PMID- 11945126
OWN - NLM
STAT- MEDLINE
DCOM- 20030408
LR  - 20190822
IS  - 0929-8673 (Print)
IS  - 0929-8673 (Linking)
VI  - 9
IP  - 5
DP  - 2002 Mar
TI  - Novel synthetic retinoids and separation of the pleiotropic retinoidal 
      activities.
PG  - 591-608
AB  - Retinoids, all-trans-retinoic acid (1a) and its analogs, act as specific 
      modulators of cellular differentiation and proliferation, through binding to and 
      activating specific nuclear receptors, retinoic acid receptors (RARs) and 
      retinoid X receptors (RXRs). Retinoids have chemotherapeutic roles in dermatology 
      and oncology, but their usefulness is restricted by the high toxicity of retinoic 
      acid and its hydrophobic analogs. We have developed various retinoidal benzoic 
      acid derivatives, and named them retinobenzoic acids. Among them, aromatic amides 
      such as Am80 (7) and Am580 (8) have superior pharmacological characteristics, 
      including RAR subtype selectivity. Structural modification based on the ligand 
      superfamily concept afforded several types of RAR antagonists, benzimidazole 
      derivatives, BIPh (41) and BIBn (42), and dibenzodiazepine derivatives, LE135 
      (46) and LE540 (47). LE135 (46) is a unique antagonist with RARbeta-selectivity. 
      During investigations on the structure-activity relationships of retinobenzoic 
      acids, several retinoid synergists (RXRs agonists), such as HX600 (49), DA113 
      (55h) and TZ335 (57), have been found. These compounds are expected to modulate 
      other nuclear receptors which form heterodimers with RXRs, besides retinoids. 
      Further, we found some RXRs antagonists, HX531 (60) and HX603 (61), which inhibit 
      the activation of both RXR homodimers and RXR RAR heterodimers. In this review, 
      we describe our investigations on these structurally and biologically unique 
      retinoids and retinoid-regulatory compounds.
FAU - Kagechika, Hiroyuki
AU  - Kagechika H
AD  - Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, 
      Bunkyo-ku, Tokyo, Tokyo 113-0033, Japan. kage@mol.f.u-tokyo.ac.jp
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Retinoids)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/pharmacology
MH  - Drug Design
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Retinoids/*chemistry/*pharmacology
MH  - Structure-Activity Relationship
RF  - 81
EDAT- 2002/04/12 10:00
MHDA- 2003/04/09 05:00
CRDT- 2002/04/12 10:00
PHST- 2002/04/12 10:00 [pubmed]
PHST- 2003/04/09 05:00 [medline]
PHST- 2002/04/12 10:00 [entrez]
AID - 10.2174/0929867024606975 [doi]
PST - ppublish
SO  - Curr Med Chem. 2002 Mar;9(5):591-608. doi: 10.2174/0929867024606975.