Calcipotriol|112965-21-6|安捷凯

Background

Calcipotriol is a synthetic vitamin D₃?analog with high affinity for vitamin D receptors^[1]. Calcipotriol is mainly used to treat psoriasis. It is also effective in certain keratotic diseases (ichthyosis) as well as localized scleroderma and vitiligo, and has important immunomodulatory functions?^[2].

In vitro, calcipotriol (10nM) treated HL-60 cells for 24h caused cell apoptosis, but caused cell differentiation at a higher dose (100nM)^[3]. Calcipotriol (0.001-10μM) treated SCC13 cells for 4 days, dose-dependently inhibited cell proliferation and stimulated cell differentiation, but did not induce SCC13 cell apoptosis, and specifically inhibited the autocrine activation of the EGFR signaling pathway?^[4].

In vivo, calcipotriol combined with BDP ointment (40 mg, once daily, administered topically on the skin) treated rats with psoriasis-like dermatitis. Compared with the vaseline treatment group, it significantly inhibited ear skin thickening and Transepidermal water loss^[5]. Calcipotriol (0.1mg/kg) can reduce knee joint swelling and relieve synovitis through a single intra-articular injection in ZIA rats?^[6].

参考文献:

[1] Sakabe J, et al. Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes[J].Acta Dermato-Venereologica, 2014, 94(5).

[2] Guilhou JJ. Le Calcipotriol [Calcipotriol]. Ann Dermatol Venereol. 2001 Mar;128(3 Pt 1):229-37. French. PMID: 11319386.

[3] Milczarek M, Chodyński M, Filip-Psurska B, et al. Synthesis and biological activity of diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, against human HL-60 leukemia and MCF-7 breast cancer cells[J]. Cancers, 2013, 5(4): 1355-1378.

[4] Lee E A, Jeon S H, Yi J Y, et al. Calcipotriol inhibits autocrine phosphorylation of EGF receptor in a calcium-dependent manner, a possible mechanism for its inhibition of cell proliferation and stimulation of cell differentiation[J]. Biochemical and biophysical research communications, 2001, 284(2): 419-425.

[5] Satake K, Amano T, Okamoto T. Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis[J]. European Journal of Pharmacology, 2018, 826: 31-38.

[6]??Huhtakangas J A, Huovinen J, Laaksonen S, et al. A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats[J]. Plos one, 2021, 16(4): e0250352.

卡泊三醇(Calcipotriol)是一种合成的维生素D3 类似物,对维生素D受体具有高亲和力[1]。卡泊三醇主要用于治疗银屑病,对某些角化性疾病(鱼鳞病)以及局部硬皮病和白癜风也有效,并具有重要的免疫调节功能[2]。

在体外,卡泊三醇(10nM)处理HL-60细胞24h,引起细胞凋亡,但在更高剂量(100nM)时引起细胞分化[3]。卡泊三醇(0.001-10μM)处理SCC13细胞4天,剂量依赖性地抑制细胞增殖并刺激细胞分化,但不诱导SCC13细胞凋亡,且特异性地抑制了EGFR信号通路的自分泌激活[4]。

在体内,卡泊三醇联合BDP软膏(40mg,每日一次,给药方式为皮肤局部涂抹)治疗银屑病样皮炎大鼠,与凡士林治疗组相比,显著抑制了耳部皮肤增厚和经皮水分流失[5]。卡泊三醇(0.1 mg/kg)通过单次关节内注射治疗ZIA大鼠,可以减轻膝关节肿胀,缓解滑膜炎[6]。

Protocol

Cell experiment [1]:

Cell lines

HL-60 cells

Preparation Method

HL-60 cells were pre-exposed to calcipotriol (0.1, 1, 10, 100 nM) for 24h, and then incubated with CIS for the next 48h.

Reaction Conditions

0.1, 1, 10, 100 nM; 24 h

Applications

Calcipotriol caused the apoptosis of HL-60 cells at the dose of 10nM, but in a higher dose (100nM) caused cell differentiation.

Animal experiment [2]:

Animal models

Male Hairless HWY rats

Preparation Method

HWY rats received a daily topical dose of 10mg/ear or 25mg/back skin of 5% IMQ cream for 4 consecutive days in order to induce psoriasis-like skin dermatitis. Ears were treated with Vaseline, BDP, or Calcipotriol/BDP at doses of 10mg/ear and 40 mg/ear 1 hour after each application of IMQ.

Dosage form

10mg, 40 mg; apply topically to skin

Applications

Compared with the vaseline treatment group, 40 mg/ear calcipotriol/BDP ointment significantly inhibited ear thickening and transepidermal water loss.

参考文献:

[1] Milczarek M, Chodyński M, Filip-Psurska B, et al. Synthesis and biological activity of diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, against human HL-60 leukemia and MCF-7 breast cancer cells[J]. Cancers, 2013, 5(4): 1355-1378.
[2]Satake K, Amano T, Okamoto T. Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis[J]. European Journal of Pharmacology, 2018, 826: 31-38.