Synonym
MSX122; MSX 122; MSX-122.
IUPAC/Chemical Name
N,N'-(1,4-phenylenebis(methylene))bis(pyrimidin-2-amine)
InChi Key
PXZXYRKDDXKDTK-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H16N6/c1-7-17-15(18-8-1)21-11-13-3-5-14(6-4-13)12-22-16-19-9-2-10-20-16/h1-10H,11-12H2,(H,17,18,21)(H,19,20,22)
SMILES Code
C1(CNC2=NC=CC=N2)=CC=C(CNC3=NC=CC=N3)C=C1
Appearance
white 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
More Info
MSX-122 is a potent inhibitor of the chemokine receptor CXCR4, which is activated by stromal derived factor-1 (SDF-1). The interaction between SDF-1 and CXCR4 has been shown to promote chemotaxis and angiogenesis in multiple cancer cell types. In preclinical studies, MSX-122 has displayed a favorable pharmacodynamic and safety profile while inhibiting the function of CXCR4, thus affecting downstream cellular events. [source: http://www.gabio.org/pr_details.aspx?subid=121] .
Biological target:
MSX-122 is an active partial antagonist of CXCR4, inhibiting CXCR4/CXCL12 actions, with an IC50 of ∼10 nM.
In vitro activity:
To determine whether MSX-122 directly binds to the CXCL12 site on CXCR4, a highly sensitive radiotracer technique, using a fluorine-18 radiolabeled MSX-122 analog (MSX-122F) in which one pyrimidine ring of MSX-122 was labeled by fluorine-18 (Figure 1D) was utilized. It was postulated that MSX-122 bound to CXCR4 can interfere with the “lock and key” mechanism between CXCR4 and CXCL12, which can result in inhibiting key functional signaling such as Matrigel invasion and cAMP modulation without displacing CXCL12. 100 nM MSX-122 effectively blocked invasion of 78% MDA-MB-231 cells while the same concentration of AMD3100 blocked invasion of 62% cells. CXCR4 and CXCL12 are also known to play critical roles in endothelial cell migration and tubular organization. While AMD3100 at 100 nM blocked 43% of CXCL12-induced tubular network formation, MSX-122 blocked 63% at the same concentration (Figure 2B). In conclusion, MSX-122, a small novel molecule that is a partial CXCR4 antagonist without mobilizing stem cells has been developed. This can be safer for long-term blockade of metastasis than other reported CXCR4 antagonists.
Reference: PLoS One. 2012; 7(4): e34038. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317778/
In vivo activity:
To test the impact of CXCR4 blockade with either AMD3100 or MSX-122 on development of radiation-induced PF, AMD3100, 10 mg/kg, s.c. or MSX-122, 10 mg/kg i.p. was administered to Female C57BL/6 mice for 20-weeks. It was found from the initial pilot experiment that a single 20-Gy dose to the lung at the 20-week time-point resulted in fully 90% of untreated mice developing PF confirmed by both trichrome staining-positivity (maximum score 12) and CT scan showing a significant volume with density > -200 HU. Both histology-based and CT-based assessments show that MSX-122 significantly attenuated the development of fibrosis by 70%, while AMD3100 only trended towards reduction in fibrosis (Figure 5A). Representative micrographs of trichrome-staining in each group at low and high power are shown, with obvious blue staining in the vehicle only group indicating significant deposition of collagen (Figure 5B). The AMD3100-treated group showed 50% mortality during the 20-weeks of treatment, while no mortality was observed in the MSX-122- or vehicle-treated (irradiated) groups. These results suggest that the CXCR4/CXCL12-axis is critical in the development of radiation-induced PF in a mouse model and that CXCR4 inhibition may alleviate potential radiation-induced lung injury. Examining possible use of MSX-122 for blocking PF among patients undergoing thoracic irradiation warrants further investigations.
