trka in 1

TrkA-IN-1 is a potent and selective inhibitor of Tropomyosin-related kinase A (TrkA) (IC50: 99 nM in a cell-based assay) with analgesic activity.

ITK/TRKA-IN-1 is a chemical compound that functions as a dual inhibitor of IL-2-inducible T-cell kinase (ITK) and tropomyosin receptor kinase A (TRKA). With an IC50 value of 1.0 nM, it effectively inhibits the activity of ITK, while demonstrating a remarkable 96% inhibition of TRKA.

RET/TRKA-IN-1 (Compound 13) 是一种同时抑制 RET (IC50=0.375 µM) 和 TRKA 的双功能抑制剂。它对 LC-2 和 KM12 细胞的活力具有显著抑制效果，GI50 分别为 0.72 和 0.25 μM。此外，RET/TRKA-IN-1 能够在 G1 期引起细胞周期停滞。

FLT3/TrKA-IN-1 是一种有效的 FLT3/TrKA 双激酶抑制剂，能够作用于 FLT3 (IC50: 43.8 nM)、FLT3-ITD (IC50: 97.2 nM)、FLT3-TKD (IC50: 92.5 nM) 和 TrKA (IC50: 23.6 nM)。FLT3/TrKA-IN-1 能够将细胞周期阻滞在 G0/G1 期，并诱导细胞凋亡 (apoptosis)，具有抗增殖作用。FLT3/TrKA-IN-1 具有潜力进行急性髓性白血病 (AML) 的研究。

hTrkA-IN-1 is a potent and orally active inhibitor of TrkA kinase with an IC 50 of 1.3 nM, compound 2.hTrkA-IN-1 can be used for the study of inflammatory disease, such as prostatitis, pelvic, et al.

TrkA-IN-10 (PI-15R) 是一种选择性TrkA抑制剂，其对于TrkA、TrkB和TrkC的IC50值分别为17 nM、8 nM和5 nM，用于癌症研究。

DS-1205b free base 是有效的AXL 激酶选择性抑制剂，IC50为 1.3 nM。它对MER，MET 和TRKA 也有抑制作用，IC50分别为 63、104 和 407 nM。 它可以抑制细胞迁移和肿瘤生长。

RIPK1-IN-7 是一种选择性有效的 RIPK1 抑制剂，Kd 值为 4 nM，IC50值为 11 nM。在实验性 B16 黑色素瘤肺转移模型中表现出优异的抗转移活性。

TrkA-IN-8 (Compound 2) 是一种抑制TrkA的抑制剂，其Kd值为3.3 µM。RTKs-IN-1 在肺癌细胞系中表现出浓度依赖性的细胞生长抑制作用，并可能应用于非小细胞肺癌的研究。

Ganglioside GM1is a monosialylated ganglioside and the prototypic ganglioside for those containing one sialic acid residue.1,2It is found in a large variety of cells, including immune cells and neurons, and is enriched in lipid rafts in the cell membrane.3It associates with growth factor receptors, including TrkA, TrkB, and the GDNF receptor complex containing Ret and GFRα, and is required for TrkA expression on the cell surface. Ganglioside GM1interacts with other proteins to increase calcium influx, affecting various calcium-dependent processes, including inducing neuronal outgrowth during differentiation. Ganglioside GM1acts as a receptor for cholera toxin, which binds to its oligosaccharide group, facilitating toxin cell entry into epithelial cells of the jejunum.4,5Similarly, it is bound by the heat-labile enterotoxin fromE. coliin the pathogenesis of traveler's diarrhea.6Ganglioside GM1gangliosidosis, characterized by a deficiency in GM1-β-galactosidase, the enzyme that degrades ganglioside GM1, leads to accumulation of the gangliosides GM1and GA1in neurons and can be fatal in infants.1Levels of ganglioside GM1are decreased in the substantia nigra pars compacta in postmortem brain from patients with Parkinson's disease.3Ganglioside GM1mixture contains a mixture of ovine ganglioside GM1molecular species with primarily C18:0 fatty acyl chain lengths, among various others. [Matreya, LLC. Catalog No. 1544] 1.Kolter, T.Ganglioside biochemistryISRN Biochem.506160(2012) 2.Mocchetti, I.Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophinsCell Mol. Life Sci.62(19-20)2283-2294(2005) 3.Ledeen, R.W., and Wu, G.The multi-tasked life of GM1 ganglioside, a true factotum of natureTrends Biochem. Sci.40(7)407-418(2015) 4.Turnbull, W.B., Precious, B.L., and Homans, S.W.Dissecting the cholera toxin-ganglioside GM1 interaction by isothermal titration calorimetryJ. Am. Chem. Soc.126(4)1047-1054(2004) 5.Blank, N., Schiller, M., Krienke, S., et al.Cholera toxin binds to lipid rafts but has a limited specificity for ganglioside GM1Immunol. Cell Biol.85(5)378-382(2007) 6.Minke, W.E., Roach, C., Hol, W.G., et al.Structure-based exploration of the ganglioside GM1 binding sites of Escherichia coli heat-labile enterotoxin and cholera toxin for the discovery of receptor antagonistsBiochemistry38(18)5684-5692(1999)

ALK-IN-9 (compound 40) is a highly effective ALK inhibitor. It demonstrates remarkable inhibitory activity against cell proliferation, with IC50 values of <0.2 nM for Ba/F3-EML4-ALK, KM 12 (TPM3-TRKA), and KG-l cell (OP2-FGFR1).

