Aramchol (aramchol meglumine)

This metabolic rewiring provides a strong biological rationale for precision therapeutics.We trace the clinical development of desaturase inhibitors, highlighting the recent entry of SCD1 inhibitor, MTI-301, in a Phase 1 clinical trial for solid tumors and the potential repurposing of Aramchol, while detailing how FADS2 plasticity (the "sapienic shunt") drives therapeutic resistance. By integrating these insights into desaturation lipidomics, metabolic modulation via diet-drug interactions, synergistic combination regimens, and stimuli-responsive nanomedicine, we highlight the translational potential of targeting lipid desaturation to overcome metabolic plasticity and treatment resistance in aggressive malignancies.

P1, N=16, Completed, Galmed Pharmaceuticals Ltd | Active, not recruiting --> Completed

Knock down of SCD1 enhanced the percentage of dead cells in vehicle control treated cells but did not alter the abilities of drugs to kill tumor cells. Our data demonstrates that UM cells are killed by treatment with aramchol plus regorafenib plus metformin via enhanced autophagic flux and that this combination may have the potential to control UM tumors that have metastasized to the liver.

P1, N=32, Recruiting, Galmed Pharmaceuticals Ltd | Not yet recruiting --> Recruiting

Our study identifies SCD1-mediated lipid remodeling as a key driver of enhanced membrane fluidity and metastatic potential in CM. Inhibition of SCD1 increases lipid saturation, reduces membrane fluidity, induces oxidative stress, and suppresses liver and lung metastasis. The MAFG-METTL14-SCD1 axis thus represents a critical regulator of CM progression, and combined therapeutic targeting with aramchol and S-HFD offers promising translational potential.

P1, N=32, Not yet recruiting, Galmed Pharmaceuticals Ltd

P1, N=16, Active, not recruiting, Galmed Pharmaceuticals Ltd | Trial completion date: May 2025 --> Dec 2025

The combination treatment showed a significant reduction of 21.64% (P < 0.05) in lipid accumulation relative to individual treatment with Bixin or Montelukast and was comparable with the reference drug Aramchol (21.83%). The markers of oxidative stress were also significantly reduced (P < 0.05), evidenced by decreased MDA (42.25%), RNS levels (32.59%), and ROS levels (30.72%) in the combination group. These findings suggest that Bixin and Montelukast in combination hold potential for managing the multiple aspects in the pathophysiology of NAFLD development and progression.

Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect. Knock down of Beclin1 reduced the lethality of regorafenib and aramchol as single agents and when combined whereas knock down of LAMP2 or BID did not reduce killing caused by aramchol as a single agent but did reduce the lethality of regorafenib alone and regorafenib plus aramchol. In vivo using the HuH7 adult hepatoma cell line, regorafenib and aramchol interacted to suppress tumor growth without normal tissue toxicities.

P2, N=0, Withdrawn, Galmed Pharmaceuticals Ltd | N=24 --> 0 | Suspended --> Withdrawn

P1, N=16, Active, not recruiting, Galmed Pharmaceuticals Ltd | Not yet recruiting --> Active, not recruiting | Trial primary completion date: Jan 2025 --> May 2025

P1, N=16, Not yet recruiting, Galmed Pharmaceuticals Ltd | Initiation date: Oct 2024 --> Jan 2025