Padoporfin (Tookad)

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

MedKoo CAT#: 202185

CAS#: 274679-00-4

Description: Padoporfin is a new faster acting photosensitiser that clears within a few hours. In normal rat colon, after sensitisation with an intravenous bolus of Padoporfin, light was delivered to a single point on the mucosa and the extent of PDT necrosis measured 3 days later. The lesion diameter was greatest with the highest dose of drug and light and the shortest drug light interval (DLI), falling rapidly with a DLI more than 5 min. In tumours transplanted subcutaneously or into the colon, the extent of necrosis only started falling with a DLI greater than 15 min, suggesting a possible window for tumour selectivity. Histological changes 3 days after PDT were essentially the same as those seen with longer acting photosensitisers. The lesion dimensions were comparable to the largest ones seen with other photosensitisers under similar experimental conditions. WST09 is a powerful photosensitiser that produces PDT effects similar to those seen with longer acting drugs, but with the major advantages of a short DLI and rapid clearance (source: Int J Cancer. 2006 Jan 15;118(2):477-82.).


Price and Availability

Size
Price

Size
Price

Size
Price

Padoporfin, is not in stock. We temporally do not accept order of custom synthesis for this product since raw material is not available. We will list price if this product is in stock in the future.


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 202185
Name: Padoporfin (Tookad)
CAS#: 274679-00-4
Chemical Formula: C35H36N4O6Pd
Exact Mass: 714.16697
Molecular Weight: 715.1
Elemental Analysis: C, 58.79; H, 5.07; N, 7.83; O, 13.42; Pd, 14.88


Synonym: WST-09; WST09; WST 09; Pd-Bacteriopheophorbide; Pd-BPheid, Tookad.

IUPAC/Chemical Name: Hydrogen [(22R,7R,8R,17S,18S)-3-[12-acetyl-7-ethyl-22-(methoxycarbonyl)-3,8,13,17-tetramethyl-21-oxo-21,22,7,8,17,18-hexahydrocyclopenta[at]porphyrin-18-yl]propanoato(3-)-kappaN21,kappaN22,kappaN23,kappaN24]palladate(1-).

InChi Key: GPIVNYFDHQDTDZ-GDUCSYRESA-L

InChi Code: InChI=1S/C35H38N4O6.Pd/c1-8-19-14(2)21-13-26-28(18(6)40)16(4)23(37-26)11-22-15(3)20(9-10-27(41)42)32(38-22)30-31(35(44)45-7)34(43)29-17(5)24(39-33(29)30)12-25(19)36-21;/h11-15,19-20,31H,8-10H2,1-7H3,(H3,36,37,38,39,40,41,42,43);/q;+2/p-2/t14-,15+,19-,20+,31-;/m1./s1

SMILES Code: CC[C@@H]1[C@H](C2=[N]3C1=CC4=C(C5=C6C([C@H](C5=O)C(OC)=O)=C7[C@H]([C@@H](C(C=C8C(C)=C9C(C)=O)=[N]7[Pd]3(N8C9=C2)N64)C)CCC(O)=O)C)C


Technical Data

Appearance:
Solid powder

Purity:
>95% (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 soluble 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).

Harmonized System Code:
293490


Additional Information

Tookad (palladium bacteriopherophorbide photosensitizer, WST09) is a palladium-metalated bacteriopherophorbide derived from BChl, the bacterial equivalent of plant chlorophyll. Tookad possesses a high molar extinction coefficient ( 1.086 X 105 M-1cm -1 in chloroform), maximum absorption wavelength in the near-infrared region (763 nm), light penetration depth of 4 mm using a 763 nm light source (compared to 1.6 mm light penetration with Photofrin using a 630 nm light source) and fast PKs—95% of compound is cleared from circulation of mice in 15 min preventing accumulation in tissues, a characteristic necessary for localized tumor and isolated metastases treatment. In addition, it has been shown to have a plasma half-life of about 20 min in mice. Tookad-based PDT possesses an advantage over several well-established PDT regimens in terms of its short drug exposure–light interval. This facilitates minimal delay between administration of drug and irradiation with light. When activated, Tookad targets the vasculature of the tumor, initiating inflammation, hypoxia, necrosis and tumor eradication Accourding to O'Connor et al review paper, Tookad appears to be photochemically and pharmacologically superior to other clinically used photosensitizers to date. There is little or no skin-associated photosensitivity due to the extremely short half-life of the drug. A further advantage is its ability to be activated at a relatively long wavelength resulting in greater tissue penetration. Tookad overcomes several of the disadvantages associated with first generation photosensitizers and also appears to be superior to various second generation photosensitizers developed. Although it has yet to be clinically approved, preclinical studies to date would indicate that Tookad represents a promising photosensitizer in the PDTbased treatment of nonsuperficial cancers such as those of the prostate. [source: Porphyrin and nonporphyrin photosensitizers in oncology: preclinical and clinical advances in photodynamic therapy. O'Connor AE, Gallagher WM, Byrne AT. Photochem Photobiol. 2009 Sep-Oct;85(5):1053-74.]
 