Trk-IN-7 (compound I-6) is a highly potent inhibitor of TRK, exhibiting IC50 values ranging from 0.25-10 nM for TRKA, TRKB, and TRKC, respectively. In addition, Trk-IN-7 demonstrates notable inhibition against EML4-ALK (IC50 <15 nM), as well as ALK G1202R, ALK C1156Y, ALK R1275Q, ALK F1174L, ALK L1197M, and ALK G1269A (IC50 = 5-50 nM) [1].

Trk-IN-20 is a 3-vinylindazole derivative compound that effectively inhibits the functions of Trk kinases. It accomplishes this by suppressing the phosphorylation of TrkA, TrkB, and TrkC, with IC50 values of 1.6 nM, 2.9 nM, and 2.0 nM, respectively [1].

Trk-IN-8, a powerful TRK inhibitor, demonstrates excellent potency against TRKAa, TRKA(G595R), and TRKC(G623R) with IC50 values of 0.42 nM, 0.89 nM, and 1.5 nM, respectively (WO2021115401A1, compound 3) [1].

Trk-IN-10 (Compound 14j) is a highly effective inhibitor of TRK, with an IC50 of 0.86 nM against TrkA and 6.92 nM against TrkA G595R. As an RTK, Trk plays a crucial role as a drug target in solid tumors. Trk-IN-10 (IC50 = 350 nM against ALK) demonstrates superior selectivity in inhibiting Trk, which has potential implications for toxicity reduction [1].

TRK/ALK-IN-1 是一种有效的 TRK 和 ALK 双重抑制剂。TRK/ALK-IN-1 在酶促测定中与抗增殖活性非常吻合，对 TRKA、ALKIC50值分别为 2.2、9.3 和 38 nM< sup>WT 和 ALKL1196M。TRK/ALK-IN-1具有研究癌症疾病的潜力。

TRKII-IN-1 是一种有效的 II 型TRK抑制剂，对TRKA/B/C及TRKAG667C的IC50分别为3.3、6.4、4.3 和 9.4 nM。此外，TRKII-IN-1 对FLT3、RET和VEGFR2也具有抑制作用，其IC50分别为1.3、9.9 和 71.1 nM。TRKII-IN-1 主要用于TRK驱动的癌症研究。

TrkA-IN-4 是一种有效和具有口服活性的 TrkA 变构抑制剂，是TrkA-IN-3 的前药。TrkA-IN-4 显示出有效的抗伤害作用。

Bedinvetmab (ZTS-00508841) 是一种犬源单克隆抗体 (mAb)，靶向神经生长因子 (NGF)。Bedinvetmab 阻止 NGF 与其受体肌动蛋白受体激酶 A (trkA) 及 p75 神经营养素受体 (p75NTR) 的结合。Bedinvetmab 主要用于骨关节炎研究。

TRAF6 peptide TFA是一种抑制TRAF6-p62相互作用的特异性分子，可抑制NGF依赖的TrkA泛素化，展现在阿尔茨海默症（AD）、帕金森病、ALS、创伤性脑损伤、癫痫和中风等神经系统疾病研究中的应用潜力。

Tanezumab(RN-624) 是一种针对NGF（神经生长因子）的人源化单克隆抗体，通过阻断NGF与p75和TrkA受体的相互作用，从而抑制外周痛觉纤维的敏感化与传导，治疗各种急性与慢性疼痛，包括骨关节炎、膝关节炎、神经痛等。

TRK-IN-23 (compound 24b) 是一款口服活性TRK抑制剂，对TRKA、TRKC、TRKAG595R、TRKAF589L和TRKAG667C 表现出高效的抑制作用，其IC50值分别为0.5 nM、9 nM、14 nM、4.4 nM和4.8 nM。此外，TRK-IN-23 能够诱导含有TRKAG595R和TRKAG667C突变的Ba/F3细胞系进行细胞凋亡(apoptosis)。

TRK-IN-24（compound 10g）是一种针对Trk Receptor的抑制剂，它对TRKA、TRKC、TRKAG595R、TRKAG667C和TRKAF589L的抑制作用的IC50值分别达到5.21、4.51、6.77、1.42和6.13 nM。该化合物在BaF3-CD74-NTRK1G595R和BaF3-CD74-NTRK1G667C异种移植模型中显示出明显的抗肿瘤活性。此外，TRK-IN-24 能有效抑制携带SF、GK、xDFG等单点突变的Ba/F3细胞增殖，其IC50范围为1.43至47.56 nM。

Multi-kinase-IN-6 (compound 10e) 是一种效能极高的多激酶抑制剂，具有对 TrkA、ALK2、c-KIT、EGFR、PIM1、CK2α、CHK1 和 CDK2 等多种酶的显著抑制作用。在 MCF7、HCT116 和 EKVX 癌细胞系上，其抗增殖活性突出，IC50 值分别达到 3.36 μM、1.40 μM 与 3.49 μM。此外，Multi-kinase-IN-6 能引起 MCF7 与 HCT116 细胞的细胞周期在 G1/S 期及 G1 期停滞，并有效诱导凋亡。