PQR626 is a rapamycin analogue. PQR626 is a highly efficient, selective, orally bioactive mTOR inhibitor that can cross the BBB (blood-brain barrier), with IC50 and Kis of 5 nM and 3.6 nM respectively. PQR626 may be utilized in the study of neurological diseases.

Physicochemical Properties

Molecular Formula	C20H27F2N7O2
Molecular Weight	435.470890283585
Exact Mass	435.219
CAS #	1927857-98-4
PubChem CID	121334440
Appearance	Light yellow to yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	582
Defined Atom Stereocenter Count	3
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
InChi Key	YXQKBQLVKBUCLZ-UPJWGTAASA-N
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
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
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)

Biological Activity

Targets	IC50: 5 nM (mTOR)[1]
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].
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].
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.
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).
References	[1]. Treatment of neurological disorders. WO2017198346A1. [2]. 4-(Difluoromethyl)-5-(4-((3 R,5 S)-3,5-dimethylmorpholino)-6-(( R)-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a Potent, Orally Available, and Brain-Penetrant mTOR Inhibitor for the Treatment of Neurological Dis.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (229.64 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.