Synonym
SID 3712249 , MLS000054131, MiR-544 Inhibitor 1
IUPAC/Chemical Name
1,8-Diamino-3,6-di-1-pyrrolidinyl-2,7-naphthyridine-4-carbonitrile
InChi Key
SSWVPYMSHHEYAB-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H21N7/c18-10-12-11-9-13(23-5-1-2-6-23)21-15(19)14(11)16(20)22-17(12)24-7-3-4-8-24/h9H,1-8H2,(H2,19,21)(H2,20,22)
SMILES Code
N#CC1=C(N2CCCC2)N=C(N)C3=C1C=C(N4CCCC4)N=C3N
Purity
>95% (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 and DMF
Shelf Life
>3 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
Biological target:
Under hypoxic conditions, SID 3712249 (20 nM) increases MTOR mRNA expression and decreases the mRNA expression of the genes encoding miR-544, HIF-1α, and ATM in MDA-MB-231, MCF-7, and MCF-10A cells. It induces apoptosis in MDA-MB-231 cells in a hypoxia- and mTOR-dependent manner when used at a concentration of 20 nM. SID 3712249 (20 nM) enhances the sensitivity of MCF-7 and MDA-MB-231 cells cultured under hypoxic conditions to decreases in cell viability induced by 5-fluorouracil. It reduces tumor growth in an MDA-MB-231 mouse xenograft model.
In vivo activity:
RNA-directed chemical probes, such as SID 3712249, could serve as lead therapeutics, enabling the interrogation of complex cellular networks in cells and animals. Application of SID 3712249 to hypoxic tumor cells selectively inhibited production of the mature miRNA, sensitized cells to 5-fluorouracil, and derepressed mRNAs affected by miR-544 in cellulo and in vivo, including boosting mTOR expression. SID 3712249 sensitized tumor cells to hypoxia-associated apoptosis at a 25-fold lower concentration than a 2'-O-methyl RNA antagomir and was just as selective.
Reference: ACS Chem Biol. 2015 Oct 16;10(10):2267-76. https://pubmed.ncbi.nlm.nih.gov/26181590/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
10.0 |
30.92 |
|
| DMSO |
10.0 |
30.92 |
|
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
323.40
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. Haga CL, Velagapudi SP, Strivelli JR, Yang WY, Disney MD, Phinney DG. Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling. ACS Chem Biol. 2015 Oct 16;10(10):2267-76. doi: 10.1021/acschembio.5b00265. Epub 2015 Jul 30. PMID: 26181590; PMCID: PMC4876818.
In vivo protocol:
1. Haga CL, Velagapudi SP, Strivelli JR, Yang WY, Disney MD, Phinney DG. Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling. ACS Chem Biol. 2015 Oct 16;10(10):2267-76. doi: 10.1021/acschembio.5b00265. Epub 2015 Jul 30. PMID: 26181590; PMCID: PMC4876818.
1: Pan C, Xiang L, Pan Z, Wang X, Li J, Zhuge L, Fang P, Xie Q, Hu X. MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer. Cancer Cell Int. 2018 Apr 3;18:52. doi: 10.1186/s12935-018-0542-y. eCollection 2018. PubMed PMID: 29636640; PubMed Central PMCID: PMC5883289.
An, H., Elvers, K. T., Gillespie, J. A., Jones, K., Atack, J. R., Grubisha, O., & Shelkovnikova, T. A. (2022). A toolkit for the identification of NEAT1_2/paraspeckle modulators. Nucleic Acids Research, 50(20), e119-e119.
