ASX-173 is an orally active asparagine synthetase (ASNS) inhibitor with an IC50 of 0.113 μM and a Ki of 0.4 nM. It enhances the anticancer activity of L-Asparaginase (ASNase). When combined with ASNase, ASX-173 disrupts nucleotide synthesis and induces cell cycle arrest, apoptosis (apoptosis), and autophagy (autophagy) in leukemia cells. This combination also slows the growth of OCI-AML2 xenograft tumors. ASX-173 is applicable in research on acute lymphoblastic leukemia, acute myeloid leukemia, colorectal cancer, and other cancers.

ASX-173, within a concentration range of 0.1-1000 nM over 24 hours, inhibits the transcription of multiple endogenous Wnt target genes, including AXIN1, DKK1, CD133/PROM1, and MYC, in HCT-116 cells. It demonstrates potent cytotoxicity in MDA-MB-231, SW620, and A375 cells cultured in DMEM medium but shows minimal or no toxicity in RPMI-1640 medium. ASX-173, between 0-500 nM, can restore the sensitivity of ASNS-deficient RS4;11 cells to ASNase. Furthermore, concentrations of 0-1250 nM enhance ASNase's anticancer activity in ASNS-positive cancer cell lines such as OPM-2, MOLP-8, AMO-1, Jurkat, H929, MV4;11, and HT1080. ASX-173, at a range of 0-1500 nM, increases sensitivity to both ASNase WT and glutaminase-deficient ASNase variants (ASNase Q59L) in OVCAR-8, 92.1_D3, 92.1_M3, and OCI-AML2 cells. Under conditions lacking Asparagine, ASX-173 shows anticancer activity at concentrations of 0-1500 nM when combined with medium or low-dose ASNase (0.025 IU/mL) in most tested cell lines such as MV4;11, Jurkat, and A172. At 0-500 nM over 48 hours, ASX-173 induces cell cycle arrest, apoptosis, and autophagy in MV4;11 leukemia cells and RS4;11_ASNS cells in the absence of Asparagine. Additionally, at 80 nM for 24 hours, ASX-173 disrupts nucleotide biosynthesis in OCI-AML2 leukemia cells treated with 0.025 IU/mL ASNase (Spectrila).

ASX-173 (50 mg/kg, oral, once daily, for 2 weeks) enhances the anticancer effectiveness of ASNase (5,000 IU/kg, intraperitoneal injection) in NSG mice xenografted with OCI-AML2 leukemia cells expressing luciferase.