Sparsomycin

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 Search

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

Molecular Formula	C13H19N3O5S2
Molecular Weight	361.437
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26046698 | https://www.ncbi.nlm.nih.gov/pubmed/3664930 | https://www.ncbi.nlm.nih.gov/pubmed/3365303 | https://www.ncbi.nlm.nih.gov/pubmed/6874860

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

Title	Date	PubMed
Protein synthesis in Mycobacterium tuberculosis H37Rv and the effect of streptomycin in streptomycin-susceptible and -resistant strains.	1973 Sep	4202339
Sparsomycin Biosynthesis Highlights Unusual Module Architecture and Processing Mechanism in Non-ribosomal Peptide Synthetase.	2015 Aug 21	26046698

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:15:38 GMT 2023` Edited by `admin` on `Fri Dec 15 19:15:38 GMT 2023`
Record UNII	6C940P63E7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Sparsomycin

Official Name

English

2-PROPENAMIDE, N-(1-(HYDROXYMETHYL)-2-(((METHYLTHIO)METHYL)SULFINYL)ETHYL)-3-(1,2,3,4-TETRAHYDRO-6-METHYL-2,4-DIOXO-5-PYRIMIDINYL)-, (S-(E))-

Common Name

English

NSC-59729

Code

English

sparsomycin [INN]

Common Name

English

U-19183

Code

English

(+)-SPARSOMYCIN

Common Name

English

SPARSOMYCIN [USAN]

Common Name

English

SPARSOMYCIN [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C259