Dr. Bin Su

Dr.Su's research focuses on anti-cancer and anti-trypanosome drug development

1. Hsp27 inhibitor development. The expression of heat shock proteins (Hsp) is increased under lethal conditions, which is a typical response when cancer cells are stressed by chemotherapies. Hsp27, a small heat shock protein, shows a very tight correlation with anti-cancer drug resistance. Its over-expression enhances the survival of mammalian cells exposed to anti-cancer agents. Through biotinylated small molecular probe, affinity chromatography and proteomic approaches, our lab identified small molecule compound binding to Hsp27. Systematic ligand based optimization dramatically increased the cell proliferation inhibition and apoptosis inducing activities of the compounds. Drug candidates developed in this project have been tested by the Developmental Therapeutic Program at the National Cancer Institute for screening against 60 human cancer cell lines, representing leukemia, melanoma, and cancers of the lung, colon, CNS, ovary, renal, prostate, and breast. Our lab currently further optimizes the drug candidates to improve the ADME profile.

2. Selective tubulin inhibitors for the treatment of African trypanosomiasis. By collaborating with Dr. Bibo Li at BGES, we screened the small molecule compound library generated in our lab with T.brucei which is the parasite causing African sleep disease. Interestingly, we identified several lead compounds that selectively inhibited the parasite growth, and did not affect the mammalian cell proliferation. These compounds selectively interfere with parasite tubulin, and do not block the mammalian tubulin function. There is a great potential to develop cheap, easy make drug candidates for the treatment of the parasite disease.

Fatma Salem
Ph.D. Student

As a faculty member at CSU

63. Yaxin Li, Cody Orahoske, Fatma Salem, Aidyn Johnson, Christia Tannous, Lucas Devole, Wenjing Zhang, Justin D. Lathia, Bingcheng Wang, and Bin Su*. Lead Optimization of Androgen Receptor-HSP27 Disrupting Agents in Glioblastoma, J. Med. Chem. 2023, 66, 8, 5567¨C5583

62. Orahoske CM, Afrin M, Li Y, Hanna J, Marbury M, Li B, Su B*. Identification of Prazosin as a Potential Flagellum Attachment Zone 1(FAZ1) Inhibitor for the Treatment of Human African Trypanosomiasis. ACS Infect Dis. 2022 Aug 12;8(8):1711-1726.

?????61. Li Y, Orahoske CM, Urmetz SM, Zhang W, Huang Y, Gan C, Su B*. Identification of estrogen receptor down-regulators for endocrine resistant breast cancer. J Steroid Biochem Mol Biol. 2022 Aug 4;224:106162.

60. Bobba V, Li Y, Afrin M, Dano R, Zhang W, Li B, Su B. Synthesis and biological evaluation of imidamide analogs as selective anti-trypanosomal agents. Bioorg Med Chem. 2022 May 1;61:116740. doi: 10.1016/j.bmc.2022.116740. Epub 2022 Apr 4. PubMed PMID: 35396128; PubMed Central PMCID: PMC9074797.

59. Li Y, Dano R, Li C, Zhang W, Lathia JD, Wang B, Su B. Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC-MS/MS. Biomed Chromatogr. 2022 Jan 3;:e5310

58. Li Y, Orahoske CM, Dano R, Zhang W, Li B, Su B*. Pharmacokinetic study of an anti-trypanosome agent with different formulations and administration routes in mice by HPLC-MS/MS. Biomed Chromatogr. 2021 Oct;35(10):e5169.

