Novel therapeutic candidates, identified by molecular modeling, induce γ-globin gene expression in vivo

Blood Cells, Molecules, and Diseases

Volumn 47, Issue 2, 2011, Pages 107-116

  Boosalis, Michael S ^a   Castaneda, Serguei A ^a   Trudel, Marie ^b   Mabaera, Rodwell ^c   White, Gary L ^d   Lowrey, Christopher H ^c   Emery, David W ^e   Mpollo, Marthe Sandrine Eiymo Mwa ^b   Shen, Ling ^a   Wargin, William A ^f   Bohacek, Regine ^g   Faller, Douglas V ^a   Perrine, Susan P ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^c DARTMOUTH MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f PK PM Associates LLC   (United States)

^g Boston De Novo Design   (United States)

Author keywords

Butyrate; Fetal hemoglobin; Hemoglobinopathy; Small molecules

Indexed keywords

COMPOUND AB; COMPOUND RB12; COMPOUND RB13; COMPOUND RB14; COMPOUND RB15; COMPOUND RB16; COMPOUND RB17; COMPOUND RB19; COMPOUND RB21; COMPOUND RB28; COMPOUND RB29; COMPOUND RB3; COMPOUND RB30; COMPOUND RB7; COMPOUND RB9; COMPOUND ST20; GAMMA GLOBIN; HEMATOLOGIC AGENT; HEMOGLOBIN A; HEMOGLOBIN F; UNCLASSIFIED DRUG;

ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BABOON; BETA THALASSEMIA; CLINICAL ARTICLE; COMPUTER MODEL; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISEASE SEVERITY; DRUG BIOAVAILABILITY; DRUG DETERMINATION; DRUG INHIBITION; DRUG STRUCTURE; ERYTHROID PRECURSOR CELL; GENE EXPRESSION REGULATION; HEMOGLOBINOPATHY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOLECULAR DYNAMICS; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE;

ADMINISTRATION, ORAL; ANEMIA; ANIMALS; BETA-GLOBINS; BETA-THALASSEMIA; BIOLOGICAL AGENTS; CELLS, CULTURED; DRUG DESIGN; ERYTHROID PRECURSOR CELLS; FETAL HEMOGLOBIN; GAMMA-GLOBINS; GENE EXPRESSION; HUMANS; INJECTIONS, INTRAVENOUS; MICE; MICE, TRANSGENIC; MODELS, MOLECULAR; PAPIO; PHLEBOTOMY; POLYMERASE CHAIN REACTION; RNA, MESSENGER; SMALL MOLECULE LIBRARIES;

MUS MUSCULUS; PAPIO;

EID: 79960843759     PISSN: 10799796     EISSN: 10960961     Source Type: Journal    
DOI: 10.1016/j.bcmd.2011.04.008     Document Type: Article

References (50)

