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Chemical Compound Review:

Vellutan (1S,3S,5Z)-5-[(2E)-2- [(1R,3aR,7aR)-1-[(2R...

Synonyms: Bonalfa, Curatoderm, tacalcitol, Apsor, Tacalcitolum, ...

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Disease relevance of Bonalfa

Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191) [1].
In the present study, we evaluated effects of (24R)-1,24-dihydroxycholecalciferol (PRI-2191) on hydrogen peroxide- and excitatory amino acid-induced neuronal damage in human neuroblastoma (SH-SY5Y) cell line [2].
The obtained results suggest potential usefulness of PRI 2191 in the treatment of neurodegenerative diseases [2].
Importantly, in freshly obtained acute myeloid leukemia (AML)-M2 cells exposed to PRI-2191, a novel deltanoid with a modified side chain, upregulation of C/EBPbeta paralleled the induction of monocytic differentiation [3].

High impact information on Bonalfa

PRI-2191 alone had no effect on gene expression, but it enhanced the seizure-evoked expression of HSP-70, had an opposite effect on BDNF mRNA level and did not affect prepro-TRH mRNA level [4].
Summing up, the present study demonstrated that subchronic administration of PRI-2191 significantly modulated the seizure-related changes in both the brain and the peripheral immune system of rats [4].
An immunological study revealed that PRI-2191 reversed the seizure-induced decrease in the proliferative activity of splenocytes and their ability to produce interferon-gamma [4].
C-25 hydroxylation of 1alpha,24(R)-dihydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1): metabolism studies with human keratinocytes and rat recombinant CYP24A1 [5].
In addition, analogues PRI-1906 and PRI-2191 were screened against cells of human leukaemia HL-60 line and against normal human skin fibroblasts [6].

Gene context of Bonalfa

On the other hand, wortmannin did not affect the neuroprotective effects of 1,25 dihydroxyvitamin D(3) This suggests that the activation of PI3-K/Akt signaling pathway plays an important role in the mechanism of inhibitory action of PRI-2191 on hydrogen peroxide-evoked toxicity in SH-SY5Y cells [7].

References

Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191). Wietrzyk, J., Pełczyńska, M., Madej, J., Dzimira, S., Kuśnierczyk, H., Kutner, A., Szelejewski, W., Opolski, A. Steroids (2004) [Pubmed]
Neuroprotective effects of (24R)-1,24-dihydroxycholecalciferol in human neuroblastoma SH-SY5Y cell line. Tetich, M., Kutner, A., Leskiewicz, M., Budziszewska, B., Lasoń, W. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
The rationale for deltanoids in therapy for myeloid leukemia: role of KSR-MAPK-C/EBP pathway. Studzinski, G.P., Wang, X., Ji, Y., Wang, Q., Zhang, Y., Kutner, A., Harrison, J.S. J. Steroid Biochem. Mol. Biol. (2005) [Pubmed]
Effects of PRI-2191--a low-calcemic analog of 1,25-dihydroxyvitamin D3 on the seizure-induced changes in brain gene expression and immune system activity in the rat. Tetich, M., Dziedzicka-Wasylewska, M., Kuśmider, M., Kutner, A., Leśkiewicz, M., Jaworska-Feil, L., Budziszewska, B., Kubera, M., Myint, A.M., Basta-Kaim, A., Skowroński, M., Lasoń, W. Brain Res. (2005) [Pubmed]
C-25 hydroxylation of 1alpha,24(R)-dihydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1): metabolism studies with human keratinocytes and rat recombinant CYP24A1. Astecker, N., Bobrovnikova, E.A., Omdahl, J.L., Gennaro, L., Vouros, P., Schuster, I., Uskokovic, M.R., Ishizuka, S., Wang, G., Reddy, G.S. Arch. Biochem. Biophys. (2004) [Pubmed]
Antiproliferative activity in vitro of side-chain analogues of calcitriol against various human normal and cancer cell lines. Opolski, A., Wietrzyk, J., Chrobak, A., Marcinkowska, E., Wojdat, E., Kutner, A., Radzikowski, C. Anticancer Res. (1999) [Pubmed]
Involvement of PI3-K in neuroprotective effects of the 1,25-dihydroxyvitamin D(3) analogue - PRI-2191. Regulska, M., Leśkiewicz, M., Budziszewska, B., Kutner, A., Basta-Kaim, A., Kubera, M., Jaworska-Feil, L., Lasoń, W. Pharmacological reports : PR (2006) [Pubmed]

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