192441-08-0

Basic information

• Product Name: Lomeguatrib
• Synonyms: 6-[(4-bromothiophen-2-yl)methoxy]-7H-purin-2-amine;Lomeguatrib;2-Amino-6-[(4-bromo-2-thienyl)methoxy]-9H-purine;6-((4-Bromo-2-thienyl)methoxy)purin-2-amine;C521206;2-AMino-6-(4-broMothiophen-2-ylMethoxy)-9H-purine;6-[(4-BroMo-2-thienyl)Methoxy] -1H-purin-2-aMine;6-[(4-BroMo-2-thienyl)Methoxy]-9H-purin-2-aMine
• CAS NO: 192441-08-0
• Molecular Formula: C₁₀H₈BrN₅OS
• Molecular Weight: 326.17
• Product Categories: Inhibitor of MGMT.;Epigenetics;Inhibitors
• Mol File: 192441-08-0.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 683.8 °C at 760 mmHg
• Flash Point: 367.3 °C
• Appearance: white to beige/
• Density: 2.07
• Vapor Pressure: 1.5E-18mmHg at 25°C
• Refractive Index: 1.797
• Storage Temp.: room temp
• Solubility: DMSO: soluble10mg/mL, clear
• PKA: 9.42±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Lomeguatrib(CAS DataBase Reference)
• NIST Chemistry Reference: Lomeguatrib(192441-08-0)
• EPA Substance Registry System: Lomeguatrib(192441-08-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: UO7420000
• Hazardous Substances Data: 192441-08-0(Hazardous Substances Data)

Usage

Description

Lomeguatrib, with the chemical formula 192441-08-0, is a potent inhibitor of O6-Methylguanine-DNA Methyltransferase (MGMT), an essential DNA repair protein. It exhibