Back to products

Browse products

Approved anticancer agents

Anticancer agents in trials

Anticancer agents in preclinical trials

Anticancer molecular libraries

MedKoo product information:

Taltobulin

Description of taltobulin: Taltobulin (formerly HTI-286) is a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. HTI-286 was a potent inhibitor of proliferation (mean IC50 = 2.5 ± 2.1 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine.

Current developer:   Wyeth Inc.

Taltobulin (HTI-286, SPA-110) is a novel antimitotic agent that inhibits the polymerization of tubulin, disrupts microtubule dynamics in cells and induces mitotic arrest and apoptosis. Relative to the antimicrotubule drugs in use, taltobulin exhibits significantly less interaction with the multidrug resistance protein (P-glycoprotein) and is effective in inhibiting human tumor xenografts in nude mouse models where paclitaxel and vincristine are ineffective. Taltobulin administered i.v. or p.o. in saline inhibits the growth of numerous human tumors without the side effects associated with formulations. Taltobulin is in clinical development. (from drugs of the future).

 1: Niu C, Ho DM, Zask A, Ayral-Kaloustian S. Absolute configurations of tubulin inhibitors taltobulin (HTI-286) and HTI-042 characterized by X-ray diffraction analysis and NMR studies. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1535-8. Epub 2010 Jan 20. PubMed PMID: 20137930.

2: Matsui Y, Hadaschik BA, Fazli L, Andersen RJ, Gleave ME, So AI. Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Mol Cancer Ther. 2009 Aug;8(8):2402-11. Epub 2009 Jul 22. PubMed PMID: 19625496.

3: Singh R, Sharma M, Joshi P, Rawat DS. Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17. Review. PubMed PMID: 18690825.

4: Balasubramanian R, Raghavan B, Steele JC, Sackett DL, Fecik RA. Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives. Bioorg Med Chem Lett. 2008 May 1;18(9):2996-9. Epub 2008 Mar 20. PubMed PMID: 18411048.

5: Hadaschik BA, Adomat H, Fazli L, Fradet Y, Andersen RJ, Gleave ME, So AI. Intravesical chemotherapy of high-grade bladder cancer with HTI-286, a synthetic analogue of the marine sponge product hemiasterlin. Clin Cancer Res. 2008 Mar 1;14(5):1510-8. PubMed PMID: 18316576.

6: Hadaschik BA, Ettinger S, Sowery RD, Zoubeidi A, Andersen RJ, Roberge M, Gleave ME. Targeting prostate cancer with HTI-286, a synthetic analog of the marine sponge product hemiasterlin. Int J Cancer. 2008 May 15;122(10):2368-76. PubMed PMID: 18240145.

7: Vashist YK, Tiffon C, Stoupis C, Redaelli CA. Inhibition of hepatic tumor cell proliferation in vitro and tumor growth in vivo by taltobulin, a synthetic analogue of the tripeptide hemiasterlin. World J Gastroenterol. 2006 Nov 14;12(42):6771-8. PubMed PMID: 17106924.

8: Milton MJ, Thomas Williamson R, Koehn FE. Mapping the bound conformation and protein interactions of microtubule destabilizing peptides by STD-NMR spectroscopy. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4279-82. Epub 2006 Jun 12. PubMed PMID: 16765596.

9: Hari M, Loganzo F, Annable T, Tan X, Musto S, Morilla DB, Nettles JH, Snyder JP, Greenberger LM. Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules. Mol Cancer Ther. 2006 Feb;5(2):270-8. PubMed PMID: 16505100.

10: Zask A, Kaplan J, Musto S, Loganzo F. Hybrids of the hemiasterlin analogue taltobulin and the dolastatins are potent antimicrotubule agents. J Am Chem Soc. 2005 Dec 21;127(50):17667-71. PubMed PMID: 16351096.

11: Ravi M, Zask A, Rush TS 3rd. Structure-based identification of the binding site for the hemiasterlin analogue HTI-286 on tubulin. Biochemistry. 2005 Dec 6;44(48):15871-9. PubMed PMID: 16313189.

