2. Immunology/Inflammation Stem Cell/Wnt JAK/STAT Signaling
  3. Interleukin Related STAT
  4. Madindoline A

Madindoline A 是一种具备口服活性的 gp130 拮抗剂，其 KD 为 288 μM。Madindoline A 可抑制 IL-6 和 IL-11 诱导的破骨细胞生成，抑制 IL-6 刺激的血清淀粉样 A 蛋白产生，抑制骨吸收和骨丢失，还可抑制依赖 IL-6 与 IL-11 的细胞系生长，以及依赖 IL-6 的 Stat3 酪氨酸磷酸化。Madindoline A 可用于研究激素依赖性绝经后骨质疏松症。

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Madindoline A

Madindoline A Chemical Structure

CAS No. : 184877-64-3

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Madindoline A 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

Madindoline A is an orally active gp130 antagonist with a KD of 288 μM. Madindoline A inhibits IL-6- and IL-11-induced osteoclastogenesis, suppresses IL-6-stimulated serum amyloid A protein production, inhibits bone resorption and bone loss, and also inhibits IL-6- and IL-11-dependent cell line growth, as well as IL-6-dependent Stat3 tyrosine phosphorylation. Madindoline A is applicable for the research of hormone-dependent postmenopausal osteoporosis[1][2].

IC50 & Target[1][2]

IL-6

 

Stat-3

 

细胞效力
(Cellular Effect)
Cell Line Type Value Description References
HepG2 CC50
> 100 μM
Compound: (+)-Madindoline A
Cytotoxicity against human HepG2 cells
Cytotoxicity against human HepG2 cells
[PMID: 26810262]
HepG2 IC50
21 μM
Compound: (+)-Madindoline A
Inhibition of gp130-IL6/IL-Ralpha interaction in human HepG2 cells assessed as inhibition of IL-6-induced STAT3 activation by luciferase reporter gene assay
Inhibition of gp130-IL6/IL-Ralpha interaction in human HepG2 cells assessed as inhibition of IL-6-induced STAT3 activation by luciferase reporter gene assay
[PMID: 26810262]
MH60 IC50
8 μM
Compound: 1
Cytotoxicity in mouse MH60 cells assessed as inhibition of recombinant human IL-6-induced growth incubated for 72 hrs by tetrazolium method
Cytotoxicity in mouse MH60 cells assessed as inhibition of recombinant human IL-6-induced growth incubated for 72 hrs by tetrazolium method
[PMID: 36971365]
体外研究
(In Vitro)

Madindoline A (0.5-70 μM；72 h) 是 IL-6 依赖型 MH-60 细胞中 IL-6 应答的竞争性选择性拮抗剂，pA2 值为 4.78，且不会影响由 IL-2、IL-3、TNF 介导的细胞生长，也不会影响非 IL-6 依赖条件下的细胞生长[1]。
Madindoline A (70 μM; 72 h) 可显著抑制 IL-6 诱导的 M1 细胞向巨噬细胞样细胞的分化，但不影响基础分化或 LIF 诱导的分化[1]。
Madindoline A (100 μM; 15 min) 可抑制 HepG2 细胞中由 IL-6 诱导的 STAT3 酪氨酸磷酸化，但不影响由 LIF 诱导的 STAT3 磷酸化[1]。
Madindoline A (30 μM；4 days) 可显著抑制小鼠颅盖骨成骨细胞与骨髓细胞共培养体系中由 IL-6 和 IL-11 诱导的破骨细胞形成，但对由 LIF、IL-1 或 1α,25 (OH) 2D3 诱导的破骨细胞形成无影响[1]。
Madindoline A (0.2-0.4 mM；预处理 30 min) 可抑制 HepG2 细胞中 IL-6 依赖性 Stat3 酪氨酸磷酸化[2]。

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

Madindoline A 相关抗体:

Cell Proliferation Assay[1]

Cell Line: IL-6-dependent MH-60 cells; IL-2-dependent CTLL-2 cells; IL-3-dependent Baf3 cells; TNF-sensitive L929 cells; IL-6-independent MH-60 cells
Concentration: 0.5, 1.75, 3.5, 7, 17.5, 35, 70 μM
Incubation Time: 72 h
Result: Did not alter growth of IL-2-dependent CTLL-2 cells, IL-3-dependent Baf3 cells, or TNF-sensitive L929 cells, nor inhibit growth of IL-6-independent MH-60 cells.
Dose-dependently suppressed IL-6-induced cell growth of IL-6-dependent MH-60 cells and caused parallel rightward shifts of IL-6 dose-response curves.
Yielded a pA2 value of 4.78 and a slope of 0.99 via Schild plot analysis, confirming competitive antagonism.

Cell Differentiation Assay[1]

Cell Line: M1 cells
Concentration: 70 μM (pre-incubation with IL-6)
Incubation Time: 72 h (pre-incubation with IL-6); 24 h (bead incubation)
Result: Significantly decreased the population of differentiated macrophage-like cells induced by IL-6.
Did not alter differentiation status relative to untreated cells when used alone.

Western Blot Analysis[2]

Cell Line: HepG2 cells
Concentration: 0.2, 0.4 mM
Incubation Time: 30 min (pretreatment)
Result: Inhibited IL-6-induced Stat3 tyrosine phosphorylation at 0.4 mM concentration.
Achieved 50% inhibition of Stat3 tyrosine phosphorylation at a concentration between 0.2 and 0.4 mM.
体内研究
(In Vivo)

Madindoline A (10-60 mg/kg；口服；单次给药) 可剂量依赖性地抑制小鼠体内 IL-6 诱导的血清淀粉样蛋白 A (SAA) 生成[1]。
Madindoline A (60 mg/kg；口服；隔日一次；持续 4 周) 可显著抑制去卵巢小鼠的骨吸收与骨丢失，且不影响其子宫重量或血清 IL-6 水平[1]。

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

Animal Model: C3H/HeJ (6-week-old female; acute-phase response induced by intraperitoneal injection of 1 μg rhIL-6 per mouse)[1]
Dosage: 10 mg/kg; 60 mg/kg
Administration: p.o.; single dose
Result: Reduced IL-6-induced serum amyloid A (SAA) levels to 34.7 ng/mL.\n
Reduced IL-6-induced serum amyloid A (SAA) levels to 16.3 ng/mL.
Animal Model: ddY (4-week-old female; postmenopausal osteoporosis induced by bilateral ovariectomy)[1]
Dosage: 10 mg/kg; 60 mg/kg
Administration: p.o.; every other day; 4 weeks
Result: Did not produce significant changes in measured parameters (bone mass, serum calcium, uterine weight, serum IL-6 levels).\n
Significantly suppressed ovariectomy-induced bone loss, resulting in a bone mass ratio of 1.92.\n
Reduced serum calcium levels to 11.3 mg/dL.\n
Did not alter uterine weight or serum IL-6 levels.
分子量

369.45

Formula

C22H27NO4
CAS 号
结构分类
初始来源
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

Madindoline A 相关分类

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Help & FAQs
  • 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:

Madindoline A184877-64-3Interleukin RelatedSTATILHepG2 cellsgp130 homodimerizationpostmenopausal osteoporosisMH-60 cellsosteoclastogenesisextracellular domainIL-11IL-6serum amyloid Agp130Inhibitorinhibitorinhibit

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