Mibefradil (Synonyms: Ro 40-5967)

目录号: HY-15553: FAQs
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摩尔计算器

Mibefradil (Ro 40-5967) 是一种钙离子通道 (calcium channel) 阻断剂，选择性作用于 T 型 Ca²⁺通道，作用于 T 型和 L 型通道，IC₅₀ 分别为 2.7 μM 和 18.6 μM。

该游离形式化合物不稳定，推荐具有相同生物学活性的稳定盐形式 Mibefradil dihydrochloride。

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Mibefradil Chemical Structure

CAS No. : 116644-53-2

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Mibefradil 的其他形式现货产品:

Mibefradil dihydrochloride

Other Forms of Mibefradil:

Mibefradil dihydrochloride In-stock
Mibefradil dihydrochloride hydrate 询价

MCE 顾客使用本产品发表的 12 篇科研文献

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N-type calcium channel L-type calcium channel P/Q-type calcium channel T-type calcium channel Calcium Channel

生物活性
实验参考方法
纯度 & 产品资料
参考文献

生物活性

Mibefradil (Ro 40-5967) is a calcium channel blocker with moderate selectivity for T-type Ca²⁺ channels displaying IC₅₀s of 2.7 μM and 18.6 μM for T-type and L-type currents, respectively^[1].

IC₅₀ & Target

IC50: 2.7 μM (T-type calcium channel), 18.6 μM (L-type calcium channel)^[1]

细胞效力
(Cellular Effect)

