| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
MS4078 is a potent PROTAC degrader of anaplastic lymphoma kinase (ALK) with a Kd of 19 nM for binding affinity to ALK. In SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells, MS4077 and MS4078 significantly and time- and concentration-dependently reduced the cellular levels of oncogenic active ALK fusion proteins. Cereblon and proteasomes were required for the ALK protein degradation that compounds 5 and 6 caused. Furthermore, SU-DHL-1 cell proliferation was potently inhibited by MS4077 and MS4078. Compound 6 is also appropriate for in vivo efficacy investigations because it demonstrated good plasma exposure in a mouse pharmacokinetic study. The next generation of ALK PROTACs was developed thanks to this study.
| Targets |
NPM-ALK (DC50 = 11 nM); EML4-ALK (DC50 = 59 nM)
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|---|---|
| ln Vitro |
MS4078 successfully stops the growth of cancer cells. With an IC50 of 33±1 nM, MS4078 (10-3, 10-2.5, 10-2, 10-1.5, 10-1, 10-0.5, 1 μM; 3 days) concentration-dependently inhibits SU-DHL-1 cell proliferation. The proliferation of NCI-H2228 cells is less sensitive to MS4078(10-2, 10-1.5, 10-1, 10-0.5, 1, 100.5 μM; 3 days) than that of SU-DHL-1 cells[1].
In SU-DHL-1 and NCI-H2228 cells, MS4078 potently lowers the levels of ALK fusion protein, inhibits ALK auto-phosphorylation, and down-steams STAT3 phosphorylation in a concentration-dependent manner. After 16 hours of treatment, MS4078 significantly lowers the NPM-ALK protein levels in SU-DHL-1 cells, with a DC50 (50% degradation) value of 11±2 nM. At 100 nM, both ALK Y1507 and STAT3 Y705 phosphorylation are inhibited to a degree of over 90%. After a 16-hour treatment, MS4078 decreases the EML4-ALK protein levels in NCI-H2228 cells with a DC50 value of 59 ± 16 nM. NCI-H2228 cells lower EML4-ALK protein levels by more than 90% at a concentration of 100 nM[1]. |
| References |
| Molecular Formula |
C45H52CLN9O8S
|
|---|---|
| Molecular Weight |
914.467887878418
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| Exact Mass |
913.33
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| Elemental Analysis |
C, 59.10; H, 5.73; Cl, 3.88; N, 13.79; O, 14.00; S, 3.51
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| CAS # |
2229036-62-6
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| Related CAS # |
2229036-62-6
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| PubChem CID |
137628668
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
64
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| Complexity |
1780
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
AYMGZLUKTNXEMY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C45H52ClN9O8S/c1-25(2)63-36-22-30(27(5)21-34(36)51-45-49-23-31(46)41(53-45)50-32-10-6-7-12-37(32)64(61,62)26(3)4)28-15-19-54(20-16-28)24-39(57)48-18-17-47-33-11-8-9-29-40(33)44(60)55(43(29)59)35-13-14-38(56)52-42(35)58/h6-12,21-23,25-26,28,35,47H,13-20,24H2,1-5H3,(H,48,57)(H,52,56,58)(H2,49,50,51,53)
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| Chemical Name |
2-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-methyl-5-propan-2-yloxyphenyl]piperidin-1-yl]-N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]acetamide
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| Synonyms |
MS-4078; MS4078; MS 4078
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 50~100 mg/mL (54.7~109.4 mM)
Ethanol: ~2 mg/mL (~2.2 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (2.27 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0935 mL | 5.4676 mL | 10.9353 mL | |
| 5 mM | 0.2187 mL | 1.0935 mL | 2.1871 mL | |
| 10 mM | 0.1094 mL | 0.5468 mL | 1.0935 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.
Eur J Med Chem.2018 May 10;151:304-314. |
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