Compound W

Inhibitor of γ-secretase; causes a decrease in the released levels of Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).

Assessing metal-metal multiple bonds in Cr-Cr, Mo-Mo, and W-W compounds and a hypothetical U-U compound: a quantum chemical study comparing DFT and multireference methods.[Pubmed:22237933]

Chemistry. 2012 Feb 6;18(6):1737-49.

To gain insights into the trends in metal-metal multiple bonding among the Group 6 elements, density functional theory has been employed in combination with multiconfigurational methods (CASSCF and CASPT2) to investigate a selection of bimetallic, multiply bonded compounds. For the compound [Ar-MM-Ar] (Ar=2,6-(C(6)H(5))(2)-C(6)H(3), M=Cr, Mo, W) the effect of the Ar ligand on the M(2) core has been compared with the analogous [Ph-MM-Ph] (Ph=phenyl, M=Cr, Mo, W) compounds. A set of [M(2)(dpa)(4)] (dpa=2,2'-dipyridylamide, M=Cr, Mo, W, U) compounds has also been investigated. All of the compounds studied here show important multiconfigurational behavior. For the Mo(2) and W(2) compounds, the sigma(2)pi(4)delta(2) configuration dominates the ground-state wavefunction, contributing at least 75%. The Cr(2) compounds show a more nuanced electronic structure, with many configurations contributing to the ground state. For the Cr, Mo, and W compounds the electronic absorption spectra have been studied, combining density functional theory and multireference methods to make absorption feature assignments. In all cases, the main features observed in the visible spectra may be assigned as charge-transfer bands. For all compounds investigated the Mayer bond order (MBO) and the effective bond order (EBO) were calculated by density functional theory and CASSCF methods, respectively. The MBO and EBO values share a similar trend toward higher values at shorter normalized metal-metal bond lengths.

Compound W, a 3,3'-diiodothyronine sulfate cross-reactive substance in serum from pregnant women--a potential marker for fetal thyroid function.[Pubmed:17314688]

Pediatr Res. 2007 Mar;61(3):307-12.

Compound W, a 3,3'-diiodothyronine sulfate (T2S) cross-reactive material in maternal serum, was found to be useful as a marker for fetal hypothyroidism. In the present report, we explored its biochemical properties and studied its concentrations in cord and in maternal serum obtained from various gestational periods and at term from different continents. Mean W concentrations, expressed as nmol/L T2S-equivalent, in maternal serum during gestation showed a moderate increase at 20-26 wk (1.57 nmol/L) and an accelerated increase to 34-40 wk (3.59 nmol/L). The mean serum level was relatively low in nonpregnant women (0.17 nmol/L). Compound W levels in cord and maternal serum at term were not significantly different among samples obtained from Taiwan compared with samples from the United States. The mean cord serum "corrected" (by hot acid digestion) concentrations of W were significantly higher than maternal serum concentrations at birth and were also higher in venous than in paired arterial samples, suggesting that the placenta may play a role in its production. We compared a total of 45 iodothyronine analogs by antibody, gel filtration, and HPLC chromatographic studies and found only one compound, N,N-dimethyl-T2S, that has close similarities to Compound W. Further studies are needed.

3,3'-Diiodothyronine sulfate cross-reactive material (compound W) in human newborns.[Pubmed:22907618]

Pediatr Res. 2012 Nov;72(5):521-4.

BACKGROUND: Thyrosulfoconjugation appears to facilitate fetal-to-maternal transfer of 3,3'-diiodothyronine-sulfate (T(2)S). Elevated maternal levels of T(2)S cross-reactive material (Compound W) are found in humans, with higher levels found in venous cord blood than in arterial samples. These findings are consistent with the postulate that the placenta plays an essential role in Compound W production. METHODS: Serum Compound W levels were measured by a T(2)S-specific radioimmunoassay in 60 serum samples from newborns with hyperbilirubinemia, age 1-30 d. In addition, 59 maternal serum samples, from day 1 to day 7 after uneventful deliveries, were studied. RESULTS: As compared with day 1, at day 5, the mean (+/-SE) Compound W level fell to 43.5 +/- 6.8% (decay half-life (t(1/2)) = 4.12 d) and to 33.7 +/- 4.6% (decay t(1/2) = 2.82 d) in the newborn and maternal groups, respectively. In the mothers, the level continued to decline along the same slope through day 7. In the newborns, however, the mean Compound W level entered a slower phase of decay after the fifth day with a decay t(1/2) = 10.9 d. CONCLUSION: Compound W is cleared at similar rates in newborn and postpartum maternal sera. This is consistent with the postulate that Compound W is produced in the placenta.

Thyroid function and 3,3'-diiodothyronine sulfate cross-reactive substance (compound W) in maternal hyperthyroidism with antithyroid treatment.[Pubmed:20713348]

Endocr Pract. 2011 Mar-Apr;17(2):170-6.

OBJECTIVE: To test whether the serial measurement of maternal levels of Compound W, a 3,3'-diiodothyronine sulfate cross-reactive substance, can serve as a potential indicator of fetal thyroid function in pregnant women receiving antithyroid medication. METHODS: Compound W was measured repeatedly in serum of pregnant women with hyperthyroidism treated with antithyroid medication. Free thyroxine levels of mothers and serum thyroid-stimulating hormone levels of 1-day-old neonates were analyzed by local clinical or state laboratories. RESULTS: Use of minimal antithyroid medication impaired the progressive increase of Compound W seen in euthyroid mothers during pregnancy. At term, depressed Compound W levels in maternal serum were found in 7 of 22 pregnancies; in 1 case, maternal Compound W was suppressed and newborn thyroid-stimulating hormone was elevated. Seven mothers with treated hyperthyroidism failed to show an increase in serum levels of Compound W after midterm. CONCLUSION: Normal progression of maternal serum Compound W may be an index of normal fetal thyroid development in mothers with hyperthyroidism treated with necessary antithyroid medication.

Secretion of the Notch-1 Abeta-like peptide during Notch signaling.[Pubmed:16434391]

J Biol Chem. 2006 Mar 24;281(12):7890-8.

The canonical pathway of Notch signaling is mediated by regulated intramembrane proteolysis (RIP). In the pathway, ligand binding results in sequential proteolysis of the Notch receptor, and presenilin (PS)-dependent intramembrane proteolysis at the interface between the membrane and cytosol liberates the Notch-1 intracellular domain (NICD), a transcription modifier. Because the degradation of the Notch-1 transmembrane domain is thought to require an additional cleavage near the middle of the transmembrane domain, extracellular small peptides (Notch-1 Abeta-like peptide (Nbeta)) should be produced. Here we showed that Nbeta species are indeed secreted during the process of Notch signaling. We identified mainly two distinct molecular species of novel Nbeta, Nbeta21 and C-terminally elongated Nbeta25, which were produced in an approximately 5:1 ratio. This process is reminiscent of the production of Alzheimer disease-associated Abeta. PS pathogenic mutants increased the production of the longer species of Abeta (Abeta42) from beta-amyloid protein precursor. We revealed that several Alzheimer disease mutants also cause a parallel increase in the secretion of the longer form of Nbeta. Strikingly, chemicals that modify the Abeta42 level caused parallel changes in the Nbeta25 level. These results demonstrated that the characteristics of C-terminal elongation of Nbeta and Abeta are almost identical. In addition, because many other type 1 membrane-bound receptors release intracellular domains by PS-dependent intramembrane proteolysis, we suspect that the release of Abeta- or Nbeta-like peptides is a common feature of the proteolysis during RIP signaling. We anticipate that this study will open the door to searches for markers of RIP signaling and surrogate markers for Abeta42 production.