Salinosporamides and Methods for Use Thereof
AssigneeThe Regents of the University of California
InventorsWilliam Fenical, Paul Jensen, Tracy Mincer, Robert H.R. Feling
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Abstract
The present invention is based on the discovery that certain fermentation products of the marine actinomycete strains CNB392 and CNB476 are effective inhibitors of hyperproliferative mammalian cells. The CNB392 and CNB476 strains lie within the family Micromonosporaceae, and the generic epithet Salinospora has been proposed for this obligate marine group. The reaction products produced by this strain are classified as salinosporamides, and are particularly advantageous in treating neoplastic disorders due to their low molecular weight, low IC50 values, high pharmaceutical potency, and selectivity for cancer cells over fungi.
Claims15
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound having the structure:
- wherein the pharmaceutical composition further comprises sucrose.
A method of treating a mammalian cell proliferative disorder comprising administering a therapeutically effective amount of a compound of the structure (I):
- wherein:
- R1 to R3 are each independently —H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, substituted cycloalkyl, alkoxy, substituted alkoxy, thioalkyl, substituted thioalkyl, hydroxy, halogen, amino, amido, carboxyl, —C(O)H, acyl, oxyacyl, carbamate, sulfonamide or sulfuryl;
- Each R4 is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl;
- E1 to E4 are each independently —O, —NR5, or —S, wherein R5 is —H or C1C6 alkyl;
- X is 0 to 8;
- and
- An additional anti-neoplastic agent.
Dependencies are inferred from the claim text.