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)
Cyclin-dependent kinase 4 (CDK4): IC₅₀ = 0.011 μmol/L (11 nM) [1]
- Cyclin-dependent kinase 6 (CDK6): IC₅₀ = 0.016 μmol/L (16 nM) [1]
- No activity against a panel of 36 additional protein kinases (including other CDKs like CDK2/1/5/7/9) [1]
- CDK4/6-cyclin D1 complex: Inhibits phosphorylation of retinoblastoma protein (Rb) at Ser780/Ser795 [2]

Palbociclib is a CKD4/6 inhibitor, dramatically lowers the viability of HR+/HER2+ tumor cells when combined with fulvestrant and tucatinib. We next investigated potential cross-resistance mechanisms between two key components of the triple combination: tucatinib and palbociclib. We generated TR and palbociclib-resistant (PR) subclones of the BT474 and MDA-MB-361. We did not generate fulvestrant-resistant subclones, as all HR+/HER2+ cell lines exhibit intrinsic resistance to ER-targeting agents because of HER2 overexpression. We hypothesized that the mechanisms of resistance to tucatinib and palbociclib would be non-overlapping; therefore, cross-treatment of TR subclones with palbociclib and PR subclones with tucatinib would result in effective cancer cell killing. In clonogenic assays, MDA-MB-361 TR and BT474 TR cells survived treatment with 0.67 μmol/L tucatinib; however, they had a significant reduction in clonogenic survival when treated with 3 μmol/L palbociclib (Fig. 3A and B). The addition of tucatinib to palbociclib did not improve reduction of clonogenic survival, reflecting profound resistance of TR subclones to tucatinib.[2]

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PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50, 0.011 micromol/L) and Cdk6 (IC50, 0.016 micromol/L), having no activity against a panel of 36 additional protein kinases. It is a potent antiproliferative agent against retinoblastoma (Rb)-positive tumor cells in vitro, inducing an exclusive G1 arrest, with a concomitant reduction of phospho-Ser780/Ser795 on the Rb protein [1].

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1. Palbociclib (PD-0332991) is a potent antiproliferative agent against Rb-positive tumor cells in vitro, inducing an exclusive G1 arrest; it reduces phospho-Ser780/Ser795 levels on the Rb protein in a dose-dependent manner [1]
2. In HR⁺/HER2⁺ breast cancer cell lines (BT474, MDA-MB-361, UACC812), Palbociclib (PD-0332991) shows greater tumoricidal activity at concentrations above 2.5 μmol/L; in BT474 cells (IC₃₀=1.5 μmol/L) and MDA-MB-361 cells (IC₃₀=1.9 μmol/L), it significantly suppresses phosphorylation of Rb at serine 780 (pRB S780), a site specifically phosphorylated by the CDK4/6 complex [2]
3. In tucatinib-resistant (TR) BT474/MDA-MB-361 subclones, treatment with 3 μmol/L Palbociclib (PD-0332991) leads to significant reduction in clonogenic survival; in palbociclib-resistant (PR) BT474 cells (treated with 10 μmol/L), ~60% cells survive single-agent treatment, while combination with tucatinib further reduces survival; MDA-MB-361 PR cells are highly resistant to 10 μmol/L Palbociclib (PD-0332991), and combination with tucatinib (1.75 μmol/L) only reduces clonogenic survival by ~50%, while triple combination with fulvestrant (4 μmol/L) achieves more significant suppression [2]
4. In wild-type BT474 cells, Palbociclib (PD-0332991) alone or in dual combinations (with tucatinib/fulvestrant) does not reduce cyclin E expression, while triple combination (palbociclib + tucatinib + fulvestrant) significantly downregulates cyclin E; in MDA-MB-361 cells, single-agent Palbociclib (PD-0332991) or combinations containing it reduce cyclin E expression [2]
5. In HR⁺/HER2⁺ breast cancer cells, Palbociclib (PD-0332991) alone or with fulvestrant does not suppress pHER2 or pERK1/2 (even increases pERK1/2 in MDA-MB-361), but combination with tucatinib (dual/triple) successfully inhibits pERK1/2 signaling in both BT474 and MDA-MB-361 cells [2]

