TH588 Property

Boiling point:

545.7±60.0 °C(Predicted)

Density 

1.505±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 5 mg/ml).

form 

powder

pka

5.90±0.10(Predicted)

color 

white to light brown

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Safety

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

TH588 Chemical Properties,Usage,Production

Description

TH588 (1609960-31-7) is a first-in-class nudix hydrolase family inhibitor.1?MTH1/NUDT1 is a family member that “sanitizes” oxidized deoxynucleotide triphosphates (dNTP) preventing their incorporation into DNA and thus avoiding DNA damage and cell death.? TH588 inhibits MTH1/NUDT1 (IC50?= 5 nM) leading to cell death in several cancer cell lines while not affecting normal cells.? Active?in vitro?and?in vivo.? Recent evidence has raised doubts about the cancer-killing ability of MTH1 inhibition.2,3?Conversely, TH588 has been also shown to decrease osteosarcoma cell viability, impair cell cycle, and increase apoptosis via an MTH1-dependent pathway.4

Uses

TH 588 acts as a novel potent and selective permeable inhibitor of the nudix hydrolase MTH1 protein. It acts as a good tool to show the non-oncogene addiction concept to anti-cancer treatments.

Biochem/physiol Actions

TH588 is a potent inhibitor of human 7,8-Dihydro-8-oxoguaninetriphosphatase MTH1 (NUDT1) with an IC50 value of 5 nM and good metabolic stability. MTH1 hydrolyzes oxidized purine nucleoside triphosphates that might otherwise be incorporated into DNA/RNA and contribute to DNA damage. MTH1 removal of oxidized nucleotides that result from increased levels of reactive oxygen species (ROS) in fast-proliferating cancer cells helps protect cancer cells from proliferative stress and prevent cancer cell death. TH588 is considered a new target for cancer therapy. TH588 is highly selective towards MTH1, with no relevant inhibition of other members of the nudix protein family or a panel of 87 enzymes, GPCRs, kinases, ion channels and transporter. TH588 has been shown to selectively kill a variety of cancer cell lines and with in vivo activity shown for TH588 in SW480 colorectal and MCF7 breast tumour xenografts.

storage

Store at -20°C

References

1) Gad?et al. (2014),?MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool; Nature,?508?215 2) Petrocchi et al. (2016)?Identification of potent and selective MTH1 inhibitors; Bioorg. Med. Chem. Lett.,?26?1503 3) Kettle?et al. (2016),?Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival; J. Med. Chem.,?59?2346 4) Moukengue?et al. (2020),?TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model; EBioMedicine,?53?102704