视黄酸，也称为全反式视黄酸，或 ATRA，是维生素 A 的高效衍生物，几乎是所有重要的生理过程和功能所必需的。它在 530 多个不同基因的转录控制中发挥作用。视黄酸的作用机制是通过其作为核视黄酸受体 (RARα-γ) 的激活配体的作用，与视黄酸 X 受体 (RXRα-γ) 结合形成异二聚体[1]。视黄酸 (RA) 的 Kd 值在 100 至 200 nM 之间，以低亲和力与 PPARα 和 PPARγ 结合。另一方面，视黄酸与 PPARβ/δ 结合时表现出高亲和力和同种型选择性，Kd 为 17 nM [2]。视黄酸 (RA) 受体 RARα、RARβ、RARγ 和 PPARβ/δ 以及视黄酸结合蛋白 CRABP-II 和 FABP5 由未分化的 P19 细胞表达。用视黄酸处理细胞诱导分化导致 CRABP-II 短暂过度表达和 FABP5 下调，这在相关蛋白质和 mRNA 水平上检测到。经过最初的下降后，成熟神经元中的 FABP5 蛋白和 mRNA 水平与未分化的 P19 细胞相比上升了 2-2.5 倍。 PPARβ/δ和RARα的水平没有受到分化诱导的显着影响。到第 4 天，RARγ mRNA 水平下降了近 5 倍，并且在成熟神经元中保持较低水平 [3]。视黄酸 (RA) 是由视黄醇（维生素 A）产生的一种形态发生素，在细胞发育、分化和器官发生中发挥着至关重要的作用。视黄酸与视黄酸受体 (RAR) 和视黄酸 X 受体 (RXR) 相互作用，调节靶基因的表达 [4]。

