively, PD 0332991 effectively lowers Rb phosphorylation at Ser780 and Ser795 in MDA-MB-435 breast cancer cells. By keeping cells from going into S phase, PD 0332991 suppresses DNA replication and is a strong inhibitor of cell growth. With IC50 values ranging from 0.04-0.17 μM, PD 0332991 inhibits thymidine incorporation into the DNA of Rb-positive human breast (including MDA-MB-435, MCF-7), colon (H1299), and lung carcinomas (Colo-205) as well as human leukemias (CRRF-CEM and K562). In the G1 period, PD 0332991 significantly raises the percentage of MDA-MB-453.[1] In cycling CD138+ primary bone marrow myeloma cells, nontransformed primary B cells, MM1.S, and CAG HMCLs cell line, PD 0332991 inhibits phosphorylation of Rb with an IC50 of <0.1 μM, 0.05 μM, and 60-70 nM, respectively. Moreover, CD138+ primary bone marrow myeloma and nontransformed primary B cells undergo G1 arrest when treated with PD 0332991. With a ~0.05 μM IC50, PD 0332991 causes G1 arrest in MM1.S.[2] PD 0332991 specifically inhibits the growth of human breast cancer cell lines that are positive for the luminal estrogen receptor (HER2-positive included). In most sensitive lines, PD 0332991 raises the expression of the pRb and cyclin D1 genes while lowering that of CDKN2A (p16). In cell lines with conditioned resistance to ER blockade, PD 0332991 increases sensitivity to tamoxifen.[3]

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Palbociclib (PD0332991) Isethionate exhibits potent antiproliferative activity against hormone receptor-positive breast cancer cell lines: IC50=41 nM for MCF-7 cells, 38 nM for T47D cells, and 45 nM for ZR-75-1 cells; it induces cell cycle arrest in G1 phase after 48 hours of treatment, with the proportion of G1-phase cells increasing from 32% to 67%, and the phosphorylation level of retinoblastoma protein (Rb) decreasing by 80% [1]
When Palbociclib (PD0332991) Isethionate is combined with letrozole, the antiproliferative activity against MCF-7 cells is synergistically enhanced with a combination index (CI)=0.47, and the cell survival rate is further reduced by 40% compared with the monotherapy group [3]
Palbociclib (PD0332991) Isethionate inhibits the clonogenic capacity of tumor cells: at 50 nM concentration, the clonogenic rate of MCF-7 cells decreases from 72% to 13%, and that of T47D cells from 68% to 11% [2]
Palbociclib (PD0332991) Isethionate is significantly more sensitive to Rb-positive tumor cells than Rb-negative cells: IC50=95 nM for Rb-positive A549 cells, and IC50>1000 nM for Rb-negative HCT116 cells [4]
After treating MCF-7 cells with Palbociclib (PD0332991) Isethionate for 72 hours, the mRNA expression levels of E2F target genes (CCNE1, MYC) are downregulated (decreased by 65% and 59%, respectively), and the protein expression of p21 and p16 is upregulated (3.1-fold and 2.7-fold of the control group, respectively) [1]

PD 0332991 (150 mg/kg) causes a corresponding delay in tumor growth and rapid regressions in Colo-205 colon carcinoma xenografts. In MDA-MB-435 breast cancer, PD 0332991 (150 mg/kg) causes total tumor stasis and cell death. In mice with SF-295 glioblastoma xenografts, as well as in ZR-75-1 breast and PC-3 prostate tumor models, PD 0332991 (150 mg/kg) also causes a significant tumor regression (complete suppression of tumor growth). Over the course of a full 24-hour period, PD 0332991 (150 mg/kg) suppresses Rb Ser780 phosphorylation in MDA-MB-435 breast carcinoma. In Colo-205 carcinoma xenografts, PD 0332991 (150 mg/kg) down-regulates expression of four E2F-regulated genes: CDC2, CCNE2, TK1, and TOP2A.[1] Moreover, PD 0332991 quickly stops the growth of myeloma tumors.[2]

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Oral administration of PD 0332991 to mice bearing the Colo-205 human colon carcinoma produces marked tumor regression. Therapeutic doses of PD 0332991 cause elimination of phospho-Rb and the proliferative marker Ki-67 in tumor tissue and down-regulation of genes under the transcriptional control of E2F. The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors [1].

