ASX-173 / Asinex - LARVOL DELTA

Direct pharmacological targeting of asparagine synthetase to overcome resistance to L-asparaginase in ALL therapy. (PubMed, JCI Insight) - "When combined with L-asparaginase, ASX-173 effectively eliminated ASNS-high leukemic cells in vitro and in vivo. These findings suggest that direct targeting of ASNS provides therapeutic benefit in leukemias that express high ASNS and are resistant to GCN2 inhibition under asparagine-depleted conditions."

Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • KRAS

Characterization of a novel inhibitor of asparagine synthetase that activates the integrated stress response (AACR 2026) - "The structure indicates that ASX-173 promotes ATP hydrolysis and blocks ammonia transfer, supporting an uncompetitive mechanism.These findings establish ASX-173 as a potent ASNS inhibitor with strong cellular target engagement and ISR-inducing activity. The heightened sensitivity of GCN2-deficient cells and the synergy with GCN2 inhibition highlight the therapeutic potential of dual ISR targeting and support ASNS inhibition—alone or in combination with ISR-modulating strategies—as a promising approach for cancers dependent on asparagine metabolism."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ASNS • ATF4

The role of general control nonderepressible 2 (GCN2) kinase in leukemogenesis and therapeutic response to L-asparaginase (AACR 2025) - "Finally, we tested a newly developed inhibitor of ASNS (ASX-173), which selectively killed leukemic cells in the absence of exogenous asparagine even though their basal level expression of ASNS is high. Taken together, our results suggest that targeting GCN2 or ASNS will have therapeutic implications in ALL patients who become resistant to L-asparaginase treatment."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ATF4 • KRAS

The asns inhibitor asx-173 potentiates l-asparaginase anticancer activity (ASH 2025) - "In combination with ASNase, the resulting bicompartmental blockade of asparaginemetabolism results in potent anticancer activity, a clear mechanism of action, and in vivo efficacy. Futurestudies to optimize pharmacokinetics, test rational combinations, and examine additional cancer modelswill help to realize the full therapeutic potential of targeting asparagine metabolism for the treatment ofhematological malignancies."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Cryo-EM reveals how ASX-173 inhibits human asparagine synthetase to activate the integrated stress response. (PubMed, bioRxiv) - "Based on in vitro kinetic and thermal shift assays, we find that ASX-173 binds to the ASNS/Mg 2+ /ATP complex and is therefore a rare example of an uncompetitive enzyme inhibitor with potential therapeutic use. These findings provide a structural and mechanistic basis for targeting ASNS with small molecules, which have application in treating cancer and other human diseases."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • T Acute Lymphoblastic Leukemia • ASNS