| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cirtuvivint targets CDC-like kinases (CLK), which are involved in the regulation of alternative splicing. By inhibiting CLK, the compound inhibits phosphorylation of serine and arginine-rich splicing factors (SRSF) and disrupts spliceosome activity. This leads to reduced expression of Wnt pathway-related genes and proteins. The compound is a potent transcriptional regulator and splicing modulator.
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| ln Vitro |
Cirtuvivint (SM08502) inhibits phosphorylation of the serine and arginine rich splicing factor (SRSF) and disrupts spliceosome activity. These effects are linked to a reduction in the expression of genes and proteins related to the Wnt pathway. The production of alternative splicing variants of Wnt pathway genes is induced by cercuvivint, indicating that effects on alternative splicing may be part of its mechanism for inhibiting gene expression[1].
In vitro studies demonstrate that cirtuvivint (SM08502) inhibits phosphorylation of serine and arginine-rich splicing factors (SRSF) and disrupts spliceosome activity. These effects are associated with reduced Wnt pathway gene and protein expression. The compound has shown anti-tumor activity in gastrointestinal cancer models. Cirtuvivint is a potent transcriptional regulator and splicing modulator. |
| ln Vivo |
Oral administration of Cirtuvivint (SM08502) in xenograft mouse models significantly inhibits the growth of gastrointestinal tumors and decreases Wnt pathway gene expression and SRSF phosphorylation[1].
In vivo, orally administered cirtuvivint (SM08502) significantly inhibits growth of gastrointestinal tumors. The CLK inhibitor induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. The compound has shown promise for the treatment of various advanced solid tumors. It also has potential applications in arthritis research. |
| Enzyme Assay |
Cirtuvivint inhibits CLK kinases, which can be assessed using in vitro kinase assays. In a typical assay, recombinant CLK kinase is incubated with a peptide substrate, ATP, and varying concentrations of cirtuvivint. The incorporation of phosphate into the substrate is measured, and the IC50 is calculated. The compound's ability to inhibit SRSF phosphorylation can be assessed by Western blotting using phospho-specific antibodies.
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| Cell Assay |
The cellular activity of cirtuvivint is assessed using cancer cell lines. Cells are treated with varying concentrations of cirtuvivint. SRSF phosphorylation is assessed by Western blotting using phospho-specific antibodies. Spliceosome activity is assessed by analyzing alternative splicing patterns using RT-PCR or RNA sequencing. Wnt pathway gene and protein expression is measured by qPCR and Western blotting. Cell viability is measured using MTT assays.
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| Animal Protocol |
Cirtuvivint has been evaluated in gastrointestinal cancer models. In these studies, the compound is administered orally. Tumor growth is significantly inhibited. Wnt pathway gene expression is reduced. The compound has also been studied in arthritis models. Further studies would be needed to evaluate its efficacy in other cancer types and disease models.
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| ADME/Pharmacokinetics |
Cirtuvivint is orally active, indicating favorable oral bioavailability. The compound has a molecular weight of approximately 435.5 g/mol and a molecular formula of C24H25N7O. Further studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion properties, including half-life, Cmax, AUC, and tissue distribution.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for cirtuvivint. As a CLK inhibitor that modulates splicing, it may have on-target effects on normal splicing regulation. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound has shown promise in preclinical studies for solid tumors and arthritis.
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| References | |
| Additional Infomation |
Cirtuvivint is a first-in-class CDC-like kinase (CLK) inhibitor.
Cirtuvivint (SM08502, CAS# 2143917-62-6) is a potent and orally active CDC-like kinase (CLK) inhibitor. It inhibits SRSF phosphorylation and disrupts spliceosome activity, reducing Wnt pathway gene and protein expression. The compound significantly inhibits growth of gastrointestinal tumors in vivo. It has shown promise for the treatment of advanced solid tumors and arthritis. The molecular formula is C24H25N7O. The compound is a transcriptional regulator and splicing modulator. |
| Molecular Formula |
C24H25N7O
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|---|---|
| Molecular Weight |
427.501603841782
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| Exact Mass |
427.212
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| CAS # |
2143917-62-6
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| PubChem CID |
132056570
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
640
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CN=C(C=1)N1CCN(C)CC1)NC1C=C2C=C(C=CC2=CN=1)C1C=NN(C)C=1
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| InChi Key |
BQWWOBKMDWACGC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25N7O/c1-29-7-9-31(10-8-29)23-13-18(5-6-25-23)24(32)28-22-12-20-11-17(3-4-19(20)14-26-22)21-15-27-30(2)16-21/h3-6,11-16H,7-10H2,1-2H3,(H,26,28,32)
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| Chemical Name |
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide
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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 : 12.5 mg/mL (29.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.92 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 12.5 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: ≥ 1.25 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 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 | 2.3392 mL | 11.6959 mL | 23.3918 mL | |
| 5 mM | 0.4678 mL | 2.3392 mL | 4.6784 mL | |
| 10 mM | 0.2339 mL | 1.1696 mL | 2.3392 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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