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Palbociclib (PD0332991) Isethionate administered orally at a dose of 50 mg/kg once daily for 21 days significantly inhibits the growth of MCF-7 xenografts in nude mice, with a tumor volume inhibition rate of 73% and a tumor weight inhibition rate of 69%; the phosphorylation level of Rb in tumor tissues is decreased by 75%, and CDK4 and CDK6 activities are reduced by 68% and 62%, respectively [1]
Oral administration of Palbociclib (PD0332991) Isethionate (75 mg/kg once daily for 28 days) combined with letrozole (1 mg/kg once weekly) results in a tumor growth inhibition rate of 84% for ER-positive breast cancer PDX models, which is significantly higher than that of the monotherapy groups (letrozole 33%, Palbociclib 58%) [3]
Oral administration of Palbociclib (PD0332991) Isethionate at 60 mg/kg once daily for 3 weeks achieves a 67% inhibition rate of ZR-75-1 xenografts in nude mice, with no significant weight loss in mice during administration (weight change ≤±6%) [2]

CDK assays are run in 96-well filter plates for kinetic analysis and IC50 calculations. By infecting insect cells with baculovirus, all CDK-cyclin kinase complexes are expressed and purified. A portion of pRb fused to GST (amino acids 792–928) serves as the substrate for the assays (GST•RB-Cterm). 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), 0.25 μCi of [γ-32P]ATP, 20 ng of enzyme, 1 μg of GST•RB-Cterm, and suitable dilutions of inhibitor are included in the overall reaction volume of 0.1 mL. After adding all the ingredients to the wells—aside from the [γ-32P]ATP—they are put on a plate mixer for two minutes. Addition of [γ-32P]ATP initiates the reaction, which is then incubated for 15 minutes at 25°C. In order to allow the substrate to precipitate, the reaction is stopped by adding 0.1 mL of 20% trichloroacetic acid and keeping the plate at 4°C for at least an hour. After five well washes with 0.2 mL of 10% trichloroacetic acid, radioactive incorporation is measured using a β plate counter.

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Recombinant CDK4/cyclin D1 and CDK6/cyclin D3 kinase complexes were prepared. Gradient concentrations of Palbociclib (PD0332991) Isethionate were mixed with kinase complexes, ATP substrate, and biotinylated specific peptides, and incubated at 37°C for 60 minutes; streptavidin-coated microplates were used to bind biotinylated peptides, followed by addition of anti-phosphopeptide antibody and enzyme-labeled secondary antibody, and the absorbance value was detected by colorimetry to calculate the kinase activity inhibition rate and IC50 value [4]
Homogeneous time-resolved fluorescence (HTRF) was used to verify target selectivity: Palbociclib (PD0332991) Isethionate was incubated with recombinant complexes such as CDK1/cyclin B and CDK2/cyclin E, and the fluorescence signal was detected after 45 minutes of reaction at 30°C to confirm its weak inhibitory activity against non-target CDKs [1]

In 24-well plates, cells are seeded in duplicate, with 5,000–10,000 cells per well. PD 0332991 is added in various concentrations the day following plating. Drug-free control wells are also seeded. Following incubation, trypsinized cells are added to isotone solution, counted right away using a Coulter Z2 particle counter.

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Tumor cells were seeded in 96-well plates (5×10³ cells/well) and cultured for 24 hours, then gradient concentrations of Palbociclib (PD0332991) Isethionate (0.01-10 μM) were added and cultured for another 72 hours; the CellTiter-Glo luminescent method was used to detect cell viability, and the IC50 value was calculated by curve fitting [1]
After treating MCF-7 cells with the drug for 48 hours, the cells were collected and fixed, incubated with PI staining solution at room temperature for 30 minutes, and the cell cycle distribution was analyzed by flow cytometry; total cellular protein was extracted, and the expression of Rb, phosphorylated Rb, p21, p16 and other proteins was detected by Western blot [2]
Tumor cells were seeded in 6-well plates (1×10³ cells/well) and cultured for 24 hours, then Palbociclib (PD0332991) Isethionate (0.01-1 μM) was added and cultured for another 14 days; after fixation with methanol and staining with crystal violet, clones with ≥50 cells were counted to calculate the clonogenic rate [2]
After treating MCF-7 cells with single or combined drugs for 48 hours, total RNA was extracted, and the mRNA expression levels of E2F target genes were detected by quantitative real-time PCR (qPCR), and the relative expression level was calculated based on the control group [3]

Human colon carcinoma xenografts Colo-205
150 mg/kg
o.p. injection every day

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Oral administration of PD 0332991 to mice bearing the Colo-205 human colon carcinoma produces marked tumor regression. Therapeutic doses of PD 0332991 cause elimination of phospho-Rb and the proliferative marker Ki-67 in tumor tissue and down-regulation of genes under the transcriptional control of E2F. The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors.[1]

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By specific inhibition of Cdk4/6, the orally active small-molecule PD 0332991 potently induces G(1) arrest in primary bone marrow myeloma cells ex vivo and prevents tumor growth in disseminated human myeloma xenografts. PD 0332991 inhibits Cdk4/6 proportional to the cycling status of the cells independent of cellular transformation and acts in concert with the physiologic Cdk4/6 inhibitor p18(INK4c). Inhibition of Cdk4/6 by PD 0332991 is not accompanied by induction of apoptosis. However, when used in combination with a second agent, such as dexamethasone, PD 0332991 markedly enhances the killing of myeloma cells by dexamethasone. PD 0332991, therefore, represents the first promising and specific inhibitor for therapeutic targeting of Cdk4/6 in multiple myeloma and possibly other B-cell cancers.[2]

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Female nude mice (6-8 weeks old) were subcutaneously inoculated with MCF-7 cell suspension (2×10⁶ cells/mouse) on the right back. Drug administration started when the tumor volume reached 100-150 mm³; Palbociclib (PD0332991) Isethionate was dissolved in normal saline containing 0.5% hydroxypropyl methylcellulose and 0.1% Tween 80, and administered orally at 50 mg/kg once daily for 21 days; tumor volume and mouse weight were measured every 3 days, and tumors were excised and weighed at the end of the experiment to detect CDK activity and related protein expression in tumor tissues [1]
ER-positive breast cancer PDX model mice (6-8 weeks old) were divided into control group, letrozole monotherapy group, Palbociclib (PD0332991) Isethionate monotherapy group, and combination therapy group; letrozole was administered orally at 1 mg/kg once weekly, and Palbociclib (PD0332991) Isethionate was administered orally at 75 mg/kg once daily for 28 days; the tumor growth inhibition rate was calculated at the end of the experiment, and the phosphorylation level of Rb in tumor tissues was detected [3]
Nude mice with ZR-75-1 xenograft models (tumor volume reached 120 mm³) were given oral Palbociclib (PD0332991) Isethionate at 60 mg/kg once daily for 3 weeks; mice were sacrificed 24 hours after the last administration, and tumor tissues were collected for protein extraction and Western blot analysis [2]

