| Size | Price | |
|---|---|---|
| 5mg | ||
| 50mg | ||
| 500mg |
Purity: ≥98%
Amuvatinib Hydrochloride (MP-470) is a novel, potent, orally bioavailable and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively. It is a carbothioamide compound with potential antineoplastic activity. MP470 binds to mutant forms of the stem cell factor receptor (c-Kit; SCFR), inhibiting clinically relevant mutants of this receptor tyrosine kinase that may be associated with resistance to therapy.
| ln Vitro |
Amuvatinib (MP470) inhibits PDGFRα (D842V), PDGFRα (D816H), c-Kit (V560G), c-Kit (V654A), and c-Kit (D816V) with IC50 values of 950 nM, 10 nM, 34 nM, 127 nM, 81 nM, and 40 nM, respectively[4]. A new receptor tyrosine kinase (RTK) inhibitor called amuvatinib (MP470) has demonstrated growth inhibitory effect against several cancer cell lines. Amuvatinib (0.1–10 μM, 4 days of incubation) works well against PC-3 and LNCaP cells, with IC50 values of about 4 μM and 8 μM, respectively. Amuvatinib's IC50 on LNCaP cells dropped to 2 μM when erlotinib (10 μM) was added in addition to various dosages of the drug [5]. Only 10 μM Amuvatinib (30 h therapy) significantly decreased Akt activity (measured by Ser473 phosphorylation); erlotinib and imatinib mesylate (IM) had no such effect. Furthermore, in LNCaP cells, amuvatinib plus erlotinib totally removed Akt phosphorylation while leaving the overall quantity of Akt protein unchanged [5].
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| ln Vivo |
Four LNCaP xenograft arms, with 12 mice in each arm, were treated intraperitoneally daily with DMSO (control) or erlotinib 80 mg/kg or amuvatinib (MP470) 50 mg/kg or erlotinib Amavatinib 80 mg/kg with amvatinib 50 mg/kg for 2 weeks, followed by observation for a further 11 days. Treatment with amuvatinib or erlotinib alone demonstrated modest tumor growth inhibition (TGI), however amuvatinib plus erlotinib had a significant effect on TGI (45-65%). However, due to the high dose of amvatinib employed, only five or one mice in the combination group survived at the conclusion of treatment or the end of the trial, respectively. Therefore, the amvatinib dose was lowered to 10 mg/kg or 20 mg/kg during combination therapy. The TGI of the group receiving 10 mg/kg Amuvatinib + 80 mg/kg Erlotinib was not substantially different from the control group. However, mice receiving 20 mg/kg Amuvatinib + 80 mg/kg Erlotinib developed substantial TGI compared to the control group (p=0.01)[5].
|
| Cell Assay |
Cell Viability Assay[2]
Cell Types: Prostate cancer cell lines (LNCaP, PC-3 and DU-145) Tested Concentrations: 0.1-10 μM Incubation Duration: 4 days Experimental Results: The IC50 of LNCaP and PC-3 is approximately 4 μM, and 8μM respectively. There is only a slight effect on the viability of DU-145 cells. Western Blot Analysis[2] Cell Types: LNCaP Cell Tested Concentrations: 2,5,10 μM Incubation Duration: 30 hrs (hours) Experimental Results: Akt activity (measured by Ser473 phosphorylation) was Dramatically diminished at 10 μM. |
| Animal Protocol |
Animal/Disease Models: 48 6-7 week old SCID male mice with LNCaP xenograft model [2]
Doses: 10 mg/kg and 20 mg/kg, 50 mg/kg Route of Administration: daily intraperitoneally (ip) (ip) on days 1 to 24 Internal dosing Experimental Results: Individual treatments demonstrated modest tumor growth inhibition (TGI), while combination treatment had a significant effect on TGI (45-65%). |
| References |
[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.
[2]. Baxter PA, et al. Plasma and cerebrospinal fluid pharmacokinetics of MP470 in non-human primates. Cancer Chemother Pharmacol. 2011 Apr;67(4):809-12. [3]. 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. [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. |
| Molecular Formula |
C23H22CLN5O3S
|
|---|---|
| Molecular Weight |
483.970482349396
|
| CAS # |
1055986-67-8
|
| Related CAS # |
Amuvatinib;850879-09-3
|
| SMILES |
S=C(N1CCN(C2=C(OC3=C4C=CC=C3)C4=NC=N2)CC1)NCC5=CC=C(OCO6)C6=C5.[H]Cl
|
| InChi Key |
IKQFRXPMBGQJGE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H21N5O3S.ClH/c32-23(24-12-15-5-6-18-19(11-15)30-14-29-18)28-9-7-27(8-10-28)22-21-20(25-13-26-22)16-3-1-2-4-17(16)31-21/h1-6,11,13H,7-10,12,14H2,(H,24,32)1H
|
| Chemical Name |
N-(1,3-Benzodioxol-5-ylmethyl)-4-([1]benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide hydrochloride
|
| Synonyms |
MP470 Hydrochloride MP-470 Hydrochloride MP 470 Hydrochloride MP470
HCl MP-470 HCl MP 470 HC
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0662 mL | 10.3312 mL | 20.6624 mL | |
| 5 mM | 0.4132 mL | 2.0662 mL | 4.1325 mL | |
| 10 mM | 0.2066 mL | 1.0331 mL | 2.0662 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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