NVP-AEW541

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

NVP-AEW541 (AEW-541, AEW541) 是一种有效的选择性 IGF-1R 抑制剂，IC50 为 86 nM。

NVP-AEW541 (AEW-541, AEW541) is a potent, and selective inhibitor of IGF-1R with IC50 of 86 nM; shows weak activity for closely related InsR (IC50=2.3 uM); inhibits IGF-IR autophosphorylation and abrogates IGF-I-mediated survival and colony formation in soft agar; inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas in vivo; orally bioavailable.Blood Cancer Phase 1 Clinical(In Vitro):NVP-AEW541 inhibits the in vitro kinase activity of the recombinant IGF-IR kinase domain with an IC50 value of 0.15 μM and to be equipotent against the recombinant InsR kinase domain. NVP-AEW541 is confirmed active toward the IGF-IR kinase (IC50=86 nM) and shown to be selective at the cellular level. Indeed, NVP-AEW541 is found to be 27-fold more potent toward the native IGF-IR, as compared to the structurally related native InsR (IC50=2.3 μM). NVP-AEW541 suppresses the IGF-I-mediated survival, soft agar and proliferation of MCF-7 cells with IC50 of 0.162 μM, 0.105 μM and 1.64 μM, respectively. (In Vivo):Oral administration of NVP-AEW541 (20, 30, or 50 mg/kg) results in abrogation of basal and IGF-I-induced receptor, and PKB and MAPK phosphorylation in the NWT-21 tumor xenograft. NVP-AEW541 is administered by oral gavage [50 mg/kg in 0.2 mL of 25 mM L-(+)-tartaric acid] twice a day for 14 consecutive days. The control group is similarly treated with 0.2 mL carrier [25 mM L-(+)-tartaric acid] twice a day. Tumor volume and animal weight are measured thrice a week till the end of the treatment. At that time, animals are sacrificed and tumors are collected and formalin fixed for histologic and immunohistochemical analyses. In both cases, NVP-AEW541 treatment causes tumor shrinkage that reached the statistical significance (P=0.0156 and P=0.0111 for HTLA-230 and SK-N-BE2c, respectively).

NVP-AEW541 inhibits the in vitro kinase activity of the recombinant IGF-IR kinase domain with an IC50 value of 0.15 μM and to be equipotent against the recombinant InsR kinase domain. NVP-AEW541 is confirmed active toward the IGF-IR kinase (IC50=86 nM) and shown to be selective at the cellular level. Indeed, NVP-AEW541 is found to be 27-fold more potent toward the native IGF-IR, as compared to the structurally related native InsR (IC50=2.3 μM). NVP-AEW541 suppresses the IGF-I-mediated survival, soft agar and proliferation of MCF-7 cells with IC50 of 0.162 μM, 0.105 μM and 1.64 μM, respectively.

Oral administration of NVP-AEW541 (20, 30, or 50 mg/kg) results in abrogation of basal and IGF-I-induced receptor, and PKB and MAPK phosphorylation in the NWT-21 tumor xenograft. NVP-AEW541 is administered by oral gavage [50 mg/kg in 0.2 mL of 25 mM L-(+)-tartaric acid] twice a day for 14 consecutive days. The control group is similarly treated with 0.2 mL carrier [25 mM L-(+)-tartaric acid] twice a day. Tumor volume and animal weight are measured thrice a week till the end of the treatment. At that time, animals are sacrificed and tumors are collected and formalin fixed for histologic and immunohistochemical analyses. In both cases, NVP-AEW541 treatment causes tumor shrinkage that reached the statistical significance (P=0.0156 and P=0.0111 for HTLA-230 and SK-N-BE2c, respectively).

AEW-541 | AEW541 | AEW 541 | NVP AEW541

Angiogenesis

IGF-1R

FLT1|FLT3|IGF-1R|InsulinReceptor|Tek

Cancer

Blood cancer

475489-16-8

439.5521

C27H29N5O

>98% (HPLC)

DMSO: ≥ 51 mg/mL

NC1=C2C(N([C@H]3C[C@@H](CN4CCC4)C3)C=C2C5=CC=CC(OCC6=CC=CC=C6)=C5)=NC=N1

7H-Pyrrolo[2,3-d]pyrimidin-4-amine, 7-[cis-3-(1-azetidinylmethyl)cyclobutyl]-5-[3-(phenylmethoxy)phenyl]-

(-20℃)

With Ice Pack

≥ 2 years