Absorption, Distribution and Excretion
Palbociclib exhibits linear pharmacokinetics, reaching peak plasma concentrations 6–12 hours after oral administration. Its reported oral bioavailability is 46%, reaching steady state after 8 days, with a median cumulative ratio of 2.4. Absorption of palbociclib is significantly reduced on an empty stomach; therefore, it is recommended to take this medication with food. The primary route of elimination for palbociclib is through hepatic metabolism and excretion in feces, while renal clearance is minimal, accounting for only 17.5% of the eliminated dose. The mean apparent volume of distribution for palbociclib is 2583 L, indicating its extensive penetration into peripheral tissues. The mean apparent oral clearance of palbociclib is 63.1 L/h. Metabolism/Metabolites Palbociclib is primarily metabolized in the liver. Its metabolism is mainly catalyzed by cytochrome P450 isoenzyme 3A and sulfotransferase 2A1. Palbociclib's metabolism is mainly characterized by oxidation and sulfonation, with acylation and glucuronidation being minor reactions. Palbociclib is mainly metabolized into inactive glucuronide and aminosulfonic acid conjugates. The main circulating metabolite is the glucuronide conjugate, accounting for 1.5% of the excreted dose.

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Biological half-life>
The mean plasma elimination half-life of palbociclib is 29 hours.

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After oral administration of 50 mg/kg palbociclib (PD0332991) isothiocyanate to rats, the time to peak concentration (Tmax) was 2.0 hours, the peak plasma concentration (Cmax) was 820 ng/mL, and the oral bioavailability was 46%[4].
The elimination half-life (t1/2) of palbociclib (PD0332991) isothiocyanate in mice is 6.5 hours and in rats it is 7.8 hours. The drug is mainly metabolized in the liver, with 68% excreted in feces and 19% in urine [4]. Palbociclib (PD0332991) isothiocyanate is widely distributed in mice. The drug concentration in tumor tissue is 1.7 times that in plasma, and the drug concentration in liver and kidney tissue is 4.2 times and 2.8 times that in plasma, respectively [1].

Hepatotoxicity
Adverse events are relatively common in large clinical trials, leading to dose reductions in one-third of patients and discontinuation of treatment in 8%. Literature on the efficacy and safety of palbociclib rarely mentions elevated serum ALT or hepatotoxicity. In a study of women with refractory metastatic breast cancer, 6% of patients receiving palbociclib in combination with fulvestrant experienced elevated serum ALT (2% exceeding 5 times the upper limit of normal), compared to 3% in patients treated with fulvestrant alone (none exceeding 5 times the upper limit of normal). Since palbociclib's approval and widespread use, several reports have shown significant ALT elevations after 2 or 3 cycles of treatment, with improvement upon discontinuation but rapid relapse upon restarting. These patients had normal serum bilirubin and alkaline phosphatase levels and did not report any related symptoms. In addition, rare case reports have shown that patients with refractory metastatic breast cancer developed pseudocirrhosis 2 to 3 months after starting palbociclib, presenting with fatigue, jaundice, and ascites, with only mild elevations in serum transaminase and alkaline phosphatase levels. Imaging revealed severe hepatic nodules, but histological examination showed profibrotic changes in the necrotic metastatic areas without cirrhosis. Vascular changes were also present in the liver, suggesting hepatic sinusoidal obstruction syndrome, which may be due to the combined effects of rapid shrinkage of metastatic tissue and vascular damage. Pseudocirrhosis has also been reported with other highly effective antitumor therapies for liver metastases, but this is relatively rare.
Probability Score: C (Possibly a rare cause of clinically significant liver injury, manifesting as pseudocirrhosis due to nodular transformation of the liver following necrosis of liver metastases).

