Trametinib (GSK1120212)
Catalog No.: GC13508Purity:>98.00%Synonyms: GSK1120212, JTP-74057
مثبط لـ MEK1 و MEK2
المنتجات مخصصة للاستخدام البحثي فقط، وليست للاستخدام البشري. نحن لا نبيع للمرضى.
Cas No.: 871700-17-3
10mM (in 1mL DMSO)In Stock
$27.00
1
5mgIn Stock
$15.00
1
10mgIn Stock
$25.00
1
50mgIn Stock
$54.00
1
100mgIn Stock
$88.00
1
500mgIn Stock
$231.00
1
| Pack Size | Price | Availability | Quantity | Action |
|---|---|---|---|---|
| 10mM (in 1mL DMSO) | $27.00 | In Stock | 1 | |
| 5mg | $15.00 | In Stock | 1 | |
| 10mg | $25.00 | In Stock | 1 | |
| 50mg | $54.00 | In Stock | 1 | |
| 100mg | $88.00 | In Stock | 1 | |
| 500mg | $231.00 | In Stock | 1 |
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المراجع (Citations)
1 publicationsمنشورات الباحثين الذين استخدموا هذا المنتجالوصف (Description)
Trametinib (GSK1120212, JTP-74057) is a second-generation small molecule inhibitor of MEK kinase. It functions as allosteric, ATP noncompetitive inhibitor with nanomolar activity against both MEK 1 and MEK 2 kinases with IC50 is 0.7-14.9 nM for MEK1/MEK2[3,7].
Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells[2]. Trametinib (GSK1120212) blocked tumor necrosis factor-α and interleukin-6 production from PBMCs. AIA and CIA development were suppressed almost completely by 0.1 mg/kg of JTP-74057 or 10 mg/kg of leflunomide. In the CIA, Trametinib (GSK1120212), but not leflunomide, suppressed collagen-reactive T-cell proliferation ex vivo[1]. Among the different cell lines evaluated in the study, those with either BRAFV600E mutation or activating mutations in KRAS or NRAS were the most sensitive.Trametinib (GSK1120212) inhibited the MEK1/2-dependent activating dual phosphorylation of ERK1/2 on both T202 and Y204[4].
In xenograft models of HT-29 and COLO205 colorectal tumor cell lines, trametinib demonstrated robust anticancer activity when administered daily for 14 days, Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment, by single oral dosing of 100 mg/kg Trametinib (GSK1120212), the phosphorylation of ERK1/2 in the established tumor tissues was completely inhibited, and both p15INK4b and p27KIP1 mRNA levels were upregulated in parallel[2,5]. In patients treated with Trametinib (GSK1120212)for malignant melanoma most common adverse events observed were rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform[6].
References:
[1]. Yamaguchi T, Kakefuda R, et,al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide. Inflamm Res. 2012 May;61(5):445-54. doi: 10.1007/s00011-011-0431-5. Epub 2012 Jan 14. PMID: 22245957.
[2]. Yamaguchi T, Yoshida T, et,al. Identification of JTP-70902, a p15(INK4b)-inductive compound, as a novel MEK1/2 inhibitor. Cancer Sci. 2007 Nov;98(11):1809-16. doi: 10.1111/j.1349-7006.2007.00604.x. Epub 2007 Sep 2. PMID: 17784872.
[3]. be H, Kikuchi S, Hayakawa K, et,al.Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med Chem Lett. 2011 Feb 28;2(4):320-4. doi: 10.1021/ml200004g. PMID: 24900312; PMCID: PMC4018163.
[4]. Gilmartin AG, Bleam MR, et,al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 2011 Mar 1;17(5):989-1000. doi: 10.1158/1078-0432.CCR-10-2200. Epub 2011 Jan 18. Erratum in: Clin Cancer Res. 2012 Apr 15;18(8):2413. PMID: 21245089.
[5]. Gilmartin AG, Bleam MR, et,al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 2011 Mar 1;17(5):989-1000. doi: 10.1158/1078-0432.CCR-10-2200. Epub 2011 Jan 18. Erratum in: Clin Cancer Res. 2012 Apr 15;18(8):2413. PMID: 21245089.
[6]. Flaherty KT, Infante JR, et,al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012 Nov 1;367(18):1694-703. doi: 10.1056/NEJMoa1210093. Epub 2012 Sep 29. PMID: 23020132; PMCID: PMC3549295.
