4759-48-2 Usage
Pharmacological effects
Isotretinoin belongs to the first generation of vitamin A acid. It is a stereoisomer of all-trans vitamin A acid. Oral administration has an anti-oil effect which has special effect on severe acne. The mechanism is as follows:
① it can reduce sebaceous gland and inhibit the activity of sebaceous gland, reducing the effect of secretion of the sebaceous glands, thus inhibiting the growth of Propionibacterium which relies on lipid environment.
② it has an anti-keratosis effect, can inhibit the excess proliferation of epidermal and promote its differentiation. It also reduces the keratosis of hair follicles and the catheter of sebaceous glands.
③ it can also affect the function of lymphocytes and monocytes, and inhibit the chemotaxis of neutrophil, and thus having anti-inflammatory activity.
④ it can exert its therapeutic effect by selectively binding Vitamin A acid nuclear receptors. It can inhibit the proliferation of acne rod bacilli. Moreover it has effects of immunity stimulation at low doses, but has immunity suppression effect at high doses.
⑤ It can inhibit the biogenesis of collagenase and gelatinase in the skin, and can also inhibit the activity of ornithine decarboxylase. Owing to the major role of ornithine decarboxylase in inducing skin mutations, so isotretinoin can also suppress tumorigenesis.
⑥ when subjects to topical administration, it has a similar mechanism of action as vitamin A acid which induces the proliferation of epidermal cell, promotes the differentiation of epidermal cell granular layer into the stratum corneum. It can also regulate the horny plug occurring during some abnormal cornification processes of Hair follicle sebaceous epithelium, and thus playing a therapeutic role.
Figure 1 Structure formula of Isotretinoin
The above information is edited by the lookchem of Dai Xiongfeng.
Chemical Properties
Different sources of media describe the Chemical Properties of 4759-48-2 differently. You can refer to the following data:
1. It is orange-red flake crystals obtained from isopropanol, melting point 174~175°C. UV maximal absorption: 354nm (ε39800). Acute toxicity LD50 (20 days) mice, rat (mg/kg): 904,901 intraperitoneal injections; 3389> 4000 oral administration.
2. Yellow or orange crystalline powder or crystal, insoluble in water, slightly soluble in ethanol, very slightly soluble in ether, soluble in chloroform.
Pharmacokinetics
This product is rapidly absorbed after oral administration. The plasma concentration reaches peak within 2 to 4 hours. However, oral administration has a low bioavailability which can be boosted by postprandial medication. It has a over 99% binding rate to the plasma protein. It is mainly metabolized in the liver or intestine wall. It enters into the enterohepatic circulation in the form of prototype and metabolites. Prototype drug without any changes is excreted from the feces while metabolite is excreted from the urine. The half life of elimination lasts 10 to 20 hours.
Uses
Different sources of media describe the Uses of 4759-48-2 differently. You can refer to the following data:
1. Isotretinoin is a vitamin A class drugs that It can rapidly and strongly inhibit the cell proliferation and differentiation process of skin glands cells. It has a high effect on severe nodular cystic acne. This product has a high gastrointestinal absorption, but invalid for topical administration. It is used for treating severe acnes which cannot be treated by other drugs. It also has some effects on treating cystic acne, the party of acne, rosacea, ichthyosis, follicular keratosis and pityriasis red hair and other skin diseases.
2. isotretinoin is a retinoid derivative with improved bioavailability and percutaneous absorption for acne treatment products. Presently being studied in conjuction with the treatment of photoaged skin.
Indications
Different sources of media describe the Indications of 4759-48-2 differently. You can refer to the following data:
1. 1. Isotretinoin should be the primary choice for treatment of refractory acne, especially for severe nodular, cystic, inflammatory acne patients to whom conventional therapy is ineffective.
2. Generalized Plana or verrucous epidermal dysplasia;
3. Skin disease of abnormal cornification;
4. Cutaneous lupus erythematosus;
5. lichen planus, atrophic lichen sclerosis.
2. Isotretinoin (Accutane) alters keratinization in the
acroinfundibulum of sebaceous glands and shrinks
them, thereby reducing sebum excretion and comedogenesis.
These features underlie its usefulness in acne
vulgaris, since sebum secretion is a hallmark of acneprone
skin. Furthermore, the drug has antiinflammatory
activity.
Clinical application
Isotretinoin is an effective drug against acne. It takes effect on four processes of acne procedures, preventing the formation of acne lesions: ① inhibiting sebaceous secretion; ② inhibit the growth of acne bacillus; ③ inhibiting sebaceous hyperplasia; ④ anti-inflammatory effect. Isotretinoin has no affinity to Vitamin A acid receptors. Its exact mechanism of action is not very clear. Its anti-acne role may be related to that it or its metabolites can inhibit the proliferation and differentiation of sebaceous glands. It may also reduce the volume of the sebaceous glands, reducing the skin's DHT, down-regulate the expression of skin androgen receptor. Other possible mechanism includes reducing the hair follicle keratosis, antibacterial, anti-inflammatory effects and so on. In the 1980s, Isotretinoin is only for treating severe nodular cystic acne. Isotretinoin is now also used for treating some less-seriously acne where those related patients are often insensitive to conventional therapy, especially some patients with long-term use of antibiotics due to that acne bacillus have evolved multiple drug (such as erythromycin, tetracycline) resistance. It may also be used for some acne patients prone to scar.
Isotretinoin is usually applied with a relative high dose at the beginning in treatment of acne, such as 1 mg/(kg ? d). However, most patients follow this poorly due to adverse reactions of drugs. It was later found that 0.5 mg/(kg ? d) can also give similar therapeutic effect. In order to achieve the accumulation of appropriate amount, drug usage can be prolonged. The calculation method of accumulation of isotretinoin is using total amount of applied drugs to divide the patient body weight (mg/kg). In general, cumulative dose of 120mg/kg will effectively reduce the possibility of disease relapse. However, the maximum cumulative amount should no exceed 150mg/kg. Owing to the certain residence time of the drug in the body, the symptoms of some patients still keep going well even after stopping taking drugs, Therefore, it is not unnecessary to maintaining therapy until all lesions subsided. About one-third of patients required re-treatment (due to the persistent or recurrent disease). There are two cases of resistance to isotretinoin: closed comedones and small cystic acne. During the first 1 to 2 weeks of treatment, some patients will suffer an increasing skin lesion. Some cystic acne becomes pyogenic granuloma-like lesions. This is due to that taking isotretinoin does harm to the normal skin barrier function, leading to increased colonization of staphylococcus aureus. If some women exhibit resistance to isotretinoin therapy or suffer recurrent disease, we should observe whether hairy happens and menstrual cycle is normal. Also check the ovaries and adrenal function. Both adrenal dysfunction and high expression level of 5α-reductase can cause this issue.
Toxicity
(1) Adverse reactions of skin and mucous membranes: This is the most common adverse reaction of orally administration of isotretinoin. The higher dose of oral administration is, the higher the incidences of adverse reactions happen. Cheilitis is the mostly common with a 100% incidence, exhibiting mucosa lips dry, chapped, peeling, bleeding, which is similar to exfoliative dermatitis; Nearly 30% to 50% of patients suffer drying nasal mucosa, bleeding, reversible hair loss, dry and itching skin, dry eye. This happens especially in patients with allergies and xerosis. Those patients who wear contact lenses should not use this drug. Or we should not wear contact lenses during taking it.
(2) Teratogenicity: Animal experiments show that oral administration of isotretinoin can cause malformations, miscarriage and stillbirth. Administration during the early phase of fetal organ formation can lead to the abnormal development of the central nervous system and cardiovascular system. Administration in the later phase of pregnancy can cause fetal limb shortage and defect on urinary system.
(3) Effect on the bone: Long-term application of isotretinoin can cause bone hypertrophy, tendon ligament calcification, osteoporosis, epiphyseal atresia, thus badly affecting the growth of children and adolescents. Bone hypertrophy and tendon ligament calcification are the most common. The incidence is related to the drug dosage and duration. When treated with 1~2mg dose per day per kilogram of body weight and a4 to 5 months duration of oral isotretinoin, about 10% of patients can be detected for bone hypertrophy.
