Puzerinostat
Based on 1 Customer Validation
Puzerinostat (Purinostat) is a highly selective class I/IIb histone deacetylase (HDAC) inhibitor, with IC50 values of 0.81 nM, 1.4 nM, 1.7 nM, 3.8 nM, 11.5 nM, and 1.1 nM against HDAC1, HDAC2, HDAC3, HDAC8, HDAC6, and HDAC10, respectively. Puzerinostat enhances glutamine metabolism by upregulating GLS1. Puzerinostat induces cell Apoptosis and downregulates the expression of BCR-ABL and c-MYC. Puzerinostat delays the progression of Ph+ B-cell acute lymphoblastic leukemia and prolongs the survival of relevant mouse models. Puzerinostat regulates the immune microenvironment. Puzerinostat can be used in research related to chronic myeloid leukemia, Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia, relapsed/refractory multiple myeloma, relapsed/refractory lymphoma, diffuse large B-cell lymphoma, and double-expression lymphoma.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 98.04%
- CAS 番号: 1929583-17-4
- 分子式: C23H26N10O3
- 分子量:490.52
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
[2]|
HDAC1 0.81 nM (IC50) |
HDAC2 1.4 nM (IC50) |
HDAC3 1.7 nM (IC50) |
HDAC8 3.8 nM (IC50) |
HDAC6 11.5 nM (IC50) |
HDAC10 1.1 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MM.1S | IC50 |
<5 nM
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Antiproliferative activity against human MM1S cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human MM1S cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| RPMI-8226 | IC50 |
<5 nM
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Antiproliferative activity against human RPMI-8226 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human RPMI-8226 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| AMO1 | IC50 |
<5 nM
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Antiproliferative activity against human AMO1 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human AMO1 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| OPM-2 | IC50 |
<5 nM
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Antiproliferative activity against human OPM2 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human OPM2 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| KMS-11 | IC50 |
<5 nM
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Antiproliferative activity against human KMS-11 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human KMS-11 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| RL | IC50 |
<5 nM
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Antiproliferative activity against human RL cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human RL cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| Ramos | IC50 |
<5 nM
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Antiproliferative activity against human Ramos cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human Ramos cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| Daudi | IC50 |
<5 nM
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Antiproliferative activity against human Daudi cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human Daudi cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| Raji | IC50 |
<5 nM
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Antiproliferative activity against human Raji cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human Raji cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| TMD8 | IC50 |
<5 nM
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Antiproliferative activity against human TMD-8 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human TMD-8 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
| KARPAS-299 | IC50 |
<5 nM
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Antiproliferative activity against human Karpas299 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
Antiproliferative activity against human Karpas299 cells assessed as reduction in cell viability incubated for 72 hrs by cell viability antiproliferation assay.
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40562746 |
体外実験
Puzerinostat (20 nM; 0-48 h) induces time-dependent hyperacetylation of α-tubulin and histone H3 in LAMA84 Ph+ chronic myeloid leukemia cells[1].
Puzerinostat is a highly selective class I/IIb HDAC inhibitor with favorable cardiac safety profiles due to its weak inhibitory effect on hERG channels[3].
Puzerinostat (10-200 nM; 24-72 h) potently reduces the viability of LAMA84 and K562 Ph+ chronic myeloid leukemia cells, with an IC50 of less than 10 nM, and its effect is dose- and time-dependent[1].
Puzerinostat (72 h) potently inhibits the proliferation of multiple myeloma (MM) and lymphoma cell lines, with all IC50 values below 5 nM[3].
Treatment with Puzerinostat (5-150 nM; 24 h) induces dose-dependent G0/G1 cell cycle arrest in LAMA84 and K562 Ph+ chronic myeloid leukemia cells[1].
