他扎罗汀 (AGN 190168) 可用作佐剂或单一疗法。它有凝胶和乳霜配方。它与类固醇、卡泊三烯和光疗联合使用治疗牛皮癣，与抗生素联合治疗痤疮。肿瘤抑制因子他扎罗汀 (AGN 190168) 诱导的基因 3 在银屑病和皮肤癌中过度表达，已被证明可被他扎罗汀 (AGN 190168) 上调 [1]。 Tazorotene (AGN 190168) 可降低人表皮细胞培养物中两种与银屑病相关的标记蛋白 MRP-8（钙粒蛋白 A）和 SKALP（皮肤源性抗白蛋白 A）的表达。表皮高度增加[2]。

他扎罗汀（AGN 190168）以凝胶形式局部涂抹，直接进入皮肤。将凝胶局部应用于健康个体和银屑病患者的皮肤后，大约 4% 至 6% 的 0.1% 他扎罗汀 (AGN 190168) 凝胶保留在角质层中，2% 扩散到体内表皮和真皮10小时。它旨在将他扎罗汀 (AGN 190168) 完全、快速地转化为其活性代谢物他扎罗汀酸。在动物中，他扎罗汀酸的全身停留时间较短且组织分布有限[3]。局部给药时，他扎罗汀 (AGN 190168) 会抑制无毛小鼠表皮中肿瘤启动子 12-O-十四烷酰佛波醇 13-乙酸酯 (13-乙酸酯) 产生的鸟氨酸脱羧酶 (ODC) (TPA) 活性 [3]。

Absorption, Distribution and Excretion
Minimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.
Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.

---

Metabolism / Metabolites
Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.

---

Biological Half-Life
The half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Topical tazarotene has not been studied during breastfeeding. Some experts feel it should not be used on a large surface area (perhaps greater than 20% of body surface area) while nursing because of possible absorption. Others recommend that it not be used during breastfeeding because of its suspected mutagenic properties. If tazarotene is used, ensure that the infant's skin does not come into direct contact with the areas of maternal skin that have been treated and the infant does not ingest the product from the mother's skin.
◉ 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.

---

Protein Binding
The active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).

[1]. Talpur R, et al. Efficacy and safety of topical tazarotene: a review. Expert Opin Drug Metab Toxicol. 2009 Feb;5(2):195-210.
[2]. Nagpal S, et al. Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acidreceptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ. 1996 Dec;7(12):1783-91.
[3]. Tang-Liu DD, et al. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet. 1999 Oct;37(4):273-87.

Tazarotene is the ethyl ester of tazarotenic acid. A prodrug for tazarotenic acid, it is used for the treatment of psoriasis, acne, and sun-damaged skin. It has a role as a keratolytic drug, a prodrug and a teratogenic agent. It is a retinoid, a thiochromane, a member of pyridines, an acetylenic compound and an ethyl ester. It is functionally related to a tazarotenic acid.
Tazarotene, commonly marketed as Tazorac®, Avage®, and Zorac®, is member of the acetylenic class of retinoids. It is a prodrug that is found in topical formulations used in the treatment of various conditons, such as psoriasis, acne, and sun damaged skin (photodamage).
Tazarotene is a Retinoid.
Tazarotene is a synthetic, topical retinoid. Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. In psoriasis, tazarotene normalizes abnormal keratinocyte differentiation and reduces their hyperproliferation. (NCI04)
See also: Tazarotenic acid (has active moiety); Halobetasol propionate; tazarotene (component of); Niacinamide; tazarotene (component of) ... View More ...

---

Drug Indication
Used to treat psoriasis, acne and sun damaged skin (photodamage).
FDA Label
Treatment of lamellar ichthyosis

---

Mechanism of Action
Although the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors.

---

Pharmacodynamics
Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.

C21H21NO2S

351.464

351.129

118292-40-3

Tazarotene-d8

5381

Light yellow to yellow solid powder

1.2±0.1 g/cm3

499.8±45.0 °C at 760 mmHg

97-98ºC

256.1±28.7 °C

0.0±1.3 mmHg at 25°C

1.625

6.22

64.49

0

4

5

25

547

0

S1C2C([H])=C([H])C(C#CC3C([H])=C([H])C(C(=O)OC([H])([H])C([H])([H])[H])=C([H])N=3)=C([H])C=2C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])[H]

OGQICQVSFDPSEI-UHFFFAOYSA-N

InChI=1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3

ethyl 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate

AGN 190168, Tazarotene, Fabior, Zorac AGN190168, AGN-190168

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~50 mg/mL (~142.26 mM)
: 0.1 mg/mL (~0.28 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.11 mM) (饱和度未知) 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), 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。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (7.11 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。

---

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。