EPZ-6438 (Synonyms: E-7438,Tazemetostat) |
Catalog No.GC14062
One-Click Copy Product Info
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PZ-6438은 히스톤 H3의 27번째 라이신 (H3K27)을 메틸화하는 폴리콤 압제 복합체 2 (PRC2)의 촉매 부위인 EZH2의 강력하고 생체이용률이 높은 억제제이다. EPZ-6438은 인간 PRC2를 함유하는 야생형 EZH2의 활성을 2.5 nM의 억제 상수 Ki 값으로 억제한다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1403254-99-8
Sample solution is provided at 25 µL, 10mM.
PZ-6438은 히스톤 H3의 27번째 라이신 (H3K27)을 메틸화하는 폴리콤 압제 복합체 2 (PRC2)의 촉매 부위인 EZH2의 강력하고 생체이용률이 높은 억제제이다. EPZ-6438은 인간 PRC2를 함유하는 야생형 EZH2의 활성을 2.5 nM의 억제 상수 Ki 값으로 억제한다. EPZ-6438은 EZH2의 S-adenosylmethionine (SAM) 결합 부위와 경쟁적으로 결합하고 펩타이드나 뉴클레오좀 기질의 결합 부위와 비경쟁적으로 결합하기도 한다. EPZ-6438은 EZH1보다 35배 높은 선택성을 가진 EZH2를 선택적으로 억제한다. 연구 결과에 따르면 EPZ-6438은 MRT 모델에서 EPZ-6438 매개의 EZH2 억제가 여러 암 경로에 대한 시너지 효과를 통해 극적이고 영구적인 항종양 활성을 보였다.
Reference
[1].Sarah K. Knutson1, Natalie M. Warholic, Tim J. Wigle, Christine R. Klaus, Christina J. Allain, Alejandra Raimondi, Margaret Porter Scott, Richard Chesworth, Mikel P. Moyer, Robert A. Copeland, Victoria M. Richon, Roy M. Pollock, Kevin W. Kuntz, and Heike Keilhack. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. PNAS 2013; 110(19): 7922-7927
| 세포 실험 [1]: | |
세포 라인 | SMARCB1-deficient MRT 세포 |
제조 방법 | 용해도가 제한적입니다. 높은 농도를 얻기 위한 일반적인 팁: 튜브를 37℃에서 10분 동안 온탕처리하및/또는 초음파 수조에서 잠시 흔들어 주십시오. 원액은 -20℃ 이하에서 수개월 동안 보관할 수 있습니다. |
반응 조건 | 4-7 일 동안 |
응용 분야 | EPZ-6438은 농도 의존적으로 전역 H3K27Me3 수준을 줄입니다. 게다가 EPZ-6438은 IC₅₀ 값이 나노몰 수준인 강력한 항증식 효과를 유도합니다. EPZ-6438 처리는 CD133, DOCK4, PTPRK의 발현을 유도하고 시간 의존적으로 CDKN1A, CDKN2A, BIN1을 상향 조절합니다. |
| 동물 실험 [2]: | |
동물 모형 | EZH2-돌연변이 림프종 이종 이식을 가진 SCID 쥐 |
제조 방법 | EPZ-6438은 종양 H3K27Me3 수준을 용량 의존적으로 감소시킵니다 (EC50 = 23 nmol/L). EPZ-6438은 7일 투여/7일 휴약과 21일 투여/7일 휴약의 2주기에서 용량 의존적으로 뚜렷한 항종양 효과를 보입니다. 최저 용량 그룹을 제외한 모든 EPZ-6438 용량 그룹에서 완전한 종양 회귀가 관찰되었습니다. |
제형 | 8시간마다 매일 3회, 12시간마다 하루 2회, 또는 7일 또는 28일 중 한 번 스케줄을 경구 투여로 정합니다. |
응용 분야 | 모든 화합물의 용해도를 실내에서 테스트해 주시기 바랍니다. 실제 용해도는 이론 값과 약간 다를 수 있습니다. 이는 실험 시스템 오차로 인한 것이고 정상적인 현상입니다. |
References: 1. Knutson SK, Warholic NM, Wigle TJ et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7922-7. 2. Knutson SK, Kawano S, Minoshima Y et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther. 2014 Apr;13(4):842-54. | |
| Cas No. | 1403254-99-8 | SDF | |
| Synonyms | E-7438,Tazemetostat | ||
| Chemical Name | N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide | ||
| Canonical SMILES | CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5 | ||
| Formula | C34H44N4O4 | M.Wt | 572.74 |
| Solubility | ≥ 28.637mg/mL in DMSO | Storage | Desiccate 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.746 mL | 8.73 mL | 17.4599 mL |
| 5 mM | 349.2 μL | 1.746 mL | 3.492 mL |
| 10 mM | 174.6 μL | 873 μL | 1.746 mL |
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Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
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EPZ6438(GlpBio) was given by intraperitoneal injection at the dose of 50 mg/kg, daily.
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Cancer Research (2021). PMID: 34210752 IF: 12.703 -
Related Biological Data
IFI16 is a direct target of EZH2 and critical for activation of STING signaling and downstream CXCL10 and CXCL11.(G) EPZ/ENT treatment exhibits synergic effects with NK cells and trastuzumab (Tras) in SKBR3 cells in inducing the expression of IFI16, p-TBK1, p-IRF3, and STING.
For single-drug treatment, cancer cells were subjected to 500 nM EPZ-6438, EPZ(Glpbio) and 100 nM D9 for 5 d, or 10 nM TSA, 500 nM AZA , and 250 nM ENT for 2 d.
P Natl A Sci 119.31 (2022): e2201376119. PMID: 35878022 IF: 11.1
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