| Stereochemistry | RACEMIC |
| Molecular Formula | C10H16O |
| Molecular Weight | 152.2334 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=C)C1CCC(CO)=CC1
InChI
InChIKey=NDTYTMIUWGWIMO-UHFFFAOYSA-N
InChI=1S/C10H16O/c1-8(2)10-5-3-9(7-11)4-6-10/h3,10-11H,1,4-7H2,2H3
The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint, and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and was being tested in clinical trials in patients with refractory advanced cancers. POH was formulated in soft gelatine capsules and orally administered to cancer patients several times a day on a continuous basis. However, such clinical trials in humans yielded disappointing results, also because of the large number of capsules that had to be swallowed caused hard-to-tolerate intestinal side effects, causing many patients to withdraw from treatment due to unrelenting nausea, fatigue, and vomiting. The clinical trials in Brazil have explored intranasal POH delivery as an alternative to circumvent the toxic limitations of oral administration. In these trials, patients with recurrent malignant gliomas were given comparatively small doses of POH via simple inhalation through the nose. Results from these studies showed, that this type of long-term, daily chemotherapy was well tolerated and effective. The precise mechanism of action is still undetermined, but it is known, that perillyl alcohol plays an important role in the process of hepatoma cell invasion and migration via decreasing the activity of Notch signaling pathway and increasing E-cadherin expression regulated by Snail. Another possible mechanism is included inhibition of Na/K-ATPase (NKA). The NKA α1 subunit is known to be superexpresses in glioblastoma cells (GBM) and POH acts in signaling cascades associated with NKA can control cell proliferation and/or cellular death.
Approval Year
Cmax
AUC
T1/2
Sourcing
PubMed
Patents
Sample Use Guides
cancer: patients receive oral perillyl alcohol 4 times a day for 4 weeks. Patients continue treatment in the absence of severe toxicity and disease progression. Glioblastoma Multiforme: intranasal delivery of NEO100 (perillyl alcohol) four times a day, escalation up to four different doses to determine maximum tolerated dose. Doses of 96 mg qid, 144mg qid, 192mg qid, and 288 mg qid administered intranasally to patients with recurrent GBM for up to 6 months, disease progression or death.
Route of Administration:
Other
Perillyl alcohol (POH) inhibits cellular proliferation at the G1 phase of the cell cycle in vitro. 1.0 mM POH upregulates p15(INK4b) and p21(WAF1/Cip1), resulting in hypophosphorylation of the retinoblastoma (RB) protein and subsequent G1 arrest in human immortalized keratinocyte HaCaT cells. The induction of p15(INK4b) was mediated through its promoter, but that of p21(WAF1/Cip1) was not. The small interfering RNA (siRNA) of either p15(INK4b) or p21(WAF1/Cip1) significantly attenuated the increase in the G1 cell population caused by POH. The induction of p15(INK4b) and p21(WAF1/Cip1) and sub-sequent G1 arrest by POH was also observed in other cancer cell lines. These results suggest that the induction of p15(INK4b) as well as p21(WAF1/Cip1) is associated with the antiproliferative effect of POH.
ACTIVE MOIETY
