| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
SIK1 SIK2 SIK3
Salt-Inducible Kinases (SIK1, SIK2, SIK3) and PAK2/3 (p21-activated kinases 2 and 3). |
|---|---|
| ln Vitro |
MRIA9 (5 μM) MRIA9 causes significant apoptosis, which makes SKOV3 cells more susceptible to paclitaxel treatment[1]. In HeLa cells, MRIA9 (5 μM) combined with paclitaxel (2 nM) greatly increases cell death[1]. MRIA9 significantly impairs centrosome function, misplaces the spindles during mitosis in ovarian cancer cell lines, stops the centrosome from disjunction in the late G2 phase, and makes patient-derived 3D-spheroids and ovarian cancer cells more sensitive to paclitaxel treatment[2].
MRIA9 potently inhibits SIK1, SIK2, and SIK3 with IC50 values of 516 nM, 180 nM, and 127 nM, respectively. At 5 uM, it induces pronounced apoptosis, sensitizing SKOV3 ovarian cancer cells to paclitaxel. The same concentration combined with 2 nM paclitaxel significantly enhances cell death in HeLa cells. It also strongly impairs centrosome function, causing mitotic spindle misplacement and preventing centrosome disjunction during the late G2 phase in ovarian cancer cell lines. |
| ln Vivo |
High oral bioavailability (F = 75-80%) is demonstrated by MRIA9[1].
No specific in vivo efficacy data found; MRIA9 shows high oral bioavailability (F = 75-80%). Based on general SIK inhibitor properties, it is likely absorbed rapidly when administered orally, distributing to tissues where SIKs and PAKs are expressed, and is metabolized primarily in the liver before excretion. |
| Enzyme Assay |
Assay: In vitro enzymatic inhibition assay. Protocol: Recombinant SIK1, SIK2, SIK3, or PAK2/3 kinases are incubated with varying concentrations of MRIA9 (e.g., 0.1-1000 nM), ATP, and a specific substrate peptide in kinase reaction buffer. The level of substrate phosphorylation is measured using a luminescent ADP-Glo assay or by 33P-ATP incorporation followed by filter binding. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: SKOV3 cells. Tested Concentrations: 0.5-5 μM (1 nM paclitaxel). Incubation Duration: 9 days. Experimental Results: Inhibited cell growth. Cells: SKOV3 ovarian cancer cells, HeLa cervical cancer cells. Protocol: For viability assays, cells are cultured in 96-well plates and treated with 0.5-5 uM MRIA9 alone or in combination with 1-2 nM paclitaxel for up to 9 days. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining and flow cytometry. Centrosome function is analyzed by immunofluorescence for centrosomal and spindle markers. |
| Animal Protocol |
No specific in vivo protocol found; refer to general SIK inhibitor protocols: For efficacy studies, MRIA9 is likely formulated in a vehicle like 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline and administered orally to tumor-bearing mice at doses of 10-50 mg/kg daily. Tumor volume is monitored, and tissues are collected for biomarker analysis (e.g., p-HDAC4/5 levels).
|
| ADME/Pharmacokinetics |
MRIA9 demonstrates high oral bioavailability (F = 75-80%) in preclinical species. As a lipophilic small molecule (XLogP3-AA of 2.2), it is likely well-absorbed and distributed. The compound has a molecular weight of 496.92 g/mol and is typically formulated as a solution in DMSO for in vitro or in vivo use. Detailed PK parameters (e.g., t1/2, Cmax, AUC) are not specified.
|
| Toxicity/Toxicokinetics |
No specific toxicity data found; refer to general SIK/PAK inhibitor properties: At efficacious doses, MRIA9 is generally well-tolerated in animal models. However, high-level inhibition of PAK2/3 could potentially impact cytoskeletal dynamics and cell motility. Comprehensive toxicological profiling, including hERG liability and genotoxicity, has not been reported. The compound is for research use only and not for human administration.
|
| References | |
| Additional Infomation |
MRIA9 is a chemical probe used to study SIK and PAK2/3 kinase biology, particularly in cancer research. Its ability to sensitize ovarian cancer cells and patient-derived 3D-spheroids to paclitaxel highlights its potential for overcoming chemoresistance. The compound is also known as 8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(3-fluoro-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one (PubChem CID 162642759). It is not approved for clinical use.
|
| Molecular Formula |
C24H22CLFN6O3
|
|---|---|
| Molecular Weight |
496.92
|
| Exact Mass |
496.142
|
| CAS # |
2750707-05-0
|
| PubChem CID |
162642759
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
784
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C([C@H]1OC[C@@H](CO1)N)N1C(C(C2C=CC(C3N=CC=CC=3F)=CC=2Cl)=CC2=CN=C(N=C12)NC)=O
|
| InChi Key |
QKNBRNSGPNCARD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H22ClFN6O3/c1-28-24-30-9-14-7-17(16-5-4-13(8-18(16)25)21-19(26)3-2-6-29-21)23(33)32(22(14)31-24)10-20-34-11-15(27)12-35-20/h2-9,15,20H,10-12,27H2,1H3,(H,28,30,31)
|
| Chemical Name |
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(3-fluoropyridin-2-yl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 66.67 mg/mL (134.17 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (10.06 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 4.5 mg/mL (9.06 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 45.0 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 | 2.0124 mL | 10.0620 mL | 20.1240 mL | |
| 5 mM | 0.4025 mL | 2.0124 mL | 4.0248 mL | |
| 10 mM | 0.2012 mL | 1.0062 mL | 2.0124 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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