WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201950
CAS#: 850879-09-3 (free)
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.
MedKoo Cat#: 201950
CAS#: 850879-09-3 (free)
Chemical Formula: C23H21N5O3S
Exact Mass: 447.13651
Molecular Weight: 447.51
Elemental 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 447.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
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.
5: Choy G, Joshi-Hangal R, Oganesian A, Fine G, Rasmussen S, Collier J, Kissling J, Sahai A, Azab M, Redkar S. Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy 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 kinase inhibitor amuvatinib (MP470) sensitizes tumor cells to radio- and chemo-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, Nuchtern JG, Shi C, Inloes R, Choy G, Redkar S, Blaney SM. Plasma and cerebrospinal 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. The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma 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, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor 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 novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19. Epub 2007 Feb 26. PubMed PMID: 17325667.
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