Disease relevance of D01125

• Calcipotriene ointment has recently been approved for the treatment of moderate plaque psoriasis [1].
• Topical calcipotriol treatment in advanced breast cancer [2].
• Calcipotriol and regression in T-cell lymphoma of skin [3].
• Calcipotriol was initially converted into the 24-ketone (MC1046) and its 22,23-hydrogenated derivative (MC1080), metabolites observed in osteosarcoma, kidney, and hepatoma cell lines [4].
• Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition [5].

Psychiatry related information on D01125

• CONCLUSION: Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis [6].
• AIM: To find out the patient compliance, efficacy and tolerance to a regimen of a calcipotriol cream application in the morning and a calcipotriol ointment application in the evening [7].
• RESULTS: After 2 weeks, psoriasis scores were significantly lower (P < .001) in the combination therapy group (adjusted trunk lesion score = 0.67) compared with monotherapy with either agent (lesion scores = 1.40 calcipotriene, 1.13 clobetasol foam) [8].

High impact information on D01125

• Inefficacy of calcipotriol in skin metastases from breast cancer [9].
• At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001) [10].
• The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial [10].
• Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)(2)D(3) analog calcipotriol [11].
• The in vitro metabolism of calcipotriol was studied in two keratinocyte cell models, HPK1A and HPK1A-ras [4].

Chemical compound and disease context of D01125

• 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body [10].
• Furthermore, 1 alpha,24(S)-dihydroxyvitamin D2 was metabolized by the human keratinocyte cell line HPK1A-ras at a slower rate than either 1 alpha,25-dihydroxyvitamin D3 or calcipotriol, a drug used effectively in the treatment of psoriasis [12].
• Two analogues have been approved for use in patients: calcipotriol (Dovonex from Leo Pharmaceuticals, Copenhagen, Denmark) for the treatment of psoriasis; and 19-nor-1,25(OH)2D2 (Zemplar from Abbott Laboratories, Abbott Park, IL) for secondary hyperparathyroidism [13].
• The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group [14].
• METHODS: We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas [15].

Biological context of D01125

• The biological activity of each of the principal metabolites of calcipotriol, assessed using a growth hormone reporter gene transcriptional activation system and a vitamin D receptor assay, was found to be lower than that of calcipotriol [4].
• Divergent effects of epidermal growth factor and calcipotriol on human rectal cell proliferation [16].
• Both calcipotriol and 1,25-(OH)2D3 inhibited the proliferation of human osteoblast-like cells in a dose-dependent manner (10(-10)-10(-6) M), an effect observed at different cell densities [17].
• Effects of calcitriol, 22-oxacalcitriol, and calcipotriol on serum calcium and parathyroid hormone gene expression [18].
• Although our in vitro findings cannot be directly extrapolated to the in vivo human condition, they do suggest that the inhibitory effects of calcipotriol and anthralin on tRNA biogenesis may be implicated in the mechanisms of their antipsoriatic action [19].

Anatomical context of D01125

• Calcipotriol (10(-5) M to 10(-9) M) produced a clearcut dose response inhibition of HT-29 cell growth [20].
• Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative proctocolitis [5].
• However, calcipotriol increased Ca2+ influx in myocytes and myoblasts to a greater extent than the natural hormone, whereas MC 1288 was more active only in myoblasts [21].
• Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin [22].
• These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen-presenting cells in psoriatic epidermis [22].

Associations of D01125 with other chemical compounds

• We have studied the effects of calcitriol, oxacalcitriol, and calcipotriol on serum calcium and PTH mRNA levels in vivo and in vitro [18].
• We analyzed therefore the effects of calcipotriol and vitamin D3 on the production of plasminogen activator (PA) activity in human keratinocytes and a mouse keratinocyte cell line [23].
• Treatment with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and 20 mRNA [24].
• Here, we report the crystal structures of VDR ligand binding domain bound to two vitamin D agonists of therapeutical interest, calcipotriol and seocalcitol, which are characterized by their side chain modifications [25].
• Effects of calcitriol and its analogues, calcipotriol (MC 903) and 20-epi-1alpha,25-dihydroxyvitamin D3 (MC 1288), on calcium influx and DNA synthesis in cultured muscle cells [21].

Gene context of D01125

• Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels [26].
• During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis [27].
• Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis [28].
• On the basis of these data we hypothesize that, besides epidermal keratinocytes, another target for Calcipotriol may be the skin's own immune system, suggesting that Calcipotriol can modify T lymphocyte activity (IL-1 dependent) through a down-regulation of CAMs [29].
• Calcipotriol reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56 (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this tissue expressed the EGF receptor [16].

Analytical, diagnostic and therapeutic context of D01125

• Combination phototherapy of psoriasis with calcipotriol and narrow-band UVB [30].
• Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M) [5].
• Pooled data from clinical trials show that calcipotriol is well tolerated, with the majority of adverse events being mild and transient local reactions [31].
• Using in situ hybridization we have studied mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin from psoriatic patients before and during short-term treatment with either oral cyclosporine A or topical calcipotriol [24].
• Peak levels of 20-30% sphingomyelin hydrolysis were measured 3 h after treatment of the cells with 1 alpha,25-dihydroxyvitamin D3 or with the vitamin D3 analogue, calcipotriol [32].

References