ML-60218 is a broad spectrum (a wide range) RNA pol III inhibitor (antagonist) with IC50s of 32 and 27 μM for Saccharomyces cerevisiae and human RNA pol III, respectively. ML-60218 disrupts already assembled virions and blocks the formation of new virions without the need for retranscription of cellular RNA.

Physicochemical Properties

Molecular Formula	C19H15CL2N3O2S2
Molecular Weight	452.37
Exact Mass	450.998
CAS #	577784-91-9
PubChem CID	2824289
Appearance	Colorless to light yellow liquid
Density	1.5±0.1 g/cm3
Boiling Point	632.3±65.0 °C at 760 mmHg
Flash Point	336.2±34.3 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.715
LogP	6.83
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	662
Defined Atom Stereocenter Count	0
SMILES	CC1=C(C2=NN(C)C(=C2)NS(=O)(=O)C3=CC=CC=C3Cl)SC4=C1C=C(C=C4)Cl
InChi Key	BVBDTTLISMIOJY-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H15Cl2N3O2S2/c1-11-13-9-12(20)7-8-16(13)27-19(11)15-10-18(24(2)22-15)23-28(25,26)17-6-4-3-5-14(17)21/h3-10,23H,1-2H3
Chemical Name	2-chloro-N-[5-(5-chloro-3-methyl-1-benzothiophen-2-yl)-2-methylpyrazol-3-yl]benzenesulfonamide
Synonyms	ML 60218; ML60218; ML-60218
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

Combining SAHA with ML-60218 inhibits cycle cell processes and induces cell switching, which improves the inhibition of human pancreatic cancer cell proliferation. In PANC-1 and BxPC-3 cells, ML-60218 reverses SAHA-stimulated tRNA expression. HDACs' capacity to produce cytokines and cell cycle factors is improved by ML-60218 [2]. Using blocked tyrosine kinase (DLP) in an in vitro stress assay, ML-60218 demonstrated cytokine-inducing activity, suggesting that its target is viral. It was discovered that ML-60218 hinders VP6's capacity to form higher-order structures, which produces the protein's DLP outer layer without compromising its ability to trimerize. Electron examination of DLP treated with ML-60218 revealed structures that were dangerously damaged. NSP5 was dephosphorylated as a result of viroplasm destruction (10 μM) mediated by ML-60218 [3].

References

[1]. Novel small-molecule inhibitors of RNA polymerase III. Eukaryot Cell. 2003;2(2):256-264. [2]. Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer. Biol Open. 2012;1(4):295-307. [3]. Identification of a Small Molecule That Compromises the Structural Integrity of Viroplasms and Rotavirus Double-Layered Particles. J Virol. 2018;92(3):e01943-17. Published 2018 Jan 17.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~221.05 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2106 mL	11.0529 mL	22.1058 mL
	5 mM	0.4421 mL	2.2106 mL	4.4212 mL
	10 mM	0.2211 mL	1.1053 mL	2.2106 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.