KZR-261
Based on 1 Customer Validation
KZR-261 is a Sec61 translocase inhibitor. KZR-261 binds directly to the Sec61 channel, thereby inhibiting the biosynthesis of certain Sec61 substrate proteins, including oncogenic factors. KZR-261 activates the endoplasmic reticulum stress response. KZR-261 exhibits broad in vitro anticancer activity. KZR-261 shows antitumor efficacy in mouse models of cancer. KZR-261 can be used for the research of multiple myeloma, colorectal cancer, small cell lung cancer, pancreatic cancer, prostate cancer, non-Hodgkin's lymphoma, and mantle cell lymphoma.
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- Purity: 99.39%
- CAS No.: 2376747-46-3
- 화학식: C38H61FN6O5S2
- 분자량:765.06
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보관:Powder -20°C, 3 years , 4°C, 2 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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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
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Caspase 3 |
Caspase-7 |
In Vitro
KZR-261 (0.1-1000 nM; 1 h pre-incubation, 24 h total) reduces the cell surface expression levels of certain Sec61 substrate proteins in stimulated human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, with the highest potency observed for CD62L (IC50 = 4 nM) and IL-7R (IC50 = 12 nM)[1].
KZR-261 (250 nM; 24 h) selectively inhibits a small subset of Sec61 substrate proteins (1.7-1.8% of detected substrates) in multiple myeloma cell lines, and even fewer substrates (0.5% of detected substrates) in primary human PBMCs, with a preference for secretory and type I/II transmembrane substrates[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
KZR-261 (intravenous injection, once weekly for 3-8 weeks at 5-10 mg/kg) induces tumor growth inhibition in the HT-29 colorectal cancer xenograft model[1].
KZR-261 (administered intravenously; once weekly; for 3-8 weeks at 5 mg/kg) induces tumor growth inhibition in H82 small cell lung cancer xenografts[1].
KZR-261 (intravenous injection, once weekly for 3-8 weeks at 10 mg/kg) induces tumor growth inhibition in BxPC-3 pancreatic cancer xenografts[1].
KZR-261 (15 mg/kg; intravenous injection; once weekly; for 3-8 weeks) induces tumor growth inhibition in 22Rv1 prostate cancer xenografts[1].
KZR-261 (10 mg/kg; intravenous injection; once weekly; for 3-8 weeks) induces tumor growth inhibition in the RL non-Hodgkin's lymphoma xenograft model[1].
KZR-261 (20 mg/kg; intravenous injection; once weekly; for 3-8 weeks) induces tumor growth inhibition in Mino mantle cell lymphoma xenografts[1].
KZR-261 (10 mg/kg; intravenous injection; once weekly for 3 consecutive weeks) achieves 77% tumor growth inhibition in the MC38-hPD-L1 colorectal cancer xenograft model of hPD-1 gene-knockin mice, and combination with Pembrolizumab (HY-P9902) leads to complete tumor regression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:beige/nude/xid (female, 5-7 weeks old, implanted with 3×107 H929 cells)[1]
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Dosage:7.5 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Achieved 100% tumor growth inhibition (TGI) with minimal effects on body weight.
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Animal Model:athymic nude (female, 5-7 weeks old, implanted with 5×106 HT-29 cells)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Resulted in statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:athymic nude (female, 5-7 weeks old, implanted with 5×106 H82 cells)[1]
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Dosage:5 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Resulted in statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:athymic nude (female, 5-7 weeks old, implanted with 5×106 BxPC-3 cells)[1]
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Dosage:10 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Resulted in statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:athymic nude (male, 5-7 weeks old, implanted with 1×107 22Rv1 cells)[1]
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Dosage:15 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Achieved a greater level of tumor control than etoposide (dosed per established protocols), with statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:athymic nude (female, 5-7 weeks old, implanted with 1×107 RL cells)[1]
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Dosage:10 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Resulted in statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:athymic nude (female, 5-7 weeks old, implanted with 5×106 Mino cells)[1]
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Dosage:20 mg/kg
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Administration:i.v.; once weekly; 3-8 weeks
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Result:Resulted in statistically significant tumor growth inhibition relative to vehicle control.
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Animal Model:hPD-1 plus C57BL/6 (Biocytogen) (female, implanted with 5×105 MC38-hPD-L1 cells)[1]
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Dosage:10 mg/kg/2.5 mg/kg (pembrolizumab)
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Administration:i.v.; once weekly; 3 weeks
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Result:Achieved 77% tumor growth inhibition (TGI) by study day 27; tumor recovery was observed 1 week after the final dose, resulting in 53% TGI at that time point.
Achieved complete tumor regression (104% TGI) by study day 27; no tumors were observed within 7 days of the last dose, with complete response in 5 of 10 mice.
Chemical Information
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CAS No. 2376747-46-3
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Appearance Solid
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분자량 765.06
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화학식 C38H61FN6O5S2
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Color White to off-white
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SMILES
O=S(N1CCCN(CCCN(C[C@H](C1)C)S(N2C[C@H](N([C@@H](C2)C)C3=CC(OC)=CC(F)=C3)C)(=O)=O)CC4CCCCC4)(C5=CC=C(C=C5)N(C)C)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (130.71 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (3.27 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (3.27 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (285 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
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 |
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| DMSO | 1 mM | 1.3071 mL | 6.5354 mL | 13.0709 mL | 32.6772 mL |
| 5 mM | 0.2614 mL | 1.3071 mL | 2.6142 mL | 6.5354 mL | |
| 10 mM | 0.1307 mL | 0.6535 mL | 1.3071 mL | 3.2677 mL | |
| 15 mM | 0.0871 mL | 0.4357 mL | 0.8714 mL | 2.1785 mL | |
| 20 mM | 0.0654 mL | 0.3268 mL | 0.6535 mL | 1.6339 mL | |
| 25 mM | 0.0523 mL | 0.2614 mL | 0.5228 mL | 1.3071 mL | |
| 30 mM | 0.0436 mL | 0.2178 mL | 0.4357 mL | 1.0892 mL | |
| 40 mM | 0.0327 mL | 0.1634 mL | 0.3268 mL | 0.8169 mL | |
| 50 mM | 0.0261 mL | 0.1307 mL | 0.2614 mL | 0.6535 mL | |
| 60 mM | 0.0218 mL | 0.1089 mL | 0.2178 mL | 0.5446 mL | |
| 80 mM | 0.0163 mL | 0.0817 mL | 0.1634 mL | 0.4085 mL | |
| 100 mM | 0.0131 mL | 0.0654 mL | 0.1307 mL | 0.3268 mL |
KZR-261 Related Classifications
HY-176763 Related Classifications
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