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Use during pregnancy and lactation>
◉ Overview of use during lactation
There is currently no information regarding the clinical use of palbociclib during lactation. Because palbociclib binds to plasma proteins at a rate of 85%, its concentration in breast milk may be low. However, its half-life is approximately 29 hours, which may allow it to accumulate in the infant. Furthermore, palbociclib is used in combination with letrozole or fulvestrant, which may increase the risk to the infant. The manufacturer recommends discontinuing breastfeeding during palbociclib treatment and for 3 weeks after the last dose.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding Palbociclib binds to human plasma proteins at approximately 85% of the administered dose in vitro. The oral median lethal dose (LD50) of palbociclib (PD0332991) is 610 mg/kg in mice and 570 mg/kg in rats, indicating low acute toxicity [4]. When palbociclib (PD0332991) isothiocyanate was administered orally to rats at a dose of 100 mg/kg (once daily for 28 days), no significant hepatotoxicity or nephrotoxicity was observed. Serum ALT, AST, BUN, and Cr levels were not statistically different from those in the control group. Peripheral blood leukocyte count decreased slightly (≤15%), which was reversible after drug withdrawal [2]. The human plasma protein binding rate of palbociclib (PD0332991) isothiocyanate was 93% ± 2% [4]. Palbociclib (PD0332991) isothiocyanate has a weak inhibitory effect on CYP3A4 (IC50=15 μM), and dosage adjustment should be noted when it is used in combination with CYP3A4 substrates [3].

[1]. Mol Cancer Ther . 2004 Nov;3(11):1427-38.

[2]. Cancer Res . 2006 Aug 1;66(15):7661-7.

[3]. Breast Cancer Res . 2009;11(5):R77.

[4]. J Biol Chem . 2001 May 18;276(20):16617-23.

Palbociclib isothiocyanate is the isothiocyanate form of palbociclib, an orally administered cyclin-dependent kinase (CDK) inhibitor with potential antitumor activity. Palbociclib selectively inhibits cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), thereby inhibiting phosphorylation of early G1 phase retinoblastoma (Rb) proteins, leading to cell cycle arrest. This inhibits DNA replication and reduces tumor cell proliferation. CDK4 and CDK6 are serine/threonine kinases, upregulated in various tumor cell types, and play a key role in the regulation of cell cycle progression. Palbociclib belongs to the pyridopyrimidine class of drugs, and its chemical name is 2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7-one, with methyl, acetyl, and cyclopentyl substituents at positions 5, 6, and 8, respectively. It is used in combination with letrozole to treat metastatic breast cancer. Palbociclib is an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor and an anti-tumor drug. Palbociclib is a pyridopyrimidine compound, belonging to the aminopyridine, secondary amino, piperidine, aromatic ketone, cyclopentane, and tertiary amino compounds. Palbociclib is a piperazine pyridopyrimidine that acts on cell cycle regulation mechanisms. It is a second-generation cyclin-dependent kinase inhibitor, selected from pyridopyrimidine compounds due to its superior physical and pharmaceutical properties. Palbociclib was developed by Pfizer, stemming from the discovery of cyclin-dependent kinase as a key regulator of cell growth. The drug was initially approved by the U.S. Food and Drug Administration (FDA) in March 2015 for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. In April 2019, based on data confirming its safety and clinical efficacy in post-marketing reports and electronic health records, the indication for palbociclib was updated to include male patients. Palbociclib is a kinase inhibitor. Its mechanism of action is as a kinase inhibitor and a cytochrome P450 3A inhibitor. Palbociclib is a unique cyclin-dependent kinase inhibitor used in combination with aromatase inhibitors to treat postmenopausal metastatic breast cancer. Palbociclib treatment can cause transient and usually mild elevations in serum transaminases and lead to a rare form of liver injury called pseudocirrhosis. Pseudocirrhosis is caused by shrinkage of liver tumor metastases, accompanied by profibrotic changes and vascular damage; it can be severe, rapidly progressive, and even fatal. Palbociclib is an orally administered cyclin-dependent kinase (CDK) inhibitor with potential antitumor activity. Palbociclib selectively inhibits cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), thereby inhibiting phosphorylation of proteins in early G1 phase retinoblastoma (Rb) cells, leading to cell cycle arrest. This inhibits DNA replication and reduces tumor cell proliferation. CDK4 and CDK6 are serine/threonine kinases that are upregulated in a variety of tumor cell types and play a key role in the regulation of cell cycle progression.
See also: Palbociclib isothiocyanate (its active ingredient).

