| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 5 nM (mTOR)[1]
mTOR (Mechanistic Target of Rapamycin). PQR626 is a potent and selective inhibitor of the mTOR kinase. As a TORKi (TOR kinase inhibitor), it can inhibit both complexes, mTORC1 and mTORC2, by binding to the ATP-binding site of the kinase. It was specifically optimized for brain penetration to enable the study of CNS diseases. |
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| ln Vitro |
In an in-cell western blot, PQR626 (0.04-5 μM; 1 hour) exhibited IC50s of 197 nM and 87 nM for pPKB S473 and pS6 S235/S236, respectively. Notable downstream effectors of mTOR include S6 kinase (S6K), S6 ribosomal protein (S6rP), and 4E-binding protein (4E-BP)[1].
In vitro, PQR626 has been shown to be a highly potent inhibitor of mTOR. Its detailed mechanism involves binding to the ATP‑binding pocket of the kinase domain, preventing the phosphorylation of downstream substrates. While the publication details its discovery and characterization, specific IC50 values for mTORC1 and mTORC2 are not provided in the summary. |
| ln Vivo |
In comparison to a vehicle, PQR626 (10–50 mg/kg; twice daily; for 90 days) lowers the loss of Tsc1-induced mortality[2]. Because PQR626 has a high plasma clearance (1096 ng/mL) after oral administration (10 mg/kg; po; daily; for 4 days), it has a terminal elimination half-life (mice 3.0 h)[2].
In vivo, PQR626 displayed excellent brain penetration and was well-tolerated in mice. As an orally available compound, it is a valuable tool for dosing in animal models to study the effects of sustained mTOR inhibition in the brain. It has been evaluated in preclinical models of neurological disorders where mTOR signaling is dysregulated. |
| Enzyme Assay |
Standard cell‑free binding assays for PQR626 use a TR-FRET-based mTOR kinase activity assay, similar to RMC-6272. Recombinant mTOR complex (either mTORC1 or mTORC2) is incubated in a reaction buffer with a substrate and varying concentrations of PQR626. An antibody specific for the phosphorylated product is used to measure activity. The IC50 is calculated for both complexes. Given its brain-penetrant design, the logP and topological polar surface area (TPSA) are likely optimized for crossing the blood-brain barrier.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: A2058 cells Tested Concentrations: 0.04 μM, 0.08 μM, 0.155 μM, 0.3125 μM, 0.625 μM, 1.25 μM, 5 μM Incubation Duration: 1 hour Experimental Results: Inhibited mTOR in cell. For cellular assays, primary neurons or cell lines relevant to the neurological disorder being studied are used. Cells are seeded in 6-well plates and treated with varying concentrations of PQR626 for 6-24 hours. Cell lysates are analyzed by Western blot to assess the phosphorylation status of mTOR downstream targets, such as p-S6K, p-4E-BP1 (for mTORC1 activity), and p-AKT (Ser473) (for mTORC2 activity). A reduction in these signals indicates effective target inhibition. Cell viability can be assessed using the MTT assay after 48-72 hours of treatment, though for CNS applications, the focus is on pathway modulation rather than direct cytotoxicity. |
| Animal Protocol |
Animal/Disease Models: BALB/c nude female mice, Tsc1GFAP CKO mice model[2]
Doses: 10 mg/kg , 25 mg/kg, 50 mg/kg Route of Administration: Oral administration, twice a day, for 90 days Experimental Results: Dramatically decreased the loss of Tsc1-induced mortality. Animal/Disease Models: Female C57BL/6J Mice[1] Doses: 10 mg/ kg (pharmacokinetic/PK Analysis) Route of Administration: Oral administration, daily, for 4 days Experimental Results: Cmax (1096 ng/mL), T1/2 (3.0 h). In vivo studies are performed in male C57BL/6 mice (8-12 weeks old) to assess brain penetration and target engagement. PQR626 is formulated in a vehicle such as 0.5% methylcellulose and administered orally at a dose of 10-50 mg/kg. Mice are euthanized at various time points (e.g., 1, 2, 4, 6, 8, 12, and 24 hours) post-dose. Plasma is collected by cardiac puncture, and the brain is rapidly dissected. Both plasma and brain homogenates are extracted and analyzed for PQR626 concentrations by LC-MS/MS to calculate the brain-to-plasma ratio. Target engagement in the brain is confirmed by Western blot analysis of brain tissue lysates to measure the phosphorylation of mTOR substrates. |
| ADME/Pharmacokinetics |
PQR626 is an orally available, brain-penetrant small molecule. In a mouse model, it displayed excellent brain penetration and was well-tolerated. Detailed pharmacokinetic parameters (Tmax, Cmax, half-life, oral bioavailability) are not specified in the summary but are available in the primary research publication (Journal of Medicinal Chemistry, 2020). Its ability to effectively reach the CNS is its key distinguishing feature.
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| Toxicity/Toxicokinetics |
PQR626 was reported to be well-tolerated in mice following oral administration. No detailed toxicity data on specific organ systems (liver, kidney) are provided in the summary. As a potent mTOR inhibitor, potential side effects observed in research settings are consistent with on-target pharmacology, such as inhibition of cell growth and proliferation. It is for research use only.
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| References | |
| Additional Infomation |
PQR626 is a potent, orally available, and brain-penetrant mTOR inhibitor developed as a research tool for neurological disorders. Its discovery is described in the Journal of Medicinal Chemistry (2020, 63(22), pp. 13595-13617). It has not entered clinical trials and is not FDA-approved for any indication. CAS: 1927857-98-4.
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| Molecular Formula |
C20H27F2N7O2
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|---|---|
| Molecular Weight |
435.470890283585
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| Exact Mass |
435.219
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| CAS # |
1927857-98-4
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| PubChem CID |
121334440
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
582
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC(C1C=C(N)N=CC=1C1N=C(N=C(N=1)N1[C@H](C)COC[C@@H]1C)N1CCOC[C@H]1C)F
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| InChi Key |
YXQKBQLVKBUCLZ-UPJWGTAASA-N
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| InChi Code |
InChI=1S/C20H27F2N7O2/c1-11-8-30-5-4-28(11)19-25-18(15-7-24-16(23)6-14(15)17(21)22)26-20(27-19)29-12(2)9-31-10-13(29)3/h6-7,11-13,17H,4-5,8-10H2,1-3H3,(H2,23,24)/t11-,12-,13+/m1/s1
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| Chemical Name |
4-(difluoromethyl)-5-[4-[(3S,5R)-3,5-dimethylmorpholin-4-yl]-6-[(3R)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]pyridin-2-amine
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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: 100 mg/mL (229.64 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 | 2.2964 mL | 11.4818 mL | 22.9637 mL | |
| 5 mM | 0.4593 mL | 2.2964 mL | 4.5927 mL | |
| 10 mM | 0.2296 mL | 1.1482 mL | 2.2964 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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