小鼠胚胎细胞【Pluripotin】 | 839707-37-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 小鼠胚胎细胞【Pluripotin】
• 中文别名: N-[3-[7-[(1,3-二甲基-1H-吡唑-5-基)氨基]-1,4-二氢-1-甲基-2-氧代嘧啶并[4,5-D]嘧啶-3(2H)-基]-4-甲基苯基]-3-(三氟甲基)苯甲酰胺
• 英文名称: pluripotin
• 英文别名: N-(3-(7-(1,3-dimethyl-1H-pyrazol-5-ylamino)-1-methyl-2- oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide；N-(3-(7-((1,3-dimethyl-1H-pyrazol-5-yl)amino)-1-methyl-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide；SC1；N-[3-[7-[(2,5-dimethylpyrazol-3-yl)amino]-1-methyl-2-oxo-4H-pyrimido[4,5-d]pyrimidin-3-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide
• CAS: 839707-37-8
• 化学式: C₂₇H₂₅F₃N₈O₂
• 分子量: 550.543
• InChiKey: NBZFRTJWEIHFPF-UHFFFAOYSA-N

物化性质

• 密度：
  1.43
• 溶解度：
  DMSO：可溶10mg/mL（澄清溶液）

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

Pluripotin (SC1)是ERK1和RasGAP的双重抑制剂，Kd值分别为98 nM和212 nM。可用来维持胚胎干细胞的自我更新。Pluripotin 还可抑制 RSK1、RSK2、RSK3 和 RSK4，对应的IC50值分别为0.5 µM、2.5 µM、3.3 µM 和 10.0 µM。

靶点

Target	Value
RSK1 ()
ERK1 (Cell-free assay)	98 nM(Kd)
RasGAP (Cell-free assay)	212 nM(Kd)
RSK1 (Cell-free assay)	0.5 μM
RSK2 (Cell-free assay)	2.5 μM

体外研究

SC1是ERK1和RasGAP的双重抑制剂。同时抑制这些蛋白的活性是SC1发挥其对mES细胞的效果的充分必要条件。SC1通过抑制RasGAP的功能激活Ras。SC1提高了从C57BL/6小鼠中分离而来的干细胞的衍生效率及多潜能性。三种类型的多能干细胞（fES, ntES, and iPS细胞）与SC1共孵育可高效地生成足月的幼崽。

反应信息

• 作为产物：
  描述：

  3-(5-amino-2-methylphenyl)-7-chloro-1-methyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 二氯甲烷 、 仲丁醇 为溶剂， 反应 2.0h， 生成 小鼠胚胎细胞【Pluripotin】
  参考文献：
  名称：

  First SAR Study for Overriding NRAS Mutant Driven Acute Myeloid Leukemia

  摘要：

  GNF-7, a multitargeted kinase inhibitor, served as a dual kinase inhibitor of ACK1 and GCK, which provided a novel therapeutic strategy for overriding AML expressing NRAS mutation. This SAR study with GNF-7 derivatives, designed to target NRAS mutant-driven AML, led to identification of the extremely potent inhibitors, 10d, 10g, and 11i, which possess single-digit nanomolar inhibitory activity against both ACK1 and GCK. These substances strongly suppress proliferation of mutant NRAS expressing AML cells via apoptosis and AKT/mTOR signaling blockade. Compound lli is superior to GNF-7 in terms of kinase inhibitory activity, cellular activity, and differential cytotoxicity. Moreover, 10k possessing a favorable mouse pharmacokinetic profile prolonged life-span of Ba/F3-NRAS-G12D injected mice and significantly delayed tumor growth of OCI-AML3 xenograft model without causing the prominent level of toxicity found with GNF-7. Taken together, this study provides insight into the design of novel ACK1 and GCK dual inhibitors for overriding NRAS mutant-driven AML.

