Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0079731 (
B-cell lymphoma
)
16,671
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Two novel lectins were purified from rhizomes of two sweet flag species, namely Acorus calamus (Linn.) and Acorus gramineus (Solandin Ait.) by affinity chromatography on mannose linked epoxy-activated Sepharose 6B. The apparent molecular mass of the lectins, as determined by gel filtration chromatography, was 56 kDa for ACL and 55 kDa for AGL. In SDS-PAGE, pH 8.3, both lectins migrated with a subunit molecular mass of 13.6 kDa and 13.5 kDa, respectively, under reducing and non-reducing conditions thus indicating the absence of disulphide linkages. Acorus lectins readily agglutinated rabbit, rat and guinea pig erythrocytes. Both ACL and AGL also reacted with RBCs from sheep, goat and human ABO blood groups after neuraminidase treatment. ACL and AGL were inhibited by mannose/glucose and their derivatives. The most effective inhibitor was methyl-alpha-D-mannopyranoside. Acorus lectins were stable up to 55 degrees C, did not require metal ions for their activity and were also affected by high concentrations of denaturants like urea,
thiourea
and guanidine-HCl. These lectins showed potent mitogenic activity towards mouse splenocytes and human lymphocytes. Both ACL and AGL also significantly inhibited the growth of J774, a murine macrophage cancer cell-line and to lesser extent WEHI-279, a
B-cell lymphoma
.
...
PMID:Novel lectins from rhizomes of two Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines. 1595 73
Protein-protein interactions (PPI) between the transcriptional repressor
B-cell lymphoma
6 (BCL6) BTB domain (BCL6
BTB
) and its corepressors have emerged as a promising target for anticancer therapeutics. However, identification of potent, drug-like inhibitors of BCL6
BTB
has remained challenging. Using NMR-based screening of a library of fragment-like small molecules, we have identified a
thiourea
compound (7CC5) that binds to BCL6
BTB
. From this hit, the application of computer-aided drug design (CADD), medicinal chemistry, NMR spectroscopy, and X-ray crystallography has yielded an inhibitor, 15f, that demonstrated over 100-fold improved potency for BCL6
BTB
. This gain in potency was achieved by a unique binding mode that mimics the binding mode of the corepressor SMRT in the aromatic and the HDCH sites. The structure-activity relationship based on these new inhibitors will have a significant impact on the rational design of novel BCL6 inhibitors, facilitating the identification of therapeutics for the treatment of BCL6-dependent tumors.
...
PMID:Identification of Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design. 2996 59