57. Li Y, Orahoske CM, Geldenhuys WJ, Bhattarai A, Sabbagh A, Bobba V, Salem FM, Zhang W, Shukla GC, Lathia JD, Wang B, Su B. Small-Molecule HSP27 Inhibitor Abolishes Androgen Receptors in Glioblastoma. J Med Chem. 2021 Feb 11;64(3):1570-1583.
56. Orahoske CM, Li Y, Petty A, Salem FM, Hanna J, Zhang W, Su B, Wang B. Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth, Bioorg Med Chem. 2020 Sep 15;28(18):115656.
55. Zhao A, Li Y, Orahoske CM, Schnur B, Sabbagh A, Zhang W, Li B, Su B. Lead optimization of selective tubulin inhibitors as anti-trypanosomal agents. Bioorg Med Chem. 2019 Apr 15;27(8):1517-1528.
54. Zhong B, Li Y, Idippily N, Petty A, Su B, Wang B. A quantitative LC-MS/MS method for determination of a small molecule agonist of EphA2 in mouse plasma and brain tissue. Biomed Chromatogr. 2019 Apr;33(4):e4461.
53. Zhao A, Zheng Q, Orahoske CM, Idippily ND, Ashcraft MM, Quamine A, Su B. Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein. Bioorg Med Chem Lett. 2018 Feb 15;28(4):727-731.
52. Aaron Petty, Nethrie Idippily, Viharika Bobba, Werner J. Geldenhuys, Bo Zhong, Bin Su, Bingcheng Wang. Design and Synthesis of Small Molecule Agonists of EphA2 Receptor, European Journal of Medicinal Chemistry, 2018, Jan 1;143:1261-1276.
51. Nethrie D. Idippily, Qiaoyun Zheng, Chunfang Gan, Aicha Quamine, Morgan M. Ashcraft, Bo Zhong, Bin Su. Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone protein. Bioorg Med Chem Lett. 2017 Jun 1;27(11):2292-2295
50. Viharika Bobba, Vishal Nanavaty, Nethrie D. Idippily, Anran Zhao, Bibo Li, Bin Su. Synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosome agents. Bioorganic and Medicinal Chemistry, 2017 Jun 15;25(12):3215-3222
49. Lama R, Gan C, Idippily N, Bobba V, Danielpour D, Montano M, Su B. HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen. J Steroid Biochem Mol Biol. 168 (2017) 91?101
48. Idippily ND, Gan C, Orefice P, Peterson J, Su B. Synthesis of Vorinostat and cholesterol conjugate to enhance the cancer cell uptake selectivity. Bioorg Med Chem Lett. 2017 Feb 15;27(4):816-820.
47. Ketchart W, Yeh IJ, Zhou H, Thiagarajan PS, Lathia J, Reizes O, Exner A, Su B, Montano MM. Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism. Cancer Lett. 2016 Aug 28;379(1):60-9.
46. Zhong B, Vatolin S, Idippily ND, Lama R, Alhadad LA, Reu FJ, Su B. Structural optimization of non-nucleoside DNA methyltransferase inhibitor as anti-cancer agent. Bioorg Med Chem Lett.2016 Feb 15; 26(4): 1272-5.
45. Vishal Nanavaty, Rati lama, Ranjodh Sandhu, Bo Zhong, Daniel Kulman, Viharika Bobba, Anran Zhao, Bibo Li, Bin Su, Orally active and selective tubulin inhibitors as anti-trypanosome agents, Plos one 2016 Jan 15;11(1):e0146289.
44. Snigdha Chennamaneni, Chunfang Gan, Rati Lama, Bo Zhong, Bin Su, Indomethacin derivatives as tubulin stabilizers to inhibit cancer cell proliferation, Bioorg Med Chem. 2016, 24, 277-285.
43. Voggu RR, Alagandula R, Zhou X, Su B, Zhong B, Guo B. A rapid LC-MS/MS method for quantification of CSUOH0901, a novel antitumor agent, in rat plasma. Biomed Chromatogr. 2015 May;29(5):797-802.
42. Ramakrishna R. Voggu, Xiang Zhou, Bin Su, Baochuan Guo. A Simple and Rapid LC-MS/MS Method for the Determination of BMCL26 a Novel Anti-Parasitic Agent in Rat Plasma. Journal of analytical & bioanalytical techniques. 2015, 6:265,
41. Zhang C, Zhong B, Yang S, Pan L, Yu S, Li Z, Li S, Su B, Meng X. Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents. Bioorg Med Chem. 2015 Jul 1;23(13):3774-80.

40. Rati Lama; Bo Zhong; Daniel G Kulman; Bin Su. Bioassay guided identification of small chaperone proteins ¦Á-crystallin and Hsp27 inhibitors from Copaiba oil. Phytochemistry Letters 2014, (10) 65-75.

38. Bo Zhong, Rati Lama, Bibo Li, Bin Su. Lead optimization of dual tubulin and Hsp27 inhibitors. European journal of medicinal chemistry 2014, 80, 243-253.

37. Zhong B, Lama R, Ketchart W, Montano MM, Su B. Lead optimization of HMBA to develop potent HEXIM1 inducers. Bioorg Med Chem Lett. 2014, (24), 1410-1413

