Derwent Drug File is the definitive source of drug journal and conference information on all aspects of drug development, synthesis, evaluation, manufacture and use. The unique indexing of this information enables you to search quickly and precisely for new developments in your field, or from key competitors. In addition, the unique combination of biological and chemical information is ideal for exploring all types of structure-activity relationships. An estimated 20% of the data in Derwent Drug File is not available in any other drug database. Drug structure GIFs are available to Ovid Web users.

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<Sample 1>

Accession Number
  2001-46790
Author
  Martello L A, He L, LaMarche M J, Beauchamp T J, Smith A B, Horwitz S B.
Conference Information
  92nd Annual Meeting of the American Association for Cancer Research, 
  New Orleans, Louisiana, USA, 2001
Title
  The use of analogs and modeling to understand the relationship between taxol
  and discodermolide.
Source
  Proceedings American Association for Cancer Research Annual Meeting (42, 92
  Meet., 367, 2001)
Abbreviated Source
  Proc.Am.Assoc.Cancer Res. (42, 92 Meet., 367, 2001)
Corporate Information
  Organizations: Univ.Pennsylvania 
  Locations: New York, N.Y.; Philadelphia, Pa., USA
Abstract
  The relationship between taxol and discodermolide was investigated. These 
  drugs act synergistically against human carcinoma cell lines. Future goals 
  are aimed at understanding the similarities and differences between these 
  drugs in order to exploit this knowledge in clinical settings.
  Using newly synthetized discodermolide analogs, structure-activity 
  relationships (SAR) were obtained for cytotoxicity and microtubule 
  stabilization. Small structural changes to the discodermolide molecule such as
  removal of a hydroxyl group at C3 position or of a methyl group at C14
  position resulted in a dramatic loss in the ability of discodermolide to
  initiate tubulin polymerization. When additional modifications were made to
  these analogs, there was a decrease in total tubulin polymerization. A change
  in olefin geometry at C8 position also caused an appreciable decrease in 
  cytotoxicity. The crystal structure of discodermolide demonstrated that the
  molecule was bent into a U-shaped conformation with the 6-membered ring at one
  end and the C19 side chain at the other end. When overlaid with taxol, the
  backbone of the discodermolide molecule mimicked the northern portion of the
  taxane ring of taxol. The 6-membered ring and C19 side chain of discodermolide 
  corresponded to the C13 and C2 side chains of taxol. However, the position of 
  the discodermolide ring and the C19 side chain with respect to the side chains 
  of taxol could not be determined at this point. The crystal structure of the 
  discodermolide molecule could fit into the taxol binding pocket within 
  beta-tubulin in either of 2 orientations. Hence, 2 models were proposed, one
  of which was favored by SAR data.
  1 Refs.
Reprint Address
  Albert Einstein College of Medicine, Bronx, NY, U.S.A.
Common Terms
  IN-VITRO/FT, CARCINOMA/FT, TUMOR-CELL/FT, CYTOSTATIC/FT, SYNERGIST/FT, 
  MODE-OF-ACT./FT, STRUCT.ACT./FT, TISSUE-CULTURE/FT
Linked Terms
  1: PACLITAXEL/PH, PACLITAXEL/DI, 33069-62-4/CS, DISCODERMOLIDE/DI, 
  CYTOSTATICS/FT, P-GLYCOPROTEIN-INHIBITORS/FT, PH/FT, DI/FT
  2: DISCODERMOLIDE/PH, DISCODERMOLIDE/DI, PACLITAXEL/DI, CYTOSTATICS/FT, 
  IMMUNOSUPPRESSIVES/FT, PH/FT, DI/FT
Derwent Registry Name
  TAXOL, DISCODERM
CAS Registry Number
  33069-62-4
Thematic Groups
  Pharmacology
Profile Section
  Structure-Activity, Chemotherapy - non-clinical, Drug Interactions
Subject Headings
  IN-VITRO/FT, CARCINOMA/FT, TUMOR-CELL/FT, CYTOSTATIC/FT, SYNERGIST/FT, 
  MODE-OF-ACT./FT, STRUCT.ACT./FT, TISSUE-CULTURE/FT, PACLITAXEL/PH, 
  PACLITAXEL/DI, 33069-62-4/CS, DISCODERMOLIDE/DI, CYTOSTATICS/FT, 
  P-GLYCOPROTEIN-INHIBITORS/FT, PH/FT, DI/FT, DISCODERMOLIDE/PH, 
  DISCODERMOLIDE/DI, PACLITAXEL/DI, CYTOSTATICS/FT, IMMUNOSUPPRESSIVES/FT, 
  PH/FT, DI/FT
Language
  English
CODEN
  7780B
Update Code
  200100

<Sample 2>

Accession Number
  2003-07348
Author
  Evans T G, Hasan M, Galibert L, Caron D.
