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Amuvatinib (MP-470) Europäischer Partner

ArtNr S1244-5000
Hersteller Selleckchem
CAS-Nr. 850879-09-3
Menge 5 g
Quantity options 10 mg 1 g 10 g 10 mM/1 mL 2 mg 200 mg 5 mg 50 mg 5 g
Kategorie
Typ Inhibitors
Specific against other
Smiles C1CN(CCN1C2=NC=NC3=C2OC4=CC=CC=C43)C(=S)NCC5=CC6=C(C=C5)OCO6
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias HPK 56
Similar products Amuvatinib
Lieferbar
Manufacturer - Targets
MET
Storage Conditions
2 years -80 in solvent
Molecular Weight
447, 51
Administration
Oral gavage (qd5, 3 weeks) or intraperitoneal injection (qd5, 2 weeks)
Animal Models
Mice (athymic nude) xenograft models of HT-29, A549, and SB-CL2 cells
Cell lines
MiaPaCa-2, PANC-1, and GIST882 cells
Clinical Trials
MP-470 is currently under investigation in a Phase II clinical trial for small cell lung carcinoma.
Concentrations
0–30 uM, dissolved in DMSO
Dosages
10 mg/kg–75 mg/kg (i.p.) or 50 mg/kg–200 mg/kg (p.o.)
Formulation
Dissolved in corn oil for p.o., , Dissolved in TV-10 (60% propylene glycol, 30% PEG300, 10% water, and 150 mg/mL 2-hydroxypropyl-beta-cyclodextrin) or TV-10 (5% ethanol, 40% glycerol, 55% water, and 300 mg/mL cyclodextrin) for i.p.
IC50
10 nM, 10 nM, 10 nM, 10 nM, 10 nM, 10 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 PDGFalpha mutants (PDGFalphaV561D and PDGFalphaD842V), with IC50 of 10 nM to 8.4 uM. MP-470 hydrochloride potently inhibits the proliferation of OVCAR-3, A549, NCI-H647, DMS-153, and DMS-114 cells, with IC50 of 0.9 uM–7.86 uM. [1] MP-470 also inhibits c-Kit and PDGFalpha, with IC50 values of 31 uM and 27 uM, respectively. MP-470 demonstrates potent cytotoxicity against MiaPaCa-2, PANC-1, and GIST882 cells, with IC50 of 1.6 uM to 3.0 uM. 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 uM) inhibits tyrosine phosphorylation of AXL. [3] In LNCaP and PC-3, but not DU145 cells, MP-470 exhibits cytotoxicity with IC50 of 4 uM and 8 uM, respectively, and induces apoptosis at 10 uM. In LNCaP cells, MP-470 (10 uM) elicits G1 arrest and decreas phosphorylation of Akt and ERK1/2. [4] In SF767 cells, MP-470 (10 uM) inhibits c-Met phosphorylation and sensitizes cells to radiation. In combination with radiation, MP-470 (10 uM) inhibits glycogen synthase kinase (GSK)3beta activity, induces apoptosis, and disrupts the repair of dsDNA breaks probably through suppression of Rad51. [5] [6]
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]
Incubation Time
96 hours
Kinase Assay
[2], Kinase inhibition assay of c-Kit and PDGFalpha, For the testing of inhibitory activity against c-Kit and PDGFalpha, enzymes are incubated with varying concentrations of MP-470 and radiolabeled gamma-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.
Method
Cells are plated at a density of 2, 103 to 1, 104 cells per well in 100 uL medium on day 0 in 96-well Falcon microtitier plates. On day 1, ten uL 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 uL 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.
Solubility (25C)
DMSO 32 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information
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.

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Alle Produkte sind nur für Forschungszwecke bestimmt. Nicht für den menschlichen, tierärztlichen oder therapeutischen Gebrauch.

Menge: 5 g
Lieferbar: In stock
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