12: Nunes M, Kaplan J, Wooters J, Hari M, Minnick AA Jr, May MK, Shi C, Musto S, Beyer C, Krishnamurthy G, Qiu Y, Loganzo F, Ayral-Kaloustian S, Zask A, Greenberger LM. Two photoaffinity analogues of the tripeptide, hemiasterlin, exclusively label alpha-tubulin. Biochemistry. 2005 May 10;44(18):6844-57. PubMed PMID: 15865430.

13: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Oct;26(8):639-63. PubMed PMID: 15605126.

14: Poruchynsky MS, Kim JH, Nogales E, Annable T, Loganzo F, Greenberger LM, Sackett DL, Fojo T. Tumor cells resistant to a microtubule-depolymerizing hemiasterlin analogue, HTI-286, have mutations in alpha- or beta-tubulin and increased microtubule stability. Biochemistry. 2004 Nov 9;43(44):13944-54. PubMed PMID: 15518543.

15: Loganzo F, Hari M, Annable T, Tan X, Morilla DB, Musto S, Zask A, Kaplan J, Minnick AA Jr, May MK, Ayral-Kaloustian S, Poruchynsky MS, Fojo T, Greenberger LM. Cells resistant to HTI-286 do not overexpress P-glycoprotein but have reduced drug accumulation and a point mutation in alpha-tubulin. Mol Cancer Ther. 2004 Oct;3(10):1319-27. PubMed PMID: 15486199.

16: Yamashita A, Norton EB, Kaplan JA, Niu C, Loganzo F, Hernandez R, Beyer CF, Annable T, Musto S, Discafani C, Zask A, Ayral-Kaloustian S. Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5317-22. PubMed PMID: 15454219.

17: Zask A, Birnberg G, Cheung K, Kaplan J, Niu C, Norton E, Suayan R, Yamashita A, Cole D, Tang Z, Krishnamurthy G, Williamson R, Khafizova G, Musto S, Hernandez R, Annable T, Yang X, Discafani C, Beyer C, Greenberger LM, Loganzo F, Ayral-Kaloustian S. Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-eny l]- N(1),3-dimethyl-L-valinamide (HTI-286). J Med Chem. 2004 Sep 9;47(19):4774-86. PubMed PMID: 15341492.

18: Lo MC, Aulabaugh A, Krishnamurthy G, Kaplan J, Zask A, Smith RP, Ellestad G. Probing the interaction of HTI-286 with tubulin using a stilbene analogue. J Am Chem Soc. 2004 Aug 18;126(32):9898-9. PubMed PMID: 15303845.

19: Zask A, Birnberg G, Cheung K, Kaplan J, Niu C, Norton E, Yamashita A, Beyer C, Krishnamurthy G, Greenberger LM, Loganzo F, Ayral-Kaloustian S. D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4353-8. PubMed PMID: 15261301.

20: Niu C, Smith D, Zask A, Loganzo F, Discafani C, Beyer C, Greenberger L, Ayral-Kaloustian S. Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4329-32. PubMed PMID: 15261296.

21: Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D, Frost P, Loganzo F, Greenberger L, Barkoczy J, Pettit GR, Smith AB 3rd, Gurulingappa H, Khan S, Parmigiani G, Kinzler KW, Zhou S, Vogelstein B. Targeting vascular and avascular compartments of tumors with C. novyi-NT and anti-microtubule agents. Cancer Biol Ther. 2004 Mar;3(3):326-37. Epub 2004 Mar 12. PubMed PMID: 14739784.

22: Krishnamurthy G, Cheng W, Lo MC, Aulabaugh A, Razinkov V, Ding W, Loganzo F, Zask A, Ellestad G. Biophysical characterization of the interactions of HTI-286 with tubulin heterodimer and microtubules. Biochemistry. 2003 Nov 25;42(46):13484-95. PubMed PMID: 14621994.

23: Loganzo F, Discafani CM, Annable T, Beyer C, Musto S, Hari M, Tan X, Hardy C, Hernandez R, Baxter M, Singanallore T, Khafizova G, Poruchynsky MS, Fojo T, Nieman JA, Ayral-Kaloustian S, Zask A, Andersen RJ, Greenberger LM. HTI-286, a synthetic analogue of the tripeptide hemiasterlin, is a potent antimicrotubule agent that circumvents P-glycoprotein-mediated resistance in vitro and in vivo. Cancer Res. 2003 Apr 15;63(8):1838-45. PubMed PMID: 12702571.