Amuvatinib (MP-470)

製品コードS1244 バッチS124402

印刷

化学情報

Synonyms

HPK 56

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₃H₂₁N₅O₃S

分子量

447.51

CAS No.

850879-09-3

Solubility (25°C)*

体外

DMSO

90 mg/mL (201.11 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 Corn oil

4.5mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 90 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
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]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase inhibition assay of c-Kit and PDGFRα
キナーゼアッセイ	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.
細胞アッセイ	細胞株	MiaPaCa-2, PANC-1, and GIST882 cells
	濃度	0–30 μM, dissolved in DMSO
	反応時間	96 hours
	実験の流れ	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.
動物実験	動物モデル	Mice (athymic nude) xenograft models of HT-29, A549, and SB-CL2 cells
	投薬量	10 mg/kg–75 mg/kg (i.p.) or 50 mg/kg–200 mg/kg (p.o.)
	投与方法	Oral gavage (qd5 × 3 weeks) or intraperitoneal injection (qd5 × 2 weeks)

参考

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カスタマーフィードバック

: Data from [Data independently produced by Oncogene, 2014, 33(10), 1316-24]

: Data from [Data independently produced by Melanoma Res, 2014, 24(5), 448-53]

: Data from [Data independently produced by Nat Genet, 2012, 44(8), 852-60]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle [ Microbiol Spectr, 2023, e0510522.]	PubMed: 36995225
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258]	PubMed: 35207746
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y]	PubMed: 35118583
βIII-tubulin suppression enhances the activity of Amuvatinib to inhibit cell proliferation in c-Met positive non-small cell lung cancer cells [ Cancer Med, 2022, 10.1002/cam4.5128]	PubMed: 35946957
STING-Mediated Interferon Induction by Herpes Simplex Virus 1 Requires the Protein Tyrosine Kinase Syk [ mBio, 2021, 12(6):e0322821]	PubMed: 34933455
Establishment and characterization of NCC-MFS4-C1: a novel patient-derived cell line of myxofibrosarcoma [ Hum Cell, 2021, 34(6):1911-1918]	PubMed: 34383271
Establishment and characterization of the NCC-GCTB4-C1 cell line: a novel patient-derived cell line from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00639-4]	PubMed: 34731453
Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00579-z]	PubMed: 34304386
Establishment and characterization of NCC-MFS2-C1: a novel patient-derived cancer cell line of myxofibrosarcoma [ Hum Cell, 2020, 10.1007/s13577-020-00420-z]	PubMed: 32870449
Screening of clustered regulatory elements reveals functional cooperating dependencies in Leukemia [ bioRxiv, 2019, 10.1101/680165]	PubMed: N/A

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人間や獣医の診断であるか治療的な使用のためにでない。

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