Puzerinostat (0.25-0.5 nM; 24 h) upregulates the expression of MHC-I and MHC-II on MM1S cells in a concentration-dependent manner[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LAMA84 Ph+ chronic myelogenous leukemia cells
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Concentration:20 nM
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Incubation Time:0 h, 12 h, 24 h, 36 h, 48 h
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Result:Increased acetylation of α-tubulin and histone H3 (Ac-α-tubulin and Ac-H3) in a time-dependent manner, with visible increases starting at 12 h and peaking at 48 h, relative to unacetylated α-tubulin, histone H3, and GAPDH loading controls.\nIncreased levels of pro-apoptotic proteins P53 and BAD, decreased anti-apoptotic protein BCL-XL, and induced cleavage of caspase-8, caspase-9, caspase-3, and PARP in a time-dependent manner.
Suppressed phosphorylation of RAF, MEK, ERK, and AKT (the RAF-MEK-ERK-AKT signaling axis) in a time-dependent manner.
Reduced protein levels of BCR-ABL, c-MYC, ALOX5, EZH2, p-STAT5, and p-FAK, while increasing levels of ALOX15 and β-CATENIN, all in a time-dependent manner.
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Cell Line:Luciferase-tagged LAMA84 and K562 Ph+ chronic myelogenous leukemia cells
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Concentration:10-100 nM (LAMA84); 150-200 nM (K562)
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Incubation Time:24 h, 36 h, 48 h, 60 h, 72 h
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Result:Reduced cell viability in a dose- and time-dependent manner for both cell lines.
Caused near-complete viability loss in LAMA84 cells at 100 nM by 48 h, and near-complete viability loss in K562 cells at 200 nM by 48 h.
Achieved an IC50 of less than 10 nM against Ph+ cell lines.
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Cell Line:LAMA84 and K562 Ph+ chronic myelogenous leukemia cells
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Concentration:5-20 nM (LAMA84); 20-150 nM (K562)
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Incubation Time:24 h
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Result:Arrested LAMA84 and K562 cells in the G0/G1 phase in a dose-dependent manner.
Increased G0/G1 phase proportion in LAMA84 cells from 47.3% (control) to 84.0% at 20 nM; increased G0/G1 phase proportion in K562 cells from 31.5% (control) to 90.3% at 150 nM, with corresponding decreases in S and G2/M phases.
体内実験
Puzerinostat (5-10 mg/kg; i.p., i.v.; three times per week; for 5 consecutive weeks) significantly prolongs survival and eliminates leukemia cells in BL-2 secondary transplanted Ph+ B-ALL mouse models, with 60% of mice surviving up to day 100 at the dose of 10 mg/kg[2].
Puzerinostat (2.5-10 mg/kg) significantly prolongs survival and reduces tumor burden in PDX models of Ph+ B-ALL relapsed after tyrosine kinase inhibitor treatment, with a median overall survival (OS) of 73 days in the 10 mg/kg dose group[2].
Puzerinostat (10 mg/kg) significantly extends the median survival to 86 days, reduces serum calcium levels, ameliorates osteolytic lesions, and enhances innate and adaptive anti-tumor immune responses in the 5TMM mouse model[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:donor mice (treated with fluorouracil); recipient mice (γ-ray irradiated)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.v.; three times a week
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Result:Maintained 71.4% survival (10/14 mice) at day 90 post-BMT for 5 mg/kg dose, and 87.5% survival (7/8 mice) at day 90 post-BMT for 10 mg/kg dose, compared to 0% survival in placebo group by day 40.
Reduced peripheral blood leukemia cell (GFP+Gr-1+) burden to 1.21% (5 mg/kg) and 0.62% (10 mg/kg) by day 40.
Reduced bone marrow GFP+LSC counts to ~200 (5 mg/kg) and ~100 (10 mg/kg), compared to ~700 in placebo group.
Increased GFP+LSC apoptosis to ~38% (5 mg/kg) and ~45% (10 mg/kg), compared to ~22% in placebo group.
Reduced residual bone marrow GFP+LSC percentages to 2.0% (5 mg/kg) and 1.0% (10 mg/kg) by day 90 post-BMT, down from ~7.2% at day 14.
