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KO-947

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。

KO-947  纯度: 99.45%

KO-947是有效和选择性的 ERK1/2 激酶抑制剂，在MAPK途径失调的肿瘤中具有潜在效用。

KO-947

KO-947 Chemical Structure

CAS No. : 1695533-89-1

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Free Sample (0.1-0.5 mg)   Apply now  
5 mg ￥2050 In-stock
10 mg ￥3280 In-stock
25 mg ￥6300 In-stock
50 mg ￥9450 In-stock
100 mg ￥16000 In-stock
200 mg   询价  
500 mg   询价  

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KO-947 相关产品

•相关化合物库:

  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Immunology/Inflammation Compound Library
  • Kinase Inhibitor Library
  • MAPK Compound Library
  • Stem Cell Signaling Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Anti-Aging Compound Library
  • Reprogramming Compound Library
  • Oxygen Sensing Compound Library
  • Glutamine Metabolism Compound Library
  • Anti-Lung Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Obesity Compound Library
  • Angiogenesis Related Compound Library
  • Targeted Diversity Library
  • Anti-Liver Cancer Compound Library
  • Anti-Colorectal Cancer Compound Library

生物活性

KO-947 is a potent and selective inhibitor of ERK1/2 kinases with potential utility in MAPK pathway dysregulated tumors.

IC50 & Target[1]

ERK1

 

ERK2

 

体外研究
(In Vitro)

KO-947 is a 10 nM inhibitor of ERK with at least 50-fold selectivity against a panel of 450 kinases. KO-947 blocks ERK signaling and proliferation of tumor cells exhibiting dysregulation of MAPK pathway signaling, including mutations in BRAF, NRAS or KRAS, at low nanomolar concentrations[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.
体内研究
(In Vivo)

In cell-line derived xenograft studies, KO-947 profoundly suppresses ERK signaling for up to five days after a single dose and induces regressions in RAS- and RAF-mutant melanoma, NSCLC and pancreatic cancer models on administration schedules ranging from daily to weekly. Intermittent dosing enables comparable antitumor activity at reduced dose-intensity[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.
Clinical Trial

分子量

355.39

Formula

C21H17N5O
CAS 号

1695533-89-1
运输条件

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

4°C, protect from light

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

DMSO : 62.5 mg/mL (175.86 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.8138 mL 14.0691 mL 28.1381 mL
5 mM 0.5628 mL 2.8138 mL 5.6276 mL
10 mM 0.2814 mL 1.4069 mL 2.8138 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 (protect from 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    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (5.85 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (5.85 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

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

    Solubility: ≥ 2.08 mg/mL (5.85 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (5.85 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.8 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
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (5.85 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (5.85 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Burrows F, et al. KO-947, a potent ERK inhibitor with robust preclinical single agent activity in MAPK pathway dysregulated tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5168. doi:10.1158/1538-7445.AM2017-5168.

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Ko 143

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。

Ko 143  纯度: 99.83%

Ko 143 是有效且选择性的 ATP 结合盒亚家族 G 成员 2 (ABCG2/BCRP) 抑制剂。Ko 143 比 P-gp 和 MRP-1 运输蛋白高出 200 倍的选择性。

Ko 143

Ko 143 Chemical Structure

CAS No. : 461054-93-3

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ￥980 In-stock
5 mg ￥949 In-stock
10 mg ￥1525 In-stock
25 mg ￥3600 In-stock
50 mg ￥6678 In-stock
100 mg ￥11476 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

Ko 143 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Membrane Transporter/Ion Channel Compound Library
  • Anti-Cancer Compound Library
  • Lipid Metabolism Compound Library

生物活性

Ko 143 is a potent and selective ATP-binding cassette subfamily G member 2 (ABCG2/BCRP) inhibitor. Ko 143 displays >200-fold selectivity over P-gp and MRP-1 transporters[1][2].

IC50 & Target

EC90: 26 nM (BCRP)
体外研究
(In Vitro)

Ko143 (10 nM) significantly decreases (2.5-fold) the IC50 of MTX for HEK G2 cells and mouse G2 cells. Ko143 (1-100 μM) metabolite does not inhibit the function of ABC Transporters[1]. Reversal of drug resistance in SKF 104864A-selected mouse MEF3.8/T6400 cells and human IGROV1/T8 cells by FTC analogue Ko143. Ko143 is applied at zero, one, or eight times the EC90 concentration of 25 nM[2]. Ko143 inhibits BCRP-mediated transport of ZD 4522 in Madin-Darby Canine Kidney (MDCK) 2-BCRP421CC (wild type) cells and MDCK2-BCRP421AA (mutant type) cells[3].

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.
体内研究
(In Vivo)

Ko143 (10 mg/kg, p.o.) increases the oral availability of SKF 104864A in mice[2]. Ko143 significantly affects the pharmacokinetics of ZD 4522 in rats[3].

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.
分子量

469.57

Formula

C26H35N3O5
CAS 号

461054-93-3
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 100 mg/mL (212.96 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1296 mL 10.6480 mL 21.2961 mL
5 mM 0.4259 mL 2.1296 mL 4.2592 mL
10 mM 0.2130 mL 1.0648 mL 2.1296 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。-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    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.32 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

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

    Solubility: 2.5 mg/mL (5.32 mM); Suspended solution; Need ultrasonic and warming and heat to 50°C

    此方案可获得 2.5 mg/mL (5.32 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例，取 100 μL 25.0 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
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.32 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

  • 4.

