Protein−Ligand Docking Accounting for Receptor Side Chain and Global Flexibility in Normal Modes: Evaluation on Kinase Inhibitor Cross Docking

2008 ◽  
Vol 51 (12) ◽  
pp. 3499-3506 ◽  
Author(s):  
Andreas May ◽  
Martin Zacharias
Keyword(s):  
Kinase Inhibitor ◽  
Normal Modes ◽  
Ligand Docking ◽  
Side Chain ◽  
Cross Docking

GANM: A protein–ligand docking approach based on genetic algorithm and normal modes

2012 ◽  
Vol 219 (2) ◽  
pp. 511-520 ◽  
Author(s):  
Angélica Nakagawa Lima ◽  
Eric Allison Philot ◽  
David Perahia ◽  
Antonio Sérgio Kimus Braz ◽  
Luis P.B. Scott
Keyword(s):  
Genetic Algorithm ◽  
Normal Modes ◽  
Ligand Docking ◽  
Docking Approach

scholarly journals A new series of vitamin D analogs is highly active for clonal inhibition, differentiation, and induction of WAF1 in myeloid leukemia

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2201-2209 ◽  
Author(s):  
R Munker ◽  
T Kobayashi ◽  
E Elstner ◽  
AW Norman ◽  
M Uskokovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Line ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Active Form ◽  
Leukemic Cell ◽  
Myelogenous Leukemia ◽  
Side Chain ◽  
Vitamin D Analogs

The active form of vitamin D3 [1 alpha, 25-dihydroxyvitamin-D3 (1 alpha, 25(OH)2D3)] modulates the proliferation and differentiation of hematopoietic cells. Analogs of 1 alpha, 25(OH)2D3 that have greater potency may have the potential as adjuvant therapy for high-risk patients in remission for acute myelogenous leukemia (AML) and myelodysplastic syndromes. A new generation of 11 analogs of 1 alpha, 25(OH)2D3 has been synthesized, and we examined their effects on the human leukemic cell line HL-60. This cell line provides a sensitive monitor of activity of the 1 alpha, 25(OH)2D3 analogs. All the compounds were potent, producing a 50% clonal inhibition (ED50) in the range of 10(-8) to 10(-11) mol/L; nine of the 11 analogs had ED50s at concentrations that were at least 10-fold lower than those for the parental 1,25(OH)2D3. The most active compound [cmpd LA, (22R)-1 alpha, 25-(OH)2–16,22,23-triene-D3] had an ED50 of 2 x 10(-11) mol/L; it was also tested on clonogenic cells from patients with AML, and it achieved an ED50 of approximately 6 x 10(-11) mol/L, while 1 alpha, 25(OH)2D3 produced an ED50 of approximately 10(-8) mol/L on the same population of cells. Five different cell surface markers were examined on HL-60 cells exposed to the 1 alpha, 25(OH)2D3 analogs: HLA-DR and CD11b were induced by all of the compounds; CD13 was induced by six of the 12 compounds, including 1,25(OH)2D3; CD14 was strongly induced by all compounds; and CD38 was induced rather weakly by nine of 12 analogs. WAF1/CIP1/p21, a cyclin-dependent kinase inhibitor (CDKI), which is important in blocking the cell cycle, was examined by Western blot and was found to be induced by all of the compounds, suggesting a possible mechanism by which these analogs inhibit leukemic growth. The induction of WAF1 occurred at concentrations of vitamin D analogs as low as 10(- 10) mol/L. This structure-function study showed that a new series of 1 alpha, 25(OH)2D3 analogs was active in clonal inhibition, as well as induction of differentiation and WAF1 expression of HL-60 cells. The key structural motifs included C-16 double bond, double and/or triple bonds in the side chain, lengthening of the side chain, 20-epi- conformation of the side chain, replacement of six hydrogens at the end of the side chain with fluorines, and the removal of C-19. Consideration should be given to further in vivo testing of toxicity and efficacy to move toward a clinical trial, especially in a setting of minimal residual disease.

Representing Receptor Flexibility in Ligand Docking through Relevant Normal Modes

2005 ◽  
Vol 127 (26) ◽  
pp. 9632-9640 ◽  
Author(s):  
Claudio N. Cavasotto ◽  
Julio A. Kovacs ◽  
Ruben A. Abagyan
Keyword(s):  
Normal Modes ◽  
Ligand Docking ◽  
Receptor Flexibility

947: Chemopreventive Effects of COX-2 Inhibitor and Epidermal Growth Factor (EGF)-Receptor Kinase Inhibitor on Rat Urinary Bladder Tumorigenesis

2004 ◽  
Vol 171 (4S) ◽  
pp. 251-251
Author(s):  
Kazunori Hattori ◽  
Katsuyuki Iida ◽  
Akira Johraku ◽  
Sadamu Tsukamoto ◽  
Taeko Asano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Urinary Bladder ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Receptor Kinase ◽  
Rat Urinary Bladder ◽  
Epidermal Growth ◽  
Cox 2
Sign in / Sign up

Export Citation Format

Share Document