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| 250mg |
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| 500mg |
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Purity: ≥98%
Adapalene (Differin; Adaferin; CD271; Adapaleno; ADAPALENE; Adapalenum), structurallysimilar to vitamin A, is a synthetic, retinoic acid analog acting as a dual RAR and RXR agonist with potential anticancer activity. It activates RAR and RXR with EC50 values of 2.2, 9.3, 22 and > 1000 nM for RARβ, RARγ, RARα and RXRα receptors respectively, it is a third-generation topical retinoid mainly used in the treatment of acne. Adapalene inhibits proliferation and induces apoptosis in colorectal cancer cells in vitro and displays comedolytic activity.
| ln Vitro |
The viability of ES-2, HOV-7, MCF-7, Hela, SW1990, HT1080, and MM-468 cells is inhibited by Adapalene (1 - 200 μM; 24 h) with IC50 values of 10.36 μM, 10.81 μM, 12.00 μM, and 19.08, in that order. 19.52 μM, 21.70 μM, 31.47 μM, and μM[2]. Adapalene (10–40 μM; 24 h) decreases proliferation in vitro and causes apoptosis in ES-2 cells [2]. In LoVo or DLD1 cells, adipalene (3-30 μM; 6-24 hours) dramatically raises the G1 phase population [3]. GOT1 activity is inhibited by dipalene (1 - 200 μM) with an IC50 of 21.79 μM[2]. Transglutaminase type I, an enzyme linked to the plasma membrane, is inhibited by adipalene (10-6-10-3 nM), having an IC of 50 2.5 nM[1].
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| ln Vivo |
In BALB/C nude mice, adapalene (15–100 mg/kg; orally administered daily for 21 days) inhibits the growth of xenograft tumors derived from DLD1 cells [3].
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: Pancreatic cancer (SW1990, Aspc-1), breast cancer (mm-231, mm-468, MCF-7), liver cancer (Hep3B), cervical cancer (Hela), ovarian cancer ( HOV-7, ES-2), normal cells (CHO, L929) Tested Concentrations: 1-200 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited the viability of cancer cells with higher GOT1 protein expression. Apoptosis Analysis[2] Cell Types: ES -2 cells[2] Tested Concentrations: 10, 20, 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated a significant increase in apoptosis compared with the control group. Down regulated the expression of anti-apoptotic protein Bcl-2 and PARP. Cell Cycle Analysis[3] Cell Types: LoVo or DLD1 cells Tested Concentrations: 3, 10, 30 μM Incubation Duration: 6, 12, 24 hrs (hours) Experimental Results: Caused cell cycle arrest in G1 phase in a dose- and time-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Female BALB/C nude mice (15 g, 4-5 weeks) were injected with DLD1 cells[3]
Doses: 15, 20, 65, 100 mg/kg Route of Administration: Po daily for 21 days Experimental Results: Dramatically decreased tumor weight and volume. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm2 of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean Cmax of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng\*h/ml on day 10. Adapalene is primarily excreted by the biliary route at about 30 ng/g of the topically applied amount. Approximately 75% of the drug remains unchanged. Adapalene is rapidly cleared from blood plasma, typically undetectable after 72 hours following topical application. Metabolism / Metabolites Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug. Metabolized mainly by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route. Route of Elimination: Excretion appears to be primarily by the biliary route. Biological Half-Life In one clinical study, after ten days of treatment with 2g of 0.3% cream or gel, the terminal half-life was between 7 and 51 hours, with a mean of 17.2 ± 10.2. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Mechanistically, adapalene binds to specific retinoic acid nuclear receptors (gamma and beta) and retinoid X receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Topical adapalene has not been studied during breastfeeding. Because it is poorly absorbed after topical application, and blood levels are less than 0.25 mcg/L with long-term use, it is probably a low risk to the nursing infant. Absorption should be minimized by applying it to the smallest possible surface area of the body for the shortest time possible. Do not apply to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Toxicity Data The acute oral toxicity of adapalene in mice and rats is greater than 10 mL/kg |
| References |
[1]. Shroot B, et, al. Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103.
[2]. Wang Q, et, al. Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. Bioorg Chem. 2019 Dec;93:103315. [3]. Shi XN, et, al. Adapalene inhibits the activity of cyclin-dependent kinase 2 in colorectal carcinoma. Mol Med Rep. 2015 Nov;12(5):6501-8. |
| Additional Infomation |
Pharmacodynamics
Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported. |
| Molecular Formula |
C28H28O3
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| Molecular Weight |
412.52
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| Exact Mass |
412.203
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| CAS # |
106685-40-9
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| Related CAS # |
Adapalene sodium salt;911110-93-5;Adapalene-d3;1276433-89-6
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| PubChem CID |
60164
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
606.3±55.0 °C at 760 mmHg
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| Melting Point |
319-322ºC
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| Flash Point |
205.9±25.0 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.655
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| LogP |
8.04
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC2=CC=C(C3=CC=C(OC)C(C45C[C@@H](C[C@H](C6)C5)C[C@@H]6C4)=C3)C=C2C=C1)O
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| InChi Key |
LZCDAPDGXCYOEH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H28O3/c1-31-26-7-6-23(21-2-3-22-12-24(27(29)30)5-4-20(22)11-21)13-25(26)28-14-17-8-18(15-28)10-19(9-17)16-28/h2-7,11-13,17-19H,8-10,14-16H2,1H3,(H,29,30)
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| Chemical Name |
6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (2.42 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4241 mL | 12.1206 mL | 24.2412 mL | |
| 5 mM | 0.4848 mL | 2.4241 mL | 4.8482 mL | |
| 10 mM | 0.2424 mL | 1.2121 mL | 2.4241 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04823845 | Withdrawn | Drug: Topical Adapalene Gel 0.1% | Plantar Wart | University of Louisville | May 1, 2022 | Early Phase 1 |
| NCT01951417 | Completed Has Results | Drug: Adapalene/BPO Gel Other: Moisturizer SPF 30 |
Acne | Galderma R&D | October 2013 | Phase 4 |
| NCT05536882 | Withdrawn | Drug: Benzoyl peroxide Drug: Adapalene Gel |
Molluscum Contagiosum | University of Oklahoma | May 18, 2022 | Phase 3 |
| NCT02932267 | Completed Has Results | Drug: Adapalene 0.3% / BPO 2.5% gel | Acne Vulgaris | Galderma R&D | February 2, 2017 | Phase 3 |
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