3cxw › Citations

7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes.

Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F
J Med Chem 55 403-13 (2012)
Related entries: 3bhy, 3cy2

Cited: 32 times
EuropePMC logo PMID: 22136433

Abstract

Development of both potent and selective kinase inhibitors is a challenging task in modern drug discovery. The innate promiscuity of kinase inhibitors largely results from ATP-mimetic binding to the kinase hinge region. We present a novel class of substituted 7,8-dichloro-1-oxo-β-carbolines based on the distinct structural features of the alkaloid bauerine C whose kinase inhibitory activity does not rely on canonical ATP-mimetic hinge interactions. Intriguingly, cocrystal structures revealed an unexpected inverted binding mode and the presence of halogen bonds with kinase backbone residues. The compounds exhibit excellent selectivity over a comprehensive panel of human protein kinases while inhibiting selected kinases such as the oncogenic PIM1 at low nanomolar concentrations. Together, our biochemical and structural data suggest that this scaffold may serve as a valuable template for the design and development of specific inhibitors of various kinases including the PIM family of kinases, CLKs, DAPK3 (ZIPK), BMP2K (BIKE), and others.

Reviews - 3cxw mentioned but not cited (1)

  1. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Brault L, Gasser C, Bracher F, Huber K, Knapp S, Schwaller J. Haematologica 95 1004-1015 (2010)

Articles - 3cxw mentioned but not cited (4)

  1. Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations. Araya CL, Cenik C, Reuter JA, Kiss G, Pande VS, Snyder MP, Greenleaf WJ. Nat Genet 48 117-125 (2016)
  2. 7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F. J Med Chem 55 403-413 (2012)
  3. Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. Andreoli M, Persico M, Kumar A, Orteca N, Kumar V, Pepe A, Mahalingam S, Alegria AE, Petrella L, Sevciunaite L, Camperchioli A, Mariani M, Di Dato A, Novellino E, Scambia G, Malhotra SV, Ferlini C, Fattorusso C. J Med Chem 57 7916-7932 (2014)
  4. Flexibility of the P-loop of Pim-1 kinase: observation of a novel conformation induced by interaction with an inhibitor. Parker LJ, Watanabe H, Tsuganezawa K, Tomabechi Y, Handa N, Shirouzu M, Yuki H, Honma T, Ogawa N, Nagano T, Yokoyama S, Tanaka A. Acta Crystallogr Sect F Struct Biol Cryst Commun 68 860-866 (2012)


Reviews citing this publication (2)

  1. Death-associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes. Farag AK, Roh EJ. Med Res Rev 39 349-385 (2019)
  2. Insights from Pim1 structure for anti-cancer drug design. Ogawa N, Yuki H, Tanaka A. Expert Opin Drug Discov 7 1177-1192 (2012)

Articles citing this publication (25)

