CAS 850879-09-3|Amuvatinib (MP-470)

Introduction：Basic information about CAS 850879-09-3|Amuvatinib (MP-470), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Amuvatinib (MP-470) BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	Amuvatinib (MP-470)
CAS Number	850879-09-3	Molecular Weight	447.509
Density	1.4±0.1 g/cm3	Boiling Point	649.5±65.0 °C at 760 mmHg
Molecular Formula	C₂₃H₂₁N₅O₃S	Melting Point	/
MSDS	/	Flash Point	346.6±34.3 °C

Names

Name	N-(1,3-benzodioxol-5-ylmethyl)-4-([1]benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide
Synonym	More Synonyms

Amuvatinib (MP-470) BiologicalActivity

Description	Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively.IC50 Value: 10 nM(c-KitD816H); 40 nM(PDGFRαV561D); 81 nM(Flt3D835Y) [1]Target: c-Kit; PDGFRα; FLT3in 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 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].
Related Catalog	Signaling Pathways >>Protein Tyrosine Kinase/RTK >>c-KitSignaling Pathways >>Protein Tyrosine Kinase/RTK >>FLT3Research Areas >>Cancer
References	[1]. Bearss DJ, et al. US Patent, US/2008/0226747. [2]. Hurley LH, et al. World Patent, WO/2005/037825. [3]. Mahadevan D, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene, 2007, 26(27), 3909-3919. [4]. 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, 9, 142.

Description

Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively.IC50 Value: 10 nM(c-KitD816H); 40 nM(PDGFRαV561D); 81 nM(Flt3D835Y) [1]Target: c-Kit; PDGFRα; FLT3in 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 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].

Related Catalog

Signaling Pathways >>Protein Tyrosine Kinase/RTK >>c-KitSignaling Pathways >>Protein Tyrosine Kinase/RTK >>FLT3Research Areas >>Cancer

References

[1]. Bearss DJ, et al. US Patent, US/2008/0226747.

[2]. Hurley LH, et al. World Patent, WO/2005/037825.

[3]. Mahadevan D, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene, 2007, 26(27), 3909-3919.

[4]. 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, 9, 142.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	649.5±65.0 °C at 760 mmHg
Molecular Formula	C₂₃H₂₁N₅O₃S
Molecular Weight	447.509
Flash Point	346.6±34.3 °C
Exact Mass	447.136505
PSA	115.02000
LogP	2.79
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.739
InChIKey	FOFDIMHVKGYHRU-UHFFFAOYSA-N
SMILES	S=C(NCc1ccc2c(c1)OCO2)N1CCN(c2ncnc3c2oc2ccccc23)CC1
Storage condition	-20°C

Synonyms

Amuvatinib (MP-470)

MP470,MP-470

Amuvatinib

4-benzo[4,5]furo[3,2-d]pyrimidin-4-yl-piperazine-1-carbothioic acid (benzo[1,3]dioxol-5-ylmethyl)-amide

N-(1,3-Benzodioxol-5-ylmethyl)-4-benzofuro[3,2-d]pyrimidin-4-yl-1-piperazinecarbothioamide

Amuvatinib (MP-470,HPK 56)

N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide

HPK56

MP 470

S1244_Selleck

N-(1,3-Benzodioxol-5-ylmethyl)-4-([1]benzofuro[3,2-d]pyrimidin-4-yl)-1-piperazinecarbothioamide

1-Piperazinecarbothioamide, N-(1,3-benzodioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)-

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