(±)-Thalidomide-d4 is intended for use as an internal standard for the quantification of (±)-thalidomide (Item No. 14610) by GC- or LC-MS. (±)-Thalidomide is an immunomodulatory compound with diverse biological activities, including anticancer, anti-inflammatory, and teratogenic properties.{54394,54393,54392} It prevents polymorphonuclear leukocyte (PMN) chemotaxis when used at concentrations of 1, 10, and 100 µg/ml.{54394} (±)-Thalidomide increases IL-2-induced proliferation and IFN-γ production in primary human T cells in vitro.{54393} It enhances natural killer (NK) cell-mediated cytotoxicity in MM.1S multiple myeloma cells.{54392} Thalidomide (4 mg/animal) reduces lung IL-6, TGF-β, VEGF, angiopoietin-1, angiopoietin-2, and collagen type Iα1 expression, inhibits pulmonary angiogenesis, and attenuates fibrosis in a mouse model of bleomycin-induced pulmonary fibrosis.{54395} It induces apoptosis in primary human embryonic fibroblasts (EC50 = 8.9 µM) and induces limb and eye defects in chicken embryos (EC50 = 50 µg/kg egg weight).{54396} Formulations containing thalidomide have been used in the treatment of multiple myeloma and erythema nodosum leprosum (ENL) in non-pregnant individuals.
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An internal standard for the quantification of (±)-thalidomide by GC- or LC-MS
Formal name: 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione-4,5,6,7-d4
Synonyms: N-Phthaloylglutamimide-d4
Molecular weight: 262.3
CAS: 1219177-18-0
Purity: ≥99% deuterated forms (d1-d4)
Formulation: A 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 tetracycline repressor (TetR) is a transcriptional regulator which normally binds tightly to its palindromic tetO operator DNA, blocking gene expression.{17508} Tet causes the repressor to dissociate from the DNA, allowing transcription to occur. A novel reverse TetR (revTetR) requires tetracycline as a co-repressor to bind tetO and block transcription.{17509,17510} Anhydrotetracycline (hydrochloride) is a powerful effector in both the tetracycline repressor (TetR) and reverse TetR (revTetR) systems, binding the Tet repressor 35-fold more strongly than Tet.{17508,17511} Moreover, anhydrotetracycline poorly binds the 30S ribosomal subunit, compared to Tet,{17512} so it does not act as a general inhibitor of translation and is a poor antibiotic. Perhaps related to this, the concentration of anhydrotetracycline that inhibits eukaryotic cell growth is more than a 1,000-fold above the dose that alters transcription through TetR.{17508}
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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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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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