NSC 658497

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NSC 658497 是 Ras GEF、SOS1 的小分子抑制剂，与 SOS1 结合，Kd 为 7 uM，但不结合 H-Ras。

NSC 658497 is a small molecule inhibitor of Ras GEF, SOS1, binds to SOS1 with Kd of 7 uM but no H-Ras, competitively suppresses SOS1-Ras interaction, and dose-dependently inhibits SOS1 GEF activity; showes dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation.

NSC-658497 (0-20 μM; 2 hours; NIH/3T3 cells) dose-dependently inhibits EGF (50 ng/mL)-stimulated Ras, but not EGFR activation.Concomitant to Ras inhibition, NSC-658497 (0-100 μM; 2 hours; NIH/3T3 cells) dose-dependently inhibited the EGF activated, Ras downstream targets ERK1/2 and AKT.Consistent with these results, NSC-658497 dose-dependently suppressed Ras signaling mediated by the overexpression of an active SOS1 mutant (W729L), originally identified in Noonan’s Syndrome, in human embryonic kidney cells.NSC-658497 dose-dependently inhibits 50 nM SOS1-cat mediated GDP/GTP nucleotide exchange upon 2 μM H-Ras (aa. 1-166) in the BODIPYFL-GDP dissociation assay (IC50=15.4μM).NSC-658497 (0-60 μM; 3 days; PC-3 and DU-145 cells) inhibits proliferation of prostate cancer cells.NSC-658497 (0-60 μM; 2 hours; PC-3 and DU-145 cells) dose-dependently inhibits Ras-GTP activity and the downstream p-ERK1/2 and p-Akt activities. Cell Proliferation AssayCell Line:PC-3 and DU-145 cells Concentration:0-60 μMIncubation Time:3 days Result:Dose-dependently inhibited proliferation of PC-3 and DU-145 cells.Western Blot Analysis Cell Line:PC-3 and DU-145 cells Concentration:0-60 μM Incubation Time:2 hours Result:Dose-dependently inhibited Ras-GTP activity and the downstream p-ERK1/2 and p-Akt activities.

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NSC658497

MAPK/ERK Signaling

Ras

Ras

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909197-38-2

438.428

C20H10N2O6S2

>98% (HPLC)

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O=C1/C(C(C2=C(O1)C=CC=C2)=O)=C\N(C/3=O)C(SC3=C/C4=CC=C([N+]([O-])=O)C=C4)=S

(Z)-3-(((Z)-5-(4-nitrobenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)methylene)chroman-2,4-dione

(-20℃)

With Ice Pack

≥ 2 years