| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
CEP-28122 mesylate salt selectively targets Anaplastic Lymphoma Kinase (ALK), a receptor tyrosine kinase. It inhibits recombinant ALK kinase activity with an IC50 of 1.9 nM. It also shows high selectivity over other kinases, with a 50-fold higher selectivity for ALK.
|
|---|---|
| ln Vitro |
Treatment with CEP-28122 mesylate salt (3–3000 nM; 48 hours) inhibits the development of Karpas-299 and Sup-M2 cells in culture in a concentration-dependent manner and is associated with concentration-related caspase 3/7 activation[1]. Phosphorylation of potential ALK downstream effectors is significantly suppressed in Sup-M2 cells after treatment with CEP-28122 mesylate salt (30–1000 nM; 2 hours), suggesting that individual ALK fusion proteins mediate the downstream signaling pathways[1].
In vitro, CEP-28122 mesylate salt (3-3000 nM; 48 hours) inhibits the growth of ALK-positive Karpas-299 and Sup-M2 lymphoma cells in a concentration-dependent manner. It also suppresses the phosphorylation of ALK downstream effectors, including Stat-3, Akt, and ERK1/2 in Sup-M2 cells. |
| ln Vivo |
In Sup-M2 subcutaneous tumor xenografts in SCID mice, CEP-28122 mesylate salt (3–30 mg/kg; oral gavage; twice daily; 12 days) exhibits dose-dependent antitumor activity. In contrast, CEP-28122 has no antitumor activity in nu/nu mice bearing HCT116, indicating that the antitumor activity of CEP-28122 in NPM-ALK–positive Sup-M2 tumor models is the result of persistent NPM-ALK inhibition in tumors [1].
In vivo, CEP-28122 mesylate salt (3-30 mg/kg; oral gavage; twice daily for 12 days) exhibits dose-dependent antitumor activity in SCID mice bearing Sup-M2 subcutaneous tumor xenografts. It has no antitumor activity in ALK-negative HCT116 tumors, confirming on-target activity. |
| Enzyme Assay |
For in vitro kinase assays, recombinant ALK enzyme is incubated with a peptide substrate and ATP in a reaction buffer. Varying concentrations of CEP-28122 mesylate salt (0-1000 nM) are added to the reaction. After incubation, kinase activity is measured by quantifying phosphorylated substrate using a luminescent or fluorescence-based method.
|
| Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: Karpas-299, Sup-M2, Toledo and HuT-102 cells Tested Concentrations: 10 nM, 100 nM, 1000 nM, 10000 nM Incubation Duration: 48 hrs (hours) Experimental Results: Treatment led to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture. Western Blot Analysis [1] Cell Types: Sup-M2 cells Tested Concentrations: 30 nM, 100 nM, 300 nM, 1000 nM Incubation Duration: 2 hrs (hours) Experimental Results: Resulted in substantial suppression of phosphorylation of putative downstream effectors of ALK, including Stat-3, Akt, and ERK1/2 in Sup-M2 cells. For cell-based assays, Sup-M2 or Karpas-299 cells are plated in 96-well plates and treated with CEP-28122 mesylate salt (3-3000 nM) for 48 hours. Cell viability is measured using a luminescent cell viability assay (e.g., CellTiter-Glo). For mechanistic studies, protein lysates are analyzed by Western blot for phospho-ALK and downstream effectors. |
| Animal Protocol |
Animal/Disease Models: Female SCID (severe combined immunodeficient) mouse bearing Sup -M2 subcutaneous (sc) tumor xenografts and nu/nu (nude) mice bearing HCT116 aged 6-8 week old[1]
Doses: 3 mg/kg, 10 mg/kg and 30 mg/kg Route of Administration: po (oral gavage); twice a day; 12 days Experimental Results: CEP-28122 produced dose-dependent antitumor activity in Sup-M2 subcutaneous (sc) tumor xenografts in SCID (severe combined immunodeficient) mouse. In contrast, CEP-28122 had no antitumor activity in nu/nu (nude) mice bearing HCT116. For animal studies, female SCID mice (6-8 weeks) with established Sup-M2 xenografts (approx. 100-200 mm3) are randomized and treated with CEP-28122 mesylate salt (3, 10, 30 mg/kg) or vehicle via oral gavage twice daily for 12 days. Tumor volumes and body weights are measured twice weekly. |
| ADME/Pharmacokinetics |
CEP-28122 mesylate salt has favorable pharmacokinetic properties for an oral agent. It is orally bioactive and exhibits good systemic exposure. Studies in CD-1 mice indicate that it has good pharmacodynamic and pharmacokinetic activities, with measurable plasma levels following oral administration.
|
| Toxicity/Toxicokinetics |
In preclinical studies, no significant changes in survival rate or overt signs of toxicity were reported at therapeutic doses (e.g., up to 30 mg/kg in mice). Standard safety pharmacology studies would be required for further development. It is intended for research use only and not for human therapeutic applications.
|
| References | |
| Additional Infomation |
CEP-28122 mesylate salt (CAS: 2070009-30-0) is a third-generation, orally bioavailable ALK inhibitor derived from a diaminopyrimidine scaffold. It shows promise for research on ALK-positive cancers, including anaplastic large-cell lymphoma, non-small cell lung cancer, and neuroblastoma.
|
| Molecular Formula |
C29H39CLN6O6S
|
|---|---|
| Molecular Weight |
635.17
|
| Exact Mass |
634.234
|
| CAS # |
2070009-30-0
|
| Related CAS # |
CEP-28122;1022958-60-6
|
| PubChem CID |
91885507
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
43
|
| Complexity |
951
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
COC1=C(C=CC2=C1CC[C@H](CC2)N3CCOCC3)NC4=NC=C(C(=N4)N[C@@H]5[C@@H]6C[C@H]([C@@H]5C(=O)N)C=C6)Cl.CS(=O)(=O)O
|
| InChi Key |
PIIIZYXUYVVFSN-WWQCAQLDSA-N
|
| InChi Code |
InChI=1S/C28H35ClN6O3.CH4O3S/c1-37-25-20-8-7-19(35-10-12-38-13-11-35)6-4-16(20)5-9-22(25)32-28-31-15-21(29)27(34-28)33-24-18-3-2-17(14-18)23(24)26(30)36;1-5(2,3)4/h2-3,5,9,15,17-19,23-24H,4,6-8,10-14H2,1H3,(H2,30,36)(H2,31,32,33,34);1H3,(H,2,3,4)/t17-,18+,19+,23+,24-;/m1./s1
|
| Chemical Name |
(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide;methanesulfonic acid
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO :~6.4 mg/mL (~10.08 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5744 mL | 7.8719 mL | 15.7438 mL | |
| 5 mM | 0.3149 mL | 1.5744 mL | 3.1488 mL | |
| 10 mM | 0.1574 mL | 0.7872 mL | 1.5744 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
