HPK 56
N-(1,3-Benzodioxol-5-ylmethyl)-4-benzofuro[3,2-d]pyrimidin-4-yl-1-piperazinecarbothioamide
CAS: 850879-09-3
Molecular Formula: C23H21N5O3S
HPK 56 - Names and Identifiers
| Name | N-(1,3-Benzodioxol-5-ylmethyl)-4-benzofuro[3,2-d]pyrimidin-4-yl-1-piperazinecarbothioamide |
| Synonyms | Mp470 MP 470 HPK 56 Amuvatinib AMuvatinib MP-470(MP 470) AMuvatinib (MP-470) AMuvatinib (MP-470, HPK 56) N-(1,3-Benzodioxol-5-ylmethyl)-4-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- |
| CAS | 850879-09-3 |
| InChI | InChI=1S/C23H21N5O3S/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) |
HPK 56 - Physico-chemical Properties
| Molecular Formula | C23H21N5O3S |
| Molar Mass | 447.51 |
| Density | 1.443 |
| Boling Point | 649.5 °C at 760 mmHg |
| Flash Point | 346.6 °C |
| Solubility | Soluble in DMSO, not in water |
| Storage Condition | -20℃ |
| Use | Amuvatinib, also known as MP-470, is an orally bioavailable synthetic carbothioamide with potential antineoplastic activity. Multitargeted receptor tyrosine kinase inhibitor 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. In addition, MP470 inhibits activities of other receptor tyrosine kinases, such as c-Met, Ret oncoprotein, and mutant forms of Flt3 and PDGFR alpha, which are frequently dysregulated in variety of tumors. |
| In vitro study | MP-470 acts on MiaPaCa-2, PANC-1, and GIST882 cells and is toxic with an IC50 of 1.6 μm to 3.0 μm. MP-470 also binds to and inhibits some c-Kit mutants, including the hydrochloride salt of c-Kit MP-470 also inhibits some c-Kit mutants, including c-Kit MP-470 (1 μm) acting on MDA-MB-231 cells, inhibiting tyrosine phosphorylation of AXL. MP-470 acted on LNCaP and PC-3, but not on DU145 cells, was toxic with IC50 of 4 and 8 μm, respectively, and somewhat proliferated at 10 μm. MP-470 (10 μm) acts on LNCaP cells to arrest the cell cycle at G1 phase and reduce Akt and ERK1/2 phosphorylation. MP-470 (10 μm) acts on SF767 cells, inhibits c-Met phosphorylation, and sensitizes cells to radiation. Combined treatment with MP-470 (10 μm) and radiation inhibits GSK-3β activity, induces apoptosis, and may disrupt dsDNA B break repair by inhibiting rad51. [5,6] |
| In vivo study | MP-470(10 mg/kg-75 mg/kg by intraperitoneal injection or 50 mg/kg-200 mg/kg by oral treatment) treatment of carrier HT-29, A549, and SB-CL2 cells in a mouse xenograft model to inhibit tumor growth. MP-470(20 mg/kg) combined with Erlotinib significantly inhibited tumor growth in mice bearing LNCaP xenografts. |
HPK 56 - Reference
| Reference Show more | 1: Phillip CJ, Zaman S, Shentu S, Balakrishnan K, Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, Stellrecht CM, Gandhi V. Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines. J Hematol Oncol. 2013 Dec 10;6:92. doi: 10.1186/1756-8722-6-92. PubMed PMID: 24326130; PubMed Central PMCID: PMC3878866. 2: Asiedu MK, Beauchamp-Perez FD, Ingle JN, Behrens MD, Radisky DC, Knutson KL. AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells. Oncogene. 2014 Mar 6;33(10):1316-24. doi: 10.1038/onc.2013.57. Epub 2013 Mar 11. PubMed PMID: 23474758; PubMed Central PMCID: PMC3994701. 3: Tibes R, Fine G, Choy G, Redkar S, Taverna P, Oganesian A, Sahai A, Azab M, Tolcher AW. 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. doi: 10.1007/s00280-012-2019-3. Epub 2012 Nov 23. PubMed PMID: 23178951. 4: Gujral TS, Karp RL, Finski A, Chan M, Schwartz PE, MacBeath G, Sorger P. Profiling phospho-signaling networks in breast cancer using reverse-phase protein arrays. Oncogene. 2013 Jul 18;32(29):3470-6. doi: 10.1038/onc.2012.378. Epub 2012 Sep 3. PubMed PMID: 22945653; PubMed Central PMCID: PMC3670968. |
HPK 56 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.235 ml | 11.173 ml | 22.345 ml |
| 5 mM | 0.447 ml | 2.235 ml | 4.469 ml |
| 10 mM | 0.223 ml | 1.117 ml | 2.235 ml |
| 5 mM | 0.045 ml | 0.223 ml | 0.447 ml |
Last Update：2024-01-02 23:10:35
HPK 56 - Cell Experiment
Cell lines: MiaPaCa-2, PANC-1, and GIST882 cellsConcentrations: 0–30 μM, dissolved in DMSOIncubation Time: 96 hoursMethod: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 b
Last Update：2023-08-16 21:32:38
HPK 56 - Animal Experiment
Animal Models: Mice (athymic nude) xenograft models of HT-29, A549, and SB-CL2 cellsDosages: 10 mg/kg–75 mg/kg (i.p.) or 50 mg/kg–200 mg/kg (p.o.)Administration: Oral gavage (qd5 × 3 weeks) or intraperitoneal injection (qd5 × 2 weeks)
Last Update：2023-08-16 21:32:38
HPK 56 - Reference Information
| biological activity | Amuvatinib (MP-470) is an effective agent for c-Kit, the IC50 of the multi-target inhibitors of PDGF Alpha and Flt3 are 10 nM, 40 nM and 81 nM, respectively. Phase 2. Amuvatinib (MP-470, hpk56) is a potent, multitargeted inhibitor of c-Kit, pdgfα, and Flt3 with IC50 of 10 nM, 40 nM, and 81 nM, respectively. Amuvatinib inhibited by c-MET and c-RET. Amuvatinib also has DNA repair protein Rad51 inhibitor and anti-tumor activity. Phase 2. |
| Target | Value |
| c-Met () | |
| RAD51 () | |
| c-RET () | |
| c-Kit (D816H) () | 10 nM |
| PDGFRα (V561D) () | 40 nM |
Last Update：2024-04-09 19:05:15
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