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

MDH2-IN-2 是一种具有口服活性的 MDH2 抑制剂， IC50 为 5.9 μM。MDH2-IN-2 可降低哺乳动物细胞模型中的衰老标志物水平和衰老相关分泌表型 (SASP) 因子。MDH2-IN-2 可延长秀丽隐杆线虫的寿命并改善其健康寿命。MDH2-IN-2 可缓解衰老小鼠的组织衰老，并抑制 SASP 因子，恢复了肝肾功能。MDH2-IN-2 可用于衰老相关研究。

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MDH2-IN-2

MDH2-IN-2 Chemical Structure

CAS No. : 3047410-41-0

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MDH2-IN-2 相关抗体

Top Publications Citing Use of Products

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

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].

体外研究
(In Vitro)

MDH2-IN-2 (Compound 28i) 可抑制重组人源 MDH1 酶的活性，其 IC50 为 25.3 μM[1]。
MDH2-IN-2 (1 μM; 3 days) 可显著下调 MRC-5 细胞中多种 SASP 因子的 mRNA 水平，降低复制性衰老 MRC-5 细胞中 p53 蛋白的表达水平和 SA-β-gal 阳性细胞的比例[1]。
MDH2-IN-2 (1 μM) 可显著降低 Mitomycin C (HY-13316) 诱导衰老的 NRK-52E 细胞中 SA-β-gal 阳性细胞的比例[1]。
MDH2-IN-2 (1 μM; 5 days) 可显著降低复制性衰老 MEFs 中的 p16 蛋白表达水平和SA-β-gal 阳性细胞的比例[1]。
MDH2-IN-2 (1 μM; 5-60 minutes) 在人源和小鼠肝微粒体中均存在快速代谢周转，对应的 T1/2 值分别为 1.15 min 和 1.10 min[1]。

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

MDH2-IN-2 相关抗体:

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.
药代动力学
(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
体内研究
(In Vivo)

MDH2-IN-2 (100 μM; incorporation into NGM plates; continuous exposure) 可使野生型秀丽隐杆线虫的平均寿命延 15.49%，并改善其多项健康寿命相关指标[1]。
MDH2-IN-2 (0-50 mg/kg; i.g.; once daily; 3 weeks) 可显著抑制 Doxorubicin (HY-15142A) 诱导的早衰雄性 C57BL/6J 小鼠体内的多种 SASP 因子[1]。
MDH2-IN-2 (5-10 mg/kg; i.g.; once daily; 3 months) 在自然衰老雄性 C57BL/6J 小鼠可逆转与年龄相关的血清生化功能异常，抑制 SASP 因子的产生，降低肾脏衰老标志物的表达，并改善肾脏组织学形态[1]。

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.
分子量

536.73

Formula

C31H40N2O4S
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

MDH2-IN-2 相关分类

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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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