L-Alanosine

L-Alanosine (NSC-153353), an antibiotic from Streptomyces alanosinicus, has antineoplastic activity. L-Alanosine (NSC-153353) inhibits adenylosuccinate synthetase, which converts inosine monophospate (IMP) into adenylosuccinate. L-Alanosine is the inhibitor for methylthioadenosine phosphorylase (MTAP)^[1][2][3]. In Vitro:L-Alanosine (0.1-100 μM, 10 days) blocks the de novo purine synthesis pathway by inhibiting the activity of adenylosuccinate synthetase (ADSS), thereby inhibiting the proliferation of MTAP-deficient tumor cells CEM/ADR5000, HL-60/AR and MDA-MB-231-BCRP because these cells cannot obtain adenine through the salvage pathway^[1].
L-Alanosine (0.125-0.25 μM, 14 days) inhibits the mitochondrial function (especially mitochondrial spare respiratory capacity), reduces the stemness of GBM cells, increases a synergistic inhibitory effect with Temozolomide (HY-17364)^[4]. In Vivo:L-Alanosine (150 mg/kg, ip, three times a week for 7 weeks) exhibits antitumor activity with the combination of Temozolomide (HY-17364) in GBM 12-0160 xenograft mouse models^[4].