Reference: PLoS One. 2013; 8(11): e79768. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820649
|
Solvent |
mg/mL |
mM |
| Solubility |
| Soluble in DMSO |
0.2 |
0.70 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
292.34
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 |
Formulation protocol:
1. Liang Z, Zhan W, Zhu A, Yoon Y, Lin S, Sasaki M, Klapproth JM, Yang H, Grossniklaus HE, Xu J, Rojas M, Voll RJ, Goodman MM, Arrendale RF, Liu J, Yun CC, Snyder JP, Liotta DC, Shim H. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038. doi: 10.1371/journal.pone.0034038. Epub 2012 Apr 2. PMID: 22485156; PMCID: PMC3317778.
2. Shu HK, Yoon Y, Hong S, Xu K, Gao H, Hao C, Torres-Gonzalez E, Nayra C, Rojas M, Shim H. Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis. PLoS One. 2013 Nov 7;8(11):e79768. doi: 10.1371/journal.pone.0079768. PMID: 24244561; PMCID: PMC3820649.
In vitro protocol:
1. Liang Z, Zhan W, Zhu A, Yoon Y, Lin S, Sasaki M, Klapproth JM, Yang H, Grossniklaus HE, Xu J, Rojas M, Voll RJ, Goodman MM, Arrendale RF, Liu J, Yun CC, Snyder JP, Liotta DC, Shim H. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038. doi: 10.1371/journal.pone.0034038. Epub 2012 Apr 2. PMID: 22485156; PMCID: PMC3317778.
In vivo protocol:
1. Shu HK, Yoon Y, Hong S, Xu K, Gao H, Hao C, Torres-Gonzalez E, Nayra C, Rojas M, Shim H. Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis. PLoS One. 2013 Nov 7;8(11):e79768. doi: 10.1371/journal.pone.0079768. PMID: 24244561; PMCID: PMC3820649. 2. Liang Z, Zhan W, Zhu A, Yoon Y, Lin S, Sasaki M, Klapproth JM, Yang H, Grossniklaus HE, Xu J, Rojas M, Voll RJ, Goodman MM, Arrendale RF, Liu J, Yun CC, Snyder JP, Liotta DC, Shim H. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038. doi: 10.1371/journal.pone.0034038. Epub 2012 Apr 2. PMID: 22485156; PMCID: PMC3317778.
1: Shu HK, Yoon Y, Hong S, Xu K, Gao H, Hao C, Torres-Gonzalez E, Nayra C, Rojas M, Shim H. Inhibition of the CXCL12/CXCR4-Axis as Preventive Therapy for Radiation-Induced Pulmonary Fibrosis. PLoS One. 2013 Nov 7;8(11):e79768. doi: 10.1371/journal.pone.0079768. PubMed PMID: 24244561; PubMed Central PMCID: PMC3820649.
2: Ziarek JJ, Liu Y, Smith E, Zhang G, Peterson FC, Chen J, Yu Y, Chen Y, Volkman BF, Li R. Fragment-based optimization of small molecule CXCL12 inhibitors for antagonizing the CXCL12/CXCR4 interaction. Curr Top Med Chem. 2012;12(24):2727-40. PubMed PMID: 23368099; PubMed Central PMCID: PMC3839847.
3: Liang Z, Zhan W, Zhu A, Yoon Y, Lin S, Sasaki M, Klapproth JM, Yang H, Grossniklaus HE, Xu J, Rojas M, Voll RJ, Goodman MM, Arrendale RF, Liu J, Yun CC, Snyder JP, Liotta DC, Shim H. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038. doi: 10.1371/journal.pone.0034038. Epub 2012 Apr 2. PubMed PMID: 22485156; PubMed Central PMCID: PMC3317778.
4: de Nigris F, Schiano C, Infante T, Napoli C. CXCR4 inhibitors: tumor vasculature and therapeutic challenges. Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):251-64. Review. PubMed PMID: 22376154.