36. Zhong B, Chennamaneni S, Lama R, Yi X, Geldenhuys WJ, Pink JJ, Dowlati A, Xu Y, Zhou A, Su B. Synthesis and Anti-Cancer Mechanism Investigation of Dual Hsp27 and Tubulin Binders. Journal of Medicinal Chemistry, 2013, 56 (13), 5306?5320
35. Lama R, Zhang L, Naim JM, Williams J, Zhou A, Su B. Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing. Bioorg Med Chem. 2013, 21(4):922-31.
34. S. Chennamaneni, B. Zhong, R. Lama, B. Su, COX inhibitors Indomethacin and Sulindac derivatives as antiproliferative agents: synthesis, biological evaluation, and mechanism investigation, European Journal of Medicinal Chemistry, 2012, 56, 17-29.
33. Lama R, Sandhu R, Zhong B, Li B, Su B. Identification of selective tubulin inhibitors as potential anti-trypanosomal agents. Bioorg Med Chem Lett. 22 (2012) 5508?5516.
32. Yi X, Zhong B, Smith KM, Geldenhuys WJ, Feng Y, Pink JJ, Dowlati A, Xu Y, Zhou A, Su B. Identification of a class of novel tubulin inhibitors. Journal of Medicinal Chemistry, 2012 Apr 12;55(7):3425-35
31. Zhong B, Cai X, Chennamaneni S, Yi X, Liu L, Pink JJ, Dowlati A, Xu Y, Zhou A, Su B. FromCOX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation. European Journal of Medicinal Chemistry, 47 (2012) 432-444
30. Cai X, Zhong B, Su B, Xu S, Guo B. Development and validation of a rapid LC-MS/MS method for the determination of JCC76, a novel antitumor agent for breast cancer, in rat plasma and its application to a pharmacokinetics study. Biomed Chromatogr. 2012, 26:1118-1124
29. Zhong B, Lama R, Smith KM, Xu Y, Su B. Design and synthesis of a biotinylated probe of COX-2 inhibitor nimesulide analog JCC76. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5324-7.
28. Zhong B, Cai X, Yi X, Zhou A, Chen S, Su B. In vitro and in vivo effects of a cyclooxygenase-2 inhibitor nimesulide analog JCC76 in aromatase inhibitors-insensitive breast cancer cells. J Steroid Biochem Mol Biol. 2011 Aug;126(1-2):10-18.
27. Su B, Wong C, Hong Y, Chen S. Growth factor signaling enhances aromatase activity of breast cancer cells via post-transcriptional mechanisms. J Steroid Biochem Mol Biol. (2011), 123(3-5):101-108.
26. Su B, Cai X, Hong Y, Chen S. COX-2 inhibitor nimesulide analogs are aromatase suppressors in breast cancer cells. J Steroid Biochem Mol Biol. (2010),122(4):232-238.

As Postdoctoral Fellow at The Ohio State University and City of Hope Medical Center(2006-2009)
25. Brueggemeier RW, Su B, Darby MV, Sugimoto Y. Selective regulation of aromatase expression for drug discovery. J. Steroid Biochem. Mol. Biol. (2010), 118(4-5), 207-210.
24. Su B, Chen S. Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cell. Bioorganic & Medicinal Chemistry Letters (2009), 19(23):6733-6735
23. Chen B*, Su B*, Chen S.   A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms.    Biochemical Pharmacology (2009), 77(12), 1787-1794. * equal contribution
22. Balunas MJ, Su B,  Riswan S, Fong HHS,Brueggemeier RW Pezzuto JM, Kinghorn AD. Isolation and Characterization of Aromatase Inhibitors from Brassaiopsis glomerulata (Araliaceae). Phytochemistry Letters (2009),  2(1),  29-33
21. Su B, Tian R, Darby MV, Brueggemeier RW. Novel Sulfonanilide Analogs Decrease Aromatase Activity in Breast Cancer Cells: Synthesis, Biological Evaluation and Ligand Based Pharmacophore Identification. J Med Chem. (2008), 51(5), 1126-1135
20. Su B, Darby MV, Brueggemeier RW. Synthesis and Biological Evaluation of Novel Sulfonanilides as Antiproliferative Agents for Breast Cancer. J Com Chem. (2008), 10(3),  475-483
19. Su B, Mershon SM, Stonerock LA, Curley RW Jr, Brueggemeier RW. 4-Hydroxyphenylretinamide (4HPR) derivatives regulate aromatase activity and expression in breast cancer cells. J. Steroid Biochem. Mol. Biol. (2008), 109, 40?46
18. Balunas MJ, Su B, Brueggemeier RW, and Kinghorn AD. Natural Products as Aromatase Inhibitors (review). Anti-Cancer Agents in Medicinal Chemistry. 2008, 8(6), 646-682.

