AMXT-1501 tetrahydrochloride

• CAT Number: I046227
• CAS Number: 2444815-84-1
• Molecular Formula: C32H72Cl4N6O2
• Molecular Weight: 714.77
• Purity: ≥95%
• Synonyms: N-[(5R)-5-amino-6-[3-[4-(3-aminopropylamino)butylamino]propylamino]-6-oxohexyl]hexadecanamide;tetrahydrochloride
• InChI: InChI=1S/C32H68N6O2.4ClH/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-22-31(39)37-28-16-15-21-30(34)32(40)38-29-20-27-36-25-18-17-24-35-26-19-23-33;;;;/h30,35-36H,2-29,33-34H2,1H3,(H,37,39)(H,38,40);4*1H/t30-;;;;/m1..../s1
• InChIKey: HUWZIAHAQAFYJQ-MKUIRMANSA-N
• SMILES: CCCCCCCCCCCCCCCC(=O)NCCCCC(C(=O)NCCCNCCCCNCCCN)N.Cl.Cl.Cl.Cl

AMXT-1501 tetrahydrochloride is an orally active polyamine transport inhibitor. AMXT1501 blocks tumor growth in immunocompetent mice but not in athymic nude mice lacking T cells[1]. Combination of DFMO and AMXT‐1501 induces caspase‐3 mediated apoptosis in NB cell lines[2].
AMXT-1501 tetrahydrochloride (0.39-50 µM; 48 hours) treatment exhibits cytotoxicity against this panel of NB cell lines (BE(2)-C, SMS-KCNR and SH-SY5Y cells), with IC50 values of 17.72 µM for SMS-KCNR, 17.69 µM for BE(2)-C, and 14.13 µM for SH-SY5Y[2].
BE(2)‐C, SMS‐KCNR and SH‐SY5Y cells are exposed to AMXT-1501 tetrahydrochloride (2.5 µM) and DFMO (2.5 mM) alone or in combination (AMXT-1501 tetrahydrochloride 2.5 µM + DFMO 2.5 mM). After 96 hours exposure to AMXT-1501 tetrahydrochloride or DFMO does not significantly alter the level of noncleaved PARP, cleaved PARP and cleaved caspase 3, whereas cells treated with the combination of AMXT-1501 tetrahydrochloride with DFMO decrease the amount of noncleaved PARP and increase the amount of cleaved PARP and cleaved caspase 3[2].
AMXT-1501 tetrahydrochloride (3 mg/kg; subcutaneous injection; every day; 28 days) alone is sufficient to delay EAE onset moderately,but fails to protect animals from reaching the endpoint. However, the combination of DFMO and AMXT-1501 tetrahydrochloride are sufficient to deplete T cell polyamine pool, and consequently suppress T cell proliferation and effector function in vivo[3].

Reference

[1]. Candace S Hayes, et al. Polyamine-blocking therapy reverses immunosuppression in the tumor microenvironment. Cancer Immunol Res. 2014 Mar;2(3):274-85.
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[2]. Katherine Samal, et al. AMXT‐1501, a novel polyamine transport inhibitor, synergizes with DFMO in inhibiting neuroblastoma cell proliferation by targeting both ornithine decarboxylase and polyamine transport. Int J Cancer. 2013 Sep 15;133(6):1323-33.
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[3]. Ruohan Wu, et al. De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function. Sci Adv. 2020 Dec 16;6(51):eabc4275.
 [Content Brief]