| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
CPD-1224 targets EML4-ALK oncogenic fusion proteins. As a cereblon-binding PROTAC molecule, it simultaneously binds to the ALK protein and the CRBN E3 ubiquitin ligase, leading to ubiquitination and subsequent proteasomal degradation of ALK and its mutants L1196M and G1202R, thereby overcoming resistance to traditional ALK inhibitors.
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|---|---|
| ln Vitro |
In cellular assays, CPD-1224 promotes the degradation of ALK and the resistant mutants L1196M and G1202R, which are common mechanisms of acquired resistance to first- and second-generation ALK inhibitors. Detailed IC50 or DC50 values are not provided.
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| Enzyme Assay |
A biochemical ternary complex formation assay can be used to confirm binding of CPD-1224 to both ALK (or mutant ALK) and cereblon. Increasing concentrations of CPD-1224 are incubated with purified recombinant ALK and CRBN-DDB1 complex. Formation of the ternary complex is detected by AlphaScreen or surface plasmon resonance (SPR) technology.
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| Cell Assay |
For cellular degradation assays, ALK-dependent cancer cell lines (e.g., H3122 cells expressing EML4-ALK) are seeded and treated with increasing concentrations of CPD-1224 (0.1-1000 nM) for 4-24 hours. Cells are lysed, and ALK protein levels are measured by Western blot using an anti-ALK antibody. The DC50 (concentration required for 50% degradation) for wild-type ALK and mutants L1196M/G1202R is calculated from dose-response curves.
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| Animal Protocol |
No in vivo animal experiment data is available for CPD-1224. As an orally active PROTAC degrader, CPD-1224 is expected to show efficacy in mouse xenograft models of ALK-driven cancers, including those resistant to conventional ALK inhibitors due to L1196M or G1202R mutations.
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| ADME/Pharmacokinetics |
As an orally active compound, CPD-1224 is designed to have favorable oral bioavailability. Detailed PK parameters such as half-life, Cmax, and AUC have not been specified.
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| Toxicity/Toxicokinetics |
No specific toxicology data is reported for CPD-1224. As a PROTAC molecule that induces protein degradation, its safety profile may differ from traditional inhibitors; hook effect at high concentrations is a pharmacological consideration rather than a toxicity issue.
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| References | |
| Additional Infomation |
CPD-1224 (CAS: 2891620-68-9) is an orally active PROTAC degrader targeting EML4-ALK oncogenic fusions and degrading ALK and mutants L1196M/G1202R. It is an orally active derivative of ALK inhibitors conjugated to cereblon E3 ligase ligands. Molecular formula: C43H47ClN8O7S; molecular weight: 855.40. It is used for research into overcoming resistance to ALK inhibitors in cancer therapy.
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| Molecular Formula |
C43H47CLN8O7S
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|---|---|
| Molecular Weight |
855.40
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| Exact Mass |
854.297
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| CAS # |
2891620-68-9
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| PubChem CID |
168265663
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
60
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| Complexity |
1690
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C2CCC(NC2=O)=O)C(C2=CC=C(N3CC(C3)CN3CCC(C4C(=CC(=C(C=4)OC)NC4=NC=C(C(=N4)NC4C=CC=CC=4S(=O)(=O)C(C)C)Cl)C)CC3)C=C21)=O
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| InChi Key |
YROLXKJYDUJWRK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H47ClN8O7S/c1-24(2)60(57,58)37-8-6-5-7-33(37)46-39-32(44)20-45-43(49-39)47-34-17-25(3)30(19-36(34)59-4)27-13-15-50(16-14-27)21-26-22-51(23-26)28-9-10-29-31(18-28)42(56)52(41(29)55)35-11-12-38(53)48-40(35)54/h5-10,17-20,24,26-27,35H,11-16,21-23H2,1-4H3,(H,48,53,54)(H2,45,46,47,49)
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| Chemical Name |
5-[3-[[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-5-methoxy-2-methylphenyl]piperidin-1-yl]methyl]azetidin-1-yl]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
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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: ~14.3 mg/mL (~16.7 mM; with ultrasonication and warming by heating to 160°C)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (1.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (14.3 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1690 mL | 5.8452 mL | 11.6904 mL | |
| 5 mM | 0.2338 mL | 1.1690 mL | 2.3381 mL | |
| 10 mM | 0.1169 mL | 0.5845 mL | 1.1690 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.
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