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).

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.

Anti-inflammatory uses and pharmaceutical formulations containing this compound are covered by U. S. patent 5,643,948, and such formulations and their use in medicine are covered by European patent EP 0455271, DE P375210808, FR 0455271, GB 0455271 and SW 0455271, all assigned to PKC Pharmaceuticals, Inc., the parent company of LC Laboratories.

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