标签归档：chok

RSM-932A(Synonyms: TCD-717)

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

RSM-932A (Synonyms: TCD-717) 纯度: 99.60%

RSM-932A (TCD-717) 是一种特异性 ChoKα 抑制剂，对人重组 ChoKα 和 ChoKβ 酶的 IC50 分别为 1 和 33 μM。RSM-932A 是针对 ChoKα 的“人类首创”化合物。RSM-932A 具有有效的体外抗肿瘤增殖和体内抗肿瘤活性，且显示低毒性[ 3]。

RSM-932A(Synonyms: TCD-717)

RSM-932A Chemical Structure

CAS No. : 850807-63-5

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RSM-932A 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Anti-Cancer Compound Library

生物活性

RSM-932A (TCD-717) is a specific ChoKα inhibitor with IC50s of 1 and 33 μM for human recombinant ChoKα and ChoKβ enzymes, respectively. RSM-932A acts as the “first in humans” compound targeting ChoKα. RSM-932A is potent in vitro anti-proliferative and in vivo anti-tumoral activity against human xenografts in mice, showing high efficacy with low toxicity profiles[1][2][3].

IC50 & Target

ChoKα[1]
体外研究
(In Vitro)

RSM-932A has a potent anti-proliferative activity against most tumor-derived cell lines tested, including those derived from breast, lung, colon, bladder, liver, ovary, bone, cervix, kidney, pancreas, melanoma, and brain tumors, with IC50s of 1.3-7.1 μM for 72 hours[1].
RSM-932A (TCD-717; 2-4 µM; for 24 hours) promotes cell death of colon cancer cells[2].
RSM-932A (2-10 µM) exhibits a dosage-dependent decrease in the levels of thymidylate synthase (TS) and thymidine kinase (TK1) proteins proteins[2].
RSM-932A inhibits Streptococcus pneumoniae choline kinase (sChoK) with IC50 of 0.5 μM in LDH/PK and colorimetric enzymatic assays[3].
The minimum inhibitory concentration (MIC) of RSM-932A for S. pneumoniae is 0.4 μM, and the minimum lethal concentration (MLC) is 1.6 μM[3].
RSM-932A is a comparatively potent inhibitor with the IC50 of 1.75 μM in a steady-state reaction in which the concentration of Choline is equivalent to its Km[4].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[2]

Cell Line: DLD-1, HT29, SW620 and HCT116 CRC cell lines and the non-tumourigenic CCD-841 cell line
Concentration: 2, 3, 4 µM
Incubation Time: 24 hours
Result: Triggered to cell death.

Western Blot Analysis[2]

Cell Line: DLD-1, HT29 and SW620 cell lines
Concentration: 2, 4, 6, 8, 10 uM
Incubation Time: 24 hours
Result: A dosage-dependent decrease in the levels of thymidylate synthase (TS) and thymidine kinase (TK1) proteins.

体内研究
(In Vivo)

RSM-932A exhibits a potent in vivo anticancer activity, and lack of toxicity at the effective doses[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Athymic nu/nu mice, CD1 nude mice, and BALB/c nude (six-week-old) bearing human tumor xenografts (colon adenocarcinoma HT29, non-small cell lung cancer (NSCLC) H-460, breast adenocarcinoma MDA-MB-231)[3]
Dosage: 7.5 mg/kg, 6 mg/kg, 5 mg/kg, 3 mg/kg, 1 mg/kg, 0.3 mg/kg
Administration: Administration routes (intraperitoneal or intravenous), treatment schedule (5 consecutive days, 3 days per week, 2 days per week, 1 day per week)
Result: The LD50 was 10.9 mg/kg in mice. The effective dose used in the in vivo experiments was 7.5 mg/kg.

分子量

877.53

Formula

C46H38Br2Cl2N4
CAS 号

850807-63-5
运输条件

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

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
溶解性数据
In Vitro: 

DMSO : 16.67 mg/mL (19.00 mM; ultrasonic and warming and heat to 60°C)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.1396 mL 5.6978 mL 11.3956 mL
5 mM 0.2279 mL 1.1396 mL 2.2791 mL
10 mM 0.1140 mL 0.5698 mL 1.1396 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1.67 mg/mL (1.90 mM); Clear solution

    此方案可获得 ≥ 1.67 mg/mL (1.90 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 Shanghai Jinpan Biotech Co Ltd 网站选购。
参考文献

  • [1]. Juan Carlos Lacal, et al. Preclinical characterization of RSM-932A, a novel anticancer drug targeting the human choline kinase alpha, an enzyme involved in increased lipid metabolism of cancer cells. Mol Cancer Ther. 2015 Jan;14(1):31-9.

    [2]. Ana de la Cueva, et al. Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts. PLoS One. 2013 Jun 10;8(6):e64961.

    [3]. Tahl Zimmerman, et al. Identification and validation of novel and more effective choline kinase inhibitors against Streptococcus pneumonia. Sci Rep. 2020 Sep 22;10(1):15418.

    [4]. Tahl Zimmerman, et al. Antiplasmodial activity and mechanism of action of RSM-932A, a promising synergistic inhibitor of Plasmodium falciparum choline kinase. Antimicrob Agents Chemother. 2013 Dec;57(12):5878-88.