(4) Effect on mental activity: people suffer from acne often mentally more depressed or prone to depression. Taking isotretinoin will boost this tendency. It has been reported since 1982 (when isotretinoin first entered into market) to May 2000, the US Food and Drug Administration (FDA) has reported 431 cases of mental disorders after taking isotretinoin, wherein 37 patients commit suicide, 110 patient got depression or suicidal thoughts or suicide for hospitalized, 284 patients with depression but not hospitalized. Effect of oral administration of isotretinoin on mental activity is related to the duration of the drugs; stopping taking drugs or psychiatric treatment can alleviate the symptoms. However, symptoms can reoccur, and even deteriorate after re-treatment again or worse.
(5) Laboratory abnormalities: oral administration of isotretinoin can cause elevated level of triglycerides and cholesterol in serum.
Drug Interactions
1. Combination with warfarin can enhance the latter one’s effect.
2. Combination together with Avi A ester, vitamin A acetate or Vitamin A acid can increase the incidence and severity of adverse reactions.
3. Combination with methotrexate can increase the blood concentration of the latter one, and thus increasing the damage to the liver.
4. Combination with tetracycline can lead to brain and cause pseudo-tumor in brain and cause benigh hypertension. Clinical manifestations of hypertension are accompanied by headache, dizziness and visual disturbances.
5. Combination with carbamazepine results in decreased plasma concentrations of the latter one.
6. Combination with light-sensitive drugs increases the light-sensitive effect.
Contraindications
1. Pregnant women, lactation, patients with severe liver and kidney dysfunction.
2. Take with caution for patients of hyperlipidemia, diabetes, severe osteoporosis.
3. Avoid apply together with vitamin A, tetracycline, aspirin.
Side effects
Different sources of media describe the Side effects of 4759-48-2 differently. You can refer to the following data:
1. 1. Changed skin and mucous membrane, including cheilitis, dry mouth, facial redness, dry eyes, conjunctivitis, etc;
2. Long-term use can cause liver and kidney damage;
3. Long-term application of Isotretinoin can cause osteoporosis, epiphyseal atresia, and retardation of bone formation. The incidence is <15%;
4. Teratogenic effect is one of the more serious adverse reactions.
2. Isotretinoin is teratogenic to humans and should not be administered to pregnant women or women contemplating pregnancy. Concomitant use of isotretinoin with drugs of the tetracycline class increases the incidence of Pseudotumor cerebri. There have been recent reports of an increased risk of depression, suicide, and suicide attempts in individuals taking isotretinoin, but the causality has not been absolutely proved.Isotretinoin, like many retinoids, can lead to increase in serum aminotransferase levels, but, unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver injury with jaundice.
Originator
Accutane,Roche
Definition
ChEBI: Isotretinoin is a retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases. It has a role as a keratolytic drug, an antineoplastic agent and a teratogenic agent. It is a conjugate acid of a 13-cis-retinoate.
Preparation
Preparation of isotretinoin in a single step from β-ionone and ethyl chloride are first reacted together after which the product is further reacted with triphenylphosphine to obtain Triphenyl salt. The Triphenyl salt is further reacted with cyclopentenone derivative to produce isotretinoin and its 8Z isomer. separate out the 8Z isomer and convert it to isotretinoin through isomerization with the help of nitric acid.
Brand name
Accutane (Roche); Amnesteem
(Genpharm); Claravis (Barr); Sotret (Ranbaxy);Accutane roche;Apsor;Isotretinoin;Neovamin a acid;Neovitamin a acid;Ro 4-3780;Roacutan.
Therapeutic Function
Antiacne, Keratolytic
World Health Organization (WHO)
Isotretinoin, a retinol derivative, was introduced in 1982 exclusively for the treatment of severe acne. Its use in pregnant women has
resulted in major fetal abnormalities. The manufacturer's information emphasizes
that the drug is teratogenic and must not be given to women who are pregnant,
and that contraceptive measures must be maintained for at least four weeks after
discontinuation of treatment. In some countries, blood banks are advised not to
accept as donors persons who have taken isotretinoin within the previous four
weeks. See also under retinol (vitamin A).
General Description
Yellow-orange to orange crystalline powder; orange-brown chunky solid.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
An organic acid and unsaturated aliphatic hydrocarbon. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.
Fire Hazard
Flash point data for Isotretinoin are not available; however, Isotretinoin is probably combustible.
