WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202850
Description: Tasidotin, also know as ILX-651, is an orally active synthetic microtubule-targeted derivative of the marine depsipeptide dolastatin-15, is currently undergoing clinical evaluation for cancer treatment. Tasidotin inhibited proliferation of MCF7/GFP breast cancer cells with an IC(50) of 63 nmol/L and inhibited mitosis with an IC(50) of 72 nmol/L in the absence of detectable effects on spindle microtubule polymer mass. Tasidotin inhibited the polymerization of purified tubulin into microtubules weakly (IC(50) approximately 30 micromol/L).
MedKoo Cat#: 202850
Name: Tasidotin hydrochloride
Chemical Formula: C32H59ClN6O5
Molecular Weight: 643.3
Elemental Analysis: C, 59.75; H, 9.24; Cl, 5.51; N, 13.06; O, 12.44
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Synonym: ILX 651, ILX651, ILX-651, Tasidotin hydrochloride
IUPAC/Chemical Name: (S)-N-(tert-butyl)-1-((S)-1-((S)-2-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methylbutanoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxamide hydrochloride
InChi Key: OOKIODJYZSVHDO-QMYFOHRPSA-N
InChi Code: InChI=1S/C32H58N6O5.ClH/c1-19(2)24(33-28(40)25(20(3)4)35(10)11)30(42)36(12)26(21(5)6)31(43)38-18-14-16-23(38)29(41)37-17-13-15-22(37)27(39)34-32(7,8)9;/h19-26H,13-18H2,1-12H3,(H,33,40)(H,34,39);1H/t22-,23-,24-,25-,26-;/m0./s1
SMILES Code: O=C([C@H]1N(C([C@H]2N(C([C@@H](N(C)C([C@@H](NC([C@@H](N(C)C)C(C)C)=O)C(C)C)=O)C(C)C)=O)CCC2)=O)CCC1)NC(C)(C)C.[H]Cl
Appearance: 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: >5 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).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 643.3 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Kurtzberg LS, Roth SD, Bagley RG, Rouleau C, Yao M, Crawford JL, Krumbholz RD, Schmid SM, Teicher BA. Bone marrow CFU-GM and human tumor xenograft efficacy of three tubulin binding agents. Cancer Chemother Pharmacol. 2009 Oct;64(5):1029-38. Epub 2009 Mar 10. PubMed PMID: 19277662.
2: Kilburn LB, Bonate PL, Blaney SM, McGuffey L, Nuchtern JG, Dauser R, Thompson P, Gibson BW, Berg SL. Plasma and cerebrospinal fluid pharmacokinetics of tasidotin (ILX-651) and its metabolites in non-human primates. Cancer Chemother Pharmacol. 2009 Jul;64(2):335-40. Epub 2008 Nov 29. PubMed PMID: 19043710.
3: Bai R, Edler MC, Bonate PL, Copeland TD, Pettit GR, LudueÃ±a RF, Hamel E. Intracellular activation and deactivation of tasidotin, an analog of dolastatin 15: correlation with cytotoxicity. Mol Pharmacol. 2009 Jan;75(1):218-26. Epub 2008 Oct 16. PubMed PMID: 18927208; PubMed Central PMCID: PMC2635573.
4: Bonate PL, Beyerlein D, Crawford J, Roth S, Krumbholz R, Schmid S. Pharmacokinetics in mice implanted with xenografted tumors after intravenous administration of tasidotin (ILX651) or its carboxylate metabolite. AAPS J. 2007 Dec 14;9(3):E378-87. PubMed PMID: 18170985; PubMed Central PMCID: PMC2751490.
5: Garg V, Zhang W, Gidwani P, Kim M, Kolb EA. Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5446-54. PubMed PMID: 17875774.
6: Ray A, Okouneva T, Manna T, Miller HP, Schmid S, Arthaud L, Luduena R, Jordan MA, Wilson L. Mechanism of action of the microtubule-targeted antimitotic depsipeptide tasidotin (formerly ILX651) and its major metabolite tasidotin C-carboxylate. Cancer Res. 2007 Apr 15;67(8):3767-76. PubMed PMID: 17440090.
7: Mita AC, Hammond LA, Bonate PL, Weiss G, McCreery H, Syed S, Garrison M, Chu QS, DeBono JS, Jones CB, Weitman S, Rowinsky EK. Phase I and pharmacokinetic study of tasidotin hydrochloride (ILX651), a third-generation dolastatin-15 analogue, administered weekly for 3 weeks every 28 days in patients with advanced solid tumors. Clin Cancer Res. 2006 Sep 1;12(17):5207-15. PubMed PMID: 16951240.
8: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Jul-Aug;28(6):379-412. PubMed PMID: 16894408.
9: Cunningham C, Appleman LJ, Kirvan-Visovatti M, Ryan DP, Regan E, Vukelja S, Bonate PL, Ruvuna F, Fram RJ, Jekunen A, Weitman S, Hammond LA, Eder JP Jr. Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors. Clin Cancer Res. 2005 Nov 1;11(21):7825-33. PubMed PMID: 16278405.
10: Ebbinghaus S, Rubin E, Hersh E, Cranmer LD, Bonate PL, Fram RJ, Jekunen A, Weitman S, Hammond LA. A phase I study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously daily for 5 consecutive days every 3 weeks in patients with advanced solid tumors. Clin Cancer Res. 2005 Nov 1;11(21):7807-16. PubMed PMID: 16278403.
11: Rasila KK, Verschraegen C. Tasidotin HCl (Genzyme). Curr Opin Investig Drugs. 2005 Jun;6(6):631-8. Review. PubMed PMID: 15988915.
Tasidotin HCl (tasidotin) is a novel, third generation, synthetic, water-soluble, dolastatin pentapeptide analog of dolastatin 15. Tasidotin is metabolically stable and orally bioavailable. Tasidotin has a unique mechanism of action that appears to differ from other microtubule stabilizers such as taxanes and epothilones and tubulin inhibitors such as Vinca alkaloids. Mechanistically, tasidotin is believed to inhibit cell proliferation by suppressing spindle microtubule dynamics through a reduction of the shortening rate, reduction of the switching frequency from growth to shortening and reduction of the time microtubules grow. (from Genzyme Oncolongy).
ILX65 has a unique mechanism of action. At low concentrations ILX651 inhibits microtubule nucleation or elongation which likely disrupts mitotic spindle formation and mitosis. Chemical modification gave ILX651 a potentially enhanced therapeutic window over previous dolastatins. Cardiovascular toxicity characteristic of the dolastatins was not seen in ILX651 phase I studies. ILX651 is well-tolerated in this melanoma population. Follow-up of response and overall survival continue. Consideration should be given to further study of ILX651 in combination with other agents in the treatment of melanoma.