J-147

J-147 (Trifluoroacetamide Hydrazone)

J-147 is a synthetic trifluoroacetamide hydrazone originally developed at the Salk Institute (Schubert Laboratory). Derived from a curcumin-based screening series, J-147 was specifically engineered to address the inherent metabolic instability and poor bioavailability of the curcumin scaffold. By integrating a trifluoromethyl group, researchers successfully created a compound that retains the pharmacophore while significantly improving metabolic profile.

Technical Specifications

Mechanism of Action & Scientific Context

J-147 was identified through phenotypic screening in cell-based assays of neuronal survival rather than target-directed design. Subsequent drug-affinity chromatography identified the α-subunit of mitochondrial ATP synthase (ATP5A) as a primary binding partner.

Mechanism Clarification:

J-147 is not a mitochondrial enhancer. Research indicates it acts as a partial inhibitor of ATP synthase activity. The observed biological effects are not a result of increased energy production, but rather an adaptive, AMPK-dependent stress response triggered by the cell in response to the mild reduction in mitochondrial respiration.

Primary fields of in vitro laboratory investigation include:

• ATP Synthase Binding: Mapping target-engagement and binding kinetics with the ATP5A subunit.

• Mitochondrial Respirometry: Measuring oxygen consumption rates and membrane potential under controlled conditions.

• AMPK Signaling: Analyzing cellular stress-response pathways.

• Neuronal Cytoprotection: Utilizing cell culture models to assess protective mechanisms.

• Comparative SAR: Assessing the structure-activity relationship across curcumin-derivative series.

Storage & Handling Guidelines

To maintain molecular integrity and ensure experimental reproducibility:

• Storage Conditions: Store in a cool, dry environment.

• Light Protection: Maintain in light-protected conditions to prevent degradation.

• Solubility: The compound demonstrates poor aqueous solubility; stock solutions should be prepared in DMSO.

Research Use Only Disclaimer: This product is developed and distributed strictly as a Research Use Only (RUO) laboratory reference chemical intended exclusively for non-clinical analytical and scientific investigation. It is not an FDA-approved drug, food, cosmetic, or dietary supplement, and is strictly prohibited for human or animal consumption. Kimera Chems supplies these high-purity chemical batches solely to accredited institutional laboratories and qualified scientific investigators.