Customer Validation
- •Nature. 2017 Aug 24;548(7668):471-475.
- •Mol Cell. 2017 Oct 19;68(2):336-349.e6.
- •Nat Commun. 2017 Jun 27;8:15916.
- •Cancer Res. 2016 Nov 15;76(22):6723-6734.
- •Biochim Biophys Acta. 2017 Nov 20;1865(2):354-363.
- •Mol Oncol. 2017 Aug;11(8):1035-1049.
- •Oncotarget. 2017 Jun 27;8(40):67422-67438.
- •Biochem Pharmacol. 2017 Jan 15;124:29-42.
- •Harvard Medical School LINCS LIBRARY
Description |
LY2835219 a selective CDK4/6 inhibitor with IC50 values of 2 nM and 10 nM for CDK4 and CDK6, respectively. |
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IC50 & Target |
IC50: 2 nM (CDK4), 10 nM (CDK6)[3] |
In Vitro |
LY2835219 reduces cell viability with the IC50 values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells[1]. LY2835219 shows inhibition on A375R1-4, M14R, and SH4R with EC50 values ranging from 0.3 to 0.6 μM; LY2835219 inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC50 values of 395, 260, and 463 nM, respectively[2]. LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells[3]. |
In Vivo |
LY2835219 (45 mg/kg, p.o.) in combination with everolimus causes a cooperative antitumor effect in HNSCC xenograft tumor[1]. LY2835219 (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model[2]. |
References |
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Kinase Assay
[1] |
Cells (5 × 103) are plated in 96 well plates. Cells are treated the next day for 24 to 48 hours and then assessed for caspase-3 activity by Caspase-Glo-3/7 Assay, as per manufacturer"s instructions and a luminescence plate reader. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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Cell Assay
[1] |
LY2835219 is dissolved in DMSO to a 10 mM concentration. Cells are seeded in a 96-well plate, allowed to adhere overnight, and treated with DMSO control (0.1% v/v) or the indicated compounds for 72 h. Cell viability and proliferation are determined using a Cell Counting Kit according to the manufacturer"s instructions. The interaction between LY2835219 and mTOR inhibitor is determined using CompuSyn. Combination index (CI) values of 1 indicates and additive drug interaction, whereas a CI of < 1="" is="" synergistic="" and="" a="" ci="" of=""> 1 is antagonistic. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
Animal Administration
[1] |
LY2835219 is dissolved in 1% HEC in 20 mM phosphate buffer. Six-week-old BALB/c female nude mice are injected subcutaneously with OSC-19 (1×106) cells. When tumor sizes reach approximately 100 mm3, mice are randomized by tumor size and subjected to each treatment. At least 5 mice per treatment group are included. Each group of mice is dosed via daily oral gavage with vehicle, LY2835219 (45 mg/kg/d or 90 mg/kg/d), Everolimus (5 mg/kg/d), or a combination of both. The LY2835219 is dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0). Tumor size and body weight are measured twice weekly. Tumor volumes are calculated using the following formula: V=(L × W2)/2 (L, Length; W, width). Mice are gavaged a final time on day 14 and sacrificed the following day. The tumors are removed for Western blot and immunohistochemistry. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
References |
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Molecular Weight |
602.7 |
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Formula |
C₂₈H₃₆F₂N₈O₃S |
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CAS No. |
1231930-82-7 |
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Storage |
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Shipping | Room temperature in continental US; may vary elsewhere |
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Solvent & Solubility |
H2O: ≥ 250 mg/mL LY2835219 is dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0) and administered orally by gavage (final volume 0.2 mL)[4]. * "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">1> |
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References |
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Purity: 99.87%
COA (94 KB) HNMR (599 KB) LCMS (242 KB)
Handling Instructions (1252 KB)-
[1]. Ku BM, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13.
[2]. Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63.
[3]. Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37.
[4]. Wu T, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42.
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求助各位大神,现在想购买小分子数据库,求大神推荐。
我知道的免费的数据库有zinc
求推荐哪家公司或者研究所的小分子数据库可以购买,十分感谢!!!!!!
求助各位前辈,我最近在合成的化合物水溶性很好,非常好,以至于可以随便溶解在水里,它的六氟磷酸盐也可以随意溶解在水里(大于50uM),细胞成像实验显示它根本进不去细胞,求问有没有啥方法包裹一下让它进去?我搜了一下文献,感觉多数是把脂溶性特别好的东西包裹一下弄进去的,也许是搜索姿势不对没找到我需要的答案,**点拨啊!!!
