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Amuvatinib (MP-470)

Name: Amuvatinib (MP-470)
Brand: Selleck Chemicals
SKU: S1244
Rating: 5 (15 reviews)

Catalog No.S1244 Synonyms: HPK 56

For research use only.

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.

CAS No. 850879-09-3

Selleck's Amuvatinib (MP-470) has been cited by 15 publications

Purity & Quality Control

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c-Kit Signaling Pathway Map

Biological Activity

Description

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	Click to View More Targets

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]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

GIST	Ml\aSpVv[3Srb36gZZN{[Xl?			M2f2S2lvcGmkaYTpc44hd2ZiQWjMJIlvKGi3bXHuJGdKW1RiY3XscJMtKEmFNUC8Ne69VQ>?	NV:xTYJYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OVUyPTRpPkK2OVU2OTV2PD;hQi=>
DAOY	NWjQd2EyeUiWUzDhd5NigQ>?			M2W3W5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy\|	M3;3SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	M1HzfZFJXFNiYYPzZZk>			NFP4VYVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	NVvKOINlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC	NVXETJBkeUiWUzDhd5NigQ>?			NIP2UGVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	NFLlNoI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	NWD6NIlneUiWUzDhd5NigQ>?			MVLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy\|	NUDwXZRPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5	MVXxTHRUKGG\|c3H5			NGeyXpJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	NHPrNVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	M4\kTZFJXFNiYYPzZZk>			NVXHTYhKeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	Mmi0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Caco-2	MUfGeY5kfGmxbjDhd5NigQ>?		NFv6S2E1QCCqcoO=	NYnWT\|hNTGW2ZYLtbY5ifGmxbjDv[kBKSzVyII\hcJVmeyCob4KgbY5pcWKrdHnvckBw\iCVQWLTMWNwXi1{IHnu[JVk\WRiY4n0c5RwgGmlaYT5JI9nKEOjY3:tNkBk\WyuczDh[pRmeiB2ODDoc5VzeyCkeTDobYdpKGOxboTlcpQhcW2jZ3nu[{whUUN3ME2wMlAz\|ryP	M4DXfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIyODN6NUGvK\|5EcEWPQly8M4E,
Caco-2	MV3GeY5kfGmxbjDhd5NigQ>?		NW\uVJFFPDhiaILz	Mn33WI95cWOrdImgZYdicW6\|dDDDZYNwNTJiY3XscJMh\GW2ZYLtbY5m\CCjdDC0PEBpd3W{czDifUBqdnS{YXPlcIx2dGG{IFHUVEBkd26lZX70doF1cW:wIIXzbY5oKHSqZTDD[YxtXGm2ZYKtS4xwKEy3bXnu[ZNk\W62IFPlcIwhXmmjYnnsbZR6KEG\|c3H5MEBESzVyPUCuNFbPxE1?	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNVA{QDVzLze+R4hGVUKOPD;hQi=>
GIST882	NYHZeVVjTnWwY4Tpc44h[XO\|YYm=		NHz0dXU1KGSjeYO=	MVfJcohq[mm2aX;uJI9nKGNva3n0JIdicW5ib3[g[pVv[3Srb36gcZV1[W62IHnuJIh2dWGwIFfJV3Q5QDJiY3XscJMhdWWjc4Xy[YQh[W[2ZYKgOEBl[Xm\|IHL5JJN2dG[xcnjv[IFucW6nIFKgZZN{[XluIFnDOVA:OS54zszN	NHfV[VM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB\|OEWxM{c,S2iHTVLMQE9iRg>?
GIST882	NIr0fm5HfW6ldHnvckBie3OjeR?=		M4Drc\|k3KGi{cx?=	NYrseW1pUW6qaXLpeIlwdiCxZjDjMYtqfCCpYXnuJI9nKG[3bnP0bY9vKG23dHHueEBqdiCqdX3hckBIUVOWOEiyJINmdGy\|IHHmeIVzKDl4IHjyd{BjgSCFZXzsMXRqfGW{IFfsc{BtfWOrZnXyZZNmKGG\|c3H5MEBKSzVyPUGuOu69VQ>?	M3XWR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIyODN6NUGvK\|5EcEWPQly8M4E,
