Structural insights into the design of small molecule inhibitors that selectively antagonize Mcl-1.
The screening of a small focused library of rhodanine derivatives as inhibitors of Bcl-2 proteins led to the discovery of two structurally related compounds with different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent NMR studies with mutant proteins and in silico docking studies provide a possible rationale for the observed specificity.
Institute of Chemical and Engineering Sciences, Agency for Science Technology and Research, 1 Pesek Road, Jurong Island, Singapore. paul_bernardo@ices.a-star
Paul H
PH
Bernardo
Thirunavukkarasu
T
Sivaraman
Kah-Fei
KF
Wan
Jin
J
Xu
Janarthanan
J
Krishnamoorthy
Chun Meng
CM
Song
Liming
L
Tian
Jasmine S F
JS
Chin
Diane S W
DS
Lim
Henry Y K
HY
Mok
Victor C
VC
Yu
Joo Chuan
JC
Tong
Christina L L
CL
Chai
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005454:Fluorescence Polarization; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D053778:Thiazolidines; D019938:Cyclin D1