      Document 0082
 DOCN  DRG0082
 UNIQUE IDENTIFIER        DRG-0165
 NAME OF SUBSTANCE        Thymosin alpha 1 [Bull NY Acad Med 1989
                          Jan;65(1)]
 REGISTRY NUMBER          69521-94-4
 STANDARD CHEMICAL NAME   Thymosin alpha1 [CHEMLINE]
 SYNONYMS                 Thymosin alpha1 [CHEMLINE]
 SYNONYMS                 Thymosin alpha(1) [MeSH]
 PROTOCOL ID NUMBERS      NIAID ACTG 236
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Appears to both increase IL-2
                          receptors on lymphocytes in vitro and enhance
                          lymphocyte maturation in vivo. In one study,
                          thymosin alpha 1 enhanced CD4 lymphocyte
                          levels if given with low doses of alpha
                          interferon and AZT. In another study,
                          thymosin alpha 1 pretreatment significantly
                          restored the boosting capacity of two
                          cytokines, IL-2 and IFN, although combined
                          administration of thymosin alpha 1 with IL-2
                          or IFN did not substantially modify the
                          depressed natural killer cell response. Ten
                          HIV-positive patients treated with 600
                          mcg/day thymosin alpha 1 showed no
                          immunological or clinical improvements at
                          that dosage. A partial homology exists
                          between thymosin alpha 1 and the HIV gag gene
                          protein p17/18. In prior research, an
                          antiserum prepared against thymosin alpha 1
                          effectively neutralized the AIDS-associated
                          virus and blocked its replication in H9
                          cells. The antiviral activity of the
                          antiserum was found to be due to the region
                          of homology between thymosin alpha 1 and p17.
                          Comparison of the primary sequences of
                          thymosin alpha 1 and the gag protein revealed
                          a 44-50% homology in an 18-amino acid region,
                          between positions 11 and 28 on thymosin alpha
                          1 and positions 92 and 109 on the gag
                          protein. Normal thymosin alpha 1 levels have
                          been shown to be 670 +/- 163 pg/ml for males
                          and 652 +/- 162 pg/ml for females. [NIAID
                          ACTG 236; Bull N Y Acad Med Jan 1989;65(1)]
                          [Science May 30 1986;232(4754)]
 DISEASES STUDIED/TREATED Enhancement of CD4 lymphocyte levels in
                          patients being treated for primary HIV
                          infection [NIAID ACTG 236]
 CLASSIFICATION CODE      Immunomodulator [Current AIDS Therapies 1991]
 OTHER MAJOR USES         Treatment of hepatitis B [PR Newswire January
                          7, 1993]
 ADVERSE EFFECTS          Appeared nontoxic in humans in several
                          chronic administration studies. [NIAID ACTG
                          236] [Int J Clin Lab Res 1994;24(1)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 3100 daltons [Dorland's
                          Illustrated Medical Dictionary 27th Ed 1988]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: 28-amino acid peptide that
                          can be manufactured synthetically. A
                          lymphokine isolated from a mixture of about
                          30 low-molecular weight thymic peptides
                          called thymosin fraction 5 [Current AIDS
                          Therapies 1991]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous. [NIAID ACTG
                          236]
 MANUFACTURERS            Alpha I Biomedicals / Viral Technologies Inc
 REFERENCES               Dusheiko GM. Treatment and prevention of
                          chronic viral hepatitis. Pharmacol Ther. 1995
                          Jan;65(1):47-73.
 REFERENCES               Lopez M, Carpano S, Cavaliere R, Di Lauro L,
                          Ameglio F, Vitelli G, Frasca AM, Vici P,
                          Pignatti F, Rosselli M, et al.
                          Biochemotherapy with thymosin alpha 1,
                          interleukin-2 and dacarbazine in patients
                          with metastatic melanoma: clinical and
                          immunological effects. Ann Oncol 1994
                          Oct;5(8):741-6.
 REFERENCES               Hadden JW. T-cell adjuvants. Int J
                          Immunopharmacol. 1994 Sep;16(9):703-10.
 REFERENCES               Garaci E, Rocchi G, Perroni L, D'Agostini C,
                          Soscia F, Grelli S, Mastino A, Favalli C.
                          Combination treatment with zidovudine,
                          thymosin alpha 1 and interferon-alpha in
                          human immunodeficiency virus infection. Int J
                          Clin Lab Res. 1994;24(1):23-8.
 REFERENCES               Goldstein AL. Clinical applications of
                          thymosin alpha-1 [editorial; comment]. Cancer
                          Invest. 1994;12(5):545-7.
 REFERENCES               Mastino A, Favalli C, Grelli S, Rasi G, Pica
                          F, Goldstein AL, Garaci E. Combination
                          therapy with thymosin alpha 1 potentiates the
                          anti-tumor activity of interleukin-2 with
                          cyclophosphamide in the treatment of the
                          Lewis lung carcinoma in mice. Int J Cancer.
                          1992 Feb 1;50(3):493-9.
 REFERENCES               Garaci E, Andreoni M, Mastino A, Antonucci G,
                          Soscia F, Sarmati L, Perroni L, Giannini V,
                          Pavalli C, Rocchi G. Effect of thymosin
                          alpha-1 and interferon alpha associated with
                          zidovudine in HIV-seropositive patients. Int
                          Conf AIDS. 1991 Jun 16-21;7(2):219 (abstract
                          no. W.B.2148).
 REFERENCES               Mastino A, Favalli C, Grelli S, Innocenti F,
                          Garaci E. Thymosin alpha 1 potentiates
                          interleukin 2-induced cytotoxic activity in
                          mice. Cell Immunol. 1991 Mar;133(1):196-205.
 ENTRY MONTH              9303
 LAST REVISION DATE       960306
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