MIAPaCa2	MVzGeY5kfGmxbjDhd5NigQ>?		Moq4OEBl[Xm\|	M4C5TWlvcGmkaYTpc44hd2ZiUFTHSnJCKGmwIHj1cYFvKE2LQWDhR4EzKGOnbHzzJI1m[XO3cnXkJIFnfGW{IESg[IF6eyCkeTDzeYxnd3Kqb3ThcYlv\SCEIHHzd4F6NCCLQ{WwQVIvOc7:TR?=	NXLn[IhjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjFyM{i1NU8oRkOqRV3CUFww[T5?
PANC1	MU\GeY5kfGmxbjDhd5NigQ>?		NUT3e3MyPCCmYYnz	MYXJcohq[mm2aX;uJI9nKFCGR1\SRUBqdiCqdX3hckBRSU6FMTDj[YxteyCvZXHzeZJm\CCjZoTldkA1KGSjeYOgZpkhe3WuZn;ybI9l[W2rbnWgRkBie3OjeTygTWM2OD1\|zszN	M3zO[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFIyODN6NUGvK\|5EcEWPQly8M4E,
SF-767	M3OwZWN6fG:2b4jpZ4l1gSCjc4PhfS=>	NYW5N3FrOSC3TR?=	NYXwU5U5OjRiaILz	NHz1PI9EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUTi15NkegZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCmZXH0bEBifCBzIIXNJIFnfGW{IEK0JIhzeyCkeTDNWHMh[XO\|YYm=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNVA{QDVzLze+R4hGVUKOPD;hQi=>
SF-767	MmK1R5l1d3SxeHnjbZR6KGG\|c3H5	NV23dnFxOSC3TR?=	MUGyOEBpenN?	NXr2[Vh4S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0ZvN{[3JINmdGy\|IHHzd4V{e2WmIHHzJINmdGxiZHXheIgh[XRiMTD1UUBqdiCycnXz[Y5k\SCxZjC4NFBIgSCrb37pfolv\yC{YXTpZZRqd25iYX\0[ZIhOjRiaILzJIJ6KE2WUzDhd5NigQ>?	NGroXVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB\|OEWxM{c,S2iHTVLMQE9iRg>?
SBcl2	MX7BcpRqfHWvb4KgZZN{[Xl?		MmLEOUBl[Xm\|	M2ftPGFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPCZ4wzKGOnbHzzJJhmdm:pcnHmeIVlKGmwIHnwJIRwe2WmIHH0bJlucWNiboXk[UBud3W\|ZTDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5idIXtc5Ih\3Kxd4ToJIFldWmwaYP0[ZJm\CCjczDx[EBnd3JiNTDkZZl{	NW\ZO3N5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjFyM{i1NU8oRkOqRV3CUFww[T5?
HT-29	Mn\MSpVv[3Srb36gZZN{[Xl?			Ml3lV5VxeHKnc4Ppc44hd2ZiaX;ubZpqdmdicnHkbYF1cW:wLXnu[JVk\WRiUnHkOVEh\XiycnXzd4lwdiCrbjDoeY1idiCKVD2yPUBk\WyuczDwdoV1emWjdHXkJJdqfGhiY3;tdI92dmRiZn;scI94\WRiYomgbY9vcXqrbnegdoFlcWG2aX;uJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?=	NUS1d3FMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjFyM{i1NU8oRkOqRV3CUFww[T5?

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Growth inhibition assay	Cell viability	24950457
Western blot	p-AXL / AXL / p-AKT / AKT / ERK / Rad51	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 (from reference)

Kinase Assay: ^[2]	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]	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.
Animal Research: ^[1]	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)

References

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Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 5%DMSO+95% Corn oil For best results, use promptly after mixing. Click to purchase: Corn Oil	4.5 mg/ml

Chemical Information

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

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01357395	Completed	Drug: Amuvatinib	Small Cell Lung Carcinoma	Astex Pharmaceuticals Inc.	May 2011	Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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