[CAS NO. 2444815-84-1] AMXT-1501tetrahydrochloride
PRODUCTS SPECIFICATIONS [2444815-84-1]
DESCRIPTION [2444815-84-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 714.77 |
| Molecular Formula | C32H72Cl4N6O2 |
| SMILES | CCCCCCCCCCCCCCCC(NCCCC[C@@H](N)C(NCCCNCCCCNCCCN)=O)=O.Cl.Cl.Cl.Cl |
Summary
IC50 & Target
Polyamine transport [1]
In Vitro
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 IC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [2]
| Cell Line: | BE(2)‐C, SMS‐KCNR and SH‐SY5Y cells |
| Concentration: | 0.39 µM, 1 µM, 3.1 µM, 10 µM, 31 µM, 50 µM |
| Incubation Time: | 48 hours |
| Result: | AMXT-1501 tetrahydrochloride exhibited cytotoxicity against this panel of NB cell lines. |
Western Blot Analysis [2]
| Cell Line: | BE(2)‐C, SMS‐KCNR and SH‐SY5Y cells |
| Concentration: | 2.5 µM |
| Incubation Time: | 72 hours |
| Result: | Combination treatment with DFMO decreased the amount of noncleaved PARP and increased the amount of cleaved PARP and cleaved caspase 3 in all three cell lines. |
In Vivo
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | C57BL/6 (WT) and ODC knockout strain ( ODC cKO) mice bearing experimental autoimmune encephalomyelitis (EAE) model [3] |
| Dosage: | 3 mg/kg |
| Administration: | Subcutaneous injection; every day; 28 days |
| Result: | Displayed a delayed disease onset initially, but eventually proceeded with pathologic development and reached the endpoint. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT05500508 | Aminex Therapeutics, Inc. |
Cancer|Solid Tumor|Solid Carcinoma|Advanced Cancer|DIPG Brain Tumor|Ovary Cancer|Breast Cancer|Papillary Thyroid Cancer|Head and Neck Cancer|Gastric Cancer|Nsclc|Mesotheliomas Pleural|Mesothelioma Peritoneum|Esophageal Cancer|Diffuse Midline Glioma, H3 K27M-Mutant|Endometrial Cancer|Cervical Cancer|Melanoma|Colorectal Cancer
|
August 8, 2022 | Phase 1|Phase 2 |
| NCT03077477 | Aminex Therapeutics, Inc.|Novella Clinical|Iqvia Pty Ltd |
Neoplasms|Medication Toxicity|Tolerance
|
June 12, 2018 | Phase 1 |
| NCT03536728 | Aminex Therapeutics, Inc. |
Cancer|Solid Tumor|Solid Carcinoma|Advanced Cancer
|
June 12, 2018 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
H 2 O : 83.33 mg/mL ( 116.58 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.3991 mL | 6.9953 mL | 13.9905 mL |
| 5 mM | 0.2798 mL | 1.3991 mL | 2.7981 mL |
| 10 mM | 0.1399 mL | 0.6995 mL | 1.3991 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (69.95 mM); Clear solution; Need ultrasonic
References
- [1] Candace S Hayes, et al. Polyamine-blocking therapy reverses immunosuppression in the tumor microenvironment. Cancer Immunol Res. 2014 Mar;2(3):274-85.
- [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.
- [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.