As Graduate Student at The Ohio State University(2002-2006)
17. Su B, Diaz-Cruz ES, Landini S, Brueggemeier RW. Suppression of aromatase expression in human breast cells by novel sulfonanilides occurs via inhibition of intracellular signaling pathways. Steroids (2008), 73, 104-111
16. Balunas MJ, Su B, Brueggemeier RW, and Kinghorn AD. Xanthones from the Botanical Dietary Supplement Mangosteen (Garcinia mangostana) with Aromatase Inhibitory Activity. J Nat Prod. (2008), 71(7),  1161-1166.
15. Brueggemeier RW, Su B, Sugimoto Y, D¨ªaz-Cruz ES, Davis DD. Aromatase and COX in breast cancer: enzyme inhibitors and beyond. J. Steroid Biochem. Mol. Biol.(2007), 106(1-5), 16-23
14. Su B, Landini S, Davis DD, Brueggemeier RW. Synthesis and Biological Evaluation of Selective Aromatase Expression Regulators in Breast Cancer Cells. J Med Chem. (2007), 50(7), 1635-1644
13. Su B, Diaz-Cruz ES, Landini S, Brueggemeier RW.  Novel sulfonanilide analogues suppress aromatase expression and activity in breast cancer cells independent of COX-2 inhibition. J Med Chem. (2006), 49(4), 1413-1419.
12. Balunas MJ, Su B, Landini S, Brueggemeier RW, Kinghorn AD. Interference by Naturally Occurring Fatty Acids in a Noncellular Enzyme-Based Aromatase Bioassay. J Nat Prod. (2006), 69(4), 700-703.
11. Su B, Hackett JC, Diaz-Cruz ES, Kim YW, Brueggemeier RW. Lead optimization of 7-benzyloxy 2-(4'-pyridylmethyl)thio isoflavone aromatase inhibitors. Bioorg Med Chem. (2005), 13(23), 6571-6577.
10. Hackett JC, Kim YW, Su B, Brueggemeier RW. Synthesis and characterization of azole isoflavone inhibitors of aromatase. Bioorg Med Chem. (2005), 13(12), 4063-4070.

As Graduate Student and Research Associate at Peking University(1999-2002)
9. Li Q, Su B, Li H, Meng XB, Cai MS, Li ZJ, Zhou RL, Suo TL.  Synthesis and potential antimetastatic activity of monovalent and divalent ?-D-galactopyranosyl-(1?4)-2- acetamido-2-deoxy-d-glucopyranosides.    Carbohydrate Res. (2003), 338(3), 207-217.  
8. Li Q, Li H, Li Q, Lou QH, Su B, Cai MS, Li ZJ.  Synthesis of a spacer-armed disulfated tetrasaccharide of SB1a, a carbohydrate hapten associated with human hepatocellular carcinoma. Carbohydrate Res. (2002), 337(21-23), 1929-1934.  
7. Su B, Li H, Cai MS, Li ZJ.  On the mechanism of condensation between 5-amino-4, 6-dichloro-2-methylpyrimidine and 1-acetyl-2-imidazolin-2-one. Chinese Chemical Letters (2002), 13(3), 207-210.  
6. Niu LM, Li Q, Su B, Li H, Cai MS, Li ZJ.  Synthesis of RGD-aPEG-lactoside, a potential anti-metastasis glycoconjugate.    Journal of Chinese Pharmaceutical Sciences (2002), 11(3), 68-72.  
5. Li Q, Li Q, Li H, Su B, Lou QH, Cai MS, Li ZJ.  Studies on carbohydrates. LIV. Studies on the synthesis of an analogue of SM3, a cancer associated carbohydrate antigen of HCC.    Huaxue Xuebao (2002), 60(8), 1473-1478.  
4. Li Q, Li H, Su B, Meng XB, Cai MS, Li ZJ.  The purification of glucose type glycosyl nitrate and the synthesis of spacer-armed N-acetyllactosamines and their dimers.    Chinese Chemical Letters (2002), 13(4), 303-305.  
3. Lu YP, Su B, Li Q, Li H, Cai MS, Li ZJ.  Synthesis of a divalent O-glycoside of related trisaccharide epitope involved in the hyperacute rejection of xenotransplantation.    Huaxue Xuebao (2002), 60(2), 360-366.  
2. Su B, Cheng TM, Li ZJ.  Improved synthesis of 4,6-dichloro-2-methyl-5-[(1-acetylimidazolidin-2-ylidene)amino]pyrimidine.    Zhongguo Yiyao Gongye Zazhi  (2001),  32(8),  373-374.  
1. Li Q, Li H, Su B, Meng XB, Cai MS, Li ZJ.  Separation of 4-galactosyl-2-azido-2-deoxymannose 1-nitrate and corresponding glucose type isomer by glycosylation.    Beijing Daxue Xuebao, Yixueban (2001), 33(3), 270-273.  

Patents
1. Su B, Zhou A, Xu Y. Amide Derivatives of Benzene-Sulfonanilide, Pharmaceutical Composition Thereof and Method for Cancer Treatment Using the Same. US 12/906,315. PCT / WO 2012/054417 A1.
2. Brueggemeier RW, Su B, Diaz-Cruz ES, Landini S. Sulfonanilide Analogs as Selective Aromatase Modulators (SAMs). PCT Int. Appl.  (2007), 67pp. CODEN: PIXXD2  WO  2007120379  A2  20071025  CAN 147:502104  AN 2007:1207552
3. Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD, Breast Cancer Chemoprevention and Chemotherapy using the Botanical Dietary Supplement Garcinia mangostana L. (Mangosteen) as an Aromatase Inhibitor. PCT Int. Appl.  (2009),     CODEN: PIXXD2  WO  2009011811  A1  20090122  AN 2009:85491