Cell Line	Type	Value	Description	References
A2780	IC₅₀	24.23 μM Compound: Mibefradil	Cytotoxicity against human A2780 cells after 48 hrs by MTT assay Cytotoxicity against human A2780 cells after 48 hrs by MTT assay	[PMID: 24220170]
A2780/Taxol	IC₅₀	35.26 μM Compound: Mibefradil	Cytotoxicity against human paclitaxel-resistant A2780T cells after 48 hrs by MTT assay Cytotoxicity against human paclitaxel-resistant A2780T cells after 48 hrs by MTT assay	[PMID: 24220170]
A549	IC₅₀	24.8 μM Compound: Mibefradil	Cytotoxicity against human A549 cells after 48 hrs by MTT assay Cytotoxicity against human A549 cells after 48 hrs by MTT assay	[PMID: 24529871]
A549	IC₅₀	24.9 μM Compound: Mibefradil	Cytotoxicity against human A549 cells assessed as reduction in cell viability after 48 hrs by MTT assay Cytotoxicity against human A549 cells assessed as reduction in cell viability after 48 hrs by MTT assay	[PMID: 32327350]
A549	IC₅₀	31.4 μM Compound: Mibefradil	Cytotoxicity against human A549 cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human A549 cells assessed as reduction in cell viability by MTT assay	[PMID: 26739776]
CHO	IC₅₀	0.51 μM Compound: mibefradil	Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits	[PMID: 23812503]
CHO	IC₅₀	3.3 μM Compound: Mibefradil	Inhibition of human ERG expressed in CHO cells by IONWORKS assay Inhibition of human ERG expressed in CHO cells by IONWORKS assay	[PMID: 23200256]
HEK293	IC₅₀	0.13 μM Compound: 1, Mibefradil	Antagonist activity at human alpha1H T-type calcium channel expressed in HEK293 cells by patch clamp technique Antagonist activity at human alpha1H T-type calcium channel expressed in HEK293 cells by patch clamp technique	[PMID: 18160281]
HEK293	IC₅₀	0.2 μM Compound: 1	Inhibition of human Cav3.1 alpha1G expressed in HEK293 cells assessed as inhibition of calcium influx by FLIPR assay Inhibition of human Cav3.1 alpha1G expressed in HEK293 cells assessed as inhibition of calcium influx by FLIPR assay	[PMID: 21875808]
HEK293	IC₅₀	0.56 μM Compound: Mibefradil	Inhibition of T-type CaV3.1 channel (unknown origin) expressed in HEK293 cells assessed as inhibition of calcium current by whole cell patch-clamp method Inhibition of T-type CaV3.1 channel (unknown origin) expressed in HEK293 cells assessed as inhibition of calcium current by whole cell patch-clamp method	[PMID: 24529871]
HEK293	IC₅₀	0.56 μM Compound: Mibefradil	Inhibition of t-type Cav3.1 channel (unknown origin) expressed in HEK293 cells assessed as inhibition of 50 ms depolarizing voltage step-induced current by whole cell patch-clamp method Inhibition of t-type Cav3.1 channel (unknown origin) expressed in HEK293 cells assessed as inhibition of 50 ms depolarizing voltage step-induced current by whole cell patch-clamp method	[PMID: 24220170]
HEK293	IC₅₀	0.83 μM Compound: Mibefradil	Inhibition of alpha-1G calcium channel in human HEK293 cells by whole-cell patch-clamp method Inhibition of alpha-1G calcium channel in human HEK293 cells by whole-cell patch-clamp method	[PMID: 23395659]
HEK293	IC₅₀	0.83 μM Compound: Mibefradil	Inhibition of T-type CaV3.1 channel expressed in HEK293 cells assessed as inhibition of calcium current by automated patch-clamp assay Inhibition of T-type CaV3.1 channel expressed in HEK293 cells assessed as inhibition of calcium current by automated patch-clamp assay	[PMID: 20621730]
HEK293	IC₅₀	0.84 μM Compound: mibefradil	Inhibition of alpha-1G T-type calcium channel expressed in HEK293 cells by electrophysiological method Inhibition of alpha-1G T-type calcium channel expressed in HEK293 cells by electrophysiological method	[PMID: 17074493]
HEK293	IC₅₀	0.86 μM Compound: Mibefradil	Inhibition of T-type CaV3.1 channel expressed in HEK293 cells assessed as inhibition of calcium current by manual patch-clamp assay Inhibition of T-type CaV3.1 channel expressed in HEK293 cells assessed as inhibition of calcium current by manual patch-clamp assay	[PMID: 20621730]
HEK293	IC₅₀	1 μM Compound: Mibefradil	Inhibition of human T-type calcium channel Cav3.2 expressed in T-Rex293 cells by whole cell patch clamp assay Inhibition of human T-type calcium channel Cav3.2 expressed in T-Rex293 cells by whole cell patch clamp assay	[PMID: 23200256]
HEK293	IC₅₀	1.3 μM Compound: I, Posicor	Inhibition of human ERG expressed in HEK cells by patch clamp assay Inhibition of human ERG expressed in HEK cells by patch clamp assay	[PMID: 26231163]
HEK293	IC₅₀	1.34 μM Compound: Mibefradil	Inhibition of T-type alpha1G channel expressed in HEK293 cells by whole-cell patch-clamp method Inhibition of T-type alpha1G channel expressed in HEK293 cells by whole-cell patch-clamp method	[PMID: 20659804]
HEK293	IC₅₀	1.34 μM Compound: Mibefradil	Inhibition of T-type calcium channel alpha1G expressed in human HEK293 cells assessed as inhibition of peak currents by whole-cell patch-clamp method Inhibition of T-type calcium channel alpha1G expressed in human HEK293 cells assessed as inhibition of peak currents by whole-cell patch-clamp method	[PMID: 20382529]
HEK293	IC₅₀	1.34 μM Compound: mibefradil	Antagonist activity at T type calcium channel alpha1G expressed in HEK293 cells assessed as inhibition of peak currents by whole-cell patch-clamp method Antagonist activity at T type calcium channel alpha1G expressed in HEK293 cells assessed as inhibition of peak currents by whole-cell patch-clamp method	[PMID: 18625556]
