Progesterone carboxymethyloxime, or progesterone 3-(''O''-carboxymethyl)oxime (P4-3-CMO), is a
progestin
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...
which was never marketed.
It is an
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or ora ...
prodrug
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...
of
progesterone
Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
with improved
pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...
properties.
The compound was developed in an attempt to address the poor oral pharmacokinetics of progesterone, including its very low
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
and short
biological half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...
.
These properties of progesterone are thought to be caused by its low
water solubility
An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, also known as sodium chloride (NaCl), in water w ...
and high
metabolic clearance rate due to rapid
degradation
Degradation may refer to:
Science
* Degradation (geology), lowering of a fluvial surface by erosion
* Degradation (telecommunications), of an electronic signal
* Biodegradation of organic substances by living organisms
* Environmental degradation ...
in the
intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
s and
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
.
Drugs with low aqueous solubility are not
absorbed well in the intestines because their
dissolution in water is limited.
P4-3-CMO (as the
potassium
Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...
salt
In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...
) showed water solubility that was increased by more than four orders of magnitude relative to progesterone (solubility = 9.44 mol/L and 0.0006 mol/L, respectively).
In addition, it showed an ''
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
''
terminal half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
in rat liver
microsome
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, l ...
s that was 363-fold longer than that of progesterone (half-life = 795.5 minutes and 2.2 minutes, respectively).
As such, P4-3-CMO could have both improved absorption and increased
metabolic stability
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...
relative to progesterone.
However, the compound has not been further assessed nor studied in humans.
See also
*
List of neurosteroids § Inhibitory > Synthetic > Pregnanes
*
List of progestogen esters § Oximes of progesterone derivatives
References
Abandoned drugs
Alkene derivatives
Diketones
Neurosteroids
Ketoximes
Pregnanes
Sex hormone esters and conjugates
Progestogens
Steroid oximes
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