PD0325901 |
Catalog No.GC10397
One-Click Copy Product Info
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PD0325901은 구강 활성, 선택적인 비ATP 경쟁이 믹로그렌 홉화 단백질 킨아제 (MEK) 억제제로 IC50 값이 0.33 nM이다.
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Cas No.: 391210-10-9
Sample solution is provided at 25 µL, 10mM.
PD0325901은 구강 활성, 선택적인 비ATP 경쟁이 믹로그렌 홉화 단백질 킨아제 (MEK) 억제제로 IC50 값이 0.33 nM이다. 활성화된 MEK1과 MEK2에 대한 PD0325901의 Ki 값은 1 nM[2]이다. PD0325901은 ERK1/2의 효소화를 억제하고 세포의 조사성을 유도하고 간세포의 재생 기능과 항암활성을 유지한다[3].
체외 실험에서 PD0325901(0.1 μM)을 사용하여 96시간 동안 갑상선 암(PTC) 세포 라인(K2 및 TPC-1)에 처리하면 세포 성장을 크게 억제하고 세포내에 ERK1/2의 효소화를 감소시켰다[4]. 골수 단핵/대형세포(BMMs)에 PD0325901(0.32, 0.64, 1.28 nM)을 24-96시간 동안 처리하여 골절화세포의 분화를 크게 억제하고 골절화세포 특이적인 유전자 표현을 억제하며 NF-κB 신호 전달 경로의 활성을 억제했다[5].
체내 실험에서 PD0325901(20mg/kg)을 구강 투여하여 비소형폐암(NSCLC)을 가진 쥐가 PD-1 항체의 체내 효과를 크게 향상시키고 림프구의 침투 및 기능을 증가되었다[6]. PD0325901(20mg/kg)을 투여하여 변이 유전체 간세포(TAMH) 측면 종양을 가진 쥐를 치료함으로써 암세포에서 MEK의 활성을 크게 감소했고 종양 성장 속도를 감소되었다[7].
References:
[1] You K S, Yi Y W, Cho J, et al. Dual inhibition of AKT and MEK pathways potentiates the anti-cancer effect of gefitinib in triple-negative breast cancer cells[J]. Cancers, 2021, 13(6): 1205.
[2] Brown A P, Carlson T C G, Loi C M, et al. Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration[J]. Cancer chemotherapy and pharmacology, 2007, 59: 671-679.
[3] Chen G, Guo Y, Li C, et al. Small molecules that promote self-renewal of stem cells and somatic cell reprogramming[J]. Stem Cell Reviews and Reports, 2020, 16: 511-523.
[4] Henderson Y C, Chen Y, Frederick M J, et al. MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo[J]. Molecular cancer therapeutics, 2010, 9(7): 1968-1976.
[5] Jiang T, Gong Y, Zhang W, et al. PD0325901, an ERK inhibitor, attenuates RANKL‐induced osteoclast formation and mitigates cartilage inflammation by inhibiting the NF-κB and MAPK pathways[J]. Bioorganic Chemistry, 2023, 132: 106321.
[6] Luo M, Xia Y, Wang F, et al. PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma[J]. Acta Pharmaceutica Sinica B, 2021, 11(10): 3120-3133.
[7] Hennig M, Yip‐Schneider M T, Wentz S, et al. Targeting mitogen‐activated protein kinase kinase with the inhibitor PD0325901 decreases hepatocellular carcinoma growth in vitro and in mouse model systems[J]. Hepatology, 2010, 51(4): 1218-1225.
| 세포 실험 [1]: | |
세포 라인 | PTC 세포 라인 |
제조 방법 | 세포에 0.1μM의 PD0325901을 96시간 동안 처리합니다. |
반응 조건 | 0.1μM; 96시간 |
응용 분야 | PD0325901은 PTC 세포의 성장을 현저하게 억제합니다. |
| 동물 실험 [2]: | |
동물 모형 | C57BL/6 쥐 |
제조 방법 | LLC 세포는 4-6 주령의 암컷 C57BL/6J 쥐의 옆구리에 피하 주사되었습니다. 종양의 크기가 약 50-100 mm3에 도달했을 때 종양을 가진 쥐는 무작위로 4 그룹으로 나뉘었습니다: 대조군, PD-1 항체군, PD0325901군, PD0325901+PD-1 항체군. 대조군 동물은 식염수로 처리되었습니다; PD0325901은 체중당 20mg의 용량으로 격일에 구강 내 복용되었습니다; PD-1 항체는 4일마다 한 번씩 복강 내 주사되었습니다(체중당 10mg). |
제형 | 20mg/kg; p.o. |
응용 분야 | PD0325901은 체내 실험에서 PD-1 항체의 효과를 강화하고 림프구의 침투 및 기능을 증가시켰습니다. |
참고문헌: [1] Henderson Y C, Chen Y, Frederick M J, et al. MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo[J]. Molecular cancer therapeutics, 2010, 9(7): 1968-1976. [2]Luo M, Xia Y, Wang F, et al. PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma[J]. Acta Pharmaceutica Sinica B, 2021, 11(10): 3120-3133. | |
| Cas No. | 391210-10-9 | SDF | |
| Chemical Name | N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide | ||
| Canonical SMILES | C1=CC(=C(C=C1I)F)NC2=C(C=CC(=C2F)F)C(=O)NOCC(CO)O | ||
| Formula | C16H14F3IN2O4 | M.Wt | 482.19 |
| Solubility | ≥ 24.1mg/mL 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0739 mL | 10.3694 mL | 20.7387 mL |
| 5 mM | 414.8 μL | 2.0739 mL | 4.1477 mL |
| 10 mM | 207.4 μL | 1.0369 mL | 2.0739 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)