HEK293	IC₅₀	1.34 μM Compound: mibefradil	Inhibition of T-type calcium channel Cav3.1 alpha-1G subunit expressed in HEK293 cells assessed as calcium current by patch-clamp assay Inhibition of T-type calcium channel Cav3.1 alpha-1G subunit expressed in HEK293 cells assessed as calcium current by patch-clamp assay	[PMID: 17869104]
HEK293	IC₅₀	1.34 μM Compound: Mibefradil	Inhibition of T type calcium channel subunit alpha-1G expressed in HEK293 cells assessed as effect on T-type calcium currents by patch clamp method Inhibition of T type calcium channel subunit alpha-1G expressed in HEK293 cells assessed as effect on T-type calcium currents by patch clamp method	[PMID: 17150365]
HEK293	IC₅₀	1.34 μM Compound: mibefradil	Inhibition of T-type calcium channel Cav3.1 expressed in HEK293 cells co-expressing alpha1G subunit and Kir2.1 potassium channel by patch-clamp assay Inhibition of T-type calcium channel Cav3.1 expressed in HEK293 cells co-expressing alpha1G subunit and Kir2.1 potassium channel by patch-clamp assay	[PMID: 17092715]
HEK293	IC₅₀	1.34 μM Compound: mibefradil	Inhibition of T-type calcium channel Cav3.1 expressed in HEK293 cells co-expressing alpha1G subunit by whole-cell patch clamp method Inhibition of T-type calcium channel Cav3.1 expressed in HEK293 cells co-expressing alpha1G subunit by whole-cell patch clamp method	[PMID: 17064894]
HEK293	IC₅₀	1.34 μM Compound: Mibefradil	Ability to block calcium channel T type 3.1v expressed in HEK293 cells by whole cell patch clamp method Ability to block calcium channel T type 3.1v expressed in HEK293 cells by whole cell patch clamp method	[PMID: 16876404]
HEK293	IC₅₀	181 nM Compound: I, Posicor	Inhibition of recombinant Cav3.2 channel (unknown origin) expressed in HEK293 cells assessed as effect on calcium flux incubated for 3 mins by FLIPR assay Inhibition of recombinant Cav3.2 channel (unknown origin) expressed in HEK293 cells assessed as effect on calcium flux incubated for 3 mins by FLIPR assay	[PMID: 26231163]
HEK293	IC₅₀	202 nM Compound: I, Posicor	Inhibition of recombinant Cav1.2 channel (unknown origin) expressed in HEK293 cells assessed as effect on calcium flux incubated for 3 mins by FLIPR assay Inhibition of recombinant Cav1.2 channel (unknown origin) expressed in HEK293 cells assessed as effect on calcium flux incubated for 3 mins by FLIPR assay	[PMID: 26231163]
HeLa	IC₅₀	4.32 μM Compound: Mibefradil	Inhibition of Ebolavirus glycoprotein/matrix protein VP40 entry in human HeLa cells after 4.5 hrs beta-lactamase reporter assay Inhibition of Ebolavirus glycoprotein/matrix protein VP40 entry in human HeLa cells after 4.5 hrs beta-lactamase reporter assay	[PMID: 29624387]
Hepatocyte	IC₅₀	0.873 nM Compound: Mibefradil	Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs	[PMID: 18212104]
LLC-PK1	IC₅₀	1.8 μM Compound: Mibefradil	Inhibition of P-glycoprotein, human L-MDR1 expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay Inhibition of P-glycoprotein, human L-MDR1 expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay	[PMID: 12699389]
LLC-PK1	IC₅₀	10 μM Compound: Mibefradil	Inhibition of P-glycoprotein, mouse L-mdr1b expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay Inhibition of P-glycoprotein, mouse L-mdr1b expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay	[PMID: 12699389]
LLC-PK1	IC₅₀	7.4 μM Compound: Mibefradil	Inhibition of P-glycoprotein, mouse L-mdr1a expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay Inhibition of P-glycoprotein, mouse L-mdr1a expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay	[PMID: 12699389]
MDA-MB-231	IC₅₀	> 100 μM Compound: 8	Inhibition of Orai1-mediated store operated Ca2+ entry in human MDA-MB-231 cells assessed as reduction in BAPTA-induced Ca2+ depletion-stimulated SOCE activity preincubated for 15 mins followed by BAPTA addition in presence of extracellular Ca2+ by PBX-ba Inhibition of Orai1-mediated store operated Ca2+ entry in human MDA-MB-231 cells assessed as reduction in BAPTA-induced Ca2+ depletion-stimulated SOCE activity preincubated for 15 mins followed by BAPTA addition in presence of extracellular Ca2+ by PBX-ba	[PMID: 27856238]
MDA-MB-231	IC₅₀	52.1 μM Compound: 8	Inhibition of Orai1-mediated store operated Ca2+ entry in human MDA-MB-231 cells assessed as reduction of SERCA inhibition-induced ER release preincubated for 15 mins followed by CPA addition by PBX-based FLIPR assay Inhibition of Orai1-mediated store operated Ca2+ entry in human MDA-MB-231 cells assessed as reduction of SERCA inhibition-induced ER release preincubated for 15 mins followed by CPA addition by PBX-based FLIPR assay	[PMID: 27856238]
MIA PaCa-2	IC₅₀	18.4 μM Compound: Mibefradil	Cytotoxicity against human MIAPaCa2 cells after 48 hrs by MTT assay Cytotoxicity against human MIAPaCa2 cells after 48 hrs by MTT assay	[PMID: 24529871]
Oocyte	IC₅₀	108 μM Compound: Mibefradil	Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in Xenopus oocyte heterologically expressing alpha-1C subunit Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in Xenopus oocyte heterologically expressing alpha-1C subunit	[PMID: 22761000]
Oocyte	IC₅₀	288 μM Compound: Mibefradil	Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in Xenopus oocyte heterologically expressing alpha-1C subunit Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in Xenopus oocyte heterologically expressing alpha-1C subunit	[PMID: 22761000]
SK-OV-3	IC₅₀	20.54 μM Compound: Mibefradil	Cytotoxicity against human SKOV3 cells after 48 hrs by MTT assay Cytotoxicity against human SKOV3 cells after 48 hrs by MTT assay	[PMID: 24220170]

