| Identification | Back Directory | [Name]
LIAROZOLE DIHYDROCHLORIDE | [CAS]
1883548-96-6 | [Synonyms]
R75251 dihydrochloride
LIAROZOLE DIHYDROCHLORIDE
Liarozole dihydrochloride >=98% (HPLC) | [Molecular Formula]
C17H14Cl2N4 | [MOL File]
1883548-96-6.mol | [Molecular Weight]
345.23 |
| Chemical Properties | Back Directory | [storage temp. ]
room temp | [solubility ]
Water: ≥ 50 mg/mL (131.00 mM); DMSO: 50 mg/mL (131.00 mM) | [form ]
powder | [color ]
white to beige | [Water Solubility ]
H2O: 2mg/mL, clear |
| Hazard Information | Back Directory | [Uses]
Liarozole (R75251) dihydrochloride is an imidazole derivative and orally active retinoic acid (RA) metabolism-blocking agent (RAMBA). Liarozole dihydrochloride inhibits the cytochrome P450 (CYP26)-dependent 4-hydroxylation of RA (IC50=7 μM), resulting in increased tissue levels of RA. Liarozole dihydrochloride shows antitumoral properties[1][2][3]. | [Biological Activity]
Liarozole (R 75251R75,251) is an orally active benzimidazole-based retinoic acid (RA) metabolism blocking agent (RAMBA) th at targets multiple P450 enzymesincluding aromatase (CYP19)17-hydroxylase/17,20-lyase (CYP17A1)11-hydroxylase (CYP11B1)and RA 4-hydroxylase (CYP26). Liarozole is more effective than ketoconazole in vivo (plasma RA enhancement = 2.5 ng/mL vs. 1.3 ng/mL 2 hr after respective oral dosage of 40 mg/kg in rats) andin contrast to ketoconazoleLiarozole does not significantly affect circulating adrenal androgen levels. Liarozole is shown to effectively suppress androgen-dependent tumor expansion of R3327G Dunning prostate adenocarcinoma xenografts in rats (by 66% and 81% with 80 and 120 mg/kg/day p.o.respectively) independent of its androgen biosynthesis inhibition. | [in vivo]
Liarozole dihydrochloride (5-20 mg/kg; p.o.) reverses the vaginal keratosis caused by estrogen stimulation[5].
Liarozole dihydrochloride (40 mg/kg; p.o.) reduces tumor burden substantially[6]. | Animal Model: | Ovariectomized rats | | Dosage: | 5~20 mg/kg | | Administration: | P.o. | | Result: | Reversed the vaginal keratosis caused by estrogen stimulation. |
| Animal Model: | SCID mice | | Dosage: | 40 mg/kg | | Administration: | P.o. | | Result: | Inhibited tumor growth and survival.
|
| [IC 50]
CYP26: 7 μM (IC50) | [storage]
Store at -20°C | [References]
[1] Kuijpers AL, et al. The effects of oral liarozole on epidermal proliferation and differentiation in severe plaque psoriasis are comparable with those of acitretin. Br J Dermatol. 1998;139(3):380-389. DOI:10.1046/j.1365-2133.1998.02399.x
[2] Lucker GP, et al. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol. 1997;136(1):71-75. PMID:9039298
[3] Wouters W, et al. Effects of liarozole, a new antitumoral compound, on retinoic acid-induced inhibition of cell growth and on retinoic acid metabolism in MCF-7 human breast cancer cells. Cancer Res. 1992;52(10):2841-2846. PMID:1581897
[4] Pignatello MA, et al. Liarozole markedly increases all trans-retinoic acid toxicity in mouse limb bud cell cultures: a model to explain the potency of the aromatic retinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid. Toxicol Appl Pharmacol. 2002; 178(3):186-194. DOI:10.1006/taap.2001.9340
[5] Van Wauwe J, et al. Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic effects in vivo. J Pharmacol Exp Ther. 1992;261(2):773-779. PMID:1374473
[6] Stearns ME, et al. Liarozole and 13-cis-retinoic acid anti-prostatic tumor activity [published correction appears in Cancer Res 1993 Dec 1;53(23):5831]. Cancer Res. 1993;53(13):3073-3077. PMID:8319215 |
|
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
| Company Name: |
BOC Sciences
|
| Tel: |
|
| Website: |
https://www.bocsci.com |
| Company Name: |
Energy Chemical
|
| Tel: |
021-58432009 400-005-6266 |
| Website: |
http://www.energy-chemical.com |
| Company Name: |
R&D Systems, Inc
|
| Tel: |
18003437475 18003437475 |
| Website: |
www.rndsystems.com |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|