APC-100

• CAT Number: I002554
• CAS Number: 950-99-2
• Molecular Formula: C14H20O2
• Molecular Weight: 220.312
• Purity: ≥95%
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°Cfor short term (days to weeks), or -20 °C for long term (months).
• IUPAC Name: 2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-ol
• InChI: InChI=1S/C14H20O2/c1-8-9(2)13-11(10(3)12(8)15)6-7-14(4,5)16-13/h15H,6-7H2,1-5H3
• InChIKey: SEBPXHSZHLFWRL-UHFFFAOYSA-N
• SMILES: CC1=C(C(=C2CCC(OC2=C1C)(C)C)C)O

APC-100 is an orally available, vitamin E derivative and androgen receptor (AR) antagonist with potential anti-oxidant, chemopreventative and antineoplastic activity. APC-100 binds to ARs in target tissues thereby inhibiting androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. By inhibiting the formation of the complex between androgen activated AR- and the AP1 transcription factor JunD, the expression of androgen-responsive genes is blocked. One such gene is spermidine/spermine N1-acetyl transferase gene (SSAT) which is responsible for the breakdown of polyamines, which are produced in high levels by prostatic epithelial cells, into reactive oxygen species (ROS) that cause cellular damage. APC-100 may ultimately lead to an inhibition of growth in both AR-dependent and AR-independent prostate tumor cells.

Reference

1:Invest New Drugs. 2016 Apr;34(2):225-30. doi: 10.1007/s10637-016-0334-y. Epub 2016 Feb 29. A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer.Kyriakopoulos CE,Heath EI,Eickhoff JC,Kolesar J,Yayehyirad M,Moll T,Wilding G,Liu G, PMID: 26924129 DOI: 10.1007/s10637-016-0334-y Abstract: BACKGROUND: A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC).METHODS: This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days.RESULTS: Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8).CONCLUSIONS: APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted.