We’re improving your experience!

Starting April 21, you’ll be asked to log in or sign up for a free account after viewing 10 content pages each month.

Don’t worry—creating an account is quick and easy, and it comes with added benefits! Once logged in, you’ll not only continue accessing the content you already enjoy, but you’ll also unlock exclusive features like interactive donut plots for variant protein effects and variant impacts across the gene.

Stay tuned for these updates, and thank you for being part of our community!

Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (31361380)
Authors Gao M, Zhu H, Fu L, Li Y, Bao X, Fu H, Quan H, Wang L, Lou L
Title Pharmacological characterization of TQ05310, a potent inhibitor of isocitrate dehydrogenase 2 R140Q and R172K mutants.
Journal Vol Issue Date Pages Journal Short Title
Cancer science 110 10 2019 Oct 3306-3314 Cancer Sci
URL
Abstract Text Isocitrate dehydrogenase 2 (IDH2), an important mitochondrial metabolic enzyme involved in the tricarboxylic acid cycle, is mutated in a variety of cancers. AG-221, an inhibitor primarily targeting the IDH2-R140Q mutant, has shown remarkable clinical benefits in the treatment of relapsed or refractory acute myeloid leukemia patients. However, AG-221 has weak inhibitory activity toward IDH2-R172K, a mutant form of IDH2 with more severe clinical manifestations. Herein, we report TQ05310 as the first mutant IDH2 inhibitor that potently targets both IDH2-R140Q and IDH2-R172K mutants. TQ05310 inhibited mutant IDH2 enzymatic activity, suppressed (R)-2-hydroxyglutarate (2-HG) production and induced differentiation in cells expressing IDH2-R140Q and IDH2-R172K, but not in cells expressing wild-type IDH1/2 or mutant IDH1. TQ05310 bound to both IDH2-R140Q and IDH2-R172K, with Q316 being the critical residue mediating the binding of TQ05310 with IDH2-R140Q, but not with IDH2-R172K. TQ05310 also had favorable pharmacokinetic characteristics and profoundly inhibited 2-HG production in a tumor xenografts model. The results of the current study establish a solid foundation for further clinical investigation of TQ05310, and provide new insight into the development of novel mutant IDH2 inhibitors.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
TQ05310 TQ05310 4 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
TQ05310 IDH2 Inhibitor 5 TQ05310 inhibits IDH2, potentially resulting in increased differentiation and decreased proliferation of tumor cells (PMID: 31361380).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 R172K acute myeloid leukemia sensitive TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R172K in culture (PMID: 31361380). 31361380
IDH2 R140Q acute myeloid leukemia sensitive TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R140Q in culture (PMID: 31361380). 31361380
IDH2 R140Q high grade glioma sensitive TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R140Q in culture (PMID: 31361380). 31361380
IDH2 R172K high grade glioma sensitive TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R172K in culture (PMID: 31361380). 31361380