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GENTAUR
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P-4678 4α-Phorbol 12,13-Dibutyrate, >99%
[4α-PDBu]
| M.W. 504.63 |
C28H40O8
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[93781-54-5] |
Storage: Store at or below -20 ºC. Solubility:
Soluble in DMSO or ethanol. Disposal: A
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Negative control for studies with PDBu, Cat.
No. P-4833. |
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Please request Technical Note #13 for
additional information. |
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IMPORTANT NEW DATA: 4α-Phorbol Ester
Activation of TRPV4 Channels! Though long thought to be a
biologically inactive or extremely weak phorbol ester analog (i. e., an ED50
>25 µM for binding to protein kinase C), 4α-PDBu may prove to be a modestly
potent activator of TRPV4 channels, with utility for structure-activity
studies of this phenomenon. The supposition of agonist activity for 4α-PDBu
on TRPV4 channels is based on the potent agonist response elicited by the
very similar compound, 4α-PDD, in systems containing human VRL-2 and murine
TRP12 channels [H. Watanabe et al., J. Biol. Chem. 277:
13569-13577 (2002)]. See the entry for 4α -PDD, Cat. No. P-2170, for an
extensive description of these new and exciting results. |
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Chemical Structures. The primary
structural difference between 4α-PDBu and the highly potent phorbol
ester-type PKC activators is the configuration at C4. In the highly active
phorbol ester family, the hydroxy group at C4 is in the configuration, i.
e., rising up out of the two-dimensional structure as viewed on paper or a
computer monitor. The 4α-phorbol esters such as 4α-PDBu, 4α-PDD and 4α-PMA
have the 4-OH group oriented down below the paper or computer screen's
two-dimensional plane. |
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Nomenclature. Unless "4α" is
specified, all "phorbol" compounds are automatically defined, by operation
of standard chemical nomenclature conventions, as having the
4β-configuration, as part of the meaning of the word "phorbol". This is
much like the word "cholesterol", which automatically means that its hydroxy
group at carbon 3 is in the β configuration; there is no need to specify
"3β-cholesterol", whereas a cholesterol derivative with a 3α hydroxy group
would require a "3αa-cholesterol" specification. |
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To avoid confusion in this field, it is useful
to note that, technically, 4α-PDBu is not a "phorbol ester", it is a "4α-phorbol
ester", and the structural differences, though minor overall, are quite
significant biologically. Given the extreme differences in their biological
properties, both on PKC and TRPV4 channel-based phenomena, efforts to
maintain distinctive names for members of these two biologically quite
distinct classes of compounds appear to be well justified. |
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