K-Ras-IN-1

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Chemical Structure| 84783-01-7 同义名 : Mdk-3017
CAS号 : 84783-01-7
货号 : A234456
分子式 : C11H13NOS
纯度 : 99%+
分子量 : 207.29
MDL号 : MFCD02193415
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 K-Ras is a small GTPase that functions as a molecular switch cycling between inactive (GDP-bound) and active (GTP-bound) states. The conversion of K-Ras-GDP to K-Ras-GTP is the rate-limiting step in the activation of K-Ras and is catalyzed by guanine nucleotide exchange factors such as the son of sevenless (Sos). Mutations in K-Ras fix the protein in the active state and endow cells with capabilities that represent the hallmarks of cancer[3]. These include the ability to proliferate, evade apoptosis, reprogram cell metabolism, induce angiogenesis, activate invasion and metastasis, and escape immune destruction[4]. Indeed, aberrant K-Ras signaling plays a role in 30% of all human cancers, with the highest incidence of activating mutations found in pancreatic (70-90%), colon (30-50%), and lung (20-30%) carcinomas[5]. Downregulation of activated Ras reverses the transformed phenotype of cells and results in the dramatic regression of tumors in murine xenograft models[6]. K-Ras-IN-1（MDK-3017）is a K-Ras inhibitor that binds to K-Ras (wild type), K-Ras (G12D), K-Ras (G12V), and H-Ras and block binding to Sos which causes the inhibition of Sos-mediated nucleotide exchange. These molecules represent a starting point for obtaining probe molecules useful in elucidating new insights into Ras signaling and for discovering K-Ras inhibitors for the treatment of cancer[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.82mL

0.96mL

0.48mL

24.12mL

4.82mL

2.41mL

48.24mL

9.65mL

4.82mL
参考文献

[1]Hocker HJ, Rambahal N, et al. LIBSA--a method for the determination of ligand-binding preference to allosteric sites on receptor ensembles. J Chem Inf Model. 2014 Feb 24;54(2):530-8.

[2]Sun Q, Burke JP, et al. Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Angew Chem Int Ed Engl. 2012 Jun 18;51(25):6140-3.

[3]Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation.Cell. 2011; 144:646–74.

[4]Pylayeva-Gupta Y, et al. RAS oncogenes: weaving a tumorigenic web .Cancer. 2011; 11:761–74.

[5]Laghi L, Orbetegli O, Bianchi P, Zerbi A, Di Carlo V, Boland CR, Malesci A. Common occurrence of multiple K-RAS mutations in pancreatic cancers with associated precursor lesions and in biliary cancers Oncogene. 2002;21:4301–6.

[6] Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O’Hagan R, Pantginis J,Zhou H, Horner JW, Cordon-Cardo C, Yancopoulos GD, DePinho RA. Essential role for oncogenic Ras in tumour maintenance.Nature. 1999; 400:468–72.

[7] Sun Q, et al. Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Angew Chem Int Ed Engl. 2012 Jun 18;51(25):6140-6143.