Name: Emcitate (tiratricol) in MCT8 deficiency: Mechanism of action
Published: 2026-09-14T15:39:06-04:00

Product information and disease description Product description Product information Pharmacology

Mechanism of action

5 evidence topics · 7 sources

Thyroid hormone receptor agonism independent of MCT8

“Tiratricol is a thyroid hormone receptor (THR) agonist which, unlike triiodothyronine (T3) and thyroxine (T4), can enter cells independent of the transmembrane transporter protein MCT8.” (opens the prescribing information at this quote)
“In patients with MCT8 deficiency, X-linked loss-of-function mutations in the SLC16A2 gene encoding MCT8 impair T3 entry into target tissues.” (opens the prescribing information at this quote)
“This results in insufficient T3 activity in the brain concurrent with persistent peripheral thyrotoxicosis from accumulation of circulating T3.” (opens the prescribing information at this quote)
“Intracellular tiratricol activity at THR-independent of MCT8-mediated membrane transport, can modulate hypothalamic-pituitary-thyroid axis signaling and reduce circulating T3 in patients with MCT8 deficiency.” (opens the prescribing information at this quote)

MCT8-independent cellular entry

“Tiratricol, an analogue and metabolite of the thyroid hormone triiodothyronine (T3), has thyromimetic effects but differs from T3 in that it can enter cells independent of MCT8.” (opens the source at this quote in a new tab)

“The active substance in Emcitate, tiratricol, is very similar to T3 but it does not need MCT8 to move in and out of cells.” (opens the source at this quote in a new tab)

MCT8-independent uptake in patient fibroblasts and neural cells

“Fibroblasts from MCT8 patients showed an impaired T3 uptake compared with controls, whereas TA3 uptake was similar in patient and control fibroblasts.” (opens the source at this quote in a new tab)
“In transfected cells, TA3 did not show significant transport by MCT8.” (opens the source at this quote in a new tab)
“Most importantly, treatment of athyroid Pax8-knockout mice and Mct8/Oatp1c1-double knockout mice between postnatal days 1 and 12 with TA3 restored T3-dependent neural differentiation in the cerebral and cerebellar cortex, indicating that TA3 can replace T3 in promoting brain development.” (opens the source at this quote in a new tab)

“In vitro studies have clearly shown that Triac acts similarly in MCT8-deficient and control cells, indicating that MCT8 is not involved in cellular entry of Triac.” (opens the source at this quote in a new tab)

Thyroid receptor binding

“Tiratricol binds with high affinity to thyroid receptors and does not require MCT8 to enter cells.” (opens the source at this quote in a new tab)
“It exerts similar biologic effects to T3 and can restore normal thyroid hormone activity in MCT8-dependent tissues.” (opens the source at this quote in a new tab)

Tiratricol cellular transport

“The aim of the study was to identify transporters that facilitate TRIAC uptake into cells.” (opens the source at this quote in a new tab)
“We identified SLC22A9 and SLC29A2 as transporters mediating cellular uptake of TRIAC.” (opens the source at this quote in a new tab)
“SLC22A9 encodes the organic anion transporter 7 (OAT7), a sodium-independent organic anion transporter expressed in the plasma membrane in brain, pituitary, liver, and other organs.” (opens the source at this quote in a new tab)
“SLC29A2 encodes the equilibrative nucleoside transporter 2 (ENT2), which is ubiquitously expressed, including pituitary and brain.” (opens the source at this quote in a new tab)
“Knowledge of TRIAC transporter expression patterns, also during brain development, may thus in the future help to interpret observations on TRIAC effects, as well as understand why TRIAC may not show a desirable effect on cells or organs not expressing appropriate transporters.” (opens the source at this quote in a new tab)