  1. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Weirauch U, Beckmann N, Thomas M, Grünweller A, Huber K, Bracher F, Hartmann RK, Aigner A. Neoplasia 15 783-794 (2013)
  2. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma. Brault L, Menter T, Obermann EC, Knapp S, Thommen S, Schwaller J, Tzankov A. Br J Cancer 107 491-500 (2012)
  3. 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A. Falke H, Chaikuad A, Becker A, Loaëc N, Lozach O, Abu Jhaisha S, Becker W, Jones PG, Preu L, Baumann K, Knapp S, Meijer L, Kunick C. J Med Chem 58 3131-3143 (2015)
  4. Using halogen bonds to address the protein backbone: a systematic evaluation. Wilcken R, Zimmermann MO, Lange A, Zahn S, Boeckler FM. J Comput Aided Mol Des 26 935-945 (2012)
  5. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, Peterson JR, Dunbrack RL. Sci Signal 8 rs13 (2015)
  6. Fluorescence linked enzyme chemoproteomic strategy for discovery of a potent and selective DAPK1 and ZIPK inhibitor. Carlson DA, Franke AS, Weitzel DH, Speer BL, Hughes PF, Hagerty L, Fortner CN, Veal JM, Barta TE, Zieba BJ, Somlyo AV, Sutherland C, Deng JT, Walsh MP, MacDonald JA, Haystead TA. ACS Chem Biol 8 2715-2723 (2013)
  7. Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparum impairs blood stage replication and malaria transmission. Kern S, Agarwal S, Huber K, Gehring AP, Strödke B, Wirth CC, Brügl T, Abodo LO, Dandekar T, Doerig C, Fischer R, Tobin AB, Alam MM, Bracher F, Pradel G. PLoS One 9 e105732 (2014)
  8. Effect of single amino acid substitution observed in cancer on Pim-1 kinase thermodynamic stability and structure. Lori C, Lantella A, Pasquo A, Alexander LT, Knapp S, Chiaraluce R, Consalvi V. PLoS One 8 e64824 (2013)
  9. Halogen-enriched fragment libraries as chemical probes for harnessing halogen bonding in fragment-based lead discovery. Zimmermann MO, Lange A, Wilcken R, Cieslik MB, Exner TE, Joerger AC, Koch P, Boeckler FM. Future Med Chem 6 617-639 (2014)
  10. Design, synthesis and biological evaluation of 1,3,6-trisubstituted β-carboline derivatives for cytotoxic and anti-leishmanial potential. Lunagariya NA, Gohil VM, Kushwah V, Neelagiri S, Jain S, Singh S, Bhutani KK. Bioorg Med Chem Lett 26 789-794 (2016)
  11. Novel hinge-binding motifs for Janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteres. Gehringer M, Forster M, Pfaffenrot E, Bauer SM, Laufer SA. ChemMedChem 9 2516-2527 (2014)
  12. A novel inhibitory effect of oxazol-5-one compounds on ROCKII signaling in human coronary artery vascular smooth muscle cells. Al-Ghabkari A, Deng JT, McDonald PC, Dedhar S, Alshehri M, Walsh MP, MacDonald JA. Sci Rep 6 32118 (2016)
  13. De Novo Fragment Design for Drug Discovery and Chemical Biology. Rodrigues T, Reker D, Welin M, Caldera M, Brunner C, Gabernet G, Schneider P, Walse B, Schneider G. Angew Chem Int Ed Engl 54 15079-15083 (2015)
  14. Chemical and photochemical properties of chloroharmine derivatives in aqueous solutions. Rasse-Suriani FA, Denofrio MP, Yañuk JG, Gonzalez MM, Wolcan E, Seifermann M, Erra-Balsells R, Cabrerizo FM. Phys Chem Chem Phys 18 886-900 (2016)
  15. How to Separate Kinase Inhibition from Undesired Monoamine Oxidase A Inhibition-The Development of the DYRK1A Inhibitor AnnH75 from the Alkaloid Harmine. Wurzlbauer A, Rüben K, Gürdal E, Chaikuad A, Knapp S, Sippl W, Becker W, Bracher F. Molecules 25 E5962 (2020)
  16. Crystal structure of pim1 kinase in complex with a pyrido[4,3-d]pyrimidine derivative suggests a unique binding mode. Lee SJ, Han BG, Cho JW, Choi JS, Lee J, Song HJ, Koh JS, Lee BI. PLoS One 8 e70358 (2013)
  17. Targeting Pim Kinases and DAPK3 to Control Hypertension. Carlson DA, Singer MR, Sutherland C, Redondo C, Alexander LT, Hughes PF, Knapp S, Gurley SB, Sparks MA, MacDonald JA, Haystead TAJ. Cell Chem Biol 25 1195-1207.e32 (2018)
  18. Synthesis of desaza analogues of annomontine and canthin-4-one alkaloids. Strödke B, Gehring AP, Bracher F. Arch Pharm (Weinheim) 348 125-131 (2015)
  19. β-Carbolinone Analogues from the Ugi Silver Mine. Madhavachary R, Naveen N, Wang Y, Wang Q, Konstantinidou M, Dömling A. European J Org Chem 2018 3139-3143 (2018)
  20. Identification of type I and type II inhibitors of c-Yes kinase using in silico and experimental techniques. Ramakrishnan C, Mary Thangakani A, Velmurugan D, Anantha Krishnan D, Sekijima M, Akiyama Y, Gromiha MM. J Biomol Struct Dyn 36 1566-1576 (2018)
  21. Synthesis and Biological Evaluation of Harmirins, Novel Harmine-Coumarin Hybrids as Potential Anticancer Agents. Pavić K, Beus M, Poje G, Uzelac L, Kralj M, Rajić Z. Molecules 26 6490 (2021)
  22. Validation of chemical genetics for the study of zipper-interacting protein kinase signaling. Al-Ghabkari A, Moffat LD, Walsh MP, MacDonald JA. Proteins 86 1211-1217 (2018)
  23. Design and synthesis of thiadiazolo-carboxamide bridged β-carboline-indole hybrids: DNA intercalative topo-IIα inhibition with promising antiproliferative activity. Tokala R, Sana S, Lakshmi UJ, Sankarana P, Sigalapalli DK, Gadewal N, Kode J, Shankaraiah N. Bioorg Chem 105 104357 (2020)
  24. Visible-Light-Driven C-H Oxidation of Cyclic Tertiary Amines: Access to Synthetic Strychnos Alkaloids with Antiviral Activity. Guryev AA, Hahn F, Marschall M, Tsogoeva SB. Chemistry 25 4062-4066 (2019)
  25. Identified Isosteric Replacements of Ligands' Glycosyl Domain by Data Mining. Zhang T, Jiang S, Li T, Liu Y, Zhang Y. ACS Omega 8 25165-25184 (2023)


Quick links