Biochem/physiol Actions
13-cis-Retinoic acid (RA) has anti-inflammatory and anti-tumor action. The action of RA is mediated through RAR-β and RAR-α receptors. RA attenuates iNOS expression and activity in cytokine-stimulated murine mesangial cells. It induces mitochondrial membrane permeability transition, observed as swelling and as a decrease in membrane potential, and stimulates the release of cytochrome c implicating mechanisms through the apoptosis pathway. These activities are reversed by EGTA and cyclosporin A. RA also increases MMP-1 protein expression partially via increased transcription.
Mechanism of action
Isotretinoin binds to and activates nuclear retinoic acid receptors (RARs); activated RARs serve as transcription factors that promote cell differentiation and apoptosis. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization. Isotretinoin is rapidly absorbed orally, with peak blood concentrations 3 hours after ingestion. It is not stored in tissue, and the elimination half-life is 10 to 20 hours, either after a single dose or during chronic therapy.
Clinical Use
Isotretinoin is most useful for the treatment of severe
recalcitrant nodular acne vulgaris. It may also be helpful in other disorders of keratinization, but it is
not useful for psoriasis. High doses of isotretinoin
(2mg/kg/day) are effective as cancer chemoprevention
agents to reduce the frequency of cutaneous malignancies
in patients at increased risk, such as those with xeroderma
pigmentosum, an inherited disorder in which
DNA repair is deficient, or in immunosuppressed patients.
Safety Profile
Poison by
intraperitoneal route. Moderately toxic by
ingestion. A human teratogen by ingestion
with fetal developmental abnormalities of
the skin and appendages and other postnatal
effects. Human reproductive effects. Human
systemic effects: decreased immune
response, darrhea, hypermouhty, irritative
dermatitis, sweating. Human mutation data
reported. An experimental teratogen. Other
experimental reproductive effects. When
heated to decomposition it emits acrid
smoke and irritating fumes.
Veterinary Drugs and Treatments
Isotretinoin may be useful in treating a variety of dermatologicrelated
conditions,
including canine lamellar ichthyosis, cutaneus
T-cell lymphoma, intracutaneous cornifying epitheliomas,
multiple
epidermal inclusion cysts, comedo syndrome in Schnauzers,
and sebaceous adenitis seen in standard poodles.
Because of the concerns of teratogenic effects in humans, availability
to veterinarians may be restricted by the manufacturers and
drug distributors; obtaining the medication for veterinary patients
may be difficult.
Drug interactions
Potentially hazardous interactions with other drugs Antibacterials: possible increased risk of benign intracranial hypertension with tetracyclines - avoid. Antifungals: possible increased risk of toxicity with fluconazole, ketoconazole and voriconazole. Vitamins: increased risk of hypervitaminosis with vitamin A.
Environmental Fate
In primates (including humans), isotretinoin (Accutane) is
metabolized to a more active form, 13-cis-4-oxo-retinoic acid,
which is able to move through the placental membrane. On
its own, however, Accutane (isotretinoin) is not particularly
motile across the placental barrier, and perhaps most interestingly
tends not to bind to cellular retinoid-binding proteins
or nuclear receptors. The rapid isomerization to the all-trans
isomer, the oxidation of Accutane (isotretinoin) to 13-cis-4-
oxo-retinoic acid, and the relatively high circulation times of
these compounds may be important in explaining the teratogenic
toxicity of Accutane (isotretinoin).
Some studies have more fully explored the metabolic
products of isotretinoin. For example, isotretinoin can be
metabolized in the liver by the cytochrome P450 microsomal
enzyme system – more specifically the CYP2C8, CYP2C,
CYP3A4, and CYP2B6 isoenzymes. The metabolites produced
are numerous, including retinoic acid (tretinoin), 4-oxo-isotretinoin,
and 4-oxo-retinoic acid (4-oxo-tretinoin). This relatively
large array of retinoid metabolites may produce a variety
of effects, most notably due to their higher potency as retinoids
compared to the parent compound (isotretinoin).
It is possible that these additional metabolites are capable
of binding to a variety of retinoid receptors in order to alter
gene expression and further transcription or transrepression in
protein synthesis, which may be responsible for the toxic effects
of isotretinoin.
