Thiodiglycolic acid-d4 (TDGA-d4) contains four deuterium atoms at the 2, 2, 2’, and 2’ positions. It is intended for use as an internal standard for the quantification of TDGA by GC- or LC-mass spectrometry. TDGA is a product of interaction of the cysteine component of glutathione with two-carbon units released during catabolism. It is found in concentrations below 20 mg/l in urine of healthy individuals and elevated following ingestion of certain drugs.{30000} Determination of TDGA concentration in urine has been used to characterize the metabolism of substances participating in methionine synthesis in order to identify imbalances leading to hyperhomocystinuria.{29999} Additionally, because TDGA is used as raw material in the polymer industry, its detection in human urine has served as a biomarker for exposure to carcinogenic vapors such as vinylchloride monomer produced during polymer manufacture.{29999}
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An internal standard for the quantification of TDGA by GC- or LC-MS
Formal name: 2,2′-thiobis(acetic-2,2,2′,2′-d4 acid)
Synonyms: Dicarboxydimethyl sulfide-d4|Mercaptodiacetic Acid-d4|TDGA-d4|Thiodiacetic Acid-d4
Molecular weight: 154.2
CAS: 132090-51-8
Purity: ≥99% deuterated forms (d1-d4)
Formulation: A crystalline solid
The maintenance of embryonic stem cells in culture typically requires feeder cells and various exogenous factors found in serum. Murine embryonic stem (mES) cells can be maintained in the absence of feeder cells and serum but require the leukemia inhibitor factor (LIF) and bone morphogenic protein (BMP) to prevent differentiation and promote self-renewal. SC-1 is a small molecule activator of stem cell renewal that allows the propagation of OG2 mES cells for at least 10 passages in an undifferentiated state.{14533} The activity of SC-1 is mediated by the combined inhibition of RasGAP and ERK1 with Kd values of 98 and 212 nM, respectively.{14533} Inhibition of RasGAP increases Ras signaling via the PI3-kinase pathway which promotes self-renewal, whereas inhibition of ERK blocks differentiation.
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The nuclear factor-κB (NF-κB) regulates the expression of numerous genes involved in immunity and inflammation, cellular stress responses, growth, and apoptosis. Resveratrol, a polyphenolic trans-stilbene, is a known inhibitor of the activation of NF-κB and exhibits activity against a wide variety of cancer cells. CAY10512 is a substituted trans-stilbene analog of resveratrol that is 100-fold more potent as measured by antioxidant activity. The IC50 value for inhibition of TNFα-induced activation of NF-κB by CAY10512 is 0.15 µM compared to 20 µM by resveratrol.{14545}
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Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression and are therefore promising targets for cancer therapy. (R)-Roscovitine is a potent inhibitor of Cdk2/cyclin E with an IC50 value of 0.1 µM.{14988} It also inhibits Cdk7/cyclin H, Cdk5/p35, and cell division cycle (cdc)/cyclin B with IC50 values of 0.49, 0.16, and 0.65 µM, respectively.{14987,14988,14991} (R)-Roscovitine inhibits the growth of rapidly proliferating cells with an average IC50 value of 15.2 µM against a panel of 19 human tumor cell lines.{14988} In murine models of polycystic kidney disease, (R)-roscovitine effectively inhibited disease progression at doses of 50-100 mg/kg.{14564}
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The PtdIn phosphates play an important role in the generation and transduction of intracellular signals.{8344,4096,14518} PtdIns-(3,4,5)-P3-biotin is an affinity probe which allows the PIP3 to be detected through an interaction with the biotin ligand. This design allows PtdIns-(3,4,5)-P3-biotin to serve as a general probe for any protein with a high affinity binding interaction with inositol-(3,4,5)-triphosphate phospholipids, such as phosphatidylinositol 3-kinase, PTEN, or PH-domain-containing proteins.
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