| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: =100%
| Targets |
Tie-2 (IC50 = 1 nM); p38α (IC50 = 35 nM); p38β (IC50 = 26 nM)
|
|---|---|
| ln Vitro |
Pexmetinib is a dual inhibitor of Tie-2 and p38 MAPK, with IC50 values for Tie-2, p38α and p38β of 1 nM, 35 nM, and 26 nM, respectively. The IC50 values for pexmetinib are also 4 nM for Abl, 10 nM for Arg, 28 nM for FGFR1, 47 nM for Flt1, 42 nM for Flt4, 41 nM for Fyn, 26 nM for Hck, 25 nM for Lyn, and 26 nM for MINK, respectively. In myelodysplastic syndromes, pexmetinib (0.5, 1 μM) inhibits leukemic cell proliferation and promotes hematopoietic activity.
|
| ln Vivo |
Pexmetinib (30 mg/kg, p.o.) prevents the production of pro-inflammatory cytokines TNF and IL6 in male Swiss Webster mice in response to lipopolysaccharide (LPS) or staphylococcus enterotoxin A. ARRY-614 (25 mg/kg, p.o.) inhibits tumor growth in established RPMI 8226 xenografts and exhibits additive activity when combined with thalidomide. When combined with Taxol, ARRY-614 (30 mg/kg, p.o.) exhibits additive tumor growth inhibition activity in ovarian carcinoma A2780 xenografts.
|
| Enzyme Assay |
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.
|
| Cell Assay |
Pexmetinib, an inhibitor of TIE2/p38, is incubated with cell lines and primary samples at the recommended doses. Viability is measured using a Fluostar Omega Microplate Reader and Cell Titer Blue to determine viability[1].
|
| Animal Protocol |
Male Swiss Webster mice
30 mg/kg p.o. |
| References |
| Molecular Formula |
C31H33FN6O3
|
|
|---|---|---|
| Molecular Weight |
556.63
|
|
| Exact Mass |
556.26
|
|
| Elemental Analysis |
C, 66.89; H, 5.98; F, 3.41; N, 15.10; O, 8.62
|
|
| CAS # |
945614-12-0
|
|
| Related CAS # |
|
|
| Appearance |
Solid powder
|
|
| SMILES |
O=C(NCC1=CC(F)=CC=C1OC2=CC3=C(N(CCO)N=C3)C=C2)NC4=CC(C(C)(C)C)=NN4C5=CC=C(C)C=C5
|
|
| InChi Key |
LNMRSSIMGCDUTP-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C31H33FN6O3/c1-20-5-8-24(9-6-20)38-29(17-28(36-38)31(2,3)4)35-30(40)33-18-22-15-23(32)7-12-27(22)41-25-10-11-26-21(16-25)19-34-37(26)13-14-39/h5-12,15-17,19,39H,13-14,18H2,1-4H3,(H2,33,35,40)
|
|
| Chemical Name |
1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[[5-fluoro-2-[1-(2-hydroxyethyl)indazol-5-yl]oxyphenyl]methyl]urea
|
|
| Synonyms |
ARRY 614; ARRY614; ARRY-614; Pexmetinib
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7965 mL | 8.9826 mL | 17.9653 mL | |
| 5 mM | 0.3593 mL | 1.7965 mL | 3.5931 mL | |
| 10 mM | 0.1797 mL | 0.8983 mL | 1.7965 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04074967 | Recruiting | Drug: Phase Ib ARRY-614 + nivolumab Drug: Phase II ARRY-614 + nivolumab |
Melanoma Solid Tumor |
Jason J. Luke, MD | June 11, 2020 | Phase 1 Phase 2 |
| NCT01496495 | Completed | Drug: ARRY-614, p38/Tie2 inhibitor; oral |
Myelodysplastic Syndromes | Array Biopharma, now a wholly owned subsidiary of Pfizer |
January 2012 | Phase 1 |
| NCT00916227 | Completed | Drug: ARRY-614, p38/Tie2 inhibitor; oral |
Myelodysplastic Syndromes | Array Biopharma, now a wholly owned subsidiary of Pfizer |
June 2009 | Phase 1 |
Bone marrow levels of p-p38 and CC3. Clin Cancer Res. 2015 Mar 1; 21(5): 985–994. |
ARRY-614 Plasma Concentration-Time Profiles. Clin Cancer Res. 2015 Mar 1;21(5):985-94. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