体外研究
(In Vitro)

Mibefradil inhibits reversibly the T- and L-type currents with IC₅₀ values of 2.7 and 18.6 μM, respectively. The inhibition of the L-type current is voltage-dependent, whereas that of the T-type current is not. Ro 40-5967 blocks T-type current already at a holding potential of -100 mV^[1] At a higher concentration (20 µM), Mibefradil reduces the amplitude of excitatory junction potentials (by 37±10 %), slows the rate of repolarisation (by 44±16 %) and causes a significant membrane potential depolarisation (from −83±1 mV to −71±5 mV). At a higher Mibefradil concentration (20 µM) there is significant membrane potential depolarisation and a slowing of repolarisation. These actions of Mibefradil are consistent with K⁺ channel inhibition, which has been shown to occur in human myoblasts and other cells^[2].

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

体内研究
(In Vivo)

The hearing thresholds of the 24-26 week old C57BL/6J mice differed following the 4-week treatment period. The hearing threshold at 24 kHz is significantly decreased in the Mibefradil-treated and benidipine-treated groups compared with the saline-treated group (P<0.05)^[3]. Compared with the saline-treated group, rats receiving Mibefradil or Ethosuximide show significant lower Ca_V3.2 expression in the spinal cord and DRG^[4].

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

Clinical Trial

分子量

495.63

Formula

C₂₉H₃₈FN₃O₃

CAS 号

116644-53-2

中文名称

米贝拉地尔；米贝地尔；咪拉地尔；咪贝地尔

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

产品使用指南 (1538 KB)

参考文献

[1]. Mehrke G, et al. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8. [Content Brief]

[2]. Brain KL, et al. The sources and sequestration of Ca(2+) contributing to neuroeffector Ca(2+) transients in the mouse vas deferens. J Physiol. 2003 Dec 1;553(Pt 2):627-35. [Content Brief]

[3]. Yu YF, et al. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. Exp Ther Med. 2016 Mar;11(3):1039-1044. [Content Brief]

[4]. Shiue SJ, et al. Chronic intrathecal infusion of T-type calcium channel blockers attenuates CaV3.2 upregulation in nerve-ligated rats. Acta Anaesthesiol Taiwan. 2016 Oct 17. pii: S1875-4597(16)30071-6. [Content Brief]