[7]. Zeiser R, Andrlová H, et,al. Trametinib (GSK1120212). Recent Results Cancer Res. 2018;211:91-100. doi: 10.1007/978-3-319-91442-8_7. PMID: 30069762.
البروتوكول (Protocol)
| Kinase experiment [1]: | |
|
Preparation Method |
Two micrograms of dephosphorylated MBP (Upstate) in 0.2 M sodium carbonate (pH 9.4) was coated onto 96-well plates at 4 ¡ムovernight. After blocking with 1% BSA, the inactive forms of MEK1 (2 ng) or MEK2 (4 ng) with inactive ERK2 (50 ng) diluted in assay buffer were preincubated in the plates with test compounds£¨including Trametinib (GSK1120212)£©at room temperature for 10 min. The kinase reaction was started by the addition of active B-Raf (V599E) or c-Raf, with 10 M ATP and 12.5 mM MgCl2. After incubation at 30 C for 30 min, the phosphorylation of MBP by ERK2 was detected with peroxidase-labeled antiphosphorylated MBP antibody. |
|
Reaction Conditions |
Trametinib (GSK1120212) with protein at room temperature for 10 minutes |
|
Applications |
Trametinib (GSK1120212) binds specifically to MEK1/2.IC50 in cell-free assay was 0.92 nM/1.8 nM. |
| Cell experiment [1]: | |
|
Cell lines |
HT-29 cells |
|
Preparation Method |
Cells were precultured for 24 h and then exposed to JTP-70902. After incubation with Trametinib (GSK1120212) for 4 days, cell viability was assessed using Cell Counting Kit-8. |
|
Reaction Conditions |
0-1000nM Trametinib (GSK1120212) for 4 days |
|
Applications |
Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells. |
| Animal experiment [1]: | |
|
Animal models |
Trametinib (GSK1120212) in the nude mouse HT-29 xenograft model |
|
Preparation Method |
HT-29 cells were inoculated subcutaneously into the right flank of nude mice, and Trametinib (GSK1120212) was administered orally twice daily for 21 days starting from 5 days after the inoculation. |
|
Dosage form |
10-100mg/kg Trametinib (GSK1120212) twice daily for 21 days |
|
Applications |
Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment. |
|
References: [1]. Yamaguchi T, Yoshida T,et,al. Identification of JTP-70902, a p15(INK4b)-inductive compound, as a novel MEK1/2 inhibitor. Cancer Sci. 2007 Nov;98(11):1809-16. doi: 10.1111/j.1349-7006.2007.00604.x. Epub 2007 Sep 2. PMID: 17784872. |
|
وثائق المنتج (Product Documents)
Purity:>98.00%Appearance:A solid
الخصائص الكيميائية (Chemical Properties)
رقم CAS
871700-17-3
المرادفات
GSK1120212, JTP-74057
الاسم الكيميائي
N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
SMILES
CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC(=CC=C4)NC(=O)C)C5CC5
الصيغة الجزيئية
C26H23FIN5O4
الوزن الجزيئي
615.39
الذوبانية
≥ 15.38mg/mL in DMSO
التخزين
Store at -20°C
إرشادات عامة
اختر مذيبًا مناسبًا وفقًا لبيانات ذوبانية المنتج. بعد التحضير، قسّم المحلول المخزون إلى أجزاء لتجنب دورات التجميد والذوبان المتكررة.
استخدم المحاليل المخزونة خلال 6 أشهر عند حفظها في -80°C، أو خلال شهر واحد عند حفظها في -20°C.
لتحسين الذوبانية، سخّن الأنبوب إلى 37°C وعرّضه للموجات فوق الصوتية لمدة مناسبة.
استخدم المحاليل المخزونة خلال 6 أشهر عند حفظها في -80°C، أو خلال شهر واحد عند حفظها في -20°C.
لتحسين الذوبانية، سخّن الأنبوب إلى 37°C وعرّضه للموجات فوق الصوتية لمدة مناسبة.
شروط الشحن
تُشحن عينات التقييم مع عبوات تبريد. وتُشحن الأحجام الأخرى المتاحة في درجة حرارة الغرفة، أو مع عبوات تبريد عند الطلب.
الحاسبات (Calculators)المولارية / التخفيف / الوزن الجزيئي / تحويل الوحدات / تركيبة داخل الجسم الحي / الذوبانية
g/mol
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