Pexmetinib (ARRY-614) (Synonyms: ARRY 614) |
| رقم الكتالوجGC11857 |
Pexmetinib (ARRY-614) هو مثبط مزدوج قوي لـ Tie-2 و p38 MAPK ، مع IC50s من 1 نانومتر ، 35 نانومتر و 26 نانومتر لـ Tie-2 ، p38α ؛ و p38β ؛ على التوالي ، ويمكن استخدامها في البحث عن ابيضاض الدم النخاعي الحاد.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 945614-12-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Pexmetinib (ARRY-614) is a potent inhibitor of cytokine synthesis, via the dual inhibition of p38 mitogen-activated protein kinase (MAPK), and Tie2/Tek receptor tyrosine kinase. The in vitro IC50 values of ARR Y-614 for both Tie2 and p38 mitogen-activated protein kinase are 1000 ng/mL and 100 ng/mL, respectively [1, 2].
p38 is a group of mitogen-activated protein kinases. MAPKs are activated by the dual phosphorylation of Tyr and Thr residues in the Thr-Xaa-Tyr motif in subdomain VIII. Data indicated that p38 MAPK may mediate signaling to the nucleus [3].
ARRY-614 is active against MAPK and Tie2/Tek receptor tyrosine kinase in cells. In primary human bone marrow stromal cells, ARRY-614 inhibited basal cytokines with an IC50 value ranging from 50-100 nM [4].
In dose escalation or expansion cohorts, treatment with ARRY-614 either once daily or twice daily was applied to forty-five patients. ARRY-614 reduced the levels of circulating biomarkers and the p38 MAPK activation of bone marrow [1]. In ex vivo stimulated human whole blood, LPS-induced cytokines was inhibited by ARRY-614 with an IC50 value ranging from 50-120 nM. ARRY-614 inhibited the release of IL-6 from SEA- or LPS-challenged mice with an ED50 value less than 10 mg/kg. Combining ARRY-614 with lenalidomide inhibited both pro-inflammatory cytokines and tumor growth in vivo with higher potency, compared with either agent alone [4].
References:
[1]. Garcia-Manero G, Khoury HJ, Jabbour E, et al. A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes. Clinical Cancer Research, 2015, 21(5): 985-994.
[2]. Wollenberg LA, Corson DT, Nugent CA, et al. An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614). Clinical pharmacology: advances and applications, 2015, 7: 87.
[3]. Raingeaud J, Whitmarsh AJ, Barrett T, et al. MKK3-and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Molecular and cellular biology, 1996, 16(3): 1247-1255.
[4]. Winski S, Humphries M, Yeh T, et al. Activity of ARRY-614, an inhibitor of p38 map kinase and angiogenic targets, in hematologic malignancies. Cancer Research, 2009, 69(9 Supplement): 331-331.
|
Cell experiment: |
Cell lines and primary samples are incubated at indicated doses of of TIE2/p38 inhibitor Pexmetinib. Viability is assessed by addition of Cell Titer Blue and measured via Fluostar Omega Microplate reader[1]. |
|
References: [1]. Bachegowda L, et al. Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res. 2016 Aug 15;76(16):4841-4849. |
|
| Cas No. | 945614-12-0 | SDF | |
| المرادفات | ARRY 614 | ||
| Chemical Name | (Z)-N-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-N'-(5-fluoro-2-((1-(2-hydroxyethyl)-1H-indazol-5-yl)oxy)benzyl)carbamimidic acid | ||
| Canonical SMILES | CC1=CC=C(N2C(N/C(O)=N/CC3=CC(F)=CC=C3OC4=CC=C5C(C=NN5CCO)=C4)=CC(C(C)(C)C)=N2)C=C1 | ||
| Formula | C31H33FN6O3 | M.Wt | 556.63 |
| الذوبان | ≥ 107.6 mg/mL in DMSO, ≥ 113 mg/mL in EtOH | 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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7965 mL | 8.9826 mL | 17.9653 mL |
| 5 mM | 359.3 μL | 1.7965 mL | 3.5931 mL |
| 10 mM | 179.7 μL | 898.3 μL | 1.7965 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
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 ddH2O, 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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *