P1, N=29, Terminated, BeOne Medicines | Active, not recruiting --> Terminated; The study was discontinued following an internal decision by the sponsor

In contrast, rMETase combined with numerous first-line chemotherapeutic drugs acted selectively and synergistically against cancer cells while sparing normal cells, including co-culture models. The present results suggest that AG-270 may have limited potential as an anticancer agent.

P1/2, N=342, Recruiting, Servier Bio-Innovation LLC | Active, not recruiting --> Recruiting | N=104 --> 342

P1, N=122, Recruiting, Shouyao Holdings (Beijing) Co. LTD | Not yet recruiting --> Recruiting

P1/2, N=104, Active, not recruiting, Servier Bio-Innovation LLC | Recruiting --> Active, not recruiting

Herein, we report the design and optimization of a novel series of pyridazinone-based MAT2A inhibitors via a ring-opening strategy from AGI-41998...Mechanically, treatment with 33 markedly reduced SAM and sDMA levels both in vitro and in vivo. Collectively, these results establish pyridazinone as a privileged scaffold for MAT2A inhibition and identify compound 33 as a compelling lead for further preclinical development.

P1, N=169, Active, not recruiting, IDEAYA Biosciences | Recruiting --> Active, not recruiting

P1, N=29, Active, not recruiting, BeOne Medicines | Recruiting --> Active, not recruiting | N=140 --> 29 | Trial completion date: Dec 2028 --> Apr 2026

P1, N=122, Not yet recruiting, Shouyao Holdings (Beijing) Co. LTD

P1/2, N=118, Recruiting, Institut De Recherches Internationales Servier IRIS

AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy.

This study developed two novel MAT2A-targeted PET tracers: the 18F-labeled [18F]1d, derived from AZ-28, demonstrates rapid tumor uptake (equilibrium ∼20 min), high tumor-to-muscle ratio, and specific MAT2A binding in H1975 xenografts, though it shows some bone uptake due to defluorination; the 68Ga-labeled [68Ga]1s, based on AG-270, retains high MAT2A affinity (IC50 = 6.23 nM) and exhibits superior pharmacokinetics─low liver uptake, renal clearance, and high cellular internalization (80%)...Molecular docking confirms key interactions with the MAT2A allosteric site. Both tracers provide promising tools for solid tumor diagnosis, treatment monitoring, and precision oncology.