| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
ALK (IC50 = 2.1 nM); ALK L1196M (IC50 = 1.3 nM); ALK G1202R (IC50 = 3.9 nM)
ZX-29 targets anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase that is frequently mutated or overexpressed in various cancers, including non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma. It is a potent and selective ALK inhibitor with IC50 values of 2.1 nM for wild-type ALK, 1.3 nM for the ALK L1196M mutant, and 3.9 nM for the ALK G1202R mutant. ZX-29 is inactive against EGFR, indicating its high selectivity for ALK over other kinases. By inhibiting ALK, ZX-29 blocks downstream signaling pathways that promote cell proliferation and survival. |
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| ln Vitro |
ZX-29 (0-81 nM; 24-72 hours; NCI-H2228 cells) cell viability decreases in a dose- and time-dependent manner following ZX-29 treatment[1].
ZX-29 (10 nM; 24 hours; NCI-H2228 cells) results in the production of autophagosomes and the usual symptoms of autophagy. ZX-29 raises LC3 and Beclin1 expression levels[1]. ZX-29 (10 nM; 0-48 hours; NCI-H2228 cells) inhibits NCI-H2228 cells in the G1 phase and prevents them from proliferating[1]. ZX-29 (10-40 nM; 24-48 hours; NCI-H2228 cells) cells undergo apoptosis in response to ZX-29 treatment. ZX-29 dose-dependently increases the production of activated forms of caspase 3, downregulates the expression of the antiapoptotic protein Bcl-2, and upregulates the expression levels of the proapoptotic protein Bax[1]. ZX-29 (30-300 nM; 24 hours; NCI-H2228 cells) treatment dramatically and dose-dependently reduces the expression of p-ALK and its downstream signaling proteins, such as p-Akt and p-STAT3[1]. ZX-29 (20 nM; 0-48 hours; NCI-H2228 cells) treatment significantly increases the mRNA level of CHOP[1]. ZX-29 inhibits NCI-H2228 cell colony formation in a dose-dependent manner. ZX-29 concentration increased was accompanied by a progressive decrease in cell density as well as a sharpening and slendering of the cells' normal morphology[1]. ZX-29 demonstrates potent in vitro activity against ALK-positive cancer cells. It inhibits the kinase activity of wild-type ALK with an IC50 of 2.1 nM and shows even greater potency against the ALK L1196M (IC50 = 1.3 nM) and ALK G1202R (IC50 = 3.9 nM) mutants. The compound is inactive against EGFR, confirming its selectivity for ALK. In cellular assays, ZX-29 induces apoptosis by inducing endoplasmic reticulum (ER) stress and overcomes cell resistance caused by ALK mutations. It also induces protective autophagy and exhibits antitumor effects. These results indicate that ZX-29 is a highly potent and selective ALK inhibitor with the potential to overcome resistance mutations. |
| ln Vivo |
ZX-29 (50 mg/kg; intragastric administration; every 2 days; for a total of 7 times; female BALB/c nude mice) treatment inhibits tumor growth in a mouse xenograft model[1].
ZX-29 has demonstrated in vivo antitumor activity in mouse xenograft models. Treatment with ZX-29 suppresses tumor growth in mouse xenograft models, indicating its potential for in vivo efficacy. The compound's ability to induce apoptosis and autophagy, along with its potent ALK inhibitory activity, contributes to its antitumor effects. Further studies are needed to evaluate its pharmacokinetic properties, optimal dosing regimens, and efficacy in additional animal models. The in vivo results support the potential of ZX-29 as a therapeutic candidate for ALK-driven cancers. |
| Enzyme Assay |
The in vitro kinase assay for ZX-29 involves measuring its inhibitory activity against ALK and its mutant forms in a cell-free system. The assay is typically performed using recombinant ALK kinase domains and a peptide substrate in the presence of ATP. The phosphorylation of the substrate is quantified using radioactive or fluorescence-based detection methods. Dose-response curves are generated by incubating the enzyme with increasing concentrations of ZX-29 to calculate the IC50 values. The assay conditions are optimized to ensure that the compound's solubility is maintained, and appropriate controls are included to validate the specificity of the inhibition. Selectivity against other kinases, such as EGFR, is also assessed.
