| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
It targets cdc2-like kinase 2 (CLK2) and other members of the CLK family. By inhibiting CLK activity, it prevents the phosphorylation of SR proteins, which are key regulators of alternative splicing. This disruption leads to aberrant RNA splicing and the activation of apoptosis in cancer cells, particularly those with spliceosome mutations.
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|---|---|
| ln Vitro |
CTX-712 strongly inhibits the proliferation of human myeloid K562 and MV-4-11 cells with IC50 values of 0.15 microM and 0.036 microM, respectively. It also shows anti-leukemic activity with an IC50 of 0.078 microM in primary acute myeloid leukemia (AML) cells. It inhibits the phosphorylation of SR proteins including SRSF3/4/6, which interact with SRSF2.
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| ln Vivo |
In mouse models of myelodysplastic syndromes (MDS) and AML, oral administration of CTX-712 at 6.25 and 12.5 mg/kg for two weeks significantly inhibited tumor growth and improved survival rates, particularly in models with SRSF2 mutations (P95H and P95L). The effect was dose-dependent, with higher doses reducing tumor volume and enhancing survival.
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| Enzyme Assay |
For cell-free receptor binding, a kinase assay is performed. Recombinant CLK2 kinase (0.1-1 ng/uL) is incubated with various concentrations of CTX-712 (0.01-100 nM) in an assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT) containing 10 uM ATP and a specific peptide substrate. After 1 hour at room temperature, the reaction is stopped, and ADP production is measured using a Kinase-Glo Max kit. The IC50 of 1.4 nM is determined by fitting the luminescence data.
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| Cell Assay |
For in vitro cell assays, K562 or MV-4-11 cells are seeded in 96-well plates and treated with CTX-712 at concentrations ranging from 0.001 to 10 uM for 72 hours. Cell viability is measured using CellTiter-Glo reagent. For mechanistic studies, cells are treated with CTX-712 (0.1-1 uM) for 6-24 hours. Lysates are collected, and the phosphorylation levels of SR proteins (p-SRSF3/4/6) are analyzed via Western blot using a pan-phospho-SR protein specific antibody (e.g., mAb 1H4).
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| Animal Protocol |
For in vivo efficacy, a mouse model of MDS or AML is used. Mice bearing SRSF2 P95H mutations are orally gavaged with CTX-712 daily at doses of 6.25 mg/kg or 12.5 mg/kg for two weeks (5 days on, 2 days off). Tumor size is monitored by bioluminescence imaging or caliper measurement. Survival rates are tracked and plotted via Kaplan-Meier curves. Blood and tumor tissues are collected at endpoint for Western blot or IHC analysis of p-SR protein levels to confirm target engagement.
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| ADME/Pharmacokinetics |
CTX-712 (MW: 408.39) is orally effective and shows good solubility (≥ 2.5 mg/mL) in common formulations such as 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline. As an oral CLK inhibitor, it is expected to have favorable absorption and plasma exposure, though detailed PK parameters (T1/2, Cmax, AUC) from published studies are limited to compound-specific data.
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| Toxicity/Toxicokinetics |
As a potent anti-cancer agent, it is well-tolerated in mouse models at the doses used. Specific toxicological data, such as maximum tolerated dose (MTD), is limited but implied by the in vivo model results where 12.5 mg/kg was effective without obvious adverse effects reported. Standard safety precautions for handling potent kinase inhibitors should be observed.
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| References | |
| Additional Infomation |
CTX-712 is a novel first-in-class CLK2 inhibitor for cancer therapy, particularly for AML and MDS patients with SRSF2 mutations. It is currently in preclinical research stages. It provides a valuable tool for studying the role of RNA splicing in cancer and validating CLK2 as a therapeutic target.
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| Molecular Formula |
C19H17FN8O2
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|---|---|
| Molecular Weight |
408.39
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| Exact Mass |
408.145
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| CAS # |
2144751-78-8
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| PubChem CID |
138522180
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
605
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1=C(C)N(CC2OC([C@@H](C)F)=NN=2)C2C=C(C=NC1=2)C1C=CN2C=1C(OC)=NC=N2
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| InChi Key |
OENNTZBJPRRGFL-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C19H17FN8O2/c1-10(20)18-26-25-15(30-18)8-27-11(2)24-17-14(27)6-12(7-21-17)13-4-5-28-16(13)19(29-3)22-9-23-28/h4-7,9-10H,8H2,1-3H3/t10-/m1/s1
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| Chemical Name |
2-[(1R)-1-fluoroethyl]-5-[[6-(4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methylimidazo[4,5-b]pyridin-1-yl]methyl]-1,3,4-oxadiazole
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~25 mg/mL (~61.22 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.12 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4486 mL | 12.2432 mL | 24.4864 mL | |
| 5 mM | 0.4897 mL | 2.4486 mL | 4.8973 mL | |
| 10 mM | 0.2449 mL | 1.2243 mL | 2.4486 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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