Bristol-Myers Squibb Compnay

E. R. Squibb Sons, Inc.

Chester A Meyers

Eric M Gordon

Scott A Biller

Claudio Mapelli

David R Magnin

Mariano Barbacid

Veeraswamy Manne

A method is provided by blocking or preventing the prenylation of CAAX box containing proteins including ras oncogene products thereby preventing and/or treating ras-related tumors which includes the step of administering a therapeutically effective amount of a protein-prenyl transferase inhibitor.

Method for blocking neoplastic transformation of cells induced by ras

Disclosed herein are polypeptides of the formula R.sup.1 --AA--A.sup.1 --A.sup.2 --A.sup.3 --A.sup.4 --A.sup.5 --A.sup.6 --A.sup.7 --A.sup.8 --A.sup.9 --A.sup.10 --A.sup.11 --A.sup.12 --A.sup.13 --R.sup.2 that are useful in treatment of diabetes mellitus, wherein: AA is a single bond or a polypeptide chain of 1 to 12 natural amino acid residues; A.sup.1 is seryl, A.sup.2 is phenylalanyl, A.sup.3 is arginyl, A.sup.4 is valyl, A.sup.5 is aspartyl, A.sup.6 is leucyl, A.sup.7 is arginyl, A.sup.8 is threonyl, A.sup.9 is leucyl, A.sup.10 is leucyl, A.sup.11 is arginyl, and A.sup.12 is tyrosyl, wherein one of A.sup.1 through A.sup.12 may be replaced with a natural amino acid residue, and wherein when A.sup.12 is phenylalanyl, tyrosyl or tryptophyl, its aromatic ring may be substituted with 1 or 2 iodo atoms; A.sup.13 is a natural amino acid residue other than tyrosyl, the D-form of a natural amino acid residue, --N(R.sup.4)--CH(R.sup.3)--C(O)--, or --N(R.sup.4)--CH(R.sup.3)--CH.sub.2 --; R.sup.1 is hydrogen, lower alkyl, R.sup.5 --C(O)--, aryl, aryl(lower alkyl), cycloalkyl, cycloalkyl(lower alkyl), aryl(lower alkoxy), cycloalkyl(lower alkoxy), or arylsulfenyl, wherein the aryl or cycloalkyl may be substituted with 1 to 5 substituents selected from 1 to 5 halo, 1 to 3 nitro, 1 to 5 lower alkyl, and 1 to 5 lower alkoxy groups; R.sup.2 is hydrogen, lower alkyl, aryl, aryl(lower alkyl), cycloalkyl, cycloalkyl(lower alkyl), hydroxyl, lower alkoxy, aryloxy, aryl(lower alkoxy), cycloalkyloxy, cycloalkyl(lower alkoxy), N.sub.3, --NR.sup.6 R.sup.7, or --N(R.sup.8)--NR.sup.6 R.sup.7 ; R.sup.3 is hydrogen, --R.sup.9 --R.sup.10, or --NR.sup.6 R.sup.7, and R.sup.4 is hydrogen or alkyl, or R.sup.3 and R.sup.4 together are alkylene; and the remaining symbols are as defined in the specification.

Polypeptides derived from major histocompatibility complex Class I

Growing community of inventors

Medford, NJ, United States of America

Chester A Meyers