Cytotoxic anticancer drugs: models and concepts for drug discovery and development.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Cytotoxic anticancer drugs: models and concepts for drug discovery and development.

Dev Oncol; 68:1-409 1992. Unique Identifier : AIDSLINE ICDB/94699849
Valeriote FA; Corbett TH; Baker LH; Wayne State Univ. Sch. of Medicine, Detroit, MI

Abstract: This book presents the proceedings of a symposium, held April 26-28, 1990, in Detroit, Michigan, on models and concepts for discovery and development of cytotoxic anticancer drugs. The papers included covered these topics: drug discovery 1990; data display and analysis strategies for the NCI disease-oriented in vitro antitumor drug screen; discovery of solid-tumor active agents, using a soft agar colony-formation disk-diffusion assay; thymidylate synthase inhibition of modified quinazoline antifolates; DNA-minor groove binding anticancer agents; 2-([arylmethyl]amino)-1,3-propanediols--discovery, selection and development of four clinical candidates; mechanism-based approaches to cancer drug discovery; the role of chemical ecology in discovery and bulk production of natural products with anticancer activity; chemical approaches to improved radiotherapy; large scale anticancer drug screening at Sterling Drug, Inc; are antisense oligonucleotides therapeutic agents of the future; supercomputer-aided drug design--application in oncology and AIDS; extrachromosomal DNA as a target for drug development; prospective evaluation of a predictive model for plasma concentration-vs-time profiles of investigational anticancer drugs in patients; agent-directed preclinical toxicology for antineoplastic drugs; preclinical studies with brequinar sodium, a novel anticancer agent; diphtheria toxin-related peptide hormone fusion proteins--new toxins with therapeutic potential; anti-growth factor receptor antibodies as therapy for cancer; regulation of polyamine biosynthetic activity and homeostasis as a novel antiproliferative strategy; esperamicin A1 (BMY28175), a novel antitumor agent of the diyne-ene class; modified 2-tumor (L1210, colon 38) assay to screen for solid-tumor-selective agents; 5-fluorouracil schedule optimization in metastatic colorectal cancer; and preclinical antitumor efficacy of Taxotere, a Taxol analog, and of RP60475, a new benzopyridoindole.

Keywords: Acquired Immunodeficiency Syndrome/DRUG THERAPY Animal Antineoplastic Agents/ADVERSE EFFECTS/CHEMICAL SYNTHESIS/ PHARMACOKINETICS/THERAPEUTIC USE Cell Division Diphtheria Toxin *Drug Design Drug Screening Assays, Antitumor DNA/DRUG EFFECTS Fluorouracil/THERAPEUTIC USE Folic Acid Antagonists Homeostasis Human Oligonucleotides, Antisense/THERAPEUTIC USE Paclitaxel/*ANALOGS & DERIVATIVES/THERAPEUTIC USE Polyamines/ANTAGONISTS & INHIB Radiation-Sensitizing Agents Radiotherapy Recombinant Fusion Proteins/THERAPEUTIC USE Thymidylate Synthetase/ANTAGONISTS & INHIB Tumor Cells, Cultured MONOGRAPH
940630
M9460928

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