Amuvatinib

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WARNING: This product is for research use only, not for human or veterinary use.

Description: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.

Price and Availability

Amuvatinib (MP470), purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201950Name: AmuvatinibCAS#: 850879-09-3 (free)Chemical Formula: C23H21N5O3SExact Mass: 447.13651Molecular Weight: 447.51Elemental Analysis:C, 61.73; H, 4.73; N, 15.65; O, 10.73; S, 7.17

Related CAS #:850879-09-3 (free); 1055986-67-8 (hydrochloride)

Synonym:HPK 56; HPK-56; HPK56; MP470; MP-470; MP 470; Amuvatinib.

IUPAC/Chemical Name:N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide.

InChi Key:FOFDIMHVKGYHRU-UHFFFAOYSA-N

InChi Code: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)

SMILES Code:S=C(N1CCN(C2=C(OC3=CC=CC=C34)C4=NC=N2)CC1)NCC5=CC=C(OCO6)C6=C5

Technical Data

Additional Information

According to news published on 15 Apr 2008;  Research data build upon previous results showing that MP-470 exhibits anti-tumor activity in breast and prostate cancer cells. The fact that MP-470 in combination with erlotinib effectively suppressed the HER pathway suggests that concurrent administration of both compounds could represent a new treatment for prostate and breast cancers.According to news published on;  Research    

References

1: Phillip CJ, Zaman S, Shentu S, Balakrishnan K,Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, StellrechtCM, Gandhi V. Targeting MET kinase with the small-molecule inhibitoramuvatinib induces cytotoxicity in primary myeloma cells and cell lines.J Hematol Oncol. 2013 Dec 10;6:92. doi: 10.1186/1756-8722-6-92. PubMedPMID: 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 andregulates the function of breast cancer stem cells. Oncogene. 2014 Mar6;33(10):1316-24. doi: 10.1038/onc.2013.57. Epub 2013 Mar 11. PubMedPMID: 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 ofamuvatinib, a multi-targeted tyrosine kinase inhibitor, in patients withadvanced solid tumors. Cancer Chemother Pharmacol. 2013Feb;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, SorgerP. Profiling phospho-signaling networks in breast cancer usingreverse-phase protein arrays. Oncogene. 2013 Jul 18;32(29):3470-6. doi:10.1038/onc.2012.378. Epub 2012 Sep 3. PubMed PMID: 22945653; PubMedCentral PMCID: PMC3670968.

5: Choy G, Joshi-Hangal R, Oganesian A, Fine G, Rasmussen S, Collier J,Kissling J, Sahai A, Azab M, Redkar S. Safety, tolerability, andpharmacokinetics of amuvatinib from three phase 1 clinical studies inhealthy volunteers. Cancer Chemother Pharmacol. 2012 Jul;70(1):183-90.doi: 10.1007/s00280-012-1821-2. Epub 2012 Feb 15. PubMed PMID: 22349808.

6: Zhao H, Luoto KR, Meng AX, Bristow RG. The receptor tyrosine kinaseinhibitor amuvatinib (MP470) sensitizes tumor cells to radio- andchemo-therapies in part by inhibiting homologous recombination.Radiother Oncol. 2011 Oct;101(1):59-65. doi:10.1016/j.radonc.2011.08.013. Epub 2011 Sep 6. PubMed PMID: 21903282.

7: Baxter PA, Thompson PA, McGuffey LM, Gibson BW, Dauser RC, NuchternJG, Shi C, Inloes R, Choy G, Redkar S, Blaney SM. Plasma andcerebrospinal fluid pharmacokinetics of MP470 in non-human primates.Cancer Chemother Pharmacol. 2011 Apr;67(4):809-12. doi:10.1007/s00280-010-1380-3. Epub 2010 Jun 19. PubMed PMID: 20563581.

8: Welsh JW, Mahadevan D, Ellsworth R, Cooke L, Bearss D, Stea B. Thec-Met receptor tyrosine kinase inhibitor MP470 radiosensitizesglioblastoma cells. Radiat Oncol. 2009 Dec 22;4:69. doi:10.1186/1748-717X-4-69. PubMed PMID: 20028557; PubMed Central PMCID:PMC2806296.

9: Qi W, Cooke LS, Stejskal A, Riley C, Croce KD, Saldanha JW, Bearss D,Mahadevan D. MP470, a novel receptor tyrosine kinase inhibitor, incombination with Erlotinib inhibits the HER family/PI3K/Akt pathway andtumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142. doi:10.1186/1471-2407-9-142. PubMed PMID: 19432987; PubMed Central PMCID:PMC2685437.

10: Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K,Wisner L, Iorio M, Shakalya K, Garewal H, Nagle R, Bearss D. A noveltyrosine kinase switch is a mechanism of imatinib resistance ingastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19.Epub 2007 Feb 26. PubMed PMID: 17325667.