Crisaborole (AN-2728) 的 IC50 值为 0.49、0.54、0.61、0.83、2.4 和 5.3 μM，抑制 PDE4、TNF-α、IL-2、IFN-γ、IL-5 和 IL-10。针对 PDE4 催化结构域最有效的化合物是 crisaborole (AN-2728)，但它也对 PDE1A3、PDE3Cat 和 PDE7A1 表现出抑制作用。 crisaborole (AN-2728) 抑制 PDE 同工酶 PDE1A3、PDE3Cat、PDE4Cat 和 PDE7A1，IC50 值为 6.1、6.4、0.11 和 0.73 μM[1]。晶体学表明，当苯并氧杂硼杂环戊烯与 PDE4 催化结构域中的疏水口袋结合时，它们对 PDE4 的亲和力会增加。这些苯并氧硼杂环化合物显着减少与 AD 和 Ps 相关的细胞因子的释放[2]。 Crisaborole (AN-2728) 是一种局部使用的含硼抗炎物质。它通过抑制 PDE4 活性发挥作用，进而阻止 TNFα、IL-12、IL-23 和其他细胞因子的释放 [3]。

以 1 mg/耳×2 给药后，crisaborole (AN-2728) 对佛波酯引起的耳水肿表现出相当大的抑制作用（分别为 78% 和 68%）。 Crisaborole (AN-2728) 可能具有良好的皮肤渗透性和抗炎活性，因为其功效与地塞米松相似[1]。据报道，crisaborole (AN-2728) 具有良好的耐受性，并对功效标志物表现出显着的影响，产生与临床试验中阳性对照相似的结果[3]。

Absorption, Distribution and Excretion
Systemic concentrations of crisaborole were reached by 8 days of twice-daily topical administration. It has low systemic absorption thus poses less risk for developing systemic side effects.
Renal excretion of metabolites is the major route of elimination.

---

Metabolism / Metabolites
Crisaborole is substantially metabolized into inactive metabolites. The major metabolite 5-(4-cyanophenoxy)-2-hydroxyl benzylalcohol (metabolite 1), is formed via hydrolysis; this metabolite is further metabolized into downstream metabolites, among which 5-(4-cyanophenoxy)-2-hydroxyl benzoic acid (metabolite 2), formed via oxidation, is also a major metabolite.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of topical crisaborole during breastfeeding. Some experts recommend avoiding its use during lactation because of the lack of information. In general, drugs applied to the mother’s skin are unlikely to affect the breastfed infant unless it is applied to the nipple or other area where the infant can directly ingest it. Use of crisaborole in nursing mothers is not contraindicated by the product labeling,
◉ 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
Based on an in vitro study, crisaborole is 97% bound to human plasma proteins

[1]. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2129-32.

[2]. AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. Curr Opin Investig Drugs. 2009 Nov;10(11):1236-42.

Crisaborole is a member of the class of benzoxaboroles that is 5-hydroxy-1,3-dihydro-2,1-benzoxaborole in which the phenolic hydrogen has been replaced by a 4-cyanophenyl group. A phosphodiesterase 4 inhibitor that is used for treatment of mild to moderate atopic dermatitis in children and adults. It has a role as a phosphodiesterase IV inhibitor, an antipsoriatic and a non-steroidal anti-inflammatory drug. It is a benzoxaborole, an aromatic ether and a nitrile.
Crisaborole is a novel oxaborole approved by FDA on December 14, 2016 as Eucrisa, a topical treatment of for mild to moderate atopic dermatitis. This non-steroidal agent is efficacious in improving disease severity, reducing the risk of infection and reducing the signs and symptoms in patients 2 years old and older. It reduces the local inflammation in the skin and prevents further exacerbation of the disease with a good safety profile. Its structure contains a boron atom, which facilitates skin penetration and binding to the bimetal center of the phosphodiesterase 4 enzyme. It is currently under development as topical treatment of psoriasis.
Crisaborole is a Phosphodiesterase 4 Inhibitor. The mechanism of action of crisaborole is as a Phosphodiesterase 4 Inhibitor.

---

Drug Indication
Intended for the topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.
FDA Label
Staquis is indicated for treatment of mild to moderate atopic dermatitis in adults and paediatric patients from 2 years of age with ≤ 40% body surface area (BSA) affected.
Treatment of atopic dermatitis

---

Mechanism of Action
Inhibition of PDE4 by crisaborole leads to elevated levels of cyclic adenosine monophosphate (cAMP). Increased intracellular levels of cAMP inhibit the NF-kB pathway and suppress the release of pro-inflammatory mediators such as TNF-alfa and various interleukins that play a causative role in psoriasis and atopic dermatitis. Suppression of downstream effects in different cell types may explain the therapeutic role of crisaborole in immune-mediated skin diseases.

---

Pharmacodynamics
Crisaborole has broad-spectrum anti-inflammatory activity by mainly targeting phosphodiesterase 4 (PDE4) enzyme that is a key regulator of inflammatory cytokine production. As this enzyme is expressed in keratinocytes and immune cells, crisaborole mediates an anti-inflammatory effect on almost all inflammatory cells. Topical application of this drug is useful as it potentiates the localization of this drug in the skin and this anti-inflammatory activity is in the low micromolar range.

C14H10BNO3

251.05

251.075

906673-24-3

Crisaborole-d4;2268785-42-6

44591583

White to khaki solid powder

1.3±0.1 g/cm3

425.9±55.0 °C at 760 mmHg

211.4±31.5 °C

0.0±1.1 mmHg at 25°C

1.629

1.568

62.48

1

4

2

19

361

0

USZAGAREISWJDP-UHFFFAOYSA-N

InChI=1S/C14H10BNO3/c16-8-10-1-3-12(4-2-10)19-13-5-6-14-11(7-13)9-18-15(14)17/h1-7,17H,9H2

4-((1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)oxy)benzonitrile

AN-2728; PF06930164; AN 2728; PF-06930164; AN2728; PF 06930164; trade name: Eucrisa

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (9.96 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 (9.96 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), 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。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (9.96 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。