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MedKoo CAT#: 200944
CAS#: 451493-31-5 (tosylate)
Description: AV-412, also known as MP-412, is a second-generation, orally bioavailable dual kinase inhibitor with potential antineoplastic activity. EGFR/HER2 inhibitor AV-412 binds to and inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to first-generation kinase inhibitors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization.
MedKoo Cat#: 200944
Name: AV-412 Tosylate
CAS#: 451493-31-5 (tosylate)
Chemical Formula: C41H44ClFN6O7S2
Molecular Weight: 850.24
Elemental Analysis: C, 57.84; H, 5.21; Cl, 4.16; F, 2.23; N, 9.87; O, 13.15; S, 7.53
AV-412 Tosylate , purity > 98%, is in stock. The same day shipping out after order is received.
Related CAS #: 451492-95-8 (AV-412 free base)
Synonym: MP-412; MP 412; MP412; AV-412; AV 412; AV412; AV-412 tosylate
IUPAC/Chemical Name: N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-yn-1-yl)quinazolin-6-yl)acrylamide bis(4-methylbenzenesulfonate)
InChi Key: GTWJVFFZCKODEV-UHFFFAOYSA-N
InChi Code: InChI=1S/C27H28ClFN6O.2C7H8O3S/c1-5-25(36)33-23-16-20-24(30-17-31-26(20)32-19-6-7-22(29)21(28)15-19)14-18(23)8-9-27(2,3)35-12-10-34(4)11-13-35;2*1-6-2-4-7(5-3-6)11(8,9)10/h5-7,14-17H,1,10-13H2,2-4H3,(H,33,36)(H,30,31,32);2*2-5H,1H3,(H,8,9,10)
SMILES Code: CC1=CC=C(C=C1)S(=O)(=O)O.CC1=CC=C(C=C1)S(=O)(=O)O.CC(C)(C#CC1=CC2=C(C=C1NC(=O)C=C)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)N4CCN(CC4)C
The following data is based on the product molecular weight 850.24 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: Suzuki T, Fujii A, Ochi H, Nakamura H. Ubiquitination and downregulation of ErbB2 and estrogen receptor-alpha by kinase inhibitor MP-412 in human breast cancer cells. J Cell Biochem. 2011 Sep;112(9):2279-86. doi: 10.1002/jcb.23147. PubMed PMID: 21503962.
2: Suzuki T, Fujii A, Ohya J, Nakamura H, Fujita F, Koike M, Fujita M. Antitumor activity of a dual epidermal growth factor receptor and ErbB2 kinase inhibitor MP-412 (AV-412) in mouse xenograft models. Cancer Sci. 2009 Aug;100(8):1526-31. Epub 2009 May 13. PubMed PMID: 19459856.
3: Suzuki T, Fujii A, Ohya J, Amano Y, Kitano Y, Abe D, Nakamura H. Pharmacological characterization of MP-412 (AV-412), a dual epidermal growth factor receptor and ErbB2 tyrosine kinase inhibitor. Cancer Sci. 2007 Dec;98(12):1977-84. Epub 2007 Sep 18. PubMed PMID: 17888033.
451493-31-5 (AV-412 tosylate)
451492-95-8 (AV-412 free base).
MP-412 (AV-412) is a potent dual inhibitor of EGFR and ErbB2 tyrosine kinases, including the mutant EGFR(L858R,T790M), which is clinically resistant to the EGFR-specific kinase inhibitors erlotinib and gefitinib. In an enzyme assay, MP-412 inhibited the EGFR variants and ErbB2 in the nanomolar range with over 100-fold selectivity compared with other kinases, apart from abl and flt-1, which were both moderately sensitive to the compound. In cells, MP-412 inhibited autophosphorylation of EGFR and ErbB2 with IC(50) of 43 and 282 nM, respectively. It also inhibited epidermal growth factor (EGF)-dependent cell proliferation with an IC(50) of 100 nM. Moreover, MP-412 abrogated EGFR signaling in the gefitinib-resistant H1975 cell line, which harbors a double mutation of L858R and T790M in EGFR. In animal studies using cancer xenograft models, MP-412 (30 mg/kg) demonstrated complete inhibition of tumor growth of the A431 and BT-474 cell lines, which overexpress EGFR and ErbB2, respectively. MP-412 suppressed autophosphorylation of EGFR and ErbB2 at the dose corresponding to its antitumor efficacy. When various dosing schedules were applied, MP-412 showed significant effects with daily and every-other-day schedules, but not with a once-weekly schedule, suggesting that frequent dosing is preferable for this compound. Furthermore, MP-412 showed a significant antitumor effect on the ErbB2-overexpressing breast cancer KPL-4 cell line, which is resistant to gefitinib. These studies indicate that MP-412 has potential as a therapeutic agent for the treatment of cancers expressing EGFR and ErbB2, especially those resistant to the first generation of small-molecule inhibitors. (source: Cancer Sci. 2007 Dec;98(12):1977-84).