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| Cell Assay |
The in vitro cellular assay for ZX-29 is conducted using ALK-positive cancer cell lines, such as those harboring ALK fusions or mutations. Cells are seeded in multi-well plates and treated with ZX-29 at various concentrations. The inhibition of ALK phosphorylation and downstream signaling is measured by Western blotting or ELISA. Cell viability and proliferation are assessed using MTT or similar assays. Apoptosis is evaluated by measuring caspase activity or using Annexin V staining. Autophagy is assessed by monitoring LC3-II conversion or using fluorescent reporters. The IC50 values for cell growth inhibition are calculated from dose-response curves.
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| Animal Protocol |
Female BALB/c nude mice (4-week-old) with H2228 cells[1]
50 mg/kg Intragastric administration; every 2 days; for a total of 7 times In vivo animal experiments for ZX-29 are conducted using mouse xenograft models of ALK-driven tumors. Immunodeficient mice are implanted with ALK-positive cancer cells subcutaneously. When tumors reach a certain size, mice are treated with ZX-29 via oral gavage or intraperitoneal injection at various doses. Tumor growth is monitored by caliper measurements, and tumor weight is assessed at the end of the study. Pharmacokinetic parameters may also be assessed to correlate drug exposure with antitumor efficacy. The compound's ability to suppress tumor growth and its safety profile are evaluated in these studies. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of ZX-29 have not been extensively characterized in the available literature. Based on its chemical properties (molecular weight 518.03), the compound is expected to have moderate oral bioavailability and reasonable tissue distribution. Further studies are needed to determine its plasma half-life, clearance, volume of distribution, and protein binding. The compound's PK profile would be essential for optimizing dosing regimens in in vivo efficacy studies and for assessing its potential for further development as an anticancer therapeutic.
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| Toxicity/Toxicokinetics |
Toxicological data for ZX-29 are limited in the available literature. In vitro cytotoxicity assays typically show that the compound has a favorable selectivity index, as it inhibits ALK at concentrations well below those that cause significant cytotoxicity to normal cells. Comprehensive in vivo toxicology studies, including acute and chronic toxicity, genotoxicity, and organ-specific toxicity, have not been reported. Further safety assessments would be required to evaluate the compound's potential for clinical development.
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| References | |
| Additional Infomation |
ZX-29 is a research compound that has not yet entered clinical trials or received regulatory approval for therapeutic use. It is primarily used as a tool compound to study ALK signaling and to explore the therapeutic potential of ALK inhibitors. The compound's potent activity against ALK resistance mutations makes it a valuable candidate for further pharmacological development. Additional research is needed to optimize its pharmacokinetic properties, evaluate its efficacy in additional animal models, and assess its safety profile before it can be considered for clinical applications.
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| Molecular Formula |
C23H28CLN7O3S
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|---|---|
| Molecular Weight |
518.03
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| Exact Mass |
517.17
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| Elemental Analysis |
C, 53.33; H, 5.45; Cl, 6.84; N, 18.93; O, 9.27; S, 6.19
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| CAS # |
2254805-62-2
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| Related CAS # |
2254805-62-2
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| PubChem CID |
142497299
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
765
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4NS(=O)(=O)C)Cl)OC
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| InChi Key |
ATHZZWBANOJUOA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H28ClN7O3S/c1-30-10-12-31(13-11-30)16-8-9-20(21(14-16)34-2)27-23-25-15-17(24)22(28-23)26-18-6-4-5-7-19(18)29-35(3,32)33/h4-9,14-15,29H,10-13H2,1-3H3,(H2,25,26,27,28)
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| Chemical Name |
N-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]methanesulfonamide
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| Synonyms |
ZX29; ZX 29; ZX-29
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 mg/mL (~96.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9304 mL | 9.6520 mL | 19.3039 mL | |
| 5 mM | 0.3861 mL | 1.9304 mL | 3.8608 mL | |
| 10 mM | 0.1930 mL | 0.9652 mL | 1.9304 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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