1. Weatherall D.J. The inherited diseases of hemoglobin are an emerging global health burden. Blood 2010, 115:4331-4336.
2. Steinberg M.H., Rodgers G.P. Pharmacologic modulation of fetal hemoglobin. Medicine (Baltimore) 2001, 80:328-344.
3. Perrine S.P., Castaneda S.A., Chui D.H., Faller D.V., Berenson R.J., Siritanaratku N., Fucharoen S. Fetal globin gene inducers: novel agents and new potential. Ann. N.Y. Acad. Sci. 2010, 1202:158-164.
4. Perrine S.P. Fetal globin stimulant therapies in the beta-hemoglobinopathies: principles and current potential. Pediatr. Ann. 2008, 37:339-346.
5. Perrine S.P. Fetal globin induction-can it cure beta thalassemia?. Hematology Am. Soc. Hematol. Educ. Program 2005, 38-44.
6. Rund D., Rachmilewitz E. Beta-thalassemia. N. Engl. J. Med. 2005, 353:1135-1146.
7. Testa U. Fetal hemoglobin chemical inducers for treatment of hemoglobinopathies. Ann. Hematol. 2009, 88:505-528.
8. Steinberg M.H. Management of sickle cell disease. N. Engl. J. Med. 1999, 340:1021-1030.
9. Perrine S.P., Ginder G.D., Faller D.V., Dover G.H., Ikuta T., Witkowska H.E., Cai S.P., Vichinsky E.P., Olivieri N.F. A short-term trial of butyrate to stimulate fetal-globin-gene expression in the beta-globin disorders. N. Engl. J. Med. 1993, 328:81-86.
10. Collins A.F., Pearson H.A., Giardina P., McDonagh K.T., Brusilow S.W., Dover G.J. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood 1995, 85:43-49.
11. Atweh G.F., Sutton M., Nassif I., Boosalis V., Dover G.J., Wallenstein S., Wright E., McMahon L., Stamatoyannopoulos G., Faller D.V., Perrine S.P. Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease. Blood 1999, 93:1790-1797.
12. Olivieri N.F., Rees D.C., Ginder G.D., Thein S.L., Brittenham G.M., Waye J.S., Weatherall D.J. Treatment of thalassaemia major with phenylbutyrate and hydroxyurea. Lancet 1997, 350:491-492.
13. Reich S., Buhrer C., Henze G., Ohlendorf D., Mesche M., Sinha P., Kage A., Muller C., Vetter B., Kulozik A.E. Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia. Blood 2000, 96:3357-3363.
14. Domenica Cappellini M., Graziadei G., Ciceri L., Comino A., Bianchi P., Porcella A., Fiorelli G. Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study. Blood Cells Mol. Dis. 2000, 26:105-111.
15. Resar L.M., Segal J.B., Fitzpatric L.K., Friedmann A., Brusilow S.W., Dover G.J. Induction of fetal hemoglobin synthesis in children with sickle cell anemia on low-dose oral sodium phenylbutyrate therapy. J. Pediatr. Hematol. Oncol. 2002, 24:737-741.
16. Perrine S.P., Castaneda S.A., Boosalis M.S., White G.L., Jones B.M., Bohacek R. Induction of fetal globin in beta-thalassemia: Cellular obstacles and molecular progress. Ann. N.Y. Acad. Sci. 2005, 1054:257-265.
17. Fuchareon S., Inati A.C., Siritanaratkul N., Koussa S., Taher A., Boosalis M.S., Thein S.L., Wallis W., Bobbitt P., Thomson A., Johnson E., Berenson R.J., Perrine S.P. HQK-1001 is well tolerated and augments hemoglobin F and hemoglobin levels in patients with beta thalassemia intermedia. Blood 2010, 116:4280.
18. Kutlar A., Ataga K.I., Reid M., Blair-Britt L.A., Vichinsky E., Neumayr L., Labotka R.J., Glass J., Small-WIlliams A., Keefer J., Shen L., Boosalis M.S., Thomson A., Bobbitt P., Wallis W., Johnson E., Berenson R.J., Perrine S.P. Phase 1/2 clinical trial of HQK-1001, an oral fetal hemoglobin stimulant, in sickle cell anemia [abstract]. Blood 2010, 116:943.
19. Charache S., Terrin M.L., Moore R.D., Dover G.J., Barton F.B., Eckert S.V., McMahon R.P., Bonds D.R. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N. Engl. J. Med. 1995, 332:1317-1322.
20. Steinberg M.H. Clinical trials in sickle cell disease: adopting the combination chemotherapy paradigm. Am. J. Hematol. 2008, 83:1-3.
21. Perrine S.P., Faller D.V. Butyrate-induced reactivation of the fetal globin genes: a molecular treatment for the beta-hemoglobinopathies. Experientia 1993, 49:133-137.
22. Pace B.S., White G.L., Dover G.J., Boosalis M.S., Faller D.V., Perrine S.P. Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo. Blood 2002, 100:4640-4648.
23. Centis F., Tabellini L., Lucarelli G., Buffi O., Tonucci P., Persini B., Annibali M., Emiliani R., Iliescu A., Rapa S., Rossi R., Ma L., Angelucci E., Schrier S.L. The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with beta-thalassemia major. Blood 2000, 96:3624-3629.
24. Testa U. Apoptotic mechanisms in the control of erythropoiesis. Leukemia 2004, 18:1176-1199.
25. Yuan J., Angelucci E., Lucarelli G., Aljurf M., Snyder L.M., Kiefer C.R., Ma L., Schrier S.L. Accelerated programmed cell death (apoptosis) in erythroid precursors of patients with severe beta-thalassemia (Cooley's anemia). Blood 1993, 82:374-377.
26. Pootrakul P., Sirankapracha P., Hemsorach S., Moungsub W., Kumbunlue R., Piangitjagum A., Wasi P., Ma L., Schrier S.L. A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in Thai patients with thalassemia. Blood 2000, 96:2606-2612.
