(R)-GNE-140

Catalog No.S6675 Batch:S667502

Technical Data

Formula	C₂₅H₂₃ClN₂O₃S₂
Molecular Weight	499.04	CAS No.	2003234-63-5
Solubility (25°C)*	In vitro	DMSO	30 mg/mL (60.11 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

(R)-GNE-140 is a selective inhibitor of the LDHA and LDHB with IC50s of 3 nM and 5 nM, respectively. The R enantiomer of GNE-140 is 18-fold more potent than S enantiomer.

Targets

LDHA ^[1] (Cell-free assay)	LDHB ^[1] (Cell-free assay)
3 nM	5 nM

In vitro

(R)-GNE-140 inhibits proliferation in 37 of 347 cancer cell lines tested at a potency cut off of 5 μM. (R)-GNE-140 exhibits inhibition with two chondrosarcoma (bone) cancer cell lines that harbored IDH1 mutations (IC50 = 0.8μM).(R)-GNE-140 has submicromolar MiaPaca2 potency and inhibits proliferation in 11% of cancer cell lines in a broad panel. ^[1]

In vivo

(R)-GNE-140 presents a low Clp, and also had high bioavailability when dosed orally at 5 mg/kg to mice. At higher oral doses, ranging from 50 to 200 mg/kg, (R)-GNE-140 displays greater in vivo exposure.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines 105KC,JJ012,143B,G84,1321N1,ONS-76,G22,G140,G96,HCC1143,CAL-120,Hs 578T,SISO,SKG-II,HCT-15,KYSE-520,KMRC-1,SNU-475,SNU-423,HT-1080,NCI-H1437,NCI-H1339,LXF-289,MCAS,PA-1,Hs 38.T,59M,MIA PaCa-2,SW 1990,PSN1,GR-M,Hs 746T,MKN-74,S-117,FTC-238,B-CPAP,HEC-265 cell lines Concentrations 6 pt dose titration scheme Incubation Time 72 h Method Cells are plated using optimal seeding densities in 384-well plates using RPMI, 5% FBS, 100 ug/ml penicillin, 100 units/ml streptomycin. Optimal seeding densities are established for each cell line in order to reach 75-80% confluence at the end of the assay. The following day, cells are treated with (R)-GNE-140 using a 6 pt dose titration scheme. After 72 hours, cell viability is assessed using the CellTiter-Glo® Luminescence Cell Viability assay. Absolute inhibitory concentration (IC) values are calculated using four-parameter logistic curve fitting.
Animal Study:^{^[1]}	Animal Models Female CD-1 mice Dosages IV: 1.0 mg/kg; Oral: 5,50,100,200 mg/kg Administration IV / Oral

Cell Assay:^{^[1]}

Cell lines
105KC,JJ012,143B,G84,1321N1,ONS-76,G22,G140,G96,HCC1143,CAL-120,Hs 578T,SISO,SKG-II,HCT-15,KYSE-520,KMRC-1,SNU-475,SNU-423,HT-1080,NCI-H1437,NCI-H1339,LXF-289,MCAS,PA-1,Hs 38.T,59M,MIA PaCa-2,SW 1990,PSN1,GR-M,Hs 746T,MKN-74,S-117,FTC-238,B-CPAP,HEC-265 cell lines
Concentrations
6 pt dose titration scheme
Incubation Time
72 h
Method
Cells are plated using optimal seeding densities in 384-well plates using RPMI, 5% FBS, 100 ug/ml penicillin, 100 units/ml streptomycin. Optimal seeding densities are established for each cell line in order to reach 75-80% confluence at the end of the assay. The following day, cells are treated with (R)-GNE-140 using a 6 pt dose titration scheme. After 72 hours, cell viability is assessed using the CellTiter-Glo® Luminescence Cell Viability assay. Absolute inhibitory concentration (IC) values are calculated using four-parameter logistic curve fitting.

Animal Study:^{^[1]}

Animal Models
Female CD-1 mice
Dosages
IV: 1.0 mg/kg; Oral: 5,50,100,200 mg/kg
Administration
IV / Oral

References

[1] Purkey, Hans E. , et al.ACS Med Chem Lett. 2016 Aug 26;7(10):896-901. eCollection 2016 Oct 13.

Selleck's (R)-GNE-140 has been cited by 3 publications

Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models [ J Clin Invest, 2024, 134(17)e177606]	PubMed: 39225102
Lactate promotes myogenesis via activating H3K9 lactylation-dependent up-regulation of Neu2 expression [ J Cachexia Sarcopenia Muscle, 2023, 10.1002/jcsm.13363]	PubMed: 37919243
Host T cell dedifferentiation effects drive HIV-1 latency stability [ J Virol, 2022, jvi0197421]	PubMed: 35019721

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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