PD0325901 |
Catalog No.GC10397
One-Click Copy Product Info
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PD0325901 es un inhibidor de la cinasa mitógena activada por proteínas (MEK), selectivo, activo por vía oral y no competitivo con ATP, con un valor de IC50 de 0,33nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 391210-10-9
Sample solution is provided at 25 µL, 10mM.
PD0325901 es un inhibidor de la cinasa mitógena activada por proteínas (MEK), selectivo, activo por vía oral y no competitivo con ATP, con un valor de IC50 de 0,33 nM[1]. El valor de Ki de PD0325901 para MEK1 y MEK2 activados es de 1 nM[2]. PD0325901 inhibe la fosforilación de ERK1/2 e induce apoptosis celular, manteniendo la función de renovación de las células madre y la actividad anticancerígena[3].
In vitro, el tratamiento de líneas celulares de carcinoma papilar de tiroides (CPT) (K2 y TPC-1) con PD0325901 (0,1 μM) durante 96 h inhibió significativamente el crecimiento celular y redujo la fosforilación intracelular de ERK1/2[4]. El tratamiento de monocitos/macrófagos de médula ósea (BMMs) con PD0325901 (0,32, 0,64, 1,28 nM) durante 24-96 h inhibió significativamente la diferenciación de osteoclastos, la expresión de genes específicos de osteoclastos y la activación de la vía de señalización NF-κB[5].
In vivo, el tratamiento oral de ratones con cáncer de pulmón no microcítico (NSCLC) con PD0325901 (20 mg/kg) mejoró significativamente la eficacia in vivo de los anticuerpos PD-1 y aumentó la infiltración y función de linfocitos[6]. El tratamiento de ratones con tumores de hepatocitos transgénicos (TAMH) en el flanco con PD0325901 (20 mg/kg) redujo significativamente la actividad de MEK en las células cancerosas y disminuyó la tasa de crecimiento tumoral[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.
| Experimentos celulares [1]: | |
Líneas celulares | Líneas celulares de carcinoma papilar de tiroides (CPT). |
Método de preparación | Las células fueron tratadas con 0.1 μM de PD0325901 durante 96 horas. |
Condiciones de reacción | 0.1 μM; 96 horas. |
Áreas de aplicación | PD0325901 inhibe significativamente el crecimiento de las células de CPT. |
| Experimentos con animales [2]: | |
Modelos animales | Ratones C57BL/6. |
Método de preparación | Se inyectaron células LLC subcutáneamente en los flancos de ratones hembra C57BL/6J de 4-6 semanas de edad. Cuando los tumores alcanzaron aproximadamente 50-100 mm³, los ratones portadores de tumores fueron divididos aleatoriamente en cuatro grupos: grupo control, grupo con anticuerpo PD-1, grupo con PD0325901, y grupo con PD0325901+anticuerpo PD-1. Los animales del grupo control fueron tratados con solución salina; PD0325901 fue administrado oralmente a una dosis de 20 mg/kg cada dos días; el anticuerpo PD-1 fue inyectado por vía intraperitoneal una vez cada 4 días (10 mg/kg). |
Forma de dosificación | 20 mg/kg; administración oral (p.o.). |
Áreas de aplicación | PD0325901 mejoró la eficacia del anticuerpo PD-1 in vivo, incrementando la infiltración y la función de los linfocitos. |
Referencias: [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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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.)