Tacalcitol monohydrate

Tacalcitol monohydrate (CAS No.: 93129-94-3) is the monohydrate form of Tacalcitol (CAS No.: 57333-96-7), a synthetic analog of vitamin D₃ (1α,24(R)-dihydroxyvitamin D₃). Its core therapeutic target is the vitamin D receptor (VDR), with involvement of the calcium-sensing receptor (CaSR). It regulates the expression of genes such as CDKN1A, TYMS, and BIRC5 in a VDR-dependent manner and can transcriptionally activate the nerve growth factor (NGF) gene. The half-maximal effective concentration (ED₅₀) for inducing NGF production is 10⁻¹⁰~10⁻⁹ M, and the in vitro effective concentration range is 1~1000 nM. Specifically, 100 nM is commonly used in colorectal cancer cells (HT-29) either as a single agent or in combination with 5-fluorouracil, while the concentration range in human epidermal keratinocytes (K-TL-1) is 10⁻¹²~10⁻⁷ M (with the optimal NGF induction effect at 10⁻⁸ M). Clinically, it is available as a topical formulation (ointment/cream) for the treatment of psoriasis vulgaris, exerting its effect by regulating the proliferation and differentiation of keratinocytes. Meanwhile, it can induce cutaneous NGF synthesis (peaking within 24 hours and persisting for 96 hours), showing potential for improving peripheral neuropathy. It also enhances the anticancer activity of 5-fluorouracil by downregulating thymidylate synthase (TS), inhibiting epithelial-mesenchymal transition (EMT) and autophagy, and inducing cell cycle arrest. Additionally, it has lower calcemic toxicity than active vitamin D₃ and minimal systemic side effects when administered topically.

References:

[1] Fukuoka M, Sakurai K, Ohta T, Kiyoki M, Katayama I. Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes. Skin Pharmacol Appl Skin Physiol. 2001 Jul-Aug;14(4):226-33. doi: 10.1159/000056351. PMID: 11464105.

[2] Milczarek M, Rossowska J, Klopotowska D, Stachowicz M, Kutner A, Wietrzyk J. Tacalcitol increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating the thymidylate synthase. J Steroid Biochem Mol Biol. 2019 Jun;190:139-151. doi: 10.1016/j.jsbmb.2019.03.017. Epub 2019 Mar 25. PMID: 30923017.