D-α-Hydroxyglutaric Acid (D-2-HG) is an α-hydroxy acid that is over-produced in the human neurometabolic disease D-2-hydroxyglutaric aciduria (D-2-HGA).{26892} It is normally synthesized from 2-ketoglutarate (2-KG) by hydroxyacid-oxoacid transhydrogenase (HOT), although defects in HOT are not known to be associated with D-2-HGA.{26892} Instead, type I D-2-HGA involves mutations in D-2-hydroxyglutarate dehydrogenase, which converts D-2-HG back to 2-KG.{26892} Type II D-2-HGA results from gain-of-function mutations in isocitrate dehydrogenase 2, causing it to supplement HOT in converting 2-KG to D-2-HG.{26891,26772} In bacteria, this α-hydroxy acid may be synthesized from oxalate and propionyl-coenzyme A by an α-hydroxyglutaric acid synthetase.{26893}
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An α-hydroxy acid that is over-produced in the human neurometabolic disease D-2-hydroxyglutaric aciduria
Formal name: 2R-hydroxy-pentanedioic acid, disodium salt
Synonyms: D-2-HG|D-2-Hydroxyglutaric Acid
Molecular weight: 192.1
CAS: 103404-90-6
Purity: ≥95%
Formulation: A crystalline solid
Product Type|Biochemicals||Research Area|Endocrinology & Metabolism|Inborn Errors of Metabolism||Research Area|Neuroscience
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 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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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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