Amuvatinib (MP-470)

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.

Amuvatinib (MP-470) Chemical Structure

CAS No. 850879-09-3

Selleck's Amuvatinib (MP-470) has been cited by 13 publications

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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]
()
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10 nM 40 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
GIST M4XIbmZ2dmO2aX;uJIF{e2G7 MXPJcohq[mm2aX;uJI9nKEG[TDDpckBpfW2jbjDHTXNVKGOnbHzzMEBKSzVyPEJOwG0> NHLINpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW1OVE2PCd-Mk[1OVUyPTR:L3G+
DAOY MkfhdWhVWyCjc4PhfS=> M3vQcZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy| NX;LcJFpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673 NEO5SJdyUFSVIHHzd4F6 NFXhTI5yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?= MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SK-N-MC MYPxTHRUKGG|c3H5 Mnn0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tUWMh[2WubIO= NUjCfIQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643 NEXuZ41yUFSVIHHzd4F6 MkHVdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?= MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
LAN-5 MmTLdWhVWyCjc4PhfS=> NXnyXIY5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
OHS-50 MWXxTHRUKGG|c3H5 NIPMW5NyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz M2jaNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Caco-2 NHTlPGRHfW6ldHnvckBie3OjeR?= M{S5b|Q5KGi{cx?= NHy4RVFF\XSncn3pcoF1cW:wIH;mJGlEPTBidnHseYV{KG[xcjDpcohq[mm2aX;uJI9nKFODUmOtR49XNTJiaX7keYNm\CCleYTveI95cWOrdImgc4YhS2Glbz2yJINmdGy|IHHmeIVzKDR6IHjveZJ{KGK7IHjp[4gh[2:wdHXueEBqdWGpaX7nMEBKSzVyPUCuNFLPxE1? NGHDTXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
Caco-2 NWjPWZZjTnWwY4Tpc44h[XO|YYm= NUjKTHNvPDhiaILz NVX5[5lMXG:6aXPpeJkh[WejaX7zeEBE[WOxLUKgZ4VtdHNiZHX0[ZJucW6nZDDheEA1QCCqb4Xyd{BjgSCrboTyZYNmdGy3bHHyJGFVWCClb37j[Y51emG2aX;uJJV{cW6pIITo[UBE\WyuVHn0[ZIuT2yxIFz1cYlv\XOlZX70JGNmdGxiVnnhZoltcXS7IFHzd4F6NCCFQ{WwQVAvODcQvF2= NXz1dWh1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjFyM{i1NU8oRkOqRV3CUFww[T5?
GIST882 M1XNRWZ2dmO2aX;uJIF{e2G7 NWDQN3BHPCCmYYnz MoS4TY5pcWKrdHnvckBw\iClLXvpeEBo[WmwIH;mJIZ2dmO2aX;uJI12fGGwdDDpckBpfW2jbjDHTXNVQDh{IHPlcIx{KG2nYYP1doVlKGGodHXyJFQh\GG7czDifUB{fWyob4Loc4RidWmwZTDCJIF{e2G7LDDJR|UxRTFwNt88US=> NIrhdJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
GIST882 NYfPUFdWTnWwY4Tpc44h[XO|YYm= MWq5OkBpenN? NHvpW3VKdmirYnn0bY9vKG:oIHOtb4l1KGejaX6gc4Yh\nWwY4Tpc44hdXW2YX70JIlvKGi3bXHuJGdKW1R6OEKgZ4VtdHNiYX\0[ZIhQTZiaILzJIJ6KEOnbHytWIl1\XJiR3zvJIx2[2moZYLhd4Uh[XO|YYmsJGlEPTB;MT62{txO MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNVA{QDVzLze+R4hGVUKOPD;hQi=>
MIAPaCa2 M3HNd2Z2dmO2aX;uJIF{e2G7 MVy0JIRigXN? M17WXWlvcGmkaYTpc44hd2ZiUFTHSnJCKGmwIHj1cYFvKE2LQWDhR4EzKGOnbHzzJI1m[XO3cnXkJIFnfGW{IESg[IF6eyCkeTDzeYxnd3Kqb3ThcYlv\SCEIHHzd4F6NCCLQ{WwQVIvOc7:TR?= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNVA{QDVzLze+R4hGVUKOPD;hQi=>
PANC1 MknhSpVv[3Srb36gZZN{[Xl? MorXOEBl[Xm| NHPWclJKdmirYnn0bY9vKG:oIGDES2ZTSSCrbjDoeY1idiCSQV7DNUBk\WyuczDt[YF{fXKnZDDh[pRmeiB2IHThfZMh[nlic4Xs[o9zcG:mYX3pcoUhSiCjc4PhfUwhUUN3ME2z{txO NGTSO5k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
SF-767 M3yxRWN6fG:2b4jpZ4l1gSCjc4PhfS=> NGP2cZcyKHWP MYWyOEBpenN? MWHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTSk04PjdiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBl\WG2aDDheEAyKHWPIHHmeIVzKDJ2IHjyd{BjgSCPVGOgZZN{[Xl? NIHMZmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
SF-767 NYDHWVU3S3m2b4TvfIlkcXS7IHHzd4F6 MoHhNUB2VQ>? M1rO[VI1KGi{cx?= NEDJfFdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUTi15NkegZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCmZXH0bEBifCBzIIXNJIlvKHC{ZYPlcoNmKG:oIEiwNGd6KGmxbnn6bY5oKHKjZHnheIlwdiCjZoTldkAzPCCqcoOgZpkhVVSVIHHzd4F6 MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNVA{QDVzLze+R4hGVUKOPD;hQi=>
SBcl2 MofXRY51cXS3bX;yJIF{e2G7 MljoOUBl[Xm| MnW0RY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1LjcFIh[2WubIOgfIVvd2e{YX\0[YQhcW5iaYCg[I9{\WRiYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiC2dX3vdkBoem:5dHigZYRucW6rc4TldoVlKGG|IIHkJIZweiB3IHThfZM> NH7qNJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
HT-29 M2OyVWZ2dmO2aX;uJIF{e2G7 M2e2T3N2eHC{ZYPzbY9vKG:oIHnvcol7cW6pIILh[IlifGmxbj3pcoR2[2WmIGLh[FUyKGW6cILld5Nqd25iaX6gbJVu[W5iSGStNlkh[2WubIOgdJJmfHKnYYTl[EB4cXSqIHPvcZBwfW6mIH\vcIxwf2WmIHL5JIlwdmm8aX7nJJJi\GmjdHnvckBjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= NHfUTWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOTB|OEWxM{c,S2iHTVLMQE9iRg>?
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.

  • (Only for Reference)
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)
  • (Only for Reference)

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):
5%DMSO+95% Corn oil
For best results, use promptly after mixing.

4.5 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

Molecular Weight 447.51
Formula

C23H21N5O3S

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

In vivo Formulation Calculator (Clear solution)

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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 μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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
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Molarity Calculator

Mass Concentration Volume Molecular Weight

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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