2. Protein Tyrosine Kinase/RTK MAPK/ERK Pathway Stem Cell/Wnt Apoptosis
  3. ROS Kinase p38 MAPK ERK Apoptosis
  4. 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.

For research use only. We do not sell to patients.

SMU-037

SMU-037 Chemical Structure

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SMU-037 Related Antibodies

Top Publications Citing Use of Products

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p38 MAPK Akt1 p38α p38β MAPK13 p38δ p38γ

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ERK ERK1 ERK2 ERK5 ERK8

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Description

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[1].

In Vitro

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.

SMU-037 Related Antibodies

Western Blot Analysis[1]

Cell Line: Ba/F3-ROS1WT, Ba/F3-ROS1G2032R, Ba/F3-ROS1L2026M and A549-ROS1G2032R cells
Concentration: 1, 10, 100, and 10000 nM, 0.1, 0.3, 1 and 3 μM
Incubation Time: 8 h
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.

Cell Cycle Analysis[1]

Cell Line: Ba/F3-ROS1WT and Ba/F3-ROS1G2032R cells
Concentration: 0, 10, 30, and 100 nM
Incubation Time: 48 h
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.

Apoptosis Analysis[1]

Cell Line: Ba/F3-ROS1WT and Ba/F3-ROS1G2032R cells
Concentration: 0, 10, 30, and 100 nM
Incubation Time: 48 h
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%.
Parmacokinetics
Species Dose Route Note T1/2 Tmax Cmax CL/F Vd/F AUC0-t AUC0-∞ F
Rat[1] 25 mg/kg p.o. SD Rats 14.7 h 5.2 h 441.2 ng/mL 0.5 L/h/kg 10.0 L/kg 9324.5 ng·h/mL 10602.1 ng·h/mL 62.4 %
Rat[1] 5 mg/kg i.v. SD Rats 8.6 h 0.03 h 897.3 ng/mL 0.30 L/h/kg 3.7 L/kg 3322.7 ng·h/mL 3401.0 ng·h/mL 62.4 %
In Vivo

SMU-037 (15, 30 and 60 mg/kg, i.g., q.d. for 14 days) shows potent tumor growth inhibition in xenograft/brain metastasis mouse models[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male Balb/c nude mice (16-20 g) injected with Ba/F3 CD74-ROS1G2032R cells[1]
Dosage: 15, 30 and 60 mg/kg
Administration: i.g., q.d. for 14 days
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.
Animal Model: Male Balb/c nude mice (16-20 g) injected with A549-ROS1G2032R cells[1]
Dosage: 15, 30 and 60 mg/kg
Administration: i.g., q.d. for 14 days
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).
Animal Model: Male Balb/c nude mice (16-20 g) injected with luciferase-transduced A549-ROS1G2032R cells[1]
Dosage: 30 and 60 mg/kg
Administration: i.g., q.d. for 14 days
Result: Prominently reduced tumor load (as measured using photon flux) in the brain without obvious body weight loss.
Could penetrate blood-brain barrier.
Molecular Weight

523.02

Formula

C29H29ClF2N4O
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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SMU-037 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SMU-037SMU037SMU 037ROS Kinasep38 MAPKERKApoptosisExtracellular signal regulated kinasesA549-ROS1G2032RBa/F3-ROS1G2032RROS1ALKHCC827A549NCI-H3122NSCLCMAPK-ERKintracranialInhibitorinhibitorinhibit

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