Home Protein Tyrosine Kinase c-Kit inhibitor - FLT3 inhibitor - PDGFR inhibitor - c-Met inhibitor - c-RET inhibitor - RAD51 inhibitor - Apoptosis related activator Amuvatinib (MP-470) For research use only.

Amuvatinib (MP-470)

Synonyms: HPK 56

Amuvatinib (MP-470, HPK 56) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively. Amuvatinib suppresses c-MET and c-RET. Amuvatinib is also active as a DNA repair protein Rad51 inhibitor with antineoplastic activity. Phase 2.

Amuvatinib (MP-470) Chemical Structure

Amuvatinib (MP-470) Chemical Structure

CAS No. 850879-09-3

Purity & Quality Control

Amuvatinib (MP-470) Related Products

Signaling Pathway

c-Kit Signaling Pathways

c-Kit Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
GIST Function assay Inhibition of AXL in human GIST cells, IC50<1μM 26555154
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Caco-2 Function assay 48 hrs Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50=0.02μM ChEMBL
Caco-2 Function assay 48 hrs Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50=0.06μM ChEMBL
GIST882 Function assay 4 days Inhibition of c-kit gain of function mutant in human GIST882 cells measured after 4 days by sulforhodamine B assay, IC50=1.6μM ChEMBL
GIST882 Function assay 96 hrs Inhibition of c-kit gain of function mutant in human GIST882 cells after 96 hrs by Cell-Titer Glo luciferase assay, IC50=1.6μM ChEMBL
MIAPaCa2 Function assay 4 days Inhibition of PDGFRA in human MIAPaCa2 cells measured after 4 days by sulforhodamine B assay, IC50=2.1μM ChEMBL
PANC1 Function assay 4 days Inhibition of PDGFRA in human PANC1 cells measured after 4 days by sulforhodamine B assay, IC50=3μM ChEMBL
SF-767 Cytotoxicity assay 1 uM 24 hrs Cytotoxicity against human SF-767 cells assessed as cell death at 1 uM after 24 hrs by MTS assay ChEMBL
SF-767 Cytotoxicity assay 1 uM 24 hrs Cytotoxicity against human SF-767 cells assessed as cell death at 1 uM in presence of 800Gy ionizing radiation after 24 hrs by MTS assay ChEMBL
SBcl2 Antitumor assay 5 days Antitumor activity against human SBcl2 cells xenografted in ip dosed athymic nude mouse assessed as reduction in tumor growth administered as qd for 5 days ChEMBL
HT-29 Function assay Suppression of ionizing radiation-induced Rad51 expression in human HT-29 cells pretreated with compound followed by ionizing radiation by Western blot analysis ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description Amuvatinib (MP-470, HPK 56) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively. Amuvatinib suppresses c-MET and c-RET. Amuvatinib is also active as a DNA repair protein Rad51 inhibitor with antineoplastic activity. Phase 2.
Targets
c-Met [5] RAD51 [6] c-RET [7] c-Kit (D816H) [1] PDGFRα (V561D) [1] Click to View More Targets
10 nM 40 nM
In vitro
In vitro

The hydrochloride salt of MP-470 also inhibits several mutants of c-Kit, including c-KitD816V, c-KitD816H, c-KitV560G, and c-KitV654A, as well as a Flt3 mutant (Flt3D835Y) and two PDGFRα mutants (PDGFRαV561D and PDGFRαD842V), with IC50 of 10 nM to 8.4 μM. MP-470 potently inhibits the proliferation of OVCAR-3, A549, NCI-H647, DMS-153, and DMS-114 cells, with IC50 of 0.9 μM–7.86 μM. [1] MP-470 also inhibits c-Kit and PDGFRα, with IC50 values of 31 μM and 27 μM, respectively. MP-470 demonstrates potent cytotoxicity against MiaPaCa-2, PANC-1, and GIST882 cells, with IC50 of 1.6 μM to 3.0 μM. MP-470 also binds to and inhibits several c-Kit mutants, including c-KitK642E, c-KitD816V, and c-KitK642E/D816V. [2] In MDA-MB-231 cells, MP-470 (1 μM) inhibits tyrosine phosphorylation of AXL. [3] In LNCaP and PC-3, but not DU145 cells, MP-470 exhibits cytotoxicity with IC50 of 4 μM and 8 μM, respectively, and induces apoptosis at 10 μM. In LNCaP cells, MP-470 (10 μM) elicits G1 arrest and decreases phosphorylation of Akt and ERK1/2. [4] In SF767 cells, MP-470 (10 μM) inhibits c-Met phosphorylation and sensitizes cells to radiation. In combination with radiation, MP-470 (10 μM) inhibits glycogen synthase kinase (GSK)3β activity, induces apoptosis, and disrupts the repair of dsDNA breaks probably through suppression of Rad51. [5] [6]
Kinase Assay Kinase inhibition assay of c-Kit and PDGFRα
For the testing of inhibitory activity against c-Kit and PDGFRα, enzymes are incubated with varying concentrations of MP-470 and radiolabeled γ-32P-ATP. After 30 min, the reaction mixtures are electrophoresed on an acrylamide gel and autophosphorylation, quantitated by the amount of radioactivity incorporated into the enzyme, is assayed.
Cell Research Cell lines MiaPaCa-2, PANC-1, and GIST882 cells
Concentrations 0–30 μM, dissolved in DMSO
Incubation Time 96 hours
Method

Cells are plated at a density of 2 × 103 to 1 × 104 cells per well in 100 μL medium on day 0 in 96-well Falcon microtitier plates. On day 1, ten μL of serial dilutions of MP-470 are added to the plates in quadruplicates. After incubation for 4 days, the cells are fixed with 10% Trichloroacetic acid solution. Subsequently, they are labeled with 0.04% Sulforhodamine B (SRB) in 1% acetic acid. After multiple washes to remove the excess dye, 100 μL of 50 mM Tris solution is added to each well in order to dissolve the dye. The absorbance of each well is read on a plate reader at 570 nm. Date are expressed as the percentage of survival of control calculated from the absorbance corrected for background absorbance. The surviving percent of cells is determined by dividing the mean absorbance values of the monoclonal antibody by mean absorbance values of the control and multiplying by 100.
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay Cell viability 24950457
Western blot p-AXL / AXL / p-AKT / AKT / ERK / Rad51 24950457
In Vivo
In vivo

In mice xenograft models of HT-29, A549, and SB-CL2 cells, MP-470 (10 mg/kg–75 mg/kg via i.p. or 50 mg/kg–200 mg/kg via p.o.) inhibits tumor growth. [1] In mice bearing LNCaP xenograft, MP-470 (20 mg/kg) combined with Erlotinib significantly induces tumor growth inhibition (TGI). [4]
Animal Research Animal Models Mice (athymic nude) xenograft models of HT-29, A549, and SB-CL2 cells
Dosages 10 mg/kg–75 mg/kg (i.p.) or 50 mg/kg–200 mg/kg (p.o.)
Administration Oral gavage (qd5 × 3 weeks) or intraperitoneal injection (qd5 × 2 weeks)
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01357395 Completed
Small Cell Lung Carcinoma
Astex Pharmaceuticals Inc.
 May 2011 Phase 2

Chemical Information & Solubility

Molecular Weight 447.51 Formula

C23H21N5O3S
CAS No. 850879-09-3 SDF Download Amuvatinib (MP-470) SDF
Smiles C1CN(CCN1C2=NC=NC3=C2OC4=CC=CC=C43)C(=S)NCC5=CC6=C(C=C5)OCO6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 32 mg/mL ( (71.5 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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