Referencia número: HY-10206

Amuvatinib

(Synonyms: MP470; HPK 56)

6 Cited Publications

Revisión del cliente

Based on 6 publication(s) in Google Scholar

Amuvatinib (MP470) is an orally bioavailable multi-targeted tyrosine kinase inhibitor with potent activity against mutant c-Kit, PDGFRα, Flt3, c-Met and c-Ret. Amuvatinib (MP470) is also a DNA repair suppressor through suppression of DNA repair protein RAD51, thereby disrupting DNA damage repair. Antineoplastic activity.

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Pureza: 99.40%
No. CAS: 850879-09-3
Fòrmula: C₂₃H₂₁N₅O₃S
Peso molecular:447.51

Almacenamiento:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Amuvatinib Chemical Structure

No. CAS: 850879-09-3

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Ensayo clínico
Chemical Information
Publications (6)
Solvente y solubilidad
- In Vitro
- In Vivo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

IC₅₀ & Target^[1]

PDGFRα^V561D

40 nM (IC₅₀)

PDGFRα^D842V

81 nM (IC₅₀)

c-Kit^D816H

10 nM (IC₅₀)

c-Kit^V560G

34 nM (IC₅₀)

c-Kit^V654A

127 nM (IC₅₀)

c-Kit^D816V

950 nM (IC₅₀)

Ver todos los productos específicos de isoformas PDGFR :

Cellular Effect

Cell Line	Type	Value	Description	References
Caco-2	CC₅₀	0.06 μM Compound: AMUVATINIB	Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay	10.21203/rs.3.rs-23951/v1
Caco-2	IC₅₀	0.02 μM Compound: AMUVATINIB	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging	10.21203/rs.3.rs-23951/v1

In Vitro

Amuvatinib (MP470) inhibits c-Kit (D816V), c-Kit (D816H), c-Kit (V560G), c-Kit (V654A), PDGFRα (D842V), and PDGFRα (V561D) with IC₅₀s of 950 nM, 10 nM, 34 nM, 127 nM, 81 nM, and 40 nM, respectively^[4].
Amuvatinib (MP470), a novel receptor tyrosine kinase (RTK) inhibitor has shown growth inhibitory activity against a variety of cancer cell lines. Amuvatinib (0.1-10 μM, 4 days incubation) is effective on LNCaP and PC-3 cells with IC₅₀s of ~4 μM and 8 μM, respectively. When Erlotinib (10 μM) is combined with varying doses of Amuvatinib, the IC₅₀ of Amuvatinib decreases to 2 μM on LNCaP cells^[5].
Akt activity (as measured by phosphorylation on Ser473) is significantly reduced by 10 μM Amuvatinib (treated for 30 hours) alone but is not reduced by Erlotinib or Imatinib Mesylate (IM). Moreover, Amuvatinib plus Erlotinib completely abolished Akt phosphorylation in LNCaP cells with an unchanged total protein level of Akt^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[2]

Cell Line:

Prostate cancer cell lines (LNCaP, PC-3 and DU-145)
Concentration:

0.1-10 μM
Incubation Time:

4 days
Result:

The IC₅₀ for LNCaP and PC-3 was ~4 μM and 8 μM, respectively. Had only a modest effect on the viability of DU-145 cells.

Western Blot Analysis^[2]

Cell Line:

LNCaP cells
Concentration:

2,5,10 μM
Incubation Time:

30 hours
Result:

Akt activity (as measured by phosphorylation on Ser473) was significantly reduced at 10 μM.

In Vivo

Four LNCaP xenograft arms each with 12 mice are dosed intraperitoneally with DMSO (control) or Erlotinib 80 mg/kg or Amuvatinib (MP470) 50 mg/kg or Erlotinib 80 mg/kg plus Amuvatinib 50 mg/kg daily for 2 weeks and then observed for a further 11 days. Individual therapy with Amuvatinib or Erlotinib shows modest tumor growth inhibition (TGI), while Amuvatinib plus Erlotinib has a marked effect on TGI (45-65%). However, due to the high doses of Amuvatinib used, only five or one mouse remained alive in the combination arm at the end of treatment or at the end of the study, respectively. Therefore the Amuvatinib dose is reduced to 10 mg/kg or 20 mg/kg for the combination treatment. TGI in the group receiving 10 mg/kg Amuvatinib+80 mg/kg Erlotinib is not significantly different from the control group. However, mice receiving 20 mg/kg Amuvatinib+80 mg/kg Erlotinib have a significant TGI compared to the control group (p=0.01)^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Forty eight 6-7 week-old SCID male mice with LNCaP xenograft model^[2]
Dosage:

10 mg/kg and 20 mg/kg, 50 mg/kg
Administration:

Administered i.p. daily from days 1 to 24
Result:

Individual therapy showed modest tumor growth inhibition (TGI), while combination had a marked effect on TGI (45-65%).

