2. Metabolic Enzyme/Protease
  3. Malate Dehydrogenase (MDH)
  4. MDH2-IN-2

MDH2-IN-2 is an orally active MDH2 inhibitor with an IC50 of 5.9 μM. MDH2-IN-2 reduces the levels of senescence markers and senescence-associated secretory phenotype (SASP) factors in mammalian cell models. MDH2-IN-2 extends the lifespan and improves the healthspan of Caenorhabditis elegans. MDH2-IN-2 alleviates tissue senescence in aged mice, inhibits SASP factors, and restores liver and kidney functions. MDH2-IN-2 is applicable for senescence-related research.

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MDH2-IN-2

MDH2-IN-2 Chemical Structure

CAS No. : 3047410-41-0

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MDH2-IN-2 Related Antibodies

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Description

MDH2-IN-2 is an orally active MDH2 inhibitor with an IC50 of 5.9 μM. MDH2-IN-2 reduces the levels of senescence markers and senescence-associated secretory phenotype (SASP) factors in mammalian cell models. MDH2-IN-2 extends the lifespan and improves the healthspan of Caenorhabditis elegans. MDH2-IN-2 alleviates tissue senescence in aged mice, inhibits SASP factors, and restores liver and kidney functions. MDH2-IN-2 is applicable for senescence-related research[1].

In Vitro

MDH2-IN-2 (Compound 28i) inhibits the activity of recombinant human MDH1 enzyme, with an IC50 value of 25.3 μM[1].
MDH2-IN-2 (1 μM; 3 days) significantly downregulates the mRNA levels of various SASP factors in MRC-5 cells, and reduces the expression level of p53 protein and the proportion of SA-β-gal-positive cells in replicatively senescent MRC-5 cells[1].
MDH2-IN-2 (1 μM) significantly reduces the proportion of SA-β-gal-positive NRK-52E cells that undergo senescence induced by Mitomycin C (HY-13316)[1].
MDH2-IN-2 (1 μM; 5 days) significantly reduces the expression level of p16 protein and the proportion of SA-β-gal positive cells in replicative senescent MEFs[1].
MDH2-IN-2 (1 μM; 5-60 minutes) undergoes rapid metabolic turnover in both human and mouse liver microsomes, with corresponding T1/2 values of 1.15 min and 1.10 min, respectively[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

MDH2-IN-2 Related Antibodies

Real Time qPCR[1]

Cell Line: MRC-5 cells
Concentration: 1 μM
Incubation Time: 3 days
Result: Significantly downregulated mRNA expression of senescence-associated secretory phenotype (SASP) factors IL-1α, IL-1β, IL-8, CXCL-1, MMP-1, and MMP-3.

Western Blot Analysis[1]

Cell Line: Replicatively senescent human embryonic lung fibroblasts (MRC-5, passage 32)
Concentration: 1 μM
Incubation Time: 3 days
Result: Significantly reduced the protein expression level of p53, a key senescence-associated cell cycle regulator.

Western Blot Analysis[1]

Cell Line: Replicatively senescent mouse embryonic fibroblasts (MEFs, passage 7)
Concentration: 1 μM
Incubation Time: 5 days
Result: Significantly reduced the protein expression level of p16, a key senescence-associated cyclin-dependent kinase inhibitor.
Parmacokinetics
Species Dose Route Tmax AUC0-last T1/2
Mice[1] 10 mg/kg p.o. 0.25 h 6.38 0.79 h
Mice[1] 5 mg/kg i.v. / 12.5 0.62 h
In Vivo

MDH2-IN-2 (100 μM; incorporated into NGM plates; continuous exposure) extends the mean lifespan of wild-type Caenorhabditis elegans by 15.49% and improves multiple healthspan-related indicators[1].
MDH2-IN-2 (0-50 mg/kg; i.g.; once daily; 3 weeks) significantly inhibits multiple SASP factors in premature senescent male C57BL/6J mice induced by Doxorubicin (HY-15142A)[1].
MDH2-IN-2 (5-10 mg/kg; i.g.; once daily; 3 months) reverses age-related serum biochemical abnormalities, inhibits the production of SASP factors, reduces the expression of renal senescence markers, and improves renal histological morphology in naturally aged male C57BL/6J mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: wild-type N2[1]
Dosage: 100 μM
Administration: incorporation into NGM plates; continuous exposure
Result: Extended mean lifespan by 15.49% compared to controls.
Significantly improved egg-laying capacity compared to controls.
Increased pharyngeal pumping rate compared to controls.
Maintained body bend frequency relative to controls.
Animal Model: C57BL/6J (male, 8 weeks old, doxorubicin-induced premature aging)[1]
Dosage: 10 mg/kg; 20 mg/kg; 50 mg/kg
Administration: i.g.; once daily; 3 weeks
Result: Significantly reduced serum levels of SASP factors including IL-1β, IL-6, CXCL-1, TNF-α, MMP-1, and MMP-2 compared to Dox-only treated male mice.
Animal Model: C57BL/6J (male, 21 months old, naturally aged)[1]
Dosage: 5 mg/kg; 10 mg/kg
Administration: i.g.; once daily; 3 months
Result: Significantly reduced age-related increases in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and uric acid (UA) to levels comparable to young control mice.
Markedly reduced serum levels of SASP factors including IL-6, IL-1β, MMP-1, MMP-2, CXCL-1, GDF-15, and TNF-α.
Downregulated renal tissue expression of senescence markers p53, p21, and p16.
Significantly ameliorated age-related glomerular atrophy, inflammatory infiltration, and collagen fiber accumulation in the kidney.
Molecular Weight

536.73

Formula

C31H40N2O4S
CAS No.
SMILES

O=S(C1=CC=C(C=C1)CCNC(C2=CC=CC(OCC3CCCC3)=C2)=O)(NC45C[C@@H]6C[C@H](C5)C[C@@H](C6)C4)=O
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Purity & Documentation
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MDH2-IN-2 Related Classifications

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MDH2-IN-23047410-41-0Malate Dehydrogenase (MDH)Malate DehydrogenaseMDH2 inhibitorMRC-5 cellsNRK-52E cellsMEFsCaenorhabditis elegansC57BL/6J micesenescence
Inhibitorinhibitorinhibit

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