Title
  The use of Flt3 ligand as an adjuvant for hepatitis B vaccination of healthy
  adults.
Source
  Vaccine (21, No. 3-4, 322-29, 2002)
  Abbreviated Source
  Vaccine (21, No. 3-4, 322-29, 2002)
Abbreviated Source
  Vaccine (21, No. 3-4, 322-29, 2002)
Corporate Information
  Organizations: Univ.California, Univ.Rochester, Immunex 
  Locations: Sacramento, Cal., Rochester, N.Y.; Seattle, Wash., USA
Abstract
  S.c. administration of recombinant human Flt3-ligand (produced by 
  recombinant DNA technology in a CHO cell line) as an adjuvant for i.m.
  hepatitis B vaccine (HB vaccine, Recombivax; Merck-USA) was safe and well
  tolerated in 50 volunteers in a two-phase randomized, double-blind,
  placebo-controlled Phase I/II clinical trial comparing once-daily and
  alternate-day dosing schedules. Adverse reactions were mild and included
  headache, nausea and malaise. One patient experienced lymph node swelling
  and another developed clinical influenza. One subject developed non-painful
  induration at the site of the Flt3-ligand injection sites 1 wk after the final
  injection. Flt3-ligand induced marked increases in WBCs, monocyte counts and
  CD11c+ dendritic cells (DCs). Despite the marked increase in peripheral
  circulating DCs, no increases in hepatitis B antibody titers were observed
  after vaccination.
  Methods: In a first phase, 20 volunteers (aged 18-55 yr) were randomized to 
  received s.c. Flt3-ligand (2- ug/kg) every day (n = 10) or every other day (n 
  = 10) for 1 wk. Flt3-ligand was followed 1 day later by vaccination with HB 
  vaccine. In a 2nd phase, 30 volunteers were randomized to receive Flt3-ligand 
  or placebo on the alternate day schedule followed by HB vaccination.
  Results: The administration of the Flt3-ligand in the first phase of the study 
  resulted in a marked increase in WBC and percent monocytes with little effect 
  on the percentage of neutrophils or lymphocytes. This increase was mirrored 
  by a marked increase in the number of CD11c+ DCs on day 7. In the second phase, 
  Flt3-ligand again resulted in a marked increase in WBC and monocyte counts. 
  The QOD regimen resulted in a 14-fold increase in the percent of CD11c+ DCs 
  and a 4-fold increase in CD123bright pre-DCs as compared to the placebo group. 
  Myeloid DCs increased 23-fold and the CD123bright pre-DCs increased 6-fold. 
  WBC numbers were 1.58 times greater in the Flt3-ligand as compared to placebo 
  recipients and the monocytes increased 2.3-fold. 3 Recipients had remarkable 
  increases in antibody titers after a single injection of HB vaccine. One sera 
  was measured with a titer of 4798 mIU and the other two had titers of 804 and 
  144 mIU. In the second phase of the study, despite the remarkable increase in 
  the number of circulating DCs, no clear effect was seen on hepatitis B
  antibody responses. The geometric mean antibody titers observed between the 2
  groups was not different, despite a trend towards higher values n the 
  Flt3-ligand recipients.
