Synthesis and evaluation of antiproliferative activity of a geldanamycin-Herceptin immunoconjugate.
Geldanamycin was modified with 1,4-diaminobutane to introduce a primary amine that was subsequently employed to provide a maleimide for protein linkage. Monoclonal antibody Herceptin was then derivatized to generate thiol groups that reacted with the maleimide derivative to produce the immunoconjugate. The product showed antiproliferative activity greater than native Herceptin.
Mandler
R
R
Metabolism Branch, National Cancer Institute, NIH, Bethesda, MD 20982-1002, USA.
Dadachova
E
E
Brechbiel
J K
JK
Waldmann
T A
TA
Brechbiel
M W
MW
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016227:Benzoquinones; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D047029:Lactams, Macrocyclic; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C001277:geldanamycin