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GENTAUR
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P-8880 4α-Phorbol 12-Myristate 13-Acetate, >99%
[4α-PMA] [4α-TPA] [4α-12-O-Tetradecanoylphorbol
13-Acetate]
| M.W. 616.84 |
C36H56O8
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[63597-44-4] |
Storage: Store at or below -20 ºC. Solubility:
Soluble in DMSO or ethanol. Disposal: A
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Negative control for studies with PMA, Cat. No.
P-1680. Van Duuren, B.L. et al. Cancer Res. 39:
2644-2646 (1979). |
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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 ED
50 >25 µM for binding to protein kinase C), 4α-PMA may prove to be a
reasonably potent activator of TRPV4 channels, with utility for
structure-activity studies of this phenomenon. The supposition of agonist
activity for 4α-PMA 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-PMA 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 β configuration, i.
e., rising up out of the two-dimensional structure as depicted on paper or a
computer monitor. The 4-alpha-phorbol esters such as 4α-PMA, 4α-PDD and
4α-PDBu 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 intrinsic 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 "3α-cholesterol" specification.
To avoid confusion in this field, it is useful
to note that, technically, 4α-PMA 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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