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Chemical Structure| 850879-09-3 Chemical Structure| 850879-09-3

Structure of Amuvatinib
CAS No.: 850879-09-3

Chemical Structure| 850879-09-3

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Amuvatinib is a potent and multi-targeted inhibitor that inhibits c-Kit, PDGFRα and Flt3 with IC50 of 10, 40 and 81 nM respectively.

Synonyms: MP470; HPK 56

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Product Details of Amuvatinib

CAS No. :850879-09-3
Formula : C23H21N5O3S
M.W : 447.51
SMILES Code : S=C(N1CCN(C2=C(OC3=CC=CC=C34)C4=NC=N2)CC1)NCC5=CC=C(OCO6)C6=C5
Synonyms :
MP470; HPK 56
MDL No. :MFCD16038298
InChI Key :FOFDIMHVKGYHRU-UHFFFAOYSA-N
Pubchem ID :11282283

Safety of Amuvatinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Amuvatinib

RTK

Isoform Comparison

Biological Activity

Target
  • PDGFRα

    PDGFRα (V561D), IC50:40 nM

  • c-Kit

    c-Kit (D816H), IC50:10 nM

  • FLT3

    FLT3 (D835Y), IC50:81 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
U266 cells 25 µM 24, 48, and 72 hours Cell death rates of 28%, 40%, and 55% J Hematol Oncol. 2013 Dec 10;6:92.
RAW 264.7 cells 250 ng 24 hours To evaluate the effect of BMP7 on MAPK14 and SMAD1/5/9 phosphorylation, results showed that BMP7 treatment reduced MAPK14 expression and increased SMAD1/5/9 phosphorylation. Nat Commun. 2020 Sep 24;11(1):4840.
Maturing neurons 10 µM 24 hours Amuvatinib is neuroinhibitory to maturing neurons with an EC50=2.5 μM FEBS J. 2023 Oct;290(20):4950-4965.
344SQR cells 0, 1, 10, 100 µM 24, 48, 72 hours To evaluate the effect of SHP099 on the proliferation of 344SQR cells, results showed that SHP099 did not significantly inhibit cell proliferation. Cancer Immunol Res. 2020 Jul;8(7):883-894.
U87MG cells 10 µM 48 and 72 hours To evaluate the effect of Amuvatinib on the viability of U87MG cells, results showed that Amuvatinib single treatment significantly reduced cell viability, and the combination with LPS further decreased cell viability. Sci Rep. 2021 Jan 14;11(1):1333.
344-SQ NSCLC cells 5 nM and 15 nM 48 hours To evaluate the antitumor effect of IACS-010759 in combination with radiotherapy, results showed that in the PD-1 resistant model, IACS-010759 combined with radiotherapy significantly inhibited clonogenic formation J Immunother Cancer. 2020 Jun;8(1):e000289.
CD4+ T cells 250 ng 60 minutes To evaluate the effect of BMP7 on MAPK14 and SMAD1/5/9 phosphorylation, results showed that BMP7 treatment reduced MAPK14 expression and increased SMAD1/5/9 phosphorylation. Nat Commun. 2020 Sep 24;11(1):4840.
U266 cells 5, 10, or 25 µM Inhibited HGF-dependent MET, AKT, ERK and GSK-3-beta phosphorylation J Hematol Oncol. 2013 Dec 10;6:92.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice 344SQR tumor model Intraperitoneal injections 10 mg/kg Twice per week for two weeks To evaluate the effect of BMP7 inhibition on tumor growth and survival, results showed that BMP7 inhibition significantly reduced tumor growth and extended survival. Nat Commun. 2020 Sep 24;11(1):4840.
Mice Anti-PD1 resistant lung cancer model Intraperitoneal injection 200 µg Days 5, 8, 11, 14, 21, 28, 35, and 42 This nanoparticle-mediated combination therapy is effective at controlling the growth of irradiated and distant unirradiated tumors, enhancing animal survival, and is the only one that led to the destruction of both tumors in approximately 30% of the treated mice. J Nanobiotechnology. 2022 Sep 19;20(1):417
Mice Anti-PD1-resistant metastatic lung cancer model Intraperitoneal injection 200 mg aPD1, 50 mg aCTLA4 or NF-aCTLA4 Administered on days 7, 11, and 14, with aPD1 treatment continued on days 21, 28, 35, and 42 To evaluate the efficacy of NBTXR3 combined with anti-PD1 and nonfucosylated anti-CTLA4 in immunoradiotherapy, the results showed that this combination significantly upregulated the activities of a wide range of antitumor immune pathways, reduced the abundance of regulatory suppressor T cells, and significantly increased animal survival to 75%. Front Immunol. 2022 Nov 3;13:1022011
129 Sv/Ev mice Bilateral lung adenocarcinoma model Subcutaneous injection 3 mg/kg Every 4 days for 7 cycles To evaluate the antitumor efficacy of RDB 1462 in combination with radiotherapy, results showed that RDB 1462 significantly reduced tumor volume and prolonged survival. J Exp Clin Cancer Res. 2024 Sep 2;43(1):251

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01357395 Small Cell Lung Carcinoma PHASE2 COMPLETED 2012-05-28 University of Colorado Cancer ... More >>Center, Aurora, Colorado, 80045, United States|Winship Cancer Institute of Emory University, Atlanta, Georgia, 30322, United States|James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, United States|Washington University School of Medicine, Saint Louis, Missouri, 63108, United States|Associates in Oncology and Hematology, Chattanooga, Tennessee, 37404, United States|Vanderbilt - Ingram Cancer Center, Nashville, Tennessee, 37232, United States|MD Anderson Cancer Center, Houston, Texas, 77030, United States|Wojewódzki Szpital Specjalistyczny, Radom, Mazowieckie, 26-617, Poland|Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie w Warszawie, Warszawa, Mazowieckie, 02-781, Poland|Wojewódzki Szpital im. ?w. Ojca Pio w Przemy?lu Oddzia? Onkologiczny z Pododdzia?em Dziennej Chemioterapii, Przemy?l, Podkarpackie, 37-700, Poland|Wojewódzkie Centrum Onkologii, Gdansk, Pomorskie, 80-219, Poland|Specjalistyczny Szpital im. Alfreda Sokolowskiego, Szczecin, Zachodniopomorskie, 70-891, Poland Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.17mL

2.23mL

1.12mL

22.35mL

4.47mL

2.23mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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