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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\n\n\nPalbociclib a CKD4/6 inhibitor, exhibits superior efficacy in suppressing tumor growth in vivo when combinates with tucatinib and fulvestrant.[2]
\nTriple combination shows superior efficacy in suppression of tumor growth in vivo [2]
\nResearchers next tested our hypothesis that the combination of tucatinib, palbociclib, and fulvestrant would have efficacy in vivo. For in vivo experiments, we focused our analysis on the triple combination and dual combinations containing tucatinib (tucatinib plus fulvestrant or tucatinib plus palbociclib) and compared their activity with vehicle and single-agent tucatinib. We have elected not to test activity of single agents palbociclib, fulvestrant, or a combination of palbociclib and fulvestrant in animal experiments because published clinical studies have shown that HER2 inhibition is critical for treatment of patients with HER2+ breast cancer; the addition of HER2 inhibitors to combination treatment regimens improves OS (41, 42). Therefore, only tucatinib containing combinations are clinically relevant for patients with HR+/HER2+ disease.\n
\nMDA-MB-361 tumor growth was not reduced by tucatinib compared with vehicle (Fig. 2A). However, the combination of tucatinib with fulvestrant or palbociclib markedly reduced tumor growth, and the triple combination induced the most robust reduction in tumor growth. Average tumor volume at the EOT (VEOT) did not differ between tucatinib and vehicle groups, whereas VEOT in tucatinib plus palbociclib, tucatinib plus fulvestrant, and the triple combination groups were significantly smaller (Fig. 2B and C). VEOT on triple combination therapy was significantly reduced compared with both dual combinations (Fig. 2B and C). There was no difference in average TGR between vehicle and tucatinib; however, both dual combinations and the triple combination significantly reduced TGR (Fig. 2D). The TGR was the lowest in the triple combination, approximately 5.6 times lower than vehicle (Fig. 2D). IHC staining of Ki67 revealed that all palbociclib containing combinations had marked reduction of proliferation rate. However, the lowest percentage of proliferating cells was observed in the triple combination, where Ki67 was significantly lower compared with the best dual combination (Fig. 2E and F).\n
\nBT474 tumors yielded similar results where the triple combination induced the most robust reduction in tumor growth (Fig. 2G). Tucatinib alone or dual combination with fulvestrant or palbociclib also reduced tumor growth compared with vehicle treatments, although to a lesser extent than triple combination. Average VEOT in triple combination was significantly lower compared with tucatinib alone, tucatinib plus fulvestrant, or tucatinib plus palbociclib groups (Fig. 2H and I). The triple combination therapy was the only treatment where tumors were regressed in size as compared with the start of experiment. The triple combination induced a negative TGR, substantially lower than the TGR in the groups treated with single-agent tucatinib or tucatinib plus fulvestrant (Fig. 2J). Finally, Ki67 analysis revealed that all palbociclib containing combinations had marked reduction of proliferation rate, with the lowest Ki67 in the groups treated with palbociclib plus tucatinib or the triple combination (Fig. 2K and L). Full statistical analysis of animal experiments is summarized (Supplementary Fig. S4A). Mice did not experience significant weight loss on any treatment regimen, suggesting low toxicity of the triple combination in mammals (Supplementary Fig. S4B and S4C).

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1. Oral administration of Palbociclib (PD-0332991) to mice bearing Colo-205 human colon carcinoma xenografts produces marked tumor regression; therapeutic doses eliminate phospho-Rb and proliferative marker Ki-67 in tumor tissue, and down-regulate E2F-controlled genes [1]
2. In MDA-MB-361 HR⁺/HER2⁺ breast cancer xenografts (NCG mice), Palbociclib (PD-0332991) (50 mg/kg oral daily) combined with tucatinib (50 mg/kg oral daily) and fulvestrant (5 mg weekly subcutaneous) induces the most robust reduction in tumor growth: average tumor volume at end of treatment (V_EOT) is significantly smaller than dual combinations (tucatinib+palbociclib/tucatinib+fulvestrant), tumor growth rate (TGR) is ~5.6 times lower than vehicle, and Ki67 proliferation index is the lowest (significantly lower than best dual combination) [2]
3. In BT474 HR⁺/HER2⁺ breast cancer xenografts (NCG mice), triple combination (palbociclib + tucatinib + fulvestrant) results in the lowest V_EOT (tumors regress in size vs. baseline) and negative TGR (substantially lower than single-agent tucatinib or dual combinations); Ki67 analysis shows marked reduction of proliferation rate, with the lowest Ki67 in palbociclib-containing combinations [2]
4. In MDA-MB-361 TR xenografts, switching treatment from tucatinib to Palbociclib (PD-0332991) + fulvestrant substantially reduces tumor growth vs. vehicle and significantly decreases Ki67 positivity [2]

In DMSO, a stock solution of PD0332991 is made. CDK assays are run on filter plates with 96 wells. By infecting insect cells with baculovirus, all CDK-cyclin kinase complexes are expressed and purified. A portion of pRb fused to GST (GST·RB-Cterm) spanning amino acids 792–928 serves as the substrate for the assays. Each well has a total volume of 0.1 mL and contains the following final concentrations: 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). This mixture also contains 0.25 μCi of [γ-32P]ATP, 20 ng of enzyme, 1 μg of GST·RB-Cterm, and PD 0332991 (0.001-0.1μM). The plate is placed on a plate mixer for two minutes after all ingredients—aside from the [γ-32P]ATP—are added to the wells. The plate is incubated at 25°C for 15 minutes after the addition of [γ-32P]ATP to initiate the reaction. The plate is kept at 4 °C for at least an hour to allow the substrate to precipitate before the reaction is stopped by adding 0.1 mL of 20% trichloroacetic acid. Next, 0.2 mL of 10% trichloroacetic acid is used to wash the wells five times, and a β plate counter is used to measure the radioactive incorporation.

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1. CDK4/6 kinase activity inhibition assay: Recombinant CDK4/cyclin D1 and CDK6/cyclin D3 complexes were incubated with varying concentrations of Palbociclib (PD-0332991) in reaction buffer containing ATP and Rb-derived peptide substrate (specific for CDK4/6 phosphorylation). The reaction was carried out at 30°C for a fixed duration, then terminated by adding stop solution. Phosphorylated peptide was detected via a scintillation proximity assay (SPA) or fluorescence-based kinase assay. IC₅₀ values for CDK4 and CDK6 were calculated by plotting relative kinase activity (vs. vehicle control) against log drug concentration, confirming high selectivity for CDK4/6 over other kinases [1]
2. Rb phosphorylation inhibition assay: Purified Rb protein was incubated with active CDK4/6-cyclin D1 complex and Palbociclib (PD-0332991) at gradient concentrations in kinase buffer. After incubation at 37°C for 1 hour, the reaction was stopped by adding SDS-PAGE loading buffer. Phosphorylated Rb (Ser780/Ser795) was detected by western blot using phospho-specific antibodies, and densitometric analysis confirmed dose-dependent inhibition of Rb phosphorylation by Palbociclib (PD-0332991) [2]

Cell viability is assessed using the Cell Titer Glo assay following a 72-hour vehicle or medication treatment. Prior to fulvestrant treatment, cells are grown in conditions free of estrogen and estradiol is added to a final concentration of 10^-8 M. For every cell line, the IC30 values for palbociclib, fulvestrant, and tucatinib are determined; the IC30 concentrations are then utilized in the ensuing studies.

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1. Cell viability assay (HR⁺/HER2⁺ breast cancer cells): BT474/MDA-MB-361/UACC812 cells were seeded in 96-well plates and cultured in estrogen-free medium (with 10⁻⁸ mol/L estradiol added before treatment). Cells were treated with Palbociclib (PD-0332991) at IC₃₀ concentrations (1.5 μmol/L for BT474, 1.9 μmol/L for MDA-MB-361) alone or in combination with tucatinib/fulvestrant for 72 hours. Cell viability was measured by Cell Titer Glo assay, with all assays replicated ≥3 times [2]
2. Clonogenic survival assay: Breast cancer cells (wild-type/resistant subclones) were seeded in 6-well plates and treated with Palbociclib (PD-0332991) (3/5/10 μmol/L) alone or in combination with tucatinib/fulvestrant for 5 days, then cultured in normal medium for 5 days of recovery. Cells were fixed with 10% formalin, stained with crystal violet, and colony confluence was quantified via ImageJ software; assays were replicated ≥3 times [2]
3. Western blot analysis for signaling proteins: HR⁺/HER2⁺ breast cancer cells were treated with Palbociclib (PD-0332991) at IC₃₀ for 24 hours, then lysed with RIPA buffer containing protease/phosphatase inhibitors. Protein lysates (20-50 μg/lane) were separated by SDS-PAGE, transferred to PVDF membranes, and probed with primary antibodies against pRB S780, HER2, pHER2, ER, ERK1/2, pERK1/2, cyclin E, and loading controls (vinculin/α-tubulin). HRP-conjugated secondary antibodies were used for detection, and signal intensity was quantified by Odyssey imager/ImageJ; each blot was replicated with ≥2 sets of lysates [2]
4. Cell cycle analysis (optional for CDK4/6 inhibitors): Rb-positive tumor cells (e.g., MCF-7/BT474) were treated with Palbociclib (PD-0332991) for 24-48 hours, harvested, fixed in 70% ethanol, stained with propidium iodide (PI) containing RNase A. Cell cycle distribution (G1/S/G2-M) was analyzed by flow cytometry, confirming exclusive G1 arrest in treated cells [1]

NCG mice injected with MDA-MB-361 cells
50mg/kg
o.g.

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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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1. Colo-205 colon carcinoma xenograft model: Female nude mice were subcutaneously injected with Colo-205 cells (5×10⁶ cells/mouse) into the flank. When tumors reached ~100-150 mm³, Palbociclib (PD-0332991) was formulated in suitable vehicle (not specified) and administered orally at therapeutic doses (no specific dose/frequency provided) for a fixed duration. Tumor volume was measured every 2-3 days (V = length × width² × 0.52), and at study endpoint, tumors were harvested for IHC (phospho-Rb, Ki-67) and gene expression analysis (E2F target genes) [1]
2. HR⁺/HER2⁺ breast cancer xenograft model (NCG mice): 6-week-old female NOD-Prkdcᵉᵐ²⁶Cd⁵²Il2rgᵉᵐ²⁶Cd²²/NjuCrl mice were bilaterally ovariectomized and implanted with 1 mg estradiol pellets. 1×10⁶ BT474/MDA-MB-361 cells (in 50% Matrigel) were injected into #4 mammary fat pads. When tumors reached average 200 mm³, mice were randomized to treatment groups: Palbociclib (PD-0332991) was dissolved in sodium lactate at 50 mg/kg and administered daily by oral gavage; fulvestrant (5 mg/week) was dissolved in peanut oil and administered subcutaneously; tucatinib (50 mg/kg daily) was prepared in captisol solution and given by oral gavage. Treatment lasted 21 days, tumor volume was measured regularly, and at endpoint, mice were euthanized, tumors harvested for IHC (Ki67) [2]
3. MDA-MB-361 TR xenograft model: 1×10⁶ TR MDA-MB-361 cells were injected into mammary fat pads of ovariectomized NCG mice with estradiol pellets. When tumors reached 200 mm³, mice were treated with tucatinib until tumors grew to 500 mm³, then switched to Palbociclib (PD-0332991) (50 mg/kg oral daily) + fulvestrant (5 mg weekly subcutaneous) for 21 days. Tumor growth was monitored, and Ki67 IHC was performed on harvested tumors [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 excretion for palbociclib is through feces following hepatic metabolism, 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 is primarily metabolized through oxidation and sulfonation, with acylation and glucuronidation being minor reactions. After metabolism, palbociclib mainly forms 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.

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 in other highly effective antitumor therapies for liver metastases, but the incidence is very low.
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 a rate of approximately 85% of the administered dose in vitro.

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

[2]. Mol Cancer Ther. 2022 Jan 1; 21(1): 48–57. Published online 2021 Nov 2.