Ensayo clínico

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

No. CAS 850879-09-3
Appearance Solid
Peso molecular 447.51
Fòrmula C₂₃H₂₁N₅O₃S
Color White to off-white
SMILES

S=C(N1CCN(C2=C3OC4=CC=CC=C4C3=NC=N2)CC1)NCC5=CC=C6OCOC6=C5
Synonyms

MP470; HPK 56
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (6)

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Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Pharmacol Res

Time-dependent proteomics and drug response in expanding cancer cells. [Abstract]

2024 May 9:204:107208. PMID: 38729587
Sci Signal

Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer. [Abstract]

2019 Jul 16;12(590). pii: eaav7259. PMID: 31311847
Sci Rep

Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. [Abstract]

2021 Jan 14;11(1):1333. PMID: 33446690
Microbiol Spectr

Identification of In Vitro Inhibitors of Monkeypox Replication. [Abstract]

2023 Aug 17;11(4):e0474522. PMID: 37278625
bioRxiv

Antivirals against monkeypox infections. [Abstract]

2023 Apr 19:2023.04.19.537483. PMID: 37131608

Solvente y solubilidad

In Vitro:

DMSO : 50 mg/mL (111.73 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.2346 mL

11.1729 mL

22.3459 mL

5 mM

0.4469 mL

2.2346 mL

4.4692 mL

10 mM

0.2235 mL

1.1173 mL

2.2346 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Calculadora de molaridad

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

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

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (5.59 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (284 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instrucciones de manejo (2659 KB)

Referencias

[1]. Choy G, et al. Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers. Cancer Chemother Pharmacol. 2012 Jul;70(1):183-90. [Content Brief]

[2]. Tibes R, et al. A phase I, first-in-human dose-escalation study of amuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):463-71. [Content Brief]

[3]. Baxter PA, et al. Plasma and cerebrospinal fluid pharmacokinetics of MP470 in non-human primates. Cancer Chemother Pharmacol. 2011 Apr;67(4):809-12. [Content Brief]

[4]. David J. Bearss, et al. Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same. US20080226747A1.

[5]. Qi W, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.2346 mL	11.1729 mL	22.3459 mL	55.8647 mL
	5 mM	0.4469 mL	2.2346 mL	4.4692 mL	11.1729 mL
	10 mM	0.2235 mL	1.1173 mL	2.2346 mL	5.5865 mL
	15 mM	0.1490 mL	0.7449 mL	1.4897 mL	3.7243 mL
	20 mM	0.1117 mL	0.5586 mL	1.1173 mL	2.7932 mL
	25 mM	0.0894 mL	0.4469 mL	0.8938 mL	2.2346 mL
	30 mM	0.0745 mL	0.3724 mL	0.7449 mL	1.8622 mL
	40 mM	0.0559 mL	0.2793 mL	0.5586 mL	1.3966 mL
	50 mM	0.0447 mL	0.2235 mL	0.4469 mL	1.1173 mL
	60 mM	0.0372 mL	0.1862 mL	0.3724 mL	0.9311 mL
	80 mM	0.0279 mL	0.1397 mL	0.2793 mL	0.6983 mL
	100 mM	0.0223 mL	0.1117 mL	0.2235 mL	0.5586 mL

Keywords

Amuvatinib

6 Cited Publications

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Amuvatinib

Apoptosis Compound Library

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Publications Citing Use of MedChemExpress (MCE) Amuvatinib

Ver todos los productos específicos de isoformas PDGFR

Actividad biológica

Chemical Information

Publications (6)

Solvente y solubilidad

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

Amuvatinib Related Classifications

HY-10206 Related Classifications