 


References

 1: Madar-Balakirski N, Tempel-Brami C, Kalchenko V, Brenner O, Varon D, Scherz A, Salomon Y. Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with Tookad. PLoS One. 2010 Apr 22;5(4):e10282. PubMed PMID: 20421983; PubMed Central PMCID: PMC2858664.

2: Framme C, Sachs HG, Kobuch K, Flucke B, Birngruber R. Clinical evaluation of experimentally induced choroidal neovascularizations in pigmented rabbits by subretinal injection of lipid hydroperoxide and consecutive preliminary photodynamic treatment with Tookad. Ophthalmologica. 2008;222(4):254-64. Epub 2008 Jun 5. PubMed PMID: 18525218.

3: Huang Z, Chen Q, Dole KC, Barqawi AB, Chen YK, Blanc D, Wilson BC, Hetzel FW. The effect of Tookad-mediated photodynamic ablation of the prostate gland on adjacent tissues--in vivo study in a canine model. Photochem Photobiol Sci. 2007 Dec;6(12):1318-24. Epub 2007 Aug 22. PubMed PMID: 18046488; PubMed Central PMCID: PMC2302792.

4: Framme C, Sachs HG, Flucke B, Theisen-Kunde D, Birngruber R. Evaluation of the new photosensitizer Tookad (WST09) for photodynamic vessel occlusion of the choroidal tissue in rabbits. Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5437-46. PubMed PMID: 17122134.

5: Huang Z, Haider MA, Kraft S, Chen Q, Blanc D, Wilson BC, Hetzel FW. Magnetic resonance imaging correlated with the histopathological effect of Pd-bacteriopheophorbide (Tookad) photodynamic therapy on the normal canine prostate gland. Lasers Surg Med. 2006 Aug;38(7):672-81. PubMed PMID: 16799982; PubMed Central PMCID: PMC1850616.

6: Woodhams JH, MacRobert AJ, Novelli M, Bown SG. Photodynamic therapy with WST09 (Tookad): quantitative studies in normal colon and transplanted tumours. Int J Cancer. 2006 Jan 15;118(2):477-82. PubMed PMID: 16052532.

7: Weersink RA, Bogaards A, Gertner M, Davidson SR, Zhang K, Netchev G, Trachtenberg J, Wilson BC. Techniques for delivery and monitoring of TOOKAD (WST09)-mediated photodynamic therapy of the prostate: clinical experience and practicalities. J Photochem Photobiol B. 2005 Jun 1;79(3):211-22. Epub 2005 Mar 24. PubMed PMID: 15896648.

8: Huang Z, Chen Q, Luck D, Beckers J, Wilson BC, Trncic N, Larue SM, Blanc D, Hetzel FW. Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer. Lasers Surg Med. 2005 Jun;36(5):390-7. PubMed PMID: 15856509; PubMed Central PMCID: PMC1201403.

9: Weersink RA, Forbes J, Bisland S, Trachtenberg J, Elhilali M, Brún PH, Wilson BC. Assessment of cutaneous photosensitivity of TOOKAD (WST09) in preclinical animal models and in patients. Photochem Photobiol. 2005 Jan-Feb;81(1):106-13. PubMed PMID: 15382963.

10: Huang Z, Chen Q, Trncic N, LaRue SM, Brun PH, Wilson BC, Shapiro H, Hetzel FW. Effects of Pd-bacteriopheophorbide (TOOKAD)-mediated photodynamic therapy on canine prostate pretreated with ionizing radiation. Radiat Res. 2004 Jun;161(6):723-31. PubMed PMID: 15161347; PubMed Central PMCID: PMC1237001.

11: Plaks V, Koudinova N, Nevo U, Pinthus JH, Kanety H, Eshhar Z, Ramon J, Scherz A, Neeman M, Salomon Y. Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a biphasic apparent diffusion coefficient change as potential early MRI response marker. Neoplasia. 2004 May-Jun;6(3):224-33. PubMed PMID: 15153334; PubMed Central PMCID: PMC1502095.

12: Borle F, Radu A, Fontolliet C, van den Bergh H, Monnier P, Wagnières G. Selectivity of the photosensitiser Tookad for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model. Br J Cancer. 2003 Dec 15;89(12):2320-6. PubMed PMID: 14676813; PubMed Central PMCID: PMC2395293.

13: Borle F, Radu A, Monnier P, van den Bergh H, Wagnières G. Evaluation of the photosensitizer Tookad for photodynamic therapy on the Syrian golden hamster cheek pouch model: light dose, drug dose and drug-light interval effects. Photochem Photobiol. 2003 Oct;78(4):377-83. PubMed PMID: 14626666.

14: Tremblay A, Leroy S, Freitag L, Copin MC, Brun PH, Marquette CH. Endobronchial phototoxicity of WST 09 (Tookad), a new fast-acting photosensitizer for photodynamic therapy: preclinical study in the pig. Photochem Photobiol. 2003 Aug;78(2):124-30. PubMed PMID: 12945579.

15: Koudinova NV, Pinthus JH, Brandis A, Brenner O, Bendel P, Ramon J, Eshhar Z, Scherz A, Salomon Y. Photodynamic therapy with Pd-Bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts. Int J Cancer. 2003 May 10;104(6):782-9. PubMed PMID: 12640688.