SML2154
Deltarasin trihydrochloride
≥98% (HPLC)
别名:
(S)-1-Benzyl-2-(4-(2-(2-phenyl-1H-benzo[d]imidazol-1-yl)-2-(piperidin-4-yl)ethoxy)phenyl)-1H-benzo[d]imidazole trihydrochloride, 2-[4-[(2S)-2-(2-Phenyl-1H-benzimidazol-1-yl)-2-(4-piperidinyl)ethoxy]phenyl]-1-(phenylmethyl)-1H-benzimidazole trihydrochloride
方案
≥98% (HPLC)
表单
powder
储存条件
desiccated
颜色
white to beige
溶解性
H2O: 2 mg/mL, clear
储存温度
2-8°C
SMILES字符串
N1CCC(CC1)[C@H]([n]6c7c(nc6c8ccccc8)cccc7)COc2ccc(cc2)c3[n](c5c(n3)cccc5)Cc4ccccc4
InChI
1S/C40H37N5O/c1-3-11-29(12-4-1)27-44-36-17-9-7-15-34(36)42-39(44)32-19-21-33(22-20-32)46-28-38(30-23-25-41-26-24-30)45-37-18-10-8-16-35(37)43-40(45)31-13-5-2-6-14-31/h1-22,30,38,41H,23-28H2/t38-/m1/s1
InChI key
LTZKEDSUXKTTTC-KXQOOQHDSA-N
相关类别
生化/生理作用
Deltarasin is a membrane-permeable benzimidazole derivative that effectively abolishes cellular KRas plasma membrane localization (5 μM for 1 hr) by blocking KRas-PDEδ interaction via high affinity interaction with PDEδ prenyl-binding pocket (KD = 38 nM). Deltarasin inhibits oncogenic KRas-dependent proliferation (by ~50% of Panc-Tu-I cells; 5μM for 70 hrs) and survival (52% and 46% death induction of Panc-Tu-I and Capan-1 cells, respectively; 5μM for 24 hrs) in human pancreatic ductal adenocarcinoma (PDAC) cultures and is efficacious against Panc-Tu-I xenograft-derived tumor growth in mice in vivo (60% and 80% retardation on day 9, respectively, with 15 mg/kg q.d. or 10 mg/kg b.i.d. via i.p.).
KRas-PDEδ interaction blocker that targets PDEδ prenyl pocket with high affinity and inhibits oncogenic KRas-dependent cancer survival in vitro and in vivo.
储存分类代码
11 - Combustible Solids
WGK
WGK 3
Pablo Martín-Gago et al.
Angewandte Chemie (International ed. in English), 56(9), 2423-2428 (2017-01-21)
Small-molecule inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6δ impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (K
Gunther Zimmermann et al.
Nature, 497(7451), 638-642 (2013-05-24)
The KRAS oncogene product is considered a major target in anticancer drug discovery. However, direct interference with KRAS signalling has not yet led to clinically useful drugs. Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein
Malte Schmick et al.
Cell, 157(2), 459-471 (2014-04-15)
KRas is a major proto-oncogene product whose signaling activity depends on its level of enrichment on the plasma membrane (PM). This PM localization relies on posttranslational prenylation for membrane affinity, while PM specificity has been attributed to electrostatic interactions between
Gunther Zimmermann et al.
Journal of medicinal chemistry, 57(12), 5435-5448 (2014-06-03)
K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in
Jianman Guo et al.
American journal of cancer research, 7(4), 923-934 (2017-05-05)
Patients with Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) are predisposed to tumors of the nervous system. NF1 patients predominantly develop neurofibromas, and Malignant Peripheral Nerve Sheath Tumors (MPNST) while NF2 patients develop schwannomas and meningiomas. Here we
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