  37 Refs. 1 Figs. 4 Tbs.
Reprint Address
  Division of Infectious Diseases, University of California, Davis, PSSB, Suite 
  500, 4150 V St., Sacramento, CA 95817, U.S.A. (e-mail: tgevans@ucdavis.edu).
Common Terms
  MILD/AE, HEADACHE/AE, NAUSEA/AE, ASTHENIA/AE, LYMPH-NODE/AE, INFLUENZA/AE, 
  PNEUMOPATHY/AE, INFECTION,VIRUS/AE, IN-VIVO/FT, CASES/FT, HUMAN/FT, RANDOM/FT,
  DOUBLE/FT, BLIND-TEST/FT, PLACEBO/FT, PHASE-I/FT, PHASE-II/FT, LYMPHOCYTE/FT, 
  MONOCYTE/FT, COUNT/FT, NEUTROPHIL/FT, DENDRITIC-CELL/FT, HEPATITIS-B-VIRUS/FT,
  ANTIBODY-TITER/FT, IMMUNE-RESPONSE/FT, CLIN.TRIAL/FT, LEUKOCYTE/FT,
  ANTIGEN-PRESENTING-CELL/FT, HEPATITIS-VIRUS/FT, VIRUS/FT, IMMUNITY/FT FT
Linked Terms
  1: FLT-3-LIGAND/PH, FLT-3-LIGAND/AE, INJECTION-SITE/AE, INDURATION/AE, 
  S.C./FT, ADJUVANT/FT, RECOMBINANT/FT, ONCE-DAILY/FT, ALTERNATE/FT, 
  INJECTION/FT, DOSAGE/FT, SYNERGISTS/FT, PH/FT, AE/FT
  2: HEPATITIS-B-VACCINE/PH, HEPATITIS-B-VACCINE/AE, RECOMBIVAX/PH, 
  RECOMBIVAX/AE, MERCK-USA/FT, I.M./FT, VACCINE/FT, INJECTION/FT, VACCINES/FT,
  PH/FT, AE/FT
Derwent Registry Name
  DR9601088, HEPATBVAC
Thematic Groups
  Pharmacology, Adverse effects
Profile Section
  Immunopharmacology, Adverse Reactions, Clinical Trials
Subject Headings
  MILD/AE, HEADACHE/AE, NAUSEA/AE, ASTHENIA/AE, LYMPH-NODE/AE, INFLUENZA/AE,
  PNEUMOPATHY/AE, INFECTION, VIRUS/AE, IN-VIVO/FT, CASES/FT, HUMAN/FT,
  RANDOM/FT, DOUBLE/FT, BLIND-TEST/FT, PLACEBO/FT, PHASE-I/FT, PHASE-II/FT,
  LYMPHOCYTE/FT, MONOCYTE/FT, COUNT/FT, NEUTROPHIL/FT, DENDRITIC-CELL/FT, 
  HEPATITIS-B-VIRUS/FT, ANTIBODY-TITER/FT, IMMUNE-RESPONSE/FT, CLIN.TRIAL/FT,
  LEUKOCYTE/FT, ANTIGEN-PRESENTING-CELL/FT, HEPATITIS-VIRUS/FT, VIRUS/FT,
  IMMUNITY/FT FT, FLT-3-LIGAND/PH, FLT-3-LIGAND/AE, INJECTION-SITE/AE, 
  INDURATION/AE, S.C./FT, ADJUVANT/FT, RECOMBINANT/FT, ONCE-DAILY/FT,
  ALTERNATE/FT, INJECTION/FT, DOSAGE/FT, SYNERGISTS/FT, PH/FT, AE/FT,
  HEPATITIS-B-VACCINE/PH, HEPATITIS-B-VACCINE/AE, RECOMBIVAX/PH, RECOMBIVAX/AE,
  MERCK-USA/FT, I.M./FT, VACCINE/FT, INJECTION/FT, VACCINES/FT, PH/FT, AE/FT
Language
  English
CODEN
  VACCDE
Update Code
  200300