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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H19N3O5S2
Molecular Weight 361.437
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of Sparsomycin

SMILES

CSC[S@+]([O-])C[C@H](CO)NC(=O)\C=C\C1=C(C)NC(=O)NC1=O

InChI

InChIKey=XKLZIVIOZDNKEQ-CLQLPEFOSA-N
InChI=1S/C13H19N3O5S2/c1-8-10(12(19)16-13(20)14-8)3-4-11(18)15-9(5-17)6-23(21)7-22-2/h3-4,9,17H,5-7H2,1-2H3,(H,15,18)(H2,14,16,19,20)/b4-3+/t9-,23+/m0/s1

HIDE SMILES / InChI

Description

Sparsomycin is a model protein synthesis inhibitor that blocks peptide bond formation by binding to the large ribosome subunit. It is a unique dipeptidyl alcohol, consisting of a uracil acrylic acid moiety and a monooxo-dithioacetal group. Sparsomycin is a cytotoxic drug exhibiting a broad spectrum of in vitro activity against murine tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of cisplatin against L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of sparsomycin on murine tumors in vivo has been disappointing. Sparsomycin has shown cytostatic activity in a number of in vivo tumor systems, therefore, it was introduced in 1964 in a clinical Phase I study. Two of the five patients of this study developed an ocular toxicity, probably caused by sparsomycin, and so this Phase I study was stopped prematurely.

Originator

Approval Year

PubMed

Sample Use Guides

In Vivo Use Guide
Dog: Sparsomycin (0.7 mg/kg body weight) was injected via this catheter as a bolus injection.
Route of Administration: Intravenous
In Vitro Use Guide
Sparsomycin reacts with complex C in a two-step reaction. An initial rapid binding of the drug produces the encounter complex CI. During this step and before conversion of CI to C*I, sparsomycin behaves as a competitive inhibitor. The rapidly produced CI is isomerized slowly to a conformationally altered species C*I in which I is bound more tightly. The rate constants of this step are k6 = 2.1 min-1 and k7 = 0.095 min-1. Sparsomycin is a slow-binding inhibitor of eukaryotic peptidyltransferase (the association rate constant k7/Ki' (2 x 10(5) M-1 sec-1). When complex C is preincubated with concentrations of sparsomycin of >8 Ki and then reacts with a mixture of puromycin and sparsomycin, the inhibition becomes linear mixed noncompetitive and involves C*I instead of CI.