Taltobulin
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202760

CAS#: 228266-40-8

Description: Taltobulin, also known as HTI-286 and SPA-110, 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.


Price and Availability

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Price

1g
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Size
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2g
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Size
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5g
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Taltobulin is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202760
Name: Taltobulin
CAS#: 228266-40-8
Chemical Formula: C27H43N3O4
Exact Mass: 473.32536
Molecular Weight: 473.65
Elemental Analysis: C, 68.47; H, 9.15; N, 8.87; O, 13.51


Synonym: HTI-286, HTI 286, HTI286, SPA-110, SPA110, SPA 110, Taltobulin

IUPAC/Chemical Name: (S,E)-4-(((S)-3,3-dimethyl-1-((S)-3-methyl-2-(methylamino)-3-phenylbutanamido)-1-oxobutan-2-yl)(methyl)amino)-2,5-dimethylhex-2-enoic acid

InChi Key: ORIMBSMIPMEOFU-PSRNMDMQSA-N

InChi Code: InChI=1S/C27H43N3O4/c1-17(2)20(16-18(3)25(33)34)30(10)22(26(4,5)6)24(32)29-23(31)21(28-9)27(7,8)19-14-12-11-13-15-19/h11-17,20-22,28H,1-10H3,(H,33,34)(H,29,31,32)/b18-16+/t20-,21-,22-/m1/s1

SMILES Code: CC(C)(C)[C@@H](C(NC([C@H](C(C)(C)C1=CC=CC=C1)NC)=O)=O)N([C@@H](C(C)C)/C=C(C(O)=O)\C)C


Technical Data

Appearance:
Light yellow to yellow solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

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).


References

1: Niu C, Ho DM, Williamson RT, 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. doi: 10.1016/j.bmcl.2010.01.047. Epub 2010 Jan 20. Erratum in: Bioorg Med Chem Lett. 2012 Mar 1;22(5):2131. Williamson, Robert Thomas [added]. 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. doi: 10.1158/1535-7163.MCT-09-0148. Epub 2009 Jul 22. PubMed PMID: 19625496.

3: 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. doi: 10.1158/1078-0432.CCR-07-4475. PubMed PMID: 18316576.

4: 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. doi: 10.1002/ijc.23406. PubMed PMID: 18240145.

5: 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.

6: 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.

7: 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.

8: 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.

9: 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.

10: 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.

11: 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.

12: 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.

13: 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.