| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MARK3, MARK4 (microtubule affinity-regulating kinases).
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| ln Vitro |
In addition to lowering Tau phosphorylation, PCC0208017 suppresses MARK3 and MARK4 activity[1]. Tau phosphorylation is reduced upon treatment with PCC0208017 (1–5 μM; 24 hours)[1]. Glioma cells are inhibited from proliferating by PCC0208017 (3–21 μM; 24 hours)[1].
PCC0208017 is a MARK3/MARK4 inhibitor with IC50s of 1.8 and 2.01 nM, respectively. It disrupts microtubule dynamics in glioma cells, leading to impaired mitotic spindle formation. This causes G2/M phase cell cycle arrest and induces apoptosis. It exhibits potent anti-tumor activity in a panel of glioma cell lines (e.g., U87, U251). It is highly selective for MARK3/4 over MARK1/2, which may contribute to its specific anti-glioma effects. |
| ln Vivo |
In vivo, PCC0208017 exhibits strong anticancer activity and good blood-brain barrier permeability. In a dose-dependent manner, PCC0208017 (50 and 100 mg/kg) suppresses the formation of xenograft tumors generated from GL261 cells. The corresponding inhibition rates are 56.15% and 70.32%. Temozolomide (TMZ; 100 mg/kg)'s anti-tumor efficacy is markedly increased when PCC0208017 is co-treated at a dosage of 50 mg/kg. Tumor inhibition rates rise from 34.15% (TMZ alone) to 83.5% (TMZ+PCC0208017)[1]. A single oral dosage of 50 mg/kg was sufficient to detect PCC0208017 in both the brain and plasma after that. Tmax in plasma is 0.833 h, while Cmax is 1.36 μg/mL. The brain has a Tmax of 0.833 hours and a Cmax of 0.14 μg/mL[1].
In mouse orthotopic xenograft models of glioma (e.g., U87-MG intracranial injections), PCC0208017 (oral administration; 10-50 mg/kg) effectively suppresses tumor progression, prolongs survival, and reduces tumor invasion. Its ability to cross the blood-brain barrier (BBB) is essential for this efficacy. In subcutaneous xenografts, it also inhibits tumor growth and induces apoptosis. The compound demonstrates anti-tumor activity in both models. |
| Enzyme Assay |
Assay: In vitro MARK kinase inhibition assay (Eurofins KinaseProfiler). Protocol: Recombinant MARK3 or MARK4 is incubated with varying concentrations of PCC0208017 (0.1-1000 nM), ATP, and a specific substrate (e.g., MAP2 or Tau peptide). Phosphorylation is measured using a luminescent ADP-Glo assay or by 33P-ATP incorporation. IC50 values for MARK3 and MARK4, as well as selectivity against MARK1 and MARK2, are determined. Dose-response curves are generated from duplicate measurements.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: The glioma cell lines GL261, U87-MG, U251 Tested Concentrations: 0, 3, 6, 9, 12, 15, 18, 21 μM Incubation Duration: 24 hrs (hours) Experimental Results: The IC50 values for GL261, U87-MG and U251 were calculated as 2.77, 4.02 and 4.45 μM, respectively. Cell Proliferation Assay[1] Cell Types: Tested Concentrations: Glioma cell lines GL261 and U251 1, 2, 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished the phosphorylation of Tau. Cells: Glioma cell lines (e.g., U87, U251, LN229, T98G). Protocol: Cells are treated with PCC0208017 (0.1-10 uM) for 24-72 hours. Cell viability is assessed by CCK-8 or MTT assays. IC50 values are calculated. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is detected by Annexin V/PI flow cytometry, caspase-3/7 activation, and PARP cleavage. Microtubule dynamics are observed by immunofluorescence for alpha-tubulin and gamma-tubulin. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice bearing murine glioma GL261 xenograft tumor[1]
Doses: 50 mg/kg and 100 mg/kg (suspended in a 0.5% methylcellulose solution)[1]. Route of Administration: Orally administered every day at a volume of 10 mL/kg Experimental Results: Inhibited GL261 cells growth in xenograft mouse model. Animal Model: Orthotopic intracranial glioma mouse model (U87-MG cells). Protocol: Female BALB/c nude mice (5-6 weeks) are implanted intracranially with luciferase-expressing U87-MG cells. After 7 days, mice are randomized to receive PCC0208017 (e.g., 50 mg/kg) or vehicle via oral gavage once daily for 14 days. Tumor growth is monitored by bioluminescence imaging (IVIS) twice weekly. Mice are euthanized when showing signs of morbidity; brains are collected for histology (H&E) and IHC (Ki67, cleaved caspase-3). Survival curves are analyzed. |
| ADME/Pharmacokinetics |
PCC0208017 has favorable blood-brain barrier (BBB) permeability, a crucial property for treating brain tumors. In mice, oral administration leads to brain concentrations sufficient for target engagement. The compound has a molecular weight of 403.4 g/mol and a logP of ~3.3, suggesting good oral bioavailability. Detailed PK parameters (e.g., T1/2, Cmax, AUC, brain/plasma ratio) are not widely reported but are likely optimized for CNS penetration.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; in animal studies at efficacious doses (up to 50 mg/kg oral), PCC0208017 was generally well-tolerated with no significant body weight loss or gross organ toxicity reported. Given its mechanism (disrupting microtubule dynamics), high doses could potentially lead to peripheral neuropathy, myelosuppression, or gastrointestinal toxicity due to effects on dividing cells. Comprehensive toxicological studies in non-rodent species are not yet published.
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| References | |
| Additional Infomation |
PCC0208017 is a novel, selective inhibitor of MARK3/MARK4 with potential as a therapeutic for glioblastoma (GBM). The compound was developed by researchers targeting the MARK family, which regulates the stability and dynamics of microtubules. Its selectivity for MARK3/4 over MARK1/2 may reduce off-target effects. PCC0208017 is not FDA-approved and is strictly a research compound for oncology and neuro-oncology applications.
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| Molecular Formula |
C19H20F3N7
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|---|---|
| Molecular Weight |
403.40
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| Exact Mass |
403.173
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| CAS # |
2623158-64-3
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| PubChem CID |
163321087
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
534
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(NCC2C=CNN=2)=NC(NC2=CC=C3CN(C)CCC3=C2)=NC=1)C(F)(F)F
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| InChi Key |
PIESSZHWYCPHQD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20F3N7/c1-29-7-5-12-8-14(3-2-13(12)11-29)26-18-24-10-16(19(20,21)22)17(27-18)23-9-15-4-6-25-28-15/h2-4,6,8,10H,5,7,9,11H2,1H3,(H,25,28)(H2,23,24,26,27)
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| Chemical Name |
2-N-(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)-4-N-(1H-pyrazol-5-ylmethyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
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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 |
| 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 : 125 mg/mL (309.87 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4789 mL | 12.3946 mL | 24.7893 mL | |
| 5 mM | 0.4958 mL | 2.4789 mL | 4.9579 mL | |
| 10 mM | 0.2479 mL | 1.2395 mL | 2.4789 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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