Animal Administration ^[3]^[4]	Mice^[3] A total of 30 male C57BL/6J mice (age, 6-8 weeks) are randomized into three groups for the detection of three calcium channel receptor subunits α1G, α1H and α1I, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a further 30 C57BL/6J male mice (age, 24-26 weeks) are allocated at random into three treatment groups: Saline, Mibefradil and benidipine. Each group is subjected to auditory brainstem recording (ABR) and distortion product otoacoustic emission (DPOAE) tests following treatment. Mibefradil and benidipine are dissolved in physiological saline solution. A preliminary experiment led to the selection of dosages of 30 mg/kg/day Mibefradil and 10 mg/kg/day Benidipine. The drugs are administered to the mice by gavage for four consecutive weeks. Rats^[4] Male Sprague-Dawley rats (200-250 g) are used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [Mibefradil (0.7 μg/h) or Ethosuximide (60 μg/h)] is started after surgery for 7 days. Fluorescent immunohistochemistry and Western blotting are used to determine the expression pattern and protein level of Ca_V3.2. Hematoxylin-eosin and toluidine blue staining are used to evaluate the neurotoxicity of tested agents. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献	[1]. Mehrke G, et al. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8. [Content Brief] [2]. Brain KL, et al. The sources and sequestration of Ca(2+) contributing to neuroeffector Ca(2+) transients in the mouse vas deferens. J Physiol. 2003 Dec 1;553(Pt 2):627-35. [Content Brief] [3]. Yu YF, et al. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. Exp Ther Med. 2016 Mar;11(3):1039-1044. [Content Brief] [4]. Shiue SJ, et al. Chronic intrathecal infusion of T-type calcium channel blockers attenuates CaV3.2 upregulation in nerve-ligated rats. Acta Anaesthesiol Taiwan. 2016 Oct 17. pii: S1875-4597(16)30071-6. [Content Brief]

Animal Administration
^[3]^[4]

Mice^[3]
A total of 30 male C57BL/6J mice (age, 6-8 weeks) are randomized into three groups for the detection of three calcium channel receptor subunits α1G, α1H and α1I, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a further 30 C57BL/6J male mice (age, 24-26 weeks) are allocated at random into three treatment groups: Saline, Mibefradil and benidipine. Each group is subjected to auditory brainstem recording (ABR) and distortion product otoacoustic emission (DPOAE) tests following treatment. Mibefradil and benidipine are dissolved in physiological saline solution. A preliminary experiment led to the selection of dosages of 30 mg/kg/day Mibefradil and 10 mg/kg/day Benidipine. The drugs are administered to the mice by gavage for four consecutive weeks.
Rats^[4]
Male Sprague-Dawley rats (200-250 g) are used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [Mibefradil (0.7 μg/h) or Ethosuximide (60 μg/h)] is started after surgery for 7 days. Fluorescent immunohistochemistry and Western blotting are used to determine the expression pattern and protein level of Ca_V3.2. Hematoxylin-eosin and toluidine blue staining are used to evaluate the neurotoxicity of tested agents.

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

参考文献

[1]. Mehrke G, et al. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8. [Content Brief]

[2]. Brain KL, et al. The sources and sequestration of Ca(2+) contributing to neuroeffector Ca(2+) transients in the mouse vas deferens. J Physiol. 2003 Dec 1;553(Pt 2):627-35. [Content Brief]

[3]. Yu YF, et al. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. Exp Ther Med. 2016 Mar;11(3):1039-1044. [Content Brief]

[4]. Shiue SJ, et al. Chronic intrathecal infusion of T-type calcium channel blockers attenuates CaV3.2 upregulation in nerve-ligated rats. Acta Anaesthesiol Taiwan. 2016 Oct 17. pii: S1875-4597(16)30071-6. [Content Brief]

Mibefradil 相关分类

Cardiovascular Disease

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Mibefradil (Synonyms: Ro 40-5967)

Other Forms of Mibefradil:

MCE 顾客使用本产品发表的 12 篇科研文献

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Mibefradil (Synonyms: Ro 40-5967)

Other Forms of Mibefradil:

Mibefradil 相关抗体

MCE 顾客使用本产品发表的 12 篇科研文献

Mibefradil 相关产品

•同靶点产品:

•同靶点蛋白产品:

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生物活性

实验参考方法

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参考文献

Mibefradil 相关抗体:

Mibefradil 相关分类

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