ZX-29

Alias: ZX29; ZX 29; ZX-29
Cat No.:V39663 Purity: ≥98%
ZX-29 is a potent and specific ALK inhibitor (antagonist) with IC50s of 2.1 nM, 1.3 nM and 3.9 nM for ALK, ALK L1196M and ALK G1202R respectively, but has no activity against EGFR.
ZX-29 Chemical Structure CAS No.: 2254805-62-2
Product category: ALK
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
ZX-29 is a potent and specific ALK inhibitor (antagonist) with IC50s of 2.1 nM, 1.3 nM and 3.9 nM for ALK, ALK L1196M and ALK G1202R respectively, but has no activity against EGFR. ZX-29 causes apoptosis by inducing endoplasmic reticulum stress and overcomes cellular resistance caused by ALK mutations. ZX-29 can also induce protective autophagy and have anti-tumor effects.
Biological Activity I Assay Protocols (From Reference)
Targets
ALK (IC50 = 2.1 nM); ALK L1196M (IC50 = 1.3 nM); ALK G1202R (IC50 = 3.9 nM)
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].
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].
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
References

[1]. ZX-29, a novel ALK inhibitor, induces apoptosis via ER stress in ALK rearrangement NSCLC cells and overcomes cell resistance caused by an ALK mutation. Biochim Biophys Acta Mol Cell Res. 2020 Mar 26;1867(7):118712.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₂₃H₂₈CLN₇O₃S
Molecular Weight
518.03
Exact Mass
517.17
Elemental Analysis
C, 53.33; H, 5.45; Cl, 6.84; N, 18.93; O, 9.27; S, 6.19
CAS #
2254805-62-2
Related CAS #
2254805-62-2
Appearance
Solid powder
SMILES
CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4NS(=O)(=O)C)Cl)OC
InChi Key
ATHZZWBANOJUOA-UHFFFAOYSA-N
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)
Chemical Name
N-[2-[[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]methanesulfonamide
Synonyms
ZX29; ZX 29; ZX-29
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: 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)
Solubility Data
Solubility (In Vitro)
DMSO: ~50 mg/mL (~96.5 mM)
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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.

Biological Data
  • The effects of ZX-29 on NCI-H2228 cell proliferation. Biochim Biophys Acta Mol Cell Res . 2020 Jul;1867(7):118712.
  • ZX-29 induces apoptosis of NCI-H2228 cells. Biochim Biophys Acta Mol Cell Res . 2020 Jul;1867(7):118712.
  • ZX-29 induces ER stress. Biochim Biophys Acta Mol Cell Res . 2020 Jul;1867(7):118712.
  • ZX-29 induces protective autophagy. Biochim Biophys Acta Mol Cell Res . 2020 Jul;1867(7):118712.
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