  DOI：

  10.1021/acs.jmedchem.8b00882

文献信息

• Compounds and compositions as protein kinase inhibitors
  申请人：Sim Taebo

  公开号：US20050222177A1

  公开（公告）日：2005-10-06

  The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, c-Raf, Csk, Fes, FGFR, Flt3, Ikk, IR, JNK, Lck, Mkk, PKC, PKD, Rsk, SAPK, Syk, Trk, BTK, Src, EGFR, IGF, Mek, Ros and Tie2 kinases.

  本发明提供了一类新型化合物，包括这些化合物的药物组合物和使用这些化合物治疗或预防与异常或非调节激酶活性相关的疾病或紊乱，尤其是涉及Abl，BCR-Abl，Bmx，c-Raf，Csk，Fes，FGFR，Flt3，Ikk，IR，JNK，Lck，Mkk，PKC，PKD，Rsk，SAPK，Syk，Trk，BTK，Src，EGFR，IGF，Mek，Ros和Tie2激酶异常激活的疾病或紊乱的方法。
• COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
  申请人：Sim Taebo

  公开号：US20080221098A1

  公开（公告）日：2008-09-11

  The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, c-Raf, Csk, Fes, FGFR, Flt3, Ikk, IR, JNK, Lck, Mkk, PKC, PKD, Rsk, SAPK, Syk, Trk, BTK, Src, EGFR, IGF, Mek, Ros and Tie2 kinases.

  本发明提供了一类新型化合物，包括这些化合物的药物组合物以及使用这些化合物治疗或预防与异常或非调控激酶活性相关的疾病或疾病的方法，特别是涉及Abl、BCR-Abl、Bmx、c-Raf、Csk、Fes、FGFR、Flt3、Ikk、IR、JNK、Lck、Mkk、PKC、PKD、Rsk、SAPK、Syk、Trk、BTK、Src、EGFR、IGF、Mek、Ros和Tie2激酶异常活化的疾病或疾病。
• COMPOUNDS THAT MAINTAIN PLURIPOTENCY OF EMBRYONIC STEM CELLS
  申请人：Chen Shuibing

  公开号：US20100234400A1

  公开（公告）日：2010-09-16

  The present invention relates to methods and compositions for culturing embryonic stem (ES) cells. The methods relate to growing the ES cells in the presence of small molecules of formula (I) that maintain the pluripotency/self-renewal of the cells without feeder cells and LIF in serum-free conditions. These methods in part facilitate much more consistency in embryonic stem cell production, providing, for example, new avenues in the practical applications of embryonic stem cells in regenerative medicine.

  本发明涉及培养胚胎干细胞（ES细胞）的方法和组合物。该方法涉及在无血清条件下，通过在式（I）的小分子存在下培养ES细胞，从而维持细胞的多能性/自我更新性，而无需饲养层和LIF。这些方法在一定程度上促进了胚胎干细胞生产的更加一致性，例如，在再生医学的实际应用中提供了新途径。
• Producing mesodermal cell types and methods of using the same
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10787640B2

  公开（公告）日：2020-09-29

  Methods are provided for the generation of mesodermal cell types and derivatives thereof. Also provided are methods for generating purified populations of mesodermal cell types and derivatives thereof. The instant disclosure also provides methods of screening for cellular responses of the generated mesodermal cell types and derivatives thereof. Also provide are methods for screening for organismal phenotypes induced by introduction of the generated mesodermal cell types and derivatives thereof. Treatment methods making use of the generated mesodermal cell types and derivatives thereof are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

  提供了生成中胚层细胞类型及其衍生物的方法。还提供了生成纯化的中胚层细胞类型及其衍生物的方法。本发明还提供了筛选所产生的中胚层细胞类型及其衍生物的细胞反应的方法。本发明还提供了通过引入所产生的中胚层细胞类型及其衍生物来筛选生物表型的方法。还提供了利用生成的中胚层细胞类型及其衍生物的治疗方法。本发明还提供了用于实施本发明方法的系统、组合物和试剂盒。
• COMPOSITIONS FOR PREPARING CARDIOMYOCYTES
  申请人：The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone

  公开号：EP3043822A1

  公开（公告）日：2016-07-20