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EB-3D

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

EB-3D  纯度: 98.78%

EB-3D 是有效的选择性胆碱激酶 α (ChoKα) 抑制剂，对 ChoKα1 的 IC50 值为 1 μM。EB-3D 对 ChoKα 表达、AMPK 激活、细胞凋亡 (apoptosis)、内质网应激和脂质代谢有影响。EB-3D 在一组T-白血病细胞系中显示出强大的抗增殖活性。具有抗癌活性。

EB-3D

EB-3D Chemical Structure

CAS No. : 1839150-63-8

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10 mM * 1 mL in DMSO ￥2694 In-stock
5 mg ￥1900 In-stock
10 mg ￥3000 In-stock
50 mg ￥8300 In-stock
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EB-3D 相关产品

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  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Epigenetics Compound Library
  • Kinase Inhibitor Library
  • PI3K/Akt/mTOR Compound Library
  • Anti-Cancer Compound Library
  • Anti-Aging Compound Library
  • Antioxidants Compound Library
  • Oxygen Sensing Compound Library
  • Endoplasmic Reticulum Stress Compound Library
  • Glycolysis Compound Library
  • Cytoskeleton Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Cancer Metabolism Compound Library
  • Anti-Obesity Compound Library
  • Lipid Metabolism Compound Library
  • Glucose Metabolism Compound Library

生物活性

EB-3D is a potent and selective choline kinase α (ChoKα) inhibitor, with an IC50 of 1 μM for ChoKα1. EB-3D exerts effects on ChoKα expression, AMPK activation, apoptosis, endoplasmic reticulum stress and lipid metabolism. EB-3D exhibits a potent antiproliferative activity in a panel of T-leukemia cell lines. Anti-cancer activity[1][2][3].

IC50 & Target

IC50: 1 μM; Kd: 0.7 μM[3]
体外研究
(In Vitro)

EB-3D displays (0-100 μM; 72 hours) excellent antiproliferative activity against a wide cohort of T-leukemic cell lines, with GI GI50s 13 values in the nanomolar range[1].
EB-3D (1.25-5μM; 24 hours) induced apoptosis in leukemia cell lines[1].
EB-3D (0.5-1 μM; 24 hours) induces a G0/G1 arrest that lead to apoptosis[1].
EB-3D (0.3 μM; 48 hours) shows a first spike of activation of AMPKα after 30 minutes and a later increase in the phosphorylation of T172[1].
EB-3D (1-40 μM; 48 hours) inhibits cell growth in HepG2 cells with a GI50 of 14.55 μM[2].
EB-3D induces deregulation of the AMPK-mTOR pathway and apoptosis in leukemia T-cells[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

Cell Line: JURKAT, CCRF-CEM, HSB-2, MOLT-16, DNA-41, LOUCY, PEER, ALL-SIL cells
Concentration: 0.001, 0.01, 0.1, 1, 10, 100 μM
Incubation Time: 72 hours
Result: Inhibited JURKAT, CCRF-CEM, HSB-2, MOLT-16, DNA-41, LOUCY, PEER, and ALL-SIL cells growth with GI50s of 136.2, 478.8, 17.7, 0.9, 60.6, 200, 265, and 132 nM, respectively.

Apoptosis Analysis[1]

Cell Line: Jurkat, CCRF-CEM and HSB-2 cells
Concentration: 1.25, 2.5, 5 μM
Incubation Time: 24 hours
Result: Induced apoptosis in leukemia cell lines.

Cell Cycle Analysis[1]

Cell Line: Jurkat, CCRF-CEM and HSB-2 cells
Concentration: 0.5, 1 μM
Incubation Time: 24 hours
Result: Induces cell cycle arrest in G0/G1 phase.

Western Blot Analysis[1]

Cell Line: Jurkat cells
Concentration: 0.3 μM
Incubation Time: 48 hours
Result: Showed a first spike of activation of AMPKα after 30 minutes of treatment and a later increase in the phosphorylation of T172. The increase in S79 phosphorylation of its main target ACC (acetyl-coenzyme A (CoA) carboxylase), followed the same pattern. This rapid activation of AMPK, in turn induced a consequent reduction in mTOR phosphorylation that is visible already at 30’ and that becomes amplified at longer time probably due to the interruption of feedback loops that are characteristic of mTOR connecting pathways.

体内研究
(In Vivo)

EB-3D (1 mg/kg; i.p.; every other day) impairs mammary tumor growth in syngeneic orthotopic E0771-C57BL/6 mouse model[4].
EB-3D (2.5 mg/kg; every other day for 4 weeks) shows a reduction of the number of spontaneous lung macro- and micrometastasis[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: E0771-C57BL/6 mice[4]
Dosage: I.p.; every other day for 4 weeks
Administration: 2.5 mg/kg
Result: A reduction of the number of spontaneous lung macro- and micrometastasis.

分子量

644.44

Formula

C30H36Br2N4O2
CAS 号

1839150-63-8
运输条件

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

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据
In Vitro: 

DMSO : 50 mg/mL (77.59 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.5517 mL 7.7587 mL 15.5173 mL
5 mM 0.3103 mL 1.5517 mL 3.1035 mL
10 mM 0.1552 mL 0.7759 mL 1.5517 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
参考文献

  • [1]. Mariotto E, et al. EB-3D a novel choline kinase inhibitor induces deregulation of the AMPK-mTOR pathway and apoptosis in leukemia T-cells. Biochem Pharmacol. 2018 Sep;155:213-223.

    [2]. Sola-Leyva A, et al. Choline kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cells. Sci Rep. 2019 Mar 25;9(1):5109.

    [3]. Schiaffino-Ortega S, et al. Design, synthesis, crystallization and biological evaluation of new symmetrical biscationic compounds as selective inhibitors of human Choline Kinase α1 (ChoKα1).

    [4]. Mariotto E, et al. Choline Kinase Alpha Inhibition by EB-3D Triggers Cellular Senescence, Reduces Tumor Growth and Metastatic Dissemination in Breast Cancer. Cancers (Basel). 2018;10(10):391. Published 2018 Oct 22.

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