2017年4月26日|Filedunder:制药工业,制药企业,孤儿药,新药研发,制药常识,文献综合|Postedby:路人丙
【新闻事件】:在日前正在举行的美国神经学年会上MitsubishiTanabe公布了其ALS药物Edaravone的一个三期临床试验结果。在标准疗法基础上加入Edaravone显著改善ALS患者综合功能指标ALSFRS-R(-5.0对-7.5),同时也改善运动、呼吸等局部功能。Edaravone已经在韩国日本批准用于ALS,去年10月申请在美国上市,今年6月之前有望批准。
【药源解析】:ALS全称叫“肌肉萎缩性侧面硬化病”,也称LouGehrig氏病,因为30年代美国纽约洋基棒球队著名选手LouGehrig死于这个病。2014年风行一时的冰桶挑战让更多人知道了ALS,但ALS新药发现依然缓慢。美国目前只有riluzole这一个上市药物,能增加~10%的一年生存机会。
ALS的发病机理未知,动物模型十分不可靠,所以这个病的新药开发很难。过去10年大约只有十几个药物进入临床,基本全军覆没。走的最远的是百建艾迪的dexpramipexole,2013年初在三期临床失败。Edaravone号称是游离基清除剂,但分子机理未知。Edaravone最早作为中风药物开发,后来扩展到ALS。第一个三期临床失败,今天公布的是症状较轻患者。这个临床是日本人群,Edaravone并没有在美国IND和开展临床试验,所以如果批准将是比较特殊的情况(和Marathon的DMD药物Emflaza情况类似)。
Edaravone的另一个特殊性质是其分子结构。这个化合物分子十分简单,分子量只有174,可以算作是超小分子药物。现在有几十个分子量小于200的FDA批准药物,这类药物因为官能团数目有限不大可能与任何靶点有较高结合能,所以通常靶点未知。靶点未知又没有可靠动物模型,这类药物发现就更加困难。当然动物模型预测性差不是超小分子药物才面临的难题,多数神经系统药物、甚至现在最火热的肿瘤免疫疗法也面临同样问题。
这种临床前缺乏可靠评价体系的药物可以算是有D无R,这要求厂家冒更大的临床风险。只有潜在回报较大如没有任何标准疗法的罕见病或真正颠覆性药物如免疫疗法才可以适当采用这个模式。这个模式扩大化对厂家的长期生存是个威胁,因为新药的未知因素已经很多、成功率已经很低。没有临床前适当去风险的机会主义不可持续。
转发分享
美中药源原创文章,转载注明出处并添加超链接,商业用途需经书面授权。
★更多深度解析访问《美中药源》~
https://www.yypharm.com/?p=10664
求助大家,小分子药物最新专利申请情况跟踪,之前听别人说可以在一个网站可以导出这个信息。
不知哪位大侠知道,告知一下,不胜感激!
一、首先你要明白肽是什么...........................肽是氨基酸通过酰胺键结合而成的东西.........
二、你要明白氨基酸是什么..........................氨基酸是构成蛋白质的基本单位,多种氨基酸结合为长肽链,几条长肽链再盘旋就形成了蛋白质......................
三、关于小分子肽、短肽、多肽、寡肽.......其实都是肽.......区别只是由多少个氨基酸构成而已............
所以,你的问题可以很粗暴地理解为“蛋白质对人体有没有副作用”.......
如果你营养足够的情况下,再补充这个,会导致营养过剩,从而加重身体代谢的负荷............类似就是这样子的了...........小分子肽,一般现在用于化妆品上比较多(一ye子.植物肽面膜就是这个).......小分子肽(可以简单理解为纳米胶原蛋白),这比蛋白质(也可以粗暴理解为胶原蛋白)更加容易吸收......而用在食品上,要视乎是何种小分子肽了.....大豆肽、花生肽、大米肽....不同的肽有不同的功效.......主要可以改善风味、改善吸收、增强胃肠道功能等等.......
如题,之前没做过药代,老师给了一个600+Da的五肽,想测下药代动参数,看文献推荐上述两种方法,但是不知道选哪种更好,lcms前处理会不会影响小肽。
就是蛋白质分子的小片断
是氨基酸形成的
暂无品牌问答