Houchens D P, Ovejera A A, Sheridan M A, Johnson R K, Bogden A E, Neil G L
Cancer Treat Rep. 1979 Mar;63(3):473-6.
The antimetabolite antibiotic L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) showed significant antitumor activity against L1210 and P388 mouse leukemias and the M5076 mouse ovarian tumor. Depending on the schedule of administration, increases in lifespan of greater than 100% were observed. Activity was observed after ip, oral, or sc inoculation of AT-125 in mice inoculated with L1210 by the ip route. Lewis lung carcinoma and B16 melanoma were not affected by AT-125. The compound was used to treat human tumor xenografts in athymic (nude) mice. The MX-1 mammary tumor regressed when treated with either 8 or 16 mg/kg/day for 10 days, while a dose of 32 mg/kg was toxic. On an every-4-days x 3 schedule there was a marked slowing of MX-1 tumor growth at 50, 100, and 200 mg/kg. The LX-1 lung tumor xenograft growth was slowed significantly by a dose of 32 mg/kg. Growth of colon tumors, CX-1, CX-2, and CX-3, was not affected by AT-125.
抗代谢物抗生素L-(αS,5S)-α-氨基-3-氯-4,5-二氢-5-异恶唑乙酸（AT-125）对L1210和P388小鼠白血病以及M5076小鼠卵巢肿瘤显示出显著的抗肿瘤活性。根据给药方案的不同，观察到生存期延长超过100%。通过腹腔注射途径将L1210接种到小鼠体内后，腹腔注射、口服或皮下接种AT-125均观察到活性。Lewis肺癌和B16黑色素瘤不受AT-125影响。该化合物用于治疗无胸腺（裸）小鼠的人肿瘤异种移植。用8或16mg/kg/天治疗10天时，MX-1乳腺肿瘤消退，而32mg/kg的剂量有毒。在每4天×3的给药方案下，50、100和200mg/kg时MX-1肿瘤生长明显减缓。32mg/kg的剂量显著减缓了LX-1肺肿瘤异种移植的生长。结肠肿瘤CX-1、CX-2和CX-3的生长不受AT-125影响。
