Burzynski S R, Mohabbat M O, Lee S S
Drugs Exp Clin Res. 1986;12 Suppl 1:11-6.
Antineoplaston AS2-1 and Antineoplaston AS2-5 are degradation products of Antineoplaston A10. The initial hydrolysis of Antineoplaston A10 (3-phenylacetylamine-2, 6-piperidinedione) yields phenylacetylglutamine and phenylacetylisoglutamine. When hydrolysis is carried further the products of the reaction include phenylacetic acid, glutamic acid and ammonia. Sodium salts of phenylacetylglutamine, named Antineoplaston AS2-5, phenylacetic acid and a mixture of phenylacetylglutamine and phenylacetic acid in the ratio of 1:4, named Antineoplaston AS2-1, were submitted for tissue culture and animal toxicity studies. Tissue culture tests were carried out on breast carcinoma cell lines HBL-100 and Ki No. 1 and the results were expressed as the percentage of colony reduction based on control. Acute toxicity studies were done on a group of 88 HA/ICR Swiss mice with each of these formulations. An additional group of 160 mice was used for chronic toxicity studies of Antineoplaston AS2-1. In chronic toxicity studies the mice were injected with 92.3 mg/kg, 553.8 mg/kg and 1107.6 mg/kg of Antineoplaston AS2-1 intraperitoneally for 365 days and subjected to complete physical, gross pathology and microscopic examination. LD50 for tested formulations were as follows: Antineoplaston AS2-1: 2.83 g/kg, Antineoplaston AS2-5: 2.90 g/kg and phenylacetic acid: 2.71 g/kg. The results clearly demonstrated that Antineoplaston AS2-1 has interesting antineoplastic activity in tissue culture of breast carcinoma, and low acute and chronic toxicity in mice. Antineoplaston AS2-5 does not show significant activity in tissue culture of breast carcinoma HBL-100 and only slight antineoplastic activity in Ki No. 1. Both formulations were submitted for phase I clinical testing in cancer patients.
抗瘤酮AS2-1和抗瘤酮AS2-5是抗瘤酮A10的降解产物。抗瘤酮A10（3-苯乙酰氨基-2,6-哌啶二酮）的初始水解产生苯乙酰谷氨酰胺和苯乙酰异谷氨酰胺。当进一步水解时，反应产物包括苯乙酸、谷氨酸和氨。苯乙酰谷氨酰胺的钠盐（命名为抗瘤酮AS2-5）、苯乙酸以及苯乙酰谷氨酰胺和苯乙酸按1:4比例混合的混合物（命名为抗瘤酮AS2-1）被用于组织培养和动物毒性研究。对乳腺癌细胞系HBL-100和Ki No.1进行了组织培养试验，结果以相对于对照的集落减少百分比表示。对一组88只HA/ICR瑞士小鼠用这些制剂中的每一种进行了急性毒性研究。另外一组160只小鼠用于抗瘤酮AS2-1的慢性毒性研究。在慢性毒性研究中，小鼠腹腔注射92.3 mg/kg、553.8 mg/kg和1107.6 mg/kg的抗瘤酮AS2-1，持续365天，并进行全面的体格检查、大体病理学检查和显微镜检查。受试制剂的半数致死量如下：抗瘤酮AS2-1：2.83 g/kg，抗瘤酮AS2-5：2.90 g/kg，苯乙酸：2.71 g/kg。结果清楚地表明，抗瘤酮AS2-1在乳腺癌组织培养中具有显著的抗肿瘤活性，并且在小鼠中具有低急性和慢性毒性。抗瘤酮AS2-5在乳腺癌HBL-100组织培养中未显示出显著活性，在Ki No.1中仅具有轻微的抗肿瘤活性。这两种制剂均已提交用于癌症患者的I期临床试验。
