UZH1 is the racemate of UZH1a and UZH1b. UZH1a is a potent and specific METTL3 inhibitor (antagonist) with IC50 of 280 nM. UZH1b (IC50=28 µM) is essentially inactive. UZH1 may be used for transcriptomic regulation of cellular processes. UZH1 has anticancer effect. UZH1 can also be used as a chemical probe to study METTL3.

Physicochemical Properties

CAS #	2925713-02-4
Related CAS #	UZH1a;2813577-78-3;UZH1b;2814392-17-9
Appearance	Off-white to light brown solid powder
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

UZH1 a (2.5-160 μM; 72 h) suppresses the development of U2Os, HEK293T, and MOLM-13 cells with IC50 values of 11 μM, 67 μM, and 87 μM, respectively [1]. MOLM-13, HEK293T, and U2Os cells are inhibited in growth by UZH1 b (2.5-160 μM; 72 h), with IC50 values of 78 μM, 79 μM, and 93 μM [1]. In MOLM-13 cells, UZH1 b is less active at concentrations up to 100 μM, while UZH1 a (2.5-100 μM; 16 hours) decreases m6A methylation levels in cellular mRNA in a dose-dependent manner (IC50=4.6 μM). Low [1]. The m6A methylation levels in MOLM-13, HEK293T, and U2Os cell mRNA are decreased by UZH1 a (40 μM; 16 h) [1]. In MOLM-13 cells, UZH1a (20 μM; 16 hours) promotes apoptosis and induces cell cycle arrest [1].

References

[1]. METTL3 inhibitors for epitranscriptomic modulation of cellular processes. bioRxiv. 2020 Oct 13.

Solubility Data

Solubility (In Vitro)

DMSO : 125 mg/mL (223.73 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (8.95 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 50.0 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: ≥ 5 mg/mL (8.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (8.95 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 50.0 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.)