1430213-30-1

Basic information

• Product Name: ML216
• Synonyms: ML216;1-(4-Fluoro-3-(trifluoromethyl)phenyl)-3-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)urea;N-[4-Fluoro-3-(trifluoromethyl)phenyl]-N'-[5-(4-pyridinyl)-1,3,4-thiadiazol-2-yl]urea
• CAS NO: 1430213-30-1
• Molecular Formula: C₁₅H₉F₄N₅OS
• Molecular Weight: 383.3234728
• Mol File: 1430213-30-1.mol

Chemical Properties

• Appearance: /
• Density: 1.583±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 6.40±0.50(Predicted)
• CAS DataBase Reference: ML216(CAS DataBase Reference)
• NIST Chemistry Reference: ML216(1430213-30-1)
• EPA Substance Registry System: ML216(1430213-30-1)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1430213-30-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
ML216 is used as a therapeutic agent for the treatment of Bloom's Syndrome, a rare genetic disorder characterized by reduced BLM helicase activity and a predisposition to developing cancer. It inhibits the proliferation of BLM-expressing cells, potentially offering a targeted approach to managing the disorder and its associated cancer risks.
Used in Research Applications:
ML216 is used as a research tool in cell proliferation assays to study the effects of BLM helicase inhibition on cell growth and to investigate the role of BLM helicase in DNA repair and cancer development.

Biochem/physiol Actions

ML216 is a membrane permeable selective inhibitor of Bloom (BLM) helicase, a member of the RecQ DNA helicase family. Bloom′s syndrome, caused by a mutation in BLM, is associated with susceptibility to cancer, growth retardation, immunodeficiency, sunlight sensitivity, and fertility defects. ML216 is selective for BLM over other members of the RecQ family, especially in vivo, and appears to act at the BLM-nucleic acid substrate binding site, inhibiting DNA binding and blocking BLM′s helicase activity. ML216 could be useful in studies of tumor cells depending on the ALT (alternative lengthening of telomeres) mechanism for telomere maintenance rather than on telomerase, which are proposed to be susceptible to BLM inhibition.

Upstream product

• 2002-04-2 2-amino-5-(pyrid-4-yl)-1,3,4-thiadiazole 
• 2357-47-3 4-Fluoro-3-trifluoromethylaniline 

Relevant articles and documents

Uncovering an allosteric mode of action for a selective inhibitor of human bloom syndrome protein

BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage r

Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase

Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome.