PF 3084014 hydrobromide (Synonyms: PF-3084014 dihydrobromide; PF-03084014 dihydrobromide) |
| Catalog No.GC50251 |
PF 3084014 hydrobromide is a highly potent and selective γ-secretase inhibitor belonging to the azacycle compound class, with an IC₅₀ of 1.2nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1962925-29-6
Sample solution is provided at 25 µL, 10mM.
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PF 3084014 hydrobromide is a highly potent and selective γ-secretase inhibitor belonging to the azacycle compound class, with an IC₅₀ of 1.2nM[1]. As a transmembrane aspartyl protease complex, γ-secretase primarily functions to cleave type I transmembrane proteins such as Notch receptors and amyloid precursor protein, thereby regulating cellular processes including proliferation, differentiation, and apoptosis[2]. By inhibiting γ-secretase activity, PF 3084014 hydrobromide has demonstrated antitumor efficacy in models of hematological cancers, breast cancer, colorectal cancer, and pancreatic cancer[3].
In vitro, treatment with PF 3084014 hydrobromide (0–10μM) for 48 hours inhibited the growth of all prostate cancer cells (Du145, PC3, Du145R, and PC3R) and induced a dose-dependent reduction in the Notch pathway activation marker, Notch-1 receptor intracellular domain (NICD)[4]. When 97H and Huh7 cells were treated with PF 3084014 hydrobromide (0.5–2μM) for 48 hours, the drug downregulated cancer stem cell (CSC) markers (CD90⁺, EpCAM⁺) and stemness-related gene expression in hepatocellular carcinoma cells by inhibiting the Notch signaling pathway, significantly reducing sphere formation and proliferation capacity[5].
In vivo, PF 3084014 hydrobromide (120mg/kg) demonstrated significant antitumor efficacy in a breast cancer mouse model with MDA-MB-231Luc cells xenografts through multiple mechanisms, including inducing cell apoptosis, inhibiting cancer stem cell self-renewal, suppressing proliferation, and anti-angiogenesis[6]. Additionally, oral administration of PF 3084014 hydrobromide (125mg/kg) in colorectal cancer xenograft mice significantly reduced invasive tumor lesions and tumor volume[7].
References:
[1] Lanz TA, Wood KM, Richter KE, et al. Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014. J Pharmacol Exp Ther 2010, 334(1):269-277.
[2] Yabuuchi S, Pai SG, Campbell NR, et al. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Lett 2013, 335(1):41-51.
[3] Samon JB, Castillo-Martin M, Hadler M, et al. Preclinical analysis of the γ-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Mol Cancer Ther 2012, 11(7):1565-1575.
[4] Cui D, Dai J, Keller JM, et al. Notch Pathway Inhibition Using PF-03084014, a γ-Secretase Inhibitor (GSI), Enhances the Antitumor Effect of Docetaxel in Prostate Cancer. Clinical Cancer Research 2015, 21(20):4619-4629.
[5] Wu CX, Xu A, Zhang CC, et al. Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1–Stat3. Molecular Cancer Therapeutics 2017, 16(8):1531-1543.
[6] Zhang CC, Pavlicek A, Zhang Q, et al. Biomarker and Pharmacologic Evaluation of the γ-Secretase Inhibitor PF-03084014 in Breast Cancer Models. Clinical Cancer Research 2012, 18(18):5008-5019.
[7] Arcaroli JJ, Quackenbush KS, Purkey A, et al. Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model. Br J Cancer 2013, 109(3):667-675.
| Cell experiment [1]: | |
Cell lines | Du145, PC3, Du145 and RPC3R |
Preparation Method | Du145, PC3, Du145 and RPC3R cells were cultured in 96-well plates for overnight (2.5×103 cells/well). Cells were treated with PF 3084014 hydrobromide (0.1, 0.5, 1, 5, 10μM) or vehicle (DMSO) for 48 hours. Resazurin sodium salt (40μg) was added into 200μL medium. After 2-hour incubation, fluorescence was measured with an excitation wavelength of 550nm and emission 605nm on Multi-Mode Microplate Reader. |
Reaction Conditions | 0.1, 0.5, 1, 5, 10μM; 48h |
Applications | PF 3084014 hydrobromide inhibits the viability of prostate cancer cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | At 6 weeks of age, 2×106 luciferase labeled MDA-MB-231 cells were injected into the mammary fat pad of mice to establish tumors. Tumor-bearing mice of matched size were orally administered PF 3084014 hydrobromide twice a day for 12 consecutive days. The secondary tumor burden was evaluated using the FMT 2500 system by intravenous injection of MMPsense 680 (5nmol/mouse) 24 hours before imaging. |
Dosage form | 90mg/kg; twice per day for 12 days. |
Applications | The treatment of PF 3084014 hydrobromide can reduce the infiltration of breast cancer cells into tumor lesions. |
References: | |
| Cas No. | 1962925-29-6 | SDF | |
| Synonyms | PF-3084014 dihydrobromide; PF-03084014 dihydrobromide | ||
| Canonical SMILES | O=C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)[C@H](CCC)N[C@H]2CCC1=CC(F)=CC(F)=C1C2.Br.Br | ||
| Formula | C27H41F2N5O.2HBr | M.Wt | 651.47 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.535 mL | 7.675 mL | 15.3499 mL |
| 5 mM | 0.307 mL | 1.535 mL | 3.07 mL |
| 10 mM | 0.1535 mL | 0.7675 mL | 1.535 mL |
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Quality Control & SDS
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- Purity: >95.00%
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Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)
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