Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, such as leukemia and glioma, and result in overproduction of the (R)-enantiomer of 2- hydroxyglutarate [(R)-2-HG]. Elucidation of the role of IDH mutations and (R)-2-HG in leukemogenesis has been hampered by a lack of appropriate cell-based models. It has been recently reported that a canonical IDH1 mutant, IDH1 R132H, promoted cytokine independence and blocks differentiation in hematopoietic cells. These effects can be recapitulated by (R)-2-HG, but not (S)-2-HG, despite the fact that (S)-2-HG more potently inhibits enzymes previously linked to the pathogenesis of IDH mutant tumors, such as the 5'- methylcytosine hydroxylase TET2. This paradox is perhaps due to the ability of (S)-2-HG, but not (R)-2-HG, to inhibit the EglN prolyl hydroxylases. 2-HG has also been shown to inhibit the activity of multiple other a- KG-dependent dioxygenases, including the JmjC domain-containing histone demethylases (KDMs).
CAS Number: 103404-90-6
Molecular Weight: 192.08
D-alpha-Hydroxyglutaric acid disodium
D-2-Hydroxypentanedioic acid disodium salt
2R-hydroxy-pentanedioic acid, disodium salt
D-alpha-Hydroxyglutaric acid disodium salt
Pentanedioic acid, 2-hydroxy-, disodium salt, (R)-
r-2-hydroxyglutaric acid disodium salt
D-A-HYDROXYGLUTARIC ACID DISODIUM
[R, (+)]-2-Hydroxyglutaric acid disodium salt
Chemical Name: sodium (R)-2-hydroxypentanedioate
Appearance: Solid powder
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Water up to 100 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Powder: 4oC for 1 year, -20oC for 3 years. DMSO: 4oC for 3 month.
Shelf Life: ≥36 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
(R)-2-HG was used at 100-250 μM final concentration in vitro and in cellular assays.
- Losman JA, et al. (R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible. (2013) Science. 339(6127):1621-5.
- Ye D, et al. R-2-Hydroxyglutarate as the Key Effector of IDH Mutations Promoting Oncogenesis. (2013) Cancer Cell. 23(3):274-6.
Products are for research use only. Not for human use.
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