SELECTIVE INVITRO INHIBITION OF HUMAN MOLT-4 LYMPHOBLAST-T BY THE NOVEL PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITOR, CI-972

被引：17

作者：

GILBERTSEN, RB ^{[1
]}

DONG, MK ^{[1
]}

KOSSAREK, LM ^{[1
]}

SIRCAR, JC ^{[1
]}

KOSTLAN, CR ^{[1
]}

CONROY, MC ^{[1
]}

机构：

[1] WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT CHEM,ANN ARBOR,MI 48105

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1991年 / 178卷 / 03期

关键词：

D O I：

10.1016/0006-291X(91)91042-B

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

CI-972 (2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one monohydrochloride, monohydrate) is a competitive inhibitor of PNPase (E.C. 2.4.2.1., Ki=0.83 μM) entering clinical trials as a T cell-selective immunosuppressive agent. Neither CI-972 (≤50 μM) nor dGuo (≤10 μM) inhibited [3H]Thd uptake by human MOLT-4 (T cell) or MGL-8 (B cell) lymphoblasts, but in the presence of 10 μM dGuo, the IC50 for CI-972 decreased to 3.0 μM for MOLT-4 but remained at >50 μM for MGL-8. Inhibition of MOLT-4 growth was associated with an increase in dGTP that was dependent on CI-972 concentration and inhibited by 2′-deoxycytidine. Growth could not be restored by hypoxanthine or adenine. No alterations in GTP pools were noted in MOLT-4, and neither GTP nor dGTP were altered in MGL-8. © 1991.

引用

页码：1351 / 1358

页数：8

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