    请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

    Solubility: 2.5 mg/mL (5.32 mM); Suspended solution; Need ultrasonic

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Weidner LD, et al. The Inhibitor Ko143 Is Not Specific for ABCG2. J Pharmacol Exp Ther. 2015 Sep;354(3):384-93.

    [2]. JD Allen et al. Potent and Specific Inhibition of the Breast Cancer Resistance Protein Multidrug Transporter in Vitro and in Mouse Intestine by a Novel Analogue of Fumitremorgin C. Mol. Cancer Ther. 2002, 1, 417-425.

    [3]. Wen JH, et al. Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of ZD 4522 In Vivo and Vitro. Chin Med Sci J. 2015 Dec;30(4):218-25.

    [4]. Hou J, et al. Quantitative determination and pharmacokinetic study of the novel anti-Parkinson’s disease candidate drug FLZ in rat brain by high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2012 Jul;66:232-9.

    [5]. Liu K, et al. Metabolism of KO143, an ABCG2 inhibitor. Drug Metab Pharmacokinet. 2017 Aug;32(4):193-200.
Cell Assay
[2]

cells are plated at 400 or 1000/well in 96-well plates the night before addition of drugs. A concentration series of drug is applied along one plate axis and left for the duration of the assay. Plates are harvested after 4-5 days while untreated wells are still subconfluent. Relative cell proliferation is quantified with CyQuant or Sybr Green I fluorescent nucleic acid stains. Assays with human cell lines are performed in the presence of 0.1 μm PSC833 to inhibit confounding P-gp activity.

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 Administration
[2]

Oral toxicity of FTC analogues in mice is tested by mixing 50 mg/mL stocks in DMSO 1:1 with Tween 80 (polyoxyethylene sorbitan mono-oleate) and diluting with 5% w/v glucose such that the final volume administered by oral gavage is 10 μL/g of body weight. Pairs of mice are administered oral doses of 50 mg/kg Ko132, Ko134, Ko143, or vehicle under light methoxyflurane anesthesia. Final tests of 50 mg/kg Ko134 or Ko143 are performed on additional pairs of unanesthetized animals to observe any behavioral effects. Further, another pair of mice receive the higher dose of 100 mg/kg Ko134. For i.p. toxicity tests, the FTC analogue stocks in DMSO are dispersed in at least 10 volumes of sterile corn oil such that the injected volume is 5 μL/g of body weight. After pilot tests at lower doses show no adverse effects, mice (4 per group) are administered vehicle or 10 mg/kg i.p. of Ko132, Ko134, or Ko143. The mice are observed continuously during the first hour after administration and then at increasing intervals for 2 weeks, after which they are sacrificed for histological examination of major organs and structures including brain, salivary glands, heart, lungs, liver, adrenal glands, kidneys, urinary tract, spleen, thymus, bone marrow, pancreas, stomach, intestines, cecum, colon, testes, epididymus, skin, head, trunk, and limbs.

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.
参考文献

  • [1]. Weidner LD, et al. The Inhibitor Ko143 Is Not Specific for ABCG2. J Pharmacol Exp Ther. 2015 Sep;354(3):384-93.

    [2]. JD Allen et al. Potent and Specific Inhibition of the Breast Cancer Resistance Protein Multidrug Transporter in Vitro and in Mouse Intestine by a Novel Analogue of Fumitremorgin C. Mol. Cancer Ther. 2002, 1, 417-425.

    [3]. Wen JH, et al. Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of ZD 4522 In Vivo and Vitro. Chin Med Sci J. 2015 Dec;30(4):218-25.

    [4]. Hou J, et al. Quantitative determination and pharmacokinetic study of the novel anti-Parkinson’s disease candidate drug FLZ in rat brain by high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2012 Jul;66:232-9.

    [5]. Liu K, et al. Metabolism of KO143, an ABCG2 inhibitor. Drug Metab Pharmacokinet. 2017 Aug;32(4):193-200.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

Ziftomenib(Synonyms: KO-539)

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。

Ziftomenib (Synonyms: KO-539)

Ziftomenib (KO-539) 是一种 menin-MLL 相互作用的抑制剂，具有抗肿瘤活性 (WO2017161028A1, compound 151)。

Ziftomenib(Synonyms: KO-539)

Ziftomenib Chemical Structure

CAS No. : 2134675-36-6

规格 价格 是否有货
5 mg ￥22000 询问价格 & 货期

* Please select Quantity before adding items.

生物活性

Ziftomenib (KO-539) is a menin-MLL interaction inhibitor with antitumor activities (WO2017161028A1, compound 151)[1].

体外研究
(In Vitro)

The mixed-lineage leukemia (MLL) protein is a histone methyltransferase critical for the epigenetic regulation of gene transcription. Many acute leukemias, including acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL) and mixed-lineage leukemia (MLL), are characterized by the presence of chimeric MLL fusion proteins that result from chromosomal translocations of the MLL gene located at chromosome 11, band q23 (11q23). MLL fusion proteins lack the original histone methyltransferase activity of the C-terminus of MLL and gain the ability to regulate transcription of numerous oncogenes, including HOX and MEIS1, resulting in increased cell proliferation and decreased cell differentiation, ultimately leading to leukemogenesis[1].

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

717.87

Formula

C33H42F3N9O2S2
CAS 号

2134675-36-6
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.
参考文献

  • [1]. Tao Wu, et al. Substituted inhibitors of menin-mll and methods of use. WO2017161028A1.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务