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Merck
CN

SML4165

SLC13A3i

new

≥95% (HPLC), powder, SLC13A3 inhibitor

Synonym(s):

2-[(3-Methoxyphenyl)methyl]butanedioic acid, [(3-Methoxyphenyl)methyl]-butanedioic acid, (m-Methoxybenzyl)succinic acid, 2-(3-Methoxy-benzyl)-succinic acid, SLC13A3 Inhibitor, Solute carrier family 13 member 3 Inhibitor

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About This Item

Empirical Formula (Hill Notation):
C12H14O5
CAS Number:
20940-75-4
Molecular Weight:
238.24
MDL number:
MFCD00582472

Key Documents

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Quality Level

100

Assay

≥95% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

-10 to -25°C

SMILES string

OC(CC(CC1=CC=CC(OC)=C1)C(O)=O)=O

General description

A cell-permeable solute carrier family 13-member 3 (SLC13A3) inhibitor(SLC13A3i) targets the SLC13A3 transporter to block the oncometaboliteitaconate uptake, thereby reducing tumor ferroptosis resistance and enhancingimmune responses in SLC13A3+ tumors. By disrupting the NRF2-SLC7A11 pathway,SLC13A3i sensitizes tumor cells to ferroptosis and increases CD8+ T cellinfiltration in the tumor microenvironment. Preclinical studies show robustefficacy of SLC13A3i in both in vitro (1-5 mM) and in vivo (10-20mg/kg, i.p.) models, especially when combined with anti-PD-L1 immunotherapy,resulting in slowed tumor progression and improved immune cell engagement. Witha favorable safety profile and metabolic stability, SLC13A3i emerges as apromising immunometabolic therapeutic candidate for treating resistant cancers.

Application

SLC13A3i may be usedin studies for its role in inhibiting the uptake of itaconate in tumor cells,which may help understand tumor immune evasion mechanisms and improve cancertreatment strategies. It may also be used to explore metabolicpathways related to integrin functions and their impact on cellular processes,particularly in cancer research.

Biochem/physiol Actions

Blocks itaconate uptake, reduces tumor ferroptosis resistance, enhances immune cell infiltration, and shows promising preclinical efficacy and safety as an immunotherapy adjunct.

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Certificates of Analysis (COA)

Lot/Batch Number
0000460940
0000462524
0000460940
0000462524
0000451029

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Yizeng Fan et al.
Cell metabolism, 37(2), 514-526 (2025-01-15)
Itaconate is a metabolite catalyzed by cis-aconitate decarboxylase (ACOD1), which is mainly produced by activated macrophages and secreted into the extracellular environment to exert complex bioactivity. In the tumor microenvironment, itaconate is concentrated and induces an immunosuppressive response. However, whether
Heng Lin et al.
Cancer cell, 42(12), 2032-2044 (2024-11-13)
Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME). Here, we discover SLC13A3 is an itaconate transporter in tumor cells and endows tumor ferroptosis resistance, diminishing

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