NEO214 is an autophagy inhibitor, a covalent conjugate of the PDE4 inhibitor Rolipram and perillyl alcohol, with anticancer activity and blood-brain barrier (BBB) permeability. NEO214 can prevent autophagosome-lysosome fusion, thereby blocking autophagic flux and inducing glioma cell death. This process involves mTOR activation and TFEB (transcription factor EB) aggregation. NEO214 inhibits macroautophagy/autophagy in glioblastoma cells and has the potential to overcome chemotherapy resistance in glioblastoma.

Physicochemical Properties

Molecular Formula	C27H35NO5
Molecular Weight	453.57
Exact Mass	453.251
CAS #	1361198-80-2
PubChem CID	56846913
Appearance	Colorless to off-white ointment
LogP	5.1
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	756
Defined Atom Stereocenter Count	1
SMILES	COC1C=CC(C2CN(C(=O)OCC3CC[C@H](C(=C)C)CC=3)C(=O)C2)=CC=1OC1CCCC1
InChi Key	JDWAOYHBJSFPSD-PSDZMVHGSA-N
InChi Code	InChI=1S/C27H35NO5/c1-18(2)20-10-8-19(9-11-20)17-32-27(30)28-16-22(15-26(28)29)21-12-13-24(31-3)25(14-21)33-23-6-4-5-7-23/h8,12-14,20,22-23H,1,4-7,9-11,15-17H2,2-3H3/t20-,22?/m1/s1
Chemical Name	[(4S)-4-prop-1-en-2-ylcyclohexen-1-yl]methyl 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxopyrrolidine-1-carboxylate
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

References

[1].Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate. Autophagy. 2023 Dec;19(12):3169-3188.

Solubility Data

Solubility (In Vitro)

DMSO :~100 mg/mL (~220.47 mM; with sonication)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.51 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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: 2.5 mg/mL (5.51 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. 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. Solubility in Formulation 3: 2.5 mg/mL (5.51 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2047 mL	11.0237 mL	22.0473 mL
	5 mM	0.4409 mL	2.2047 mL	4.4095 mL
	10 mM	0.2205 mL	1.1024 mL	2.2047 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.