Toxicity evaluation
Direct studies focused on the environmental fate of Accutane
(isotretinoin) are rare in the literature. The pure compound is
insoluble in water, and highly lipophilic. Powders do not
aerosolize readily, and volatilization is extremely low. Isotretinoin
released into the environment would not be expected
to have high mobility in water or soil, and will most likely
become deposited in organic materials. Bioaccumulation is
possible, but isotretinoin is readily oxidized to form other
retinoids or metabolites that are expected to be mitigated via
natural biological pathways.
Check Digit Verification of cas no
The CAS Registry Mumber 4759-48-2 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 4,7,5 and 9 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 4759-48:
(6*4)+(5*7)+(4*5)+(3*9)+(2*4)+(1*8)=122
122 % 10 = 2
So 4759-48-2 is a valid CAS Registry Number.
InChI:InChI=1/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/p-1/b9-6+,12-11+,15-8+,16-14-
4759-48-2Relevant articles and documents
Catalytic synthesis of 9-cis-retinoids: Mechanistic insights
Kahremany, Shirin,Kubas, Adam,Tochtrop, Gregory P.,Palczewski, Krzysztof
supporting information, p. 10581 - 10595 (2019/07/22)
The regioselective Z-isomerization of thermodynamically stable all-trans retinoids remains challenging, and ultimately limits the availability of much needed therapeutics for the treatment of human diseases. We present here a novel, straightforward approach for the catalytic Z-isomerization of retinoids using conventional heat treatment or microwave irradiation. A screen of 20 transition metal-based catalysts identified an optimal approach for the regioselective production of Z-retinoids. The most effective catalytic system was comprised of a palladium complex with labile ligands. Several mechanistic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using coupled cluster methods indicate that the isomerization is initiated by catalyst dimerization followed by the formation of a cyclic, six-membered chloropalladate catalyst-substrate adduct, which eventually opens to produce the desired Z-isomer. The synthetic development described here, combined with thorough mechanistic analysis of the underlying chemistry, highlights the use of readily available transition metal-based catalysts in straightforward formats for gram-scale drug synthesis.
Z -isomerization of retinoids through combination of monochromatic photoisomerization and metal catalysis
Kahremany, Shirin,Sander, Christopher Lane,Tochtrop, Gregory P.,Kubas, Adam,Palczewski, Krzysztof
supporting information, p. 8125 - 8139 (2019/09/19)
Catalytic Z-isomerization of retinoids to their thermodynamically less stable Z-isomer remains a challenge. In this report, we present a photochemical approach for the catalytic Z-isomerization of retinoids using monochromatic wavelength UV irradiation treatment. We have developed a straightforward approach for the synthesis of Z-retinoids in high yield, overcoming common obstacles normally associated with their synthesis. Calculations based on density functional theory (DFT) have allowed us to correlate the experimentally observed Z-isomer distribution of retinoids with the energies of chemically important intermediates, which include ground- and excited-state potential energy surfaces. We also demonstrate the application of the current method by synthesizing gram-scale quantities of 9-cis-retinyl acetate 9Z-a. Operational simplicity and gram-scale ability make this chemistry a very practical solution to the problem of Z-isomer retinoid synthesis.
Synthesis of 11C-labeled retinoic acid, [11C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[11C] methylation
Suzuki, Masaaki,Takashima-Hirano, Misato,Ishii, Hideki,Watanabe, Chika,Sumi, Kengo,Koyama, Hiroko,Doi, Hisashi
supporting information, p. 3622 - 3625 (2014/07/22)
Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized 11C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of 11C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[11C] methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [11C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [11C]Tamibarotene (artificial retinoid).
Stereospecific synthesis process for tretinoin compounds
-
Page/Page column 10; 11, (2014/09/29)
A stereospecific synthesis process for tretinoin compounds comprises the following steps: using substituted triphenyl phosphine salt and β-formyl crotonic acid as raw material to carry out WITTIG reaction under the action of alkali; then adjusting the pH of the reaction liquid to 5-10; adding palladium compound or rhodium compound to carry out isomerization directly and obtain tretinoin compounds with desired configuration. The product yield of the process is high and the intermediate product in the reaction dose not need to be separated. The process is easy to operate and can save the production cost and as well is suitable for industrial production.
STEREOSPECIFIC SYNTHESIS PROCESS FOR TRETINOIN COMPOUNDS
-
Paragraph 0043; 0044, (2014/04/03)
A stereospecific synthesis process for tretinoin compounds comprises the following steps: using substituted triphenyl phosphine salt and β-formyl crotonic acid as raw material to carry out WITTIG reaction under the action of alkali; then adjusting the pH of the reaction liquid to 5-10; adding palladium compound or rhodium compound to carry out isomerization directly and obtain tretinoin compounds with desired configuration. The product yield of the process is high and the intermediate product in the reaction dose not need to be separated. The process is easy to operate and can save the production cost and as well is suitable for industrial production.
A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS
Arnold, Samuel L. M.,Amory, John K.,Walsh, Thomas J.,Isoherranen, Nina
experimental part, p. 587 - 598 (2012/05/31)
Retinol (vitamin A) circulates at 1-4 μM concentration and is easily measured in serum. However, retinol is biologically inactive. Its metabolite, retinoic acid (RA), is believed to be responsible for biological effects of vitamin A, and hence the measurement of retinol concentrations is of limited value. A UHPLC-MS/MS method using isotope-labeled internal standards was developed and validated for quantitative analysis of endogenous RA isomers and metabolites. The method was used to measure retinoids in serum samples from 20 healthy men. In the fed state, the measured concentrations were 3.1 ± 0.2 nM for at RA, 0.1 ± 0.02 nM for 9-cisRA, 5.3 ± 1.3 nM for 13-cisRA, 0.4 ± 0.4 nM for 9,13-dicisRA, and 17.2 ± 6.8 nM for 4oxo-13-cisRA. The concentrations of the retinoids were not significantly different when measured after an overnight fast (3.0 ± 0.1 nM for atRA, 0.09 ± 0.01nM for 9-cisRA, 3.9 ± 0.2 nM for 13-cisRA, 0.3 ± 0.1 nM for 9,13-dicisRA, and 11.9 ± 1.6 nM for 4oxo-13-cisRA). 11-cisRA and 4OH-RA were not detected in human serum. The high sensitivity of the MS/MS method combined with the UHPLC separation power allowed detection of endogenous 9-cis RA and 4oxo-atRA for the first time in human serum. Copyright
COMPOUNDS AND COMPOSITIONS FOR TREATING INFECTION
-
, (2012/07/31)
Compounds from 14 Kenyan plants, including from the root of Dovyalis abyssinica and Clutia robusta have been characterized and isolated, and their uses are disclosed.
A caged retinoic acid for one- and two-photon excitation in zebrafish embryos
Neveu, Pierre,Aujard, Isabelle,Benbrahim, Chouaha,Le Saux, Thomas,Allemand, Jean-Francois,Vriz, Sophie,Bensimon, David,Jullien, Ludovic
supporting information; experimental part, p. 3744 - 3746 (2009/02/07)
(Chemical Equation Presented) Escaping the cage: Retinoic acid (RA), a crucial signaling molecule for the embryogenesis of vertebrates, can be photoreleased from a simple caged derivative (cRA) upon illumination. In zebrafish embryos, cRA causes RA-induced phenotypes with one- and two-photon excitation (see picture), which opens a route to the noninvasive generation of controlled RA concentration patterns in vivo.
All-Trans-Retinol: All-Trans-13,14-Dihydroretinol Saturase and Methods of Its Use
-
Page/Page column 2; 23-24; Sheet 7/24, (2008/12/08)
Compositions of all-trans-retinol: all-trans-13,14-dihydroretinal saturase and methods of use thereof are provided.
PROCESS FOR PREPARATION OF HIGHLY PURE ISOTRETINOIN
-
Page/Page column 4, (2008/12/08)
The present invention relates to a process for preparation of isotretinoin and more specifically, to a purification process for obtaining highly pure isotretinoin that is useful as a keratolytic agent, particularly useful for the treatment of acne. The process involves treating isotretinoin containing metal contamination and/or other impurities with a base in a suitable solvent to form a solution of isotretinoin, followed by adsorption, precipiation, and filtration or centrifugation
