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I-2000 6'-Iodoresiniferatoxin, >99%

[6'-IRTX]

M.W. 754.62

C37H39IO9

Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO or ethanol.  Disposal:  A    LIGHT-SENSITIVE!

View the MSDS for this product

• Novel, high-affinity partial agonist at the human vanilloid VR1 receptor; Ki = 0.71 nM.  In a functional assay measuring induction of increases in intracellular calcium in HEK cells stably expressing hVR1, 6'-IRTX was only able to induce a 50% response relative to capsaicin.  The EC50 for 6'-IRTX in these cells was 130 nM.  In contrast to the result in cells expressing human VR1, 6'-IRTX was a full agonist, or very nearly so (92 + 6% of the capsaicin response), in HEK cells expressing the rat VR1 ortholog.  McDonnell, M.E. et al.  "Synthesis and in vitro evaluation of a novel iodinated resiniferatoxin derivative that is an agonist at the human vanilloid VR1 receptor." Bioorg. Med. Chem. Lett. 12:  1189-1192 (2002).  [N. B. In light of the data for effects on hVR1 in the article, the title should say "partial agonist" — ed.]

• Thus, 6'-IRTX shows activity intermediate between the full hVR1 agonist resiniferatoxin (Cat. No. R-6712) and the pure hVR1 antagonist 5'-IRTX (Cat. No. I-6400).

• NOTE:  The McDonnell et al. article contains a number of errors, some trivial, some quite significant:

  1. The structure depicted in Fig. 2 for 5'-IRTX is not correct; the iodine atom should be next to the free hydroxy group on the homovanillic acid moiety.  The same error occurs in the original article describing 5'-IRTX [Wahl, P. et al., Mol. Pharm. 59: 9-15 (2001)].

  2. The order of substituent citation for the substituted phenylacetic acid cited in the second sentence of the abstract should be ". . . 4-hydroxy-2-iodo-5-methoxy..." (aromatic ring substituents are listed in alphabetical order).   Likewise, the order of substituents for one of the reactants in reference 8 should be ". . . 4-acetoxy-2-iodo-5- methoxyphenylacetic acid . . ."

  3. In reference 9, which is actually a synthetic chemical procedure, the substituent position numbering and order of substituent naming are incorrect for the starting material cited in the first sentence; the correct description is ". . . 4- acetoxy-2-iodo-5-methoxy . . ."

  4. The substituent numbering of the positions of the homovanillic acid ester moiety for compound 4 in Scheme 1 is inconsistent with the position numbering in Fig. 1, the latter being the numbering system routinely used in the vanilloid field for resinifera-toxin derivatives.  (See "Nomenclature" below.)

  5. In the second-to-last paragraph on page 1190, right column, the substituent position numbering and order of substituent naming for the compound from Wahl et al. referred to in the first sentence should be ". . . 4-hydroxy-5-iodo-3-methoxy . . .".

• Nomenclature  The convention in the vanilloid field is to name and number resiniferatoxin (RTX) derivatives as substituted RTX's (this is explained further below).  In this numbering convention, all the position numbers of the diterpene and homovanillic moieties remain unchanged when new substituents are introduced.  The diterpene moiety is taken to be the parent structure, and its carbon atoms are numbered 1-20.  The carbon atoms of the homovanillic benzene ring are numbered with primes, 1'-6'.
  
  Thus, introduction of an iodine atom next to the free OH-group of RTX results in "5'-RTX", and introducing an iodine atom at the less-crowded of the two positions next to the carbon atom-bearing side chain, i. e., not next to the methoxy group, produces "6'-IRTX".  It is important to note that introduction of an iodine into that same position in free homovanillic acid itself, as a separate entity not connected to a diterpene parent, would result of renumbering of the benzene ring positions.  But because the numbering of the RTX positions does not change when substituents are introduced, 6'-IRTX is the correct name for this compound.
  
  An alternate way of naming RTX derivatives, used in several places in the McDonnell et al. paper, is technically acceptable but is not consistent with conventions in the vanilloid field and might cause extensive confusion to non-chemists.  This alternate naming scheme treats the compounds in question as 20-esters of the parent diterpene, resiniferonol 9,13,14- orthophenylacetate.  Thus, McDonnell et al. use ". . . 9,13,14-orthophenylacetylresinferonyl-20-( 4-hydroxy-2-iodo-5-methoxyphenylacetate . . ." at the top of page 1190 as the name for 6'-IRTX.  By this naming scheme, the homovanillic acid positions are numbered as if the homovanillic acid were a separate compound, in which the iodo group would properly be at position 2, rather than as part of an RTX molecule with invariant numbering.
  
  Strictly speaking, according to IUPAC rules, none of these naming and numbering schemes is remotely close to being correct.  However, the numbering scheme taking the diterpene to be the parent entity, with invariant position numbering, has now been used for many decades in the RTX and phorbol ester fields, in a literature now numbering many thousands of articles.  Thus it appears that this system would constitute the least confusing approach to designating new RTX derivatives and related compounds.

• Please inquire for bulk quantities of 6'-IRTX at substantial discounts.

• Pharmaceutical formulations containing this compound, and anti-inflammatory, anti-viral and anti-psoriatic uses, are covered by U.S. patents 5,643,948 and 5,955,501.

• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.