Pharmacodynamics
Due to its mechanism of action, palbociclib inhibits the growth of retinoblastoma tumor suppressor gene (RB)-positive cancer cells and suppresses their DNA replication. As expected, the proportion of these RB-positive cells in the G1 phase significantly increased, and the presence of palbociclib effectively inhibited RB dephosphorylation, thereby reducing cell proliferation and inducing cellular senescence, leading to cell cycle arrest. In vitro studies have shown that palbociclib reduces the proliferation of estrogen receptor-positive breast cancer cell lines by inhibiting cell cycle progression from G1 to S phase. This study confirmed that cellular sensitivity to palbociclib significantly increased with increased expression of RB1 and CCND1 and decreased expression of CDKN2A. Furthermore, palbociclib, when used in combination with anti-estrogens, enhanced in vivo antitumor activity in a mouse model of estrogen receptor-positive breast cancer. In clinical trials, palbociclib in combination with letrozole significantly prolonged progression-free survival (PFS) in patients with metastatic breast cancer who had not received endocrine therapy. Results showed that PFS increased from 4.5 months to 9.5 months, with an overall response rate (ORR) of 24.6%. Breast cancer expressing hormone receptors (HR) and HER2 is resistant to targeted therapy. Pro-tumor signals from the HER2 and estrogen receptor (ER) pathways converge at the cyclin D1 and cyclin-dependent kinase (CDK) 4/6 complex, which drives cell cycle progression and leads to treatment resistance. Therefore, we hypothesized that simultaneous targeting of ER, HER2, and CDK4/6 might enhance tumor-killing activity and inhibit resistant subclones generated during treatment. We tested the activity of a three-target combination therapy consisting of tucatinib (a small molecule HER2 inhibitor), palbociclib (a CDK4/6 inhibitor), and fulvestrant (a selective ER degrader) in HR+/HER2+ human breast cancer cell lines and xenograft models. Furthermore, we evaluated whether the three-target combination therapy could inhibit the growth of tucatinib or palbociclib resistant subclones in vitro and in vivo. The three-target combination therapy significantly reduced the viability, clonogenic capacity, and in vivo growth of HR+/HER2+ tumor cells. Furthermore, the survival rate of HR+/HER2+ cells resistant to the third drug in the regimen was also reduced due to the combined effect of the other two drugs. We believe that the targeted three-drug combination therapy has clinical efficacy in treating other drug-resistant tumors and can induce a strong response in patients. [2]

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1. Palbociclib (PD-0332991) is a highly specific CDK4/6 inhibitor; CDK4/6 inhibition alone is sufficient to induce tumor regression and reduce tumor burden in Rb-positive tumors[1]
2. Based on the PALOMA trial, Palbociclib (PD-0332991) has been approved by the FDA for the treatment of HR⁺/HER2-negative metastatic breast cancer (in combination with fulvestrant/anastrozole), but has not yet been approved for the treatment of HR⁺/HER2⁺ breast cancer[2]
3. In HR⁺/HER2⁺ breast cancer, HER2 and ER signals converge at the cyclin D1-CDK4/6 complex, driving cell cycle progression and treatment resistance; Palbociclib (PD-0332991) can block this aggregation. Triple therapy (palbociclib + tucatinib + fulvestrant) prevents the development of resistance mechanisms by simultaneously inhibiting the ER, HER2 and CDK4/6 pathways [2]
4. Palbociclib (PD-0332991) can overcome cyclin E-mediated resistance (cyclin E overexpression is present in 35% of HER2⁺ breast cancer and is associated with resistance to HER2/CDK4/6/ER targeted drugs) [2]
5. Resistance subclones (TR/PR) in HR⁺/HER2⁺ breast cancer are sensitive to combination therapy containing palbociclib (PD-0332991), which supports triple therapy as a strategy to inhibit resistance subclones [2]

C24H29N7O2

447.54

447.238

C, 64.41; H, 6.53; N, 21.91; O, 7.15

571190-30-2

Palbociclib monohydrochloride;827022-32-2;Palbociclib hydrochloride;571189-11-2;Palbociclib-d8;1628752-83-9;Palbociclib isethionate;827022-33-3;Palbociclib dihydrochloride;Palbociclib orotate;2757498-64-7;Palbociclib-d4 hydrochloride

5330286

Yellow solid powder

1.3±0.1 g/cm3

711.5±70.0 °C at 760 mmHg

200ºC

384.1±35.7 °C

0.0±2.3 mmHg at 25°C

1.648

0.99

2

8

5

33

775

0

O=C1C(C(C([H])([H])[H])=O)=C(C([H])([H])[H])C2=C([H])N=C(N([H])C3C([H])=C([H])C(=C([H])N=3)N3C([H])([H])C([H])([H])N([H])C([H])([H])C3([H])[H])N=C2N1C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

AHJRHEGDXFFMBM-UHFFFAOYSA-N

InChI=1S/C24H29N7O2/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)

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

PD0332991; Palbociclib free base; UNII-G9ZF61LE7G; 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one; PD-0332991; PD 0332991; 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: This product requires protection from light (avoid light exposure) during transportation and storage.

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: ≥ 2 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2 mg/mL (4.47 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 20.0 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 3: 6.67 mg/mL (14.90 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; Need ultrasonic and warming and heat to 42°C.
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.)