Literature DB >> 24503105

Lead optimization of HMBA to develop potent HEXIM1 inducers.

Bo Zhong1, Rati Lama1, Wannarasmi Ketchart2, Monica M Montano3, Bin Su4.   

Abstract

The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives inducing Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in LNCaP prostate cancer cells. Several compounds with unsymmetrical structures showed significantly improved activity. Distinct from HMBA, these analogs have increased hydrophobicity and can improve the short half-life of HMBA, which is one of the factors that have limited the application of HMBA in clinics. The unsymmetrical scaffolds of the new analogs provide the basis for further lead optimization of the compounds using combinatorial chemistry strategy. Published by Elsevier Ltd.

Entities:  

Keywords:  Derivatives; Drug development; HEXIM1; HMBA

Mesh：

Substances：

Year:  2014        PMID： 24503105      PMCID： PMC3982598          DOI： 10.1016/j.bmcl.2014.01.025

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  17 in total

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Authors:  V M Richon; Y Webb; R Merger; T Sheppard; B Jursic; L Ngo; F Civoli; R Breslow; R A Rifkind; P A Marks
Journal:  Proc Natl Acad Sci U S A       Date:  1996-06-11       Impact factor: 11.205

2.  HMBA induces activation of a caspase-independent cell death pathway to overcome P-glycoprotein-mediated multidrug resistance.

Authors:  A A Ruefli; M J Smyth; R W Johnstone
Journal:  Blood       Date:  2000-04-01       Impact factor: 22.113

3.  Phase I trial and clinical pharmacological evaluation of hexamethylene bisacetamide administration by ten-day continuous intravenous infusion at twenty-eight-day intervals.

Authors:  C W Young; M P Fanucchi; T Declan Walsh; L Baltzer; S Yaldaei; Y W Stevens; C Gordon; W Tong; R A Rifkind; P A Marks
Journal:  Cancer Res       Date:  1988-12-15       Impact factor: 12.701

4.  Potent cytodifferentiating agents related to hexamethylenebisacetamide.

Authors:  R Breslow; B Jursic; Z F Yan; E Friedman; L Leng; L Ngo; R A Rifkind; P A Marks
Journal:  Proc Natl Acad Sci U S A       Date:  1991-07-01       Impact factor: 11.205

5.  HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b.

Authors:  Noriaki Shimizu; Rika Ouchida; Noritada Yoshikawa; Tetsuya Hisada; Hajime Watanabe; Kensaku Okamoto; Masatoshi Kusuhara; Hiroshi Handa; Chikao Morimoto; Hirotoshi Tanaka
Journal:  Proc Natl Acad Sci U S A       Date:  2005-06-07       Impact factor: 11.205

6.  Increased HEXIM1 expression during erythroleukemia and neuroblastoma cell differentiation.

Authors:  Mimmo Turano; Giuliana Napolitano; Cyprien Dulac; Barbara Majello; Olivier Bensaude; Luigi Lania
Journal:  J Cell Physiol       Date:  2006-03       Impact factor: 6.384

7.  Approaches to optimal dosing of hexamethylene bisacetamide.

Authors:  B A Conley; M J Egorin; V Sinibaldi; G Sewack; C Kloc; L Roberts; E G Zuhowski; A Forrest; D A Van Echo
Journal:  Cancer Chemother Pharmacol       Date:  1992       Impact factor: 3.333

8.  Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor.

Authors:  Annemieke A Michels; Alessandro Fraldi; Qintong Li; Todd E Adamson; François Bonnet; Van Trung Nguyen; Stanley C Sedore; Jason P Price; David H Price; Luigi Lania; Olivier Bensaude
Journal:  EMBO J       Date:  2004-06-17       Impact factor: 11.598

9.  Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent.

Authors:  M Andreeff; R Stone; J Michaeli; C W Young; W P Tong; H Sogoloff; T Ervin; D Kufe; R A Rifkind; P A Marks
Journal:  Blood       Date:  1992-11-15       Impact factor: 22.113

10.  Inhibition of metastasis by HEXIM1 through effects on cell invasion and angiogenesis.

Authors:  W Ketchart; K M Smith; T Krupka; B M Wittmann; Y Hu; P A Rayman; Y Q Doughman; J M Albert; X Bai; J H Finke; Y Xu; A A Exner; M M Montano
Journal:  Oncogene       Date:  2012-09-10       Impact factor: 9.867
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  4 in total

1.  HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen.

Authors:  Rati Lama; Chunfang Gan; Nethrie Idippily; Viharika Bobba; David Danielpour; Monica Montano; Bin Su
Journal:  J Steroid Biochem Mol Biol       Date:  2017-02-14       Impact factor: 4.292

2.  Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism.

Authors:  Wannarasmi Ketchart; I-Ju Yeh; Haoyan Zhou; Praveena S Thiagarajan; Justin Lathia; Ofer Reizes; Agata Exner; Bin Su; Monica M Montano
Journal:  Cancer Lett       Date:  2016-05-26       Impact factor: 8.679

3.  HEXIM1 induction is mechanistically involved in mediating anti-AML activity of BET protein bromodomain antagonist.

Authors:  S G T Devaraj; W Fiskus; B Shah; J Qi; B Sun; S P Iyer; S Sharma; J E Bradner; K N Bhalla
Journal:  Leukemia       Date:  2015-06-15       Impact factor: 11.528

4.  Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.

Authors:  Monica M Montano; I-Ju Yeh; Yinghua Chen; Chris Hernandez; Janna G Kiselar; Maria de la Fuente; Adriane M Lawes; Marvin T Nieman; Philip D Kiser; James Jacobberger; Agata A Exner; Matthew C Lawes
Journal:  Breast Cancer Res       Date:  2019-12-05       Impact factor: 6.466
  4 in total

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