Target Validation Information
TTD ID	T84886
Target Name	Solute carrier family 12 member 3 (SLC12A3)
Type of Target	Successful
Drug Potency against Target	Polythiazide	Drug Info	IC50 = 120 nM	[1]
Action against Disease Model	Hydrochlorothiazide	Drug Info	Long-term thiazide diuretic use is associated with higher bone mineral density and reduced hip fracture rates, which are attributed to increased ser uM calci uM levels and decreased parathyroid activity that lead to decreased bone resorption. The present study shows that 1-100 microM hydrochlorothiazide (HCTZ) dose dependently inhibits bone resorption by isolated rat osteoclasts in the bone slice assay with an IC50 of approximately 20 microM. At these concentrations, HCTZ did not affect osteoclast survival on bone slices and had no effect on the proliferation of uMR-106 rat osteoblasts, indicating that the compound is not cytotoxic. However, such concentrations of HCTZ are unlikely to be achieved in man where therapeutic doses are usually 12.5-100 mg/day. That the invitro effect of HCTZ on bone resorption may be due to inhibition of osteoclast carbonic anhydrase is discussed.	[2]
References
REF 1	[Lack of effect of cicletanine and its sulfoconjugated metabolite on the thiazide receptor expressed in Xenopus oocytes]. Arch Mal Coeur Vaiss. 1999 Aug;92(8):1001-4.
REF 2	Hydrochlorothiazide inhibits osteoclastic bone resorption in vitro. Calcif Tissue Int. 1994 Oct;55(4):266-8.

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