mek-in-1

MEK-IN-1 is a MEK inhibitor.

Lidocaine (Alphacaine) 是一种酰胺衍生物，抑制涉及复杂电压和依赖性的钠通道，可用于研究室性心律失常。它通过调节 miR-145 表达和进一步抑制 MEK ERK 和 NF-κB 信号通路来减少胃癌细胞的生长，迁移和侵袭。

MEK RAF-IN-1 (Compound 16b) 作为一种针对MEK和RAF的抑制剂，其针对MEK1、BRAF和BRAFV600E的IC50值分别仅为28、3和3 nM。该化合物表现出明显的抗肿瘤效果，能够有效抑制体外MIA PaCa-2 (G12C KRAS)、HCT116 (G13D KRAS) 以及 C26 (G12D KRAS) 细胞的增殖，并在异种移植的结直肠癌小鼠模型中显著抑制肿瘤生长。

TAC(TERT activator compound) 作为 TERT 的激活剂，能通过 MEK ERK AP-1 级联途径增强 TERT 的转录活性。该化合物不仅促进端粒的合成，还可减少衰老标志物、炎症及衰老现象，同时维持脑部健康。这些作用突显了 TERT 在抗衰老及相关疾病治疗中的应用潜力。

PD 184161 是一种口服有效的，时间和浓度依赖的 MEK 抑制剂，IC50为10-100 nM。它诱导抑郁样行为，抑制细胞增殖并诱导细胞凋亡。

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

The Survival of Motor Neurons (SMN) protein participates in RNA splicing. Decreases in SMN, typically a consequence of defects in the smn1 gene, result in the death of motor neurons and lead to the neurodegenerative disease, spinal muscular atrophy (SMA). Cuspin-1 is a small molecule upregulator of SMN that has been shown in vitro to increase levels of SMN in SMA patient fibroblasts by 50% at 18 μM. Its mechanism of action is thought to involve increased phosphorylation of ERK to initiate Ras-Raf-MEK signaling, which results in an increased rate of SMN translation.

iMDK quarterhydrate, a potent PI3K inhibitor, is effective in inhibiting the growth factor MDK (also known as midkine or MK) while demonstrating suppression of non-small cell lung cancer (NSCLC). In combination with a MEK inhibitor, iMDK quarterhydrate demonstrates cooperative inhibition of NSCLC without causing harm to normal cells and mice [1].

Nardosinone 是一个 dbcAMP 和 staurosporine 的神经生成作用增强剂，分离自Nardostachys chinensis 中。Nardosinone 可能成为一种有用的药理学工具，不仅可用于研究神经生长因子 (NGF) 的作用机理，而且可用于研究神经毒性物质的作用机理。

MEK PI3K-IN-1（compound 6r）是一种高效的MEK PI3K抑制剂，IC50值为124 nM（MEK1）、130 nM（PI3Kα）及236 nM（PI3Kδ）。该化合物能够降低pAKT和pERK1 2的活性，并展现对肿瘤细胞的抗增殖作用。

MEK PI3K-IN-2 (compound 6s) 是一种有效的 MEK PI3K 抑制剂，其 IC50值分别为 352 nM (MEK1), 107 nM (PI3Kα), 和 137 nM (PI3Kδ)。MEK PI3K-IN-2 抑制 pAKT 和 pERK1 2 水平。MEK PI3K-IN-2 对肿瘤细胞具有抗增殖活性。

Trametiglue 是 Trametinib 的衍生物，通过独特的界面结合相互作用，以前所未有的效力和选择性靶向 KSR-MEK 和 RAF-MEK。

CML-IN-1（compound 7）是一种高效抗癌药物，针对人类慢性粒细胞白血病（CML）细胞系K562，能有效诱导凋亡（apoptosis）。该化合物主要通过显著抑制PI3K Akt信号通路的蛋白磷酸化来发挥作用，同时CML-IN-1（compound 4）也能通过抑制结直肠癌的MEK ERK信号通路来阻止细胞增殖。

MEK-IN-6（Example 69）是一种针对MEK的抑制剂，在A375细胞中有效抑制ERK1 2（THR202 Tyr204）的磷酸化，其IC50值为2 nM。此化合物主要应用于癌症研究领域。

MEK-IN-6 hydrate（compound 69）为MEK抑制剂，其对A375细胞展现出强效性，IC50仅为2 nM。

Protein kinase D (PKD), a serine threonine protein kinase activated by diacylglycerol downstream of PKC signaling, has three human isoforms that modulate cell proliferation, survival, invasion, and protein transport. CRT0066101 acts as an inhibitor of these three PKD isoforms, with IC50 values of 1, 2.5, and 2 nM for PKD1, PKD2, and PKD3, respectively. It demonstrates selectivity for PKD over a range of more than 90 protein kinases, including PKCα, PKBα, MEK, ERK, c-Raf, c-Src, and c-Abl. This specificity allows CRT0066101 to inhibit cell proliferation, induce apoptosis, and notably reduce the viability of pancreatic cancer cells both in vitro and in vivo.

Lidocaine-d10 (N,N-diethyl-d10) 是 Lidocaine 的氘代化合物。Lidocaine 的 CAS 号为 137-58-6。Lidocaine是一种酰胺衍生物，抑制涉及复杂电压和依赖性的钠通道，可用于研究室性心律失常。它通过调节 miR-145 表达和进一步抑制MEK ERK和NF-κB信号通路来减少胃癌细胞的生长，迁移和侵袭。

Potent, selective and competitive corticotropin-releasing factor CRF2 receptor antagonist (Kd values are 1.4 and 153.6 nM for binding to mouse CRF2β and rat CRF1 receptors respectively). Inhibits sauvagine-stimulated cAMP accumulation in HEK-mCRF2β cells