SMU-037
SMU-037 is an orally active and selective ROS1 inhibitor that demonstrates potent activity (IC₅₀ = 6.8 nM) and possesses the ability to penetrate the blood-brain barrier. SMU-037 shows ~25-fold selectivity over ALK, and superior sensitivity against the G2032R mutation. SMU-037 attenuates phosphorylation of ROS1 and downstream MAPK-ERK signaling pathway, leading to cell cycle arrest and apoptosis. SMU-037 effectively suppresses tumor progression in both xenograft and intracranial mouse models. SMU-037 can be used for non-small cell lung cancer (NSCLC) research.
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- 화학식: C29H29ClF2N4O
- 분자량:523.02
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
SMU-037 (compound 9y) exhibits robust activity against A549 (IC50 = 0.9 μM), HCC-78 (IC50 = 1.1 μM) and NCI-H3122 cells (IC50 = 1.1 μM), and inhibits Ba/F3 ROS1G2032R and Ba/F3 ROS1L2026R cells with IC50 values of 8.9 and 32.0 nM[1].
SMU-037 (0.001-3 μM, 8 h) attenuates phosphorylation of ROS1 and the key downstream MAPK-ERK signaling pathway in a dose-dependent manner in multiple Ba/F3 and A549 cells[1].
SMU-037 (0-100 nM, 48 h) arrests cell cycle (G0/G1 phase in ROS1WT cells and G2/M phase in ROS1G2032R cells) and induces apoptosis in both Ba/F3-ROS1WT and Ba/F3-ROS1G2032R cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3-ROS1WT, Ba/F3-ROS1G2032R, Ba/F3-ROS1L2026M and A549-ROS1G2032R cells
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Concentration:1, 10, 100, and 10000 nM, 0.1, 0.3, 1 and 3 μM
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Incubation Time:8 h
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Result:Exhibited remarkable inhibitory effects on ROS1G2032R phosphorylation at the concentration of 1000 nM.
Slightly inhibited the downstream MAPK-ERK signaling pathway at the concentration of 1000 nM, with efficacy comparable to Cabozantinib (HY-13016).
Led to attenuated phosphorylation of ROS1 and the key downstream MAPK-ERK signaling pathway in a dose-dependent manner in Ba/F3-ROS1WT and Ba/F3-ROS1L2026M cells, comparable to Crizotinib (HY-50878).
Exhibited a marked suppression of ROS1 phosphorylation at a concentration of 1 μM in A549-ROS1G2032R cells.
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Cell Line:Ba/F3-ROS1WT and Ba/F3-ROS1G2032R cells
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Concentration:0, 10, 30, and 100 nM
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Incubation Time:48 h
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Result:Significantly increased the percentage of ROS1WT cells in the G0/G1 phase.
Caused a predominant G2/M phase accumulation in ROS1G2032R cells.
The G0/G1 phase of ROS1G2032R cells increased from 57.10% (control) to 60.71%, 72.97%, and 85.28%, respectively.
The G2/M phase of ROS1G2032R cells increased from 6.14% (control) to 6.98%, 14.42%, and 27.16%, respectively.
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Cell Line:Ba/F3-ROS1WT and Ba/F3-ROS1G2032R cells
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Concentration:0, 10, 30, and 100 nM
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Incubation Time:48 h
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Result:Induced a dose-dependent increase in apoptosis.
Apoptotic rates in ROS1WT cells rose from 13.12% (control) to 16.95%, 31.50%, and 91.87%.
Apoptotic rates in ROS1G2032R cells increased from 19.85% (control) to 20.46%, 28.03%, and 54.60%.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Balb/c nude mice (16-20 g) injected with Ba/F3 CD74-ROS1G2032R cells[1]
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Dosage:15, 30 and 60 mg/kg
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Administration:i.g., q.d. for 14 days
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Result:Effectively suppressed Ba/F3 tumor growth in a dose-dependent manner, with tumor growth inhibition (TGI) values of 118, 140, and 156%, respectively.
Showed no significant body weight reduction and no morphological changes or side effects in heart, liver and kidney.
Significantly inhibited ROS1 phosphorylation in tumor tissue, demonstrating its on-target effect in vivo.
Induced prominent alterations in the morphological characteristics of tumor cells, including cellular contraction, agglutination, and marginalization of nuclear chromatin.
Significantly reduced expression level of the Ki-67 protein, indicating strong anti-proliferative activity.
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Animal Model:Male Balb/c nude mice (16-20 g) injected with A549-ROS1G2032R cells[1]
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Dosage:15, 30 and 60 mg/kg
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Administration:i.g., q.d. for 14 days
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Result:Demonstrated significant tumor regression at doses of 30 mg/kg and 60 mg/kg, comparable to the positive control Lorlatinib (HY-12215, 30 mg/kg).
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Animal Model:Male Balb/c nude mice (16-20 g) injected with luciferase-transduced A549-ROS1G2032R cells[1]
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Dosage:30 and 60 mg/kg
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Administration:i.g., q.d. for 14 days
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Result:Prominently reduced tumor load (as measured using photon flux) in the brain without obvious body weight loss.
Could penetrate blood-brain barrier.
Chemical Information
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분자량 523.02
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화학식 C29H29ClF2N4O
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SMILES
C[C@H](C1=CC(F)=CC=C1C2=CC=C(C=C2)F)OC3=C(N=CC(C4=CC=C(C=C4)N5CCNCC5)=C3)N.Cl
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SMU-037 Related Classifications
HY-178391 Related Classifications
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