27. Schrier S.L. Pathobiology of thalassemic erythrocytes. Curr. Opin. Hematol. 1997, 4:75-78.
28. Castaneda S., Boosalis M.S., Emery D., Thies A., Faller D.V., Perrine S.P. Enhancement of growth and survival and alterations in Bcl-family proteins in beta-thalassemic erythroid progenitors by novel short-chain fatty acid derivatives. Blood Cells Mol. Dis. 2005, 35:217-226.
29. Boosalis M.S., Bandyopadhyay R., Bresnick E.H., Pace B.S., Van DeMark K., Zhang B., Faller D.V., Perrine S.P. Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. Blood 2001, 97:3259-3267.
30. Mabaera R., West R.J., Conine S.J., Macari E.R., Boyd C.D., Engman C.A., Lowrey C.H. A cell stress signaling model of fetal hemoglobin induction: what doesn't kill red blood cells may make them stronger. Exp. Hematol. 2008, 36:1057-1072.
31. Constantoulakis P., Knitter G., Stamatoyannopoulos G. On the induction of fetal hemoglobin by butyrates: in vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5-AzaC and AraC. Blood 1989, 74:1963-1971.
32. Cao H., Stamatoyannopoulos G., Jung M. Induction of human gamma globin gene expression by histone deacetylase inhibitors. Blood 2004, 103:701-709.
33. Mork C.N., Faller D.V., Spanjaard R.A. A mechanistic approach to anticancer therapy: targeting the cell cycle with histone deacetylase inhibitors. Curr. Pharm. Des. 2005, 11:1091-1104.
34. Skarpidi E., Vassilopoulos G., Li Q., Stamatoyannopoulos G. Novel in vitro assay for the detection of pharmacologic inducers of fetal hemoglobin. Blood 2000, 96:321-326.
35. Bohacek R., Boosalis M.S., McMartin C., Faller D.V., Perrine S.P. Identification of novel small-molecule inducers of fetal hemoglobin using pharmacophore and 'PSEUDO' receptor models. Chem. Biol. Drug Des. 2006, 67:318-328.
36. Thorpe S.J., Thein S.L., Sampietro M., Craig J.E., Mahon B., Huehns E.R. Immunochemical estimation of haemoglobin types in red blood cells by FACS analysis. Br. J. Haematol. 1994, 87:125-132.
37. Mabaera R., Richardson C.A., Johnson K., Hsu M., Fiering S., Lowrey C.H. Developmental- and differentiation-specific patterns of human gamma- and beta-globin promoter DNA methylation. Blood 2007, 110:1343-1352.
38. Ou C.N., Rognerud C.L. Rapid analysis of hemoglobin variants by cation-exchange HPLC. Clin. Chem. 1993, 39:820-824.
39. Beauchemin H., Trudel M. Evidence for a bigenic chromatin subdomain in regulation of the fetal-to-adult hemoglobin switch. Mol. Cell. Biol. 2009, 29:1635-1648.
40. Perrine S.P., Dover G.H., Daftari P., Walsh C.T., Jin Y., Mays A., Faller D.V. Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin gene expression in vitro and in vivo. Br. J. Haematol. 1994, 88:555-561.
41. Mankidy R., Faller D.V., Mabaera R., Lowrey C.H., Boosalis M.S., White G.L., Castaneda S.A., Perrine S.P. Short-chain fatty acids induce gamma-globin gene expression by displacement of a HDAC3-NCoR repressor complex. Blood 2006, 108:3179-3186.
42. Ikuta T., Atweh G., Boosalis V., White G.L., Da Fonseca S., Boosalis M., Faller D.V., Perrine S.P. Cellular and molecular effects of a pulse butyrate regimen and new inducers of globin gene expression and hematopoiesis. Ann. N.Y. Acad. Sci. 1998, 850:87-99.
43. Ikuta T., Kan Y.W., Swerdlow P.S., Faller D.V., Perrine S.P. Alterations in protein-DNA interactions in the gamma-globin gene promoter in response to butyrate therapy. Blood 1998, 92:2924-2933.
44. Perrine S.P., Miller B.A., Faller D.V., Cohen R.A., Vichinsky E.P., Hurst D., Lubin B.H., Papayannopoulou T. Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia. Blood 1989, 74:454-459.
45. Perrine S.P., Rudolph A., Faller D.V., Roman C., Cohen R.A., Chen S.J., Kan Y.W. Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. Proc. Natl. Acad. Sci. U. S. A. 1988, 85:8540-8542.
46. Weinberg R.S., Ji X., Sutton M., Perrine S., Galperin Y., Li Q., Liebhaber S.A., Stamatoyannopoulos G., Atweh G.F. Butyrate increases the efficiency of translation of gamma-globin mRNA. Blood 2005, 105:1807-1809.
47. Little J.A., Dempsey N.J., Tuchman M., Ginder G.D. Metabolic persistence of fetal hemoglobin. Blood 1995, 85:1712-1718.
48. Perrine S.P., Greene M.F., Faller D.V. Delay in the fetal globin switch in infants of diabetic mothers. N. Engl. J. Med. 1985, 312:334-338.
49. Perrine S.P., Mankidy R., Boosalis M.S., Bieker J.J., Faller D.V. Erythroid Kruppel-like factor (EKLF) is recruited to the gamma-globin gene promoter as a co-activator and is required for gamma-globin gene induction by short-chain fatty acid derivatives. Eur. J. Haematol. 2009, 82:466-476.
50. Perrine S., Welch W.C., Keefer J., Downey R.L., Boosalis M.S., Case S., Faller D.V., Berenson R. Phase 1 clinical testing of HQK-1001, a novel oral fetal globin gene inducer [abstract]. Blood 2008, 112:130.