Combretastatin A-1 is a
combretastatin
Combretastatin is a dihydrostilbenoid found in '' Combretum caffrum''.
As a class
Combretastatins are a class of natural phenols. A variety of different natural combretastatin molecules are present in the bark of '' Combretum caffrum'', commonly ...
and a
stilbenoid
Stilbenoids are hydroxylated derivatives of stilbene. They have a C6–C2–C6 structure. In biochemical terms, they belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. Most stilbenoids are prod ...
. It can be found in ''
Combretum caffrum'', the Eastern Cape South African Bushwillow tree.
Biological effects in mammals
It is an antiangiogenic agent acting by destabilizing
tubulin
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
, which induces cell
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
of proliferating
endothelial cell
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
s.
[
]
Derivatives as drugs
Currently designated an orphan drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
The assignment of ...
by the FDA, combretastatin A1 diphosphate (OXi4503 or CA1P) is in Phase I clinical trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
s for relapsed and refractory acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
and myelodysplastic syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may ...
.
References
Combretastatins
Stilbenoids
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