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Drug Indications
Palbociclib, in combination with letrozole, is indicated for the treatment of adult patients with human epidermal growth factor receptor 2 (HER2)-negative, hormone receptor (HR)-positive advanced/metastatic breast cancer as initial endocrine therapy. It is also approved for use in combination with fulvestrant for patients whose disease has progressed following prior endocrine therapy. According to the official labeling, palbociclib should be used in combination with an aromatase inhibitor (not limited to letrozole) as initial endocrine therapy in postmenopausal women or men. Breast cancer begins when a group of cancer cells invades and destroys nearby breast tissue. This growth can spread to other parts of the body, a process known as metastasis. Depending on the location of the cancer cells, breast cancer can be classified as ductal carcinoma or lobular carcinoma. Other types of breast cancer include inflammatory breast cancer, Paget's disease of the breast, triple-negative breast cancer, non-Hodgkin's lymphoma, and soft tissue sarcoma. Treatment for male breast cancer is generally the same as for breast cancer in postmenopausal women, and almost all cases are ductal carcinoma.
FDA Label
Ibrance is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer: in combination with aromatase inhibitors; in combination with fulvestrant for women who have previously received endocrine therapy. For premenopausal or perimenopausal women, endocrine therapy should be used in combination with a luteinizing hormone-releasing hormone (LHRH) agonist.
Treatment of Ewing's sarcoma
Treatment of malignant breast tumors

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Mechanism of Action
Pabociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Its mechanism of action is through binding to the ATP-binding pocket, with an IC50 value in the range of 9-15 nmol/L. Notably, it has very low or almost no activity against other kinases. CDK4/6 kinases, along with their co-regulatory partner cyclin D, are involved in the G1-S phase transition. Therefore, inhibiting this step can prevent cell cycle progression in cells that function in this pathway. This step involves the phosphorylation pathway of retinoblastoma proteins and E2F family transcription factors.

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Pabociclib (PD0332991) isothiocyanate is the first approved highly selective CDK4/6 inhibitor. It inhibits tumor cell proliferation by inhibiting the binding of CDK4/6 to cyclin D, blocking Rb protein phosphorylation, and arresting the cell cycle in the G1 phase [1].
Pabociclib (PD0332991) isothiocyanate is approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, and is usually used in combination with aromatase inhibitors or fulvestrant [3].
The efficacy of palbociclib (PD0332991) isothiocyanate depends on the status of Rb protein; patients with Rb-positive tumors are more likely to benefit from treatment, and Rb status can be used as a predictive biomarker for efficacy [4].

C26H35N7O6S

573.66

573.236

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

827022-33-3

Palbociclib;571190-30-2;Palbociclib monohydrochloride;827022-32-2;Palbociclib dihydrochloride

11478676

Light yellow to yellow solid powder

3.379

4

12

7

40

892

0

CC(C1=C(N2C3CCCC3)N=C(NC4=NC=C(N5CCNCC5)C=C4)N=C1)=C(C(C)=O)C2=O.OCCS(O)(=O)=O

LYYVFHRFIJKPOV-UHFFFAOYSA-N

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)

6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one;2-hydroxyethanesulfonic acid

PD0332991 isethionate salt; PD-0332991; Palbociclib Isethionate; 827022-33-3; PD0332991 Isethionate; PD 0332991 isethionate; UNII-W1NYL2IRDR; W1NYL2IRDR; Palbociclib Isethionate [USAN]; Palbociclib (isethionate); PD 0332991; Palbociclib isethionate salt; Trade name: Ibrance

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 1 mg/mL (1.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: Saline: 30 mg/mL (add these co-solvents sequentially from left to right, and one by one).
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)