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
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
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
Dog: Sparsomycin (0.7 mg/kg body weight) was injected via this catheter as a bolus
injection.
Route of Administration:
Intravenous
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.