将浓度为 0.3 μM 的视黄酸 (GMP) 应用于浸入含视黄酸的鱼缸水中的胚胎后，斑马鱼在 24 和 48 小时后表现出更快的视杆细胞分化[6]。

Absorption, Distribution and Excretion
Tretinoin applied topically is expected to remain on the stratum corneum and undergo minimal systemic absorption. In one study, the topical application of radiolabelled tretinoin for 28 days was associated with a total percutaneous absorption of 2%. The extent of absorption was examined after a once-daily application of 1.9 g of the combination product with [benzoyl peroxide] for 14 days. On Day 14, at steady-state, the mean Cmax was 0.15-0.19 ng/mL for tretinoin, 0.27-0.34 ng/mL for the metabolite 4-keto 13-cis retinoic acid, and 0.13-0.28 ng/mL for 13-cis retinoic acid, respectively. The Cmax varied across different age groups (children, adolescents, and adults). The corresponding ranges for the mean AUC0-24 were 0.63-2.06, 2.39-2.89, and 0.96-1.99 ng\*h/mL. Following oral administration, the absolute bioavailability of tretinoin was approximately 50%. While the effect of food on tretinoin is unclear, food increases the oral absorption of retinoids, as a class. When the oral dose of 22.5 mg/m2 tretinoin was administered twice daily, the mean ± SD Cmax was 394 ± 89 ng/mL after the first dose and 138 ± 139 ng/mL after one week of continuous treatment. The area under the curve (AUC) was 537 ± 191 ng·h/mL after the first dose and 249 ± 185 ng·h/mL after one week of continuous treatment. The Tmax was between one and two hours.
Tretinoin metabolites are excreted in bile and urine. Following administration of radiolabeled tretinoin at doses of 2.75 mg and 50 mg - which are 0.53 to 9.6 times the approved recommended dosage based on 1.7 m², respectively - approximately 63% of the radioactivity was recovered in the urine within 72 hours, and 31% appeared in the feces within six days.
Tretinoin is rapidly and extensively distributed to tissues following oral administration but does not cross the blood-brain barrier. The apparent volume of distribution (V_d) of intravenous tretinoin is dose-dependent and significantly greater at low doses. The V_d was 0.52 ± 0.12 L/kg after 0.0125 mg/kg and 0.21 ± 0.05 L/kg after 0.25 mg/kg.
No information is available.
/MILK/ It is not known whether topically applied tretinoin is excreted in human milk.
Studies with radiolabeled drug have demonstrated that after the oral administration of 2.75 and 50 mg doses of tretinoin, greater than 90% of the radioactivity was recovered in the urine and feces. Based upon data from 3 subjects, approximately 63% of radioactivity was recovered in the urine within 72 hours and 31% appeared in the feces within 6 days.
A single 45 mg/sq m (approximately 80 mg) oral dose to APL /acute promyelocytic leukemia/ patients resulted in a mean +/- SD peak tretinoin concentration of 347 +/- 266 ng/mL. Time to reach peak concentration was between 1 and 2 hours.
The apparent volume of distribution of tretinoin has not been determined. Tretinoin is greater than 95% bound in plasma, predominately to albumin. Plasma protein binding remains constant over the concentration range of 10 to 500 ng/mL.
For more Absorption, Distribution and Excretion (Complete) data for all-trans-Retinoic acid (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Tretinoin is rapidly metabolized to form various oxidized and conjugated metabolites. It forms several metabolites stereoisomerization derivatives (9-_cis_-retinoic acid or [alitretinoin] and 13-_cis_-retinoic acid or [isotretinoin]), oxidation derivatives (4-hydroxy-retinoic acid, 4-oxo-retinoic acid, 18-hydroxy-retinoic acid, 5,6-epoxy-retinoic acid, 3,4-didehydro-retinoic acid and retinotaurine), stereoisomerization and oxidation derivatives (13-_cis_-4-oxo-retinoic acid), glucuronidation derivatives (retinoyl beta-glucuronide, 13-_cis_-retinoyl beta-glucuronide, 4-oxo-retinoyl beta-glucuronide, 5,6-epoxyretinoyl beta-glucuronide and 13-_cis_-4-oxo-retinoyl beta-glucuronide), nonpolar metabolites of retinoic acid, and retinoic acid esters. Tretinoin is metabolized by several CYP enzymes, including CYP3A4, CYP2C8, and CYP2E. It also undergoes glucuronidation by UGT2B7. The metabolites 4-oxo retinoic acid and 4-oxo _trans_ retinoic acid glucuronide have one-third of the pharmacological activity of the parent compound. When the plasma concentrations decreased to one-third of their day-one concentrations after one week of continuous therapy, tretinoin induced its own metabolism.
Evidence suggests that tretinoin induces its own metabolism. In patients with APL receiving 45 mg/sq m tretinoin daily, urinary excretion of 4-oxo trans retinoic acid glucuronide increased approximately tenfold over the course of 2-6 weeks of continuous therapy, suggesting that increased metabolism of tretinoin may be the primary mechanism leading to the decreased plasma drug concentrations observed during continued administration. Possible mechanisms for the increased clearance of tretinoin with continuous daily dosing of the drug include induction of CYP enzymes or oxidative cofactors and increased expression of cellular retinoic acid binding proteins. Increasing the dosage of tretinoin to compensate for the apparent autoinduction has not been shown to increase therapeutic response. Reduced plasma retinoid concentrations have been associated with relapse and clinical resistance, and some investigators suggest that the clinical failure of tretinoin may be related to a lack of sustained effective concentrations of the drug during prolonged treatment.
Tretinoin metabolites have been identified in plasma and urine. Cytochrome P450 enzymes have been implicated in the oxidative metabolism of tretinoin. Metabolites include 13- cis retinoic acid, 4-oxo trans retinoic acid, 4-oxo cis retinoic acid, and 4-oxo trans retinoic acid glucuronide. In APL /acute promyelocytic leukemia/ patients, daily administration of a 45 mg/SQ m dose of tretinoin resulted in an approximately tenfold increase in the urinary excretion of 4-oxo trans retinoic acid glucuronide after 2 to 6 weeks of continuous dosing, when compared to baseline values.
Ethanol fed rats showed enhanced microsomal retinoic acid metabolism (50%) accompanied by increased microsomal cytochrome P450 content (34%). The increased hepatic microsomal cytochrome P450 dependent metabolism of retinoic acid after chronic ethanol consumption may contribute to the accelerated catabolism of retinoic acid in vivo.
Following ip administration of high doses of 15-(14)C- and 10,11-(3)H-labeled retinoic acid to rats, 3 major metabolites were isolated from feces in microgram amounts by column, thin-layer and high-pressure liquid chromatography. Mass spectrometry provided identification as all-trans-4-oxoretinoic acid, all-trans-5'-hydroxy-retinoic acid and 7-trans-9-cis-11-trans-13-trans-5'-hydroxyretinoic acid.
For more Metabolism/Metabolites (Complete) data for all-trans-Retinoic acid (8 total), please visit the HSDB record page.
Tretinoin has known human metabolites that include 5,6-Epoxy-retinoic acid, All-trans-retinoyl glucuronide, 18-Hydroxyretinoic acid, and 4-Hydroxyretinoic acid.
Tretinoin is a known human metabolite of retinal.
Hepatic
Half Life: 0.5-2 hours

