Amuvatinib (MP-470)

Name: Amuvatinib (MP-470)
Brand: Selleck Chemicals
SKU: S1244
Rating: 5 (6 reviews)

For research use only.

Catalog No.S1244 Synonyms: HPK 56

6 publications

Molecular Weight(MW): 447.51

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.

Selleck's Amuvatinib (MP-470) has been cited by 6 publications

Nat Genet, 2012, 44(8):852-60

PubMed: 22751098 ( click the link to review the publication )

Oncotarget, 2016, 7(15):19620-30

PubMed: 26934000 ( click the link to review the publication )

J Pathol, 2015, 237(1):14-24

PubMed: 25965880 ( click the link to review the publication )

Cancer Res, 2014, 74(20):5878-90

PubMed: 25125659 ( click the link to review the publication )

Oncogene, 2014, 33(10):1316-24

PubMed: 23474758 ( click the link to review the publication )

Melanoma Res, 2014, 24(5):448-53

PubMed: 24950457 ( click the link to review the publication )

4 Customer Reviews

Effects of treatment for 48h with a vehicle or the indicated doses of MP-470 in parental or ER1 and ER2 cell lines in the absence and presence of erlotinib on the indicated biomarkers. Data represent 3 independent experiments.

Nat Genet 2012 44(8), 852-60. Amuvatinib (MP-470) purchased from Selleck.

Inactivation of AXL by MP470 reverses epithelial to mesenchymal transition. Immunoblot analyses of lysates from TGFβ/TNFα- treated MCF10A cells treated with varying amounts of MP470 for 72 hours.

Oncogene 2014 33(10), 1316-24. Amuvatinib (MP-470) purchased from Selleck.
Amuvatinib (3 umol/l, 72 h) leads to decreased pAXL, pAKT, and pERK expression by western blot.

Melanoma Res 2014 24(5), 448-53. Amuvatinib (MP-470) purchased from Selleck.

For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of MP-470 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 mM HCl and 0.1% Nonidet-40) was added to dissolve the formazan.

Dr. Yong-Weon Yi from Georgetown University Medical Center. Amuvatinib (MP-470) purchased from Selleck.

Purity & Quality Control

Choose Selective c-Kit Inhibitors

Biological Activity

Description

Targets

c-Kit (D816H) ^[1]	PDGFRα (V561D) ^[1]	FLT3 (D835Y) ^[1]
10 nM	40 nM	81 nM

In vitro

The hydrochloride salt of MP-470 also inhibits several mutants of c-Kit, including c-Kit^D816V, c-Kit^D816H, c-Kit^V560G, and c-Kit^V654A, as well as a Flt3 mutant (Flt3^D835Y) and two PDGFRα mutants (PDGFRα^V561D and PDGFRα^D842V), 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-Kit^K642E, c-Kit^D816V, and c-Kit^K642E/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]

Assay

Methods	Test Index	PMID
Growth inhibition assay	Cell viability; PubMed: 24950457 Melanoma Res Amuvatinib has growth inhibitory effects in NRAS but not BRAF-mutant melanoma cell lines. Melanoma cell lines were treated with increasing concentrations of amuvatinib for 72 hrs before being analyzed by the MTT assay.	24950457
Western blot	p-AXL / AXL / p-AKT / AKT / ERK / Rad51 ; PubMed: 24950457 Melanoma Res Amuvatinib (3 µM, 72 hrs), leads to decreased pAXL, pAKT and pERK expression by Western blot.	24950457

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]

Protocol

Kinase Assay:^[2]	- Collapse 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:^[2]	- Collapse 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. (Only for Reference)
Animal Research:^[1]	- Collapse 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) (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	32 mg/mL (71.5 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing.	30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Amuvatinib (MP-470) SDF

Molecular Weight	447.51
Formula	C₂₃H₂₁N₅O₃S
CAS No.	850879-09-3
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	HPK 56
Smiles	C1CN(CCN1C2=NC=NC3=C2OC4=CC=CC=C43)C(=S)NCC5=CC6=C(C=C5)OCO6

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

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Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
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Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Molarity Calculator

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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c-Kit Signaling Pathway Map

c-Kit Inhibitors with Unique Features

Most Potent Kit Inhibitor

Axitinib : c-Kit, IC50=1.7 nM.
FDA-approved Kit Inhibitor

Imatinib Mesylate (STI571) : Approved by FDA for CML, GISTs and a number of other malignancies.
Newest Kit Inhibitor

Tyrphostin AG 1296 : An inhibitor of PDGFR with IC50 of 0.3-0.5 μM, inhibiting FGFR and c-Kit with IC50 of 12.3 μM and 1.8 μM in Swiss 3T3 cells.
Classic Kit Inhibitor

Dovitinib (TKI-258, CHIR-258) : Multitargeted RTK inhibitor for class III (FLT3/c-Kit), class IV (FGFR1/3) and class V (VEGFR1-4) RTKs.

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Amuvatinib (MP-470)