Reduced myeloid leukemia cell infiltration in lungs and spleens, with tissue structure comparable to healthy mice after long-term treatment.
Reduced leukemia cells in peripheral blood again upon retreatment after relapse following treatment suspension.
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Animal Model:C57BL/6 (7-8-week female; secondary transplantation model via intravenous injection of 1×106 BL-2 cells)[2]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.p.; three times a week; five weeks; i.v.; three times a week
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Result:Prolonged median overall survival to 25.5 days in the 5 mg/kg group.
Achieved 60% (6/10) survival rate to 100 days in the 10 mg/kg group.
Nearly eliminated GFP+B220+ cells in peripheral blood of surviving mice after five weeks of treatment, with no tumor cells detected one week after treatment cessation.
Completely eliminated GFP+B220+ cells in spleens of a separate cohort after two doses of 10 mg/kg, maintaining inhibition for 26 days.
Decreased spleen weights significantly, reaching levels identical to healthy mice by day 19.
Significantly reduced GFP+B220+ cell proportions in bone marrow.
Increased Ac-H3 and Ac-H4 levels and decreased BCR-ABL, HSP90, HCK, p-SRC, and c-MYC levels in bone marrow cells.
Restored normal organ morphology in mice after three weeks of treatment.
化学情報
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CAS 番号 1929583-17-4
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性状 Solid
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分子量 490.52
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分子式 C23H26N10O3
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SMILES
O=C(C1=CN=C(N(CC2=NC3=C(N4CCOCC4)N=C(C5=CC=C(N)C=C5)N=C3N2C)C)N=C1)NO
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別名
Purinostat
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 125 mg/mL (254.83 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (291 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Qiu Q, et al. HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells. Bioactive materials. 2023 Mar;21:483-498. [Content Brief]
[2]. Yang L, et al. Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of -Induced B-Cell Acute Lymphoblastic Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 Dec 15;25(24):7527-7539. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0387 mL | 10.1933 mL | 20.3865 mL | 50.9663 mL |
| 5 mM | 0.4077 mL | 2.0387 mL | 4.0773 mL | 10.1933 mL | |
| 10 mM | 0.2039 mL | 1.0193 mL | 2.0387 mL | 5.0966 mL | |
| 15 mM | 0.1359 mL | 0.6796 mL | 1.3591 mL | 3.3978 mL | |
| 20 mM | 0.1019 mL | 0.5097 mL | 1.0193 mL | 2.5483 mL | |
| 25 mM | 0.0815 mL | 0.4077 mL | 0.8155 mL | 2.0387 mL | |
| 30 mM | 0.0680 mL | 0.3398 mL | 0.6796 mL | 1.6989 mL | |
| 40 mM | 0.0510 mL | 0.2548 mL | 0.5097 mL | 1.2742 mL | |
| 50 mM | 0.0408 mL | 0.2039 mL | 0.4077 mL | 1.0193 mL | |
| 60 mM | 0.0340 mL | 0.1699 mL | 0.3398 mL | 0.8494 mL | |
| 80 mM | 0.0255 mL | 0.1274 mL | 0.2548 mL | 0.6371 mL | |
| 100 mM | 0.0204 mL | 0.1019 mL | 0.2039 mL | 0.5097 mL |
Puzerinostat 関連分類
HY-150109A 関連分類
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Keywords
- Puzerinostat
- 1929583-17-4
- Purinostat
- HDAC
- Glutaminase
- Apoptosis
- c-Myc
- Bcr-Abl
- diffuse large B-cell lymphoma
- osteoclastogenesis
- multiple myeloma
- histone deacetylase
- chronic myelogenous leukemia
- LAMA84 cells
- K562 cells
- BaF3-BCR-ABL(T315I) cells
- leukemia stem cell
- Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia
- Inhibitor
- inhibitor
- inhibit