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Biological Half-Life
The terminal elimination half-life of tretinoin following initial dosing is 0.5 to 2 hours in patients with APL.
In patients with APL /acute promyelocytic leukemia/ receiving tretinoin orally, a terminal elimination half-life of 0.5-2 hours has been reported following initial dosing.

Toxicity Summary
IDENTIFICATION AND USE: All-trans-Retinoic acid (tretinoin) indicated for topical application in the treatment of acne vulgari. Tretinoin capsules are indicated for the induction of remission in patients with acute promyelocytic leukemia. HUMAN STUDIES: Cardiac failure occurred in 6% of patients receiving tretinoin, and cardiac arrest, myocardial infarction, stroke, and pulmonary hypertension each occurred in 3% of patients. There is a risk of arterial or venous thrombosis, involving any organ system, during the first month of tretinoin therapy. Thromboembolic events, including fatal pulmonary embolism, have been reported in patients receiving tretinoin. In one patient receiving tretinoin, fatal thromboembolism occurred during concomitant therapy with an antifibrinolytic agent. Bone marrow necrosis, sometimes fatal, has been reported in several patients receiving hydroxyurea during tretinoin therapy. Thrombocytosis has been reported rarely in patients receiving tretinoin. Rapidly evolving leukocytosis occurs in approximately 40% of patients receiving tretinoin. Retinoic acid-acute promyelocytic leukemia (RA-APL) syndrome (also known as APL differentiation syndrome), characterized by fever, dyspnea, acute respiratory distress, weight gain, pulmonary infiltrates, pleural and pericardial effusions, edema, hepatic failure, renal failure, and multiorgan failure, occurs in approximately 25% of patients receiving tretinoin for the treatment of APL. RA-APL syndrome occasionally has been accompanied by impaired myocardial contractility and episodic hypotension and can occur with or without concomitant leukocytosis. In severe cases, progressive hypoxemia requiring endotracheal intubation and mechanical ventilation may occur, and deaths secondary to progressive hypoxemia and multiorgan failure have been reported. ANIMAL STUDIES: There was no evidence of carcinogenic potential when tretinoin dosages of 0.025 mg/kg daily were administered topically to mice. When mice received 0.017 and 0.035% formulations of tretinoin applied topically, cutaneous squamous cell carcinomas and papillomas in the treatment area were observed in some female mice and dose-related hepatic tumors were observed in male mice. Experiments in vitro with cultured rat conceptuses have shown that tretinoin is a direct-acting dysmorphogen. Major defects involved the branchial arches and somites. Retinoid-induced malformations of the jaw, ears, face, skull, eyes, and heart in humans and rodents are well known. In mice that were administered a single oral dose of 100 mg/kg tretinoin on gestation days 9 or 11 and were killed on gestation day 17 skeletal defects (limbs) and cleft palate were present in 90% of the fetuses. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in rats at dosages exceeding 1 mg/kg daily. Bone anomalies also have been reported in rats when tretinoin 10 mg/kg daily was applied dermally. Topical tretinoin cream was associated with an increased incidence of cleft palate and hydrocephaly in rabbits. In rabbits treated with topical tretinoin an increased incidence of domed head and hydrocephaly was noted in some of the fetuses, typical of retinoid-induced fetal malformations in this species. Gross external, soft tissue and skeletal alterations occurred at doses higher than 0.7 mg/kg/day in mice, 2 mg/kg/day in rats, 7 mg/kg/day in hamsters, and at a dose of 10 mg/kg/day, the only dose tested, in pigtail monkey. When given subcutaneously to rabbits, tretinoin was teratogenic at a dosage of 2 mg/kg daily but not at 1 mg/kg daily. In vivo and in vitro (Ames) tests have not demonstrated that tretinoin is mutagenic. However, ingredients in the microsphere formulation of the drug have shown potential for genetic toxicity and teratogenesis. ECOTOXICITY STUDIES: In Japanese flounder, Paralichthys olivaceus, at 6-9 days post-hatching tretinoin induced the most severe deformity in all skeletons examined among retinoic acid isomers.
Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

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Interactions
Mouse mammary gland organ culture technique was utilized to determine the effects of retinoids, including trans-retinoic acid, on the prolactin-induced structural differentiation of the mammary gland. Thoracic glands from BALB/C mice pretreated with steroids differentiate in 6 days into alveolar structures in presence of insulin and prolactin. Trans-retinoic acid inhibited prolactin-induced structural changes in the glands.
To determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin and retinoic acid would enhance or antagonize the teratogenic effects of the other compound, C57BL/6N dams were treated orally on gestation days 10 or 12 with 10 ml corn oil/kg containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (0-18 ug/kg), retinoic acid (0-200 mg/kg), or combinations of the two chemicals. Dams were killed on gestation day 18 and toxicity and teratogenicity assessed. Coadministration of 2,3,7,8-tetrachlorodibenzo-p-dioxin and retinoic acid had no effect on maternal or fetal toxicity beyond what would be expected by either compound alone. Cleft palate was induced by retinoic acid at lower doses on gestation day 10 than on gestation day 12, but by 2,3,7,8-tetrachlorodibenzo-p-dioxin at lower doses on gestation day 12 than on gestation day 10. Sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hydronephrosis was similar on both gestation days 10 and 12. The limb bud defects were only observed when retinoic acid was administered on gestation day 10, not when given on gestation day 12. No other soft tissue or skeletal malformations were related to administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin or retinoic acid. No effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin was observed on the incidence or severity of limb bud defects induced by retinoic acid, nor did retinoic acid influence the incidence or severity of hydronephrosis induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the incidence of cleft palate was dramatically enhanced by coadministration of the xenobiotic and vitamin. On both gestation day 10 and 12, the dose-response curves for cleft palate induction were parallel, suggesting some similarities in mechanism between the two compounds. However, combination treatment resulted in a synergistic response that varied with the stage of development and was tissue specific.
Risk of pseudotumor cerebri (intracranial hypertension) is increased in patients receiving tretinoin. Concomitant use of other agents known to cause pseudotumor cerebri or intracranial hypertension, such as tetracyclines, may increase the risk of this condition in patients receiving tretinoin.
Concurrent use of hydroxyurea, which is cytotoxic to cells in S phase, and tretinoin, which induces cells to enter the S phase, may cause a synergistic effect leading to massive cell lysis. Bone marrow necrosis, sometimes fatal, has been reported in patients receiving hydroxyurea during tretinoin therapy. Although some clinicians have administered hydroxyurea in conjunction with tretinoin therapy to reduce leukocytosis, the safety and efficacy of this practice have not been established, and caution is recommended in the use of hydroxyurea in patients receiving tretinoin.
For more Interactions (Complete) data for all-trans-Retinoic acid (14 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 1960 mg/kg
LD50 Rat ip 96 mg/kg
LD50 Rat sc 53 mg/kg
LD50 Rat iv 78 mg/kg
For more Non-Human Toxicity Values (Complete) data for all-trans-Retinoic acid (12 total), please visit the HSDB record page.

[1]. Wu L, et al. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis. PLoS One. 2016 Apr 14;11(4):e0153556.
[2]. Shaw N, et al. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J Biol Chem. 2003 Oct 24;278(43):41589-92.
[3]. Yu S, et al. Retinoic acid induces neurogenesis by activating both retinoic acid receptors (RARs) and peroxisomeproliferator-activated receptor β/δ (PPARβ/δ). J Biol Chem. 2012 Dec 7;287(50):42195-205.
[4]. Kam RK, et al. Retinoic acid synthesis and functions in early embryonic development. Cell Biosci. 2012 Mar 22;2(1):11.
[5]. Apfel C, et al. A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7129-33.
[6]. Xiu Jun Wang, et al. Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19589-94

Therapeutic Uses
Antineoplastic Agents Keratolytic Agents
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. trans-Retinoic acid is included in the database.
Tretinoin gel and cream are indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established. /Included in US product labeling; Tretinoin, topical/
Tretinoin is used topically as a 0.05 or 0.1% cream for palliative therapy to improve dermatologic changes (e.g., fine wrinkling, mottled hyperpigmentation, roughness) associated with photodamage. /NOT included in US product labeling; Tretinoin, topical/
For more Therapeutic Uses (Complete) data for all-trans-Retinoic acid (9 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ Experienced Physician and Institution. Patients with acute promyelocytic leukemia (APL) are at high risk in general and can have severe adverse reactions to tretinoin capsules. Tretinoin capsules should therefore be administered only to patients with APL under the strict supervision of a physician who is experienced in the management of patients with acute leukemia and in a facility with laboratory and supportive services sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity, including respiratory compromise. Use of tretinoin capsules requires that the physician concludes that the possible benefit to the patient outweighs the following known adverse effects of the therapy. /Tretinoin, systemic/
/BOXED WARNING/ Retinoic Acid-APL Syndrome. About 25% of patients with APL treated with tretinoin capsules have experienced a syndrome called the retinoic acid-APL (RA-APL) syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural and pericardial effusions, edema, and hepatic, renal, and multi-organ failure. This syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multi-organ failure. The syndrome generally occurs during the first month of treatment, with some cases reported following the first dose of tretinoin capsules. The management of the syndrome has not been defined rigorously, but high-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality. At the first signs suggestive of the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg intravenously administered every 12 hours for 3 days or until the resolution of symptoms) should be immediately initiated, irrespective of the leukocyte count. The majority of patients do not require termination of tretinoin capsules therapy during treatment of the RA-APL syndrome. However, in cases of moderate and severe RA-APL syndrome, temporary interruption of tretinoin capsules therapy should be considered. /Tretinoin, systemic/
/BOXED WARNING/ During tretinoin capsules treatment about 40% of patients will develop rapidly evolving leukocytosis. Patients who present with high WBC at diagnosis (>5x10 9/L) have an increased risk of a further rapid increase in WBC counts. Rapidly evolving leukocytosis is associated with a higher risk of life-threatening complications. If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately. Some investigators routinely add chemotherapy to tretinoin capsules treatment in the case of patients presenting with a WBC count of >5x10 9/L or in the case of a rapid increase in WBC count for patients leukopenic at start of treatment, and have reported a lower incidence of the RA-APL syndrome. Consideration could be given to adding full-dose chemotherapy (including an anthracycline if not contraindicated) to the tretinoin capsules therapy on day 1 or 2 for patients presenting with a WBC count of >5x10 9/L, or immediately, for patients presenting with a WBC count of <5x10 9/L, if the WBC count reaches >/= 6x10(9)/L by day 5, or >/= 10x10(9)/L by day 10, or >/=15x10(9)/L by day 28. /Tretinoin, systemic/
/BOXED WARNING/ Teratogenic Effects. Pregnancy Category D. There is a high risk that a severely deformed infant will result if tretinoin capsules are administered during pregnancy. If, nonetheless, it is determined that tretinoin capsules represent the best available treatment for a pregnant woman or a woman of childbearing potential, it must be assured that the patient has received full information and warnings of the risk to the fetus if she were to be pregnant and of the risk of possible contraception failure and has been instructed in the need to use two reliable forms of contraception simultaneously during therapy and for 1 month following discontinuation of therapy, and has acknowledged her understanding of the need for using dual contraception, unless abstinence is the chosen method. Within 1 week prior to the institution of tretinoin capsules therapy, the patient should have blood or urine collected for a serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL. When possible, tretinoin capsules therapy should be delayed until a negative result from this test is obtained. When a delay is not possible, the patient should be placed on two reliable forms of contraception. Pregnancy testing and contraception counseling should be repeated monthly throughout the period of tretinoin capsules treatment. /Tretinoin, systemic/
For more Drug Warnings (Complete) data for all-trans-Retinoic acid (44 total), please visit the HSDB record page.

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Pharmacodynamics
Tretinoin is a vitamin A derivative that promotes cell production, proliferation, and differentiation. When used topically, tretinoin regulates epidermal cell turnover and collagen production. It also prevents collagen loss, reduces inflammation, and blocks the induction of matrix metalloproteinase (MMP), which are enzymes that disrupt collagen and elastic fibres. In short-term and long-term studies, topical application of tretinoin at doses ranging from 0.001% to 0.1% was associated with improvements in clinical signs of photoaging and fine wrinkles, increased epidermal thickness, compaction of the stratum corneum, and decreased melanin content. It also improved melanocyte differentiation and distribution, promotion of epidermal hyperplasia, and angiogenesis. Tretinoin exhibits antineoplastic activities when given orally. Tretinoin was shown to induce differentiation in tumour cells. It induced cytodifferentiation and decreased acute promyelocytic leukemia (APL) cell proliferation in culture and _in vivo_. In patients with APL, tretinoin promoted the initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission.

C20H28O2

300.4

300.208

302-79-4

Retinoic acid-d5;78996-15-3;Retinoic acid;302-79-4;11-cis-Retinoic Acid-d5;Retinoic acid-d6;2483831-72-5

444795

Yellow to light-orange crystalline powder
Crystals from ethanol

1.0±0.1 g/cm3

462.8±14.0 °C at 760 mmHg

179-184ºC

350.6±11.0 °C

0.0±2.5 mmHg at 25°C

1.556

6.83

37.3

1

2

5

22

567

0

CC1(C)C(/C=C/C(C)=C/C=C/C(C)=C/C(O)=O)=C(C)CCC1

SHGAZHPCJJPHSC-YCNIQYBTSA-N

InChI=1S/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)/b9-6+,12-11+,15-8+,16-14+

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid

All-trans Retinoic Acid; Ro 5488; Ro-5488; Vitamin A acid; ATRA; TRA; Ro5488; alltrans vitamin A acid; betaretinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; Trade names: Avita; Renova; Aberel; Aknoten; RetinA; RetinA MICRO; Vesanoid. Foreign brand names: Airol; Eudyna; RetisolA; StievaA; Cordes Vas; Dermairol; EpiAberel; StievaA Forte; Vitinoin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 2.5 mg/mL (8.32 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声和加热处理
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.32 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浮液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (8.32 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 2.5 mg/mL (8.32 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: 2.5 mg/mL (8.32 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 6 中的溶解度: 5 mg/mL (16.64 mM) in 50% PEG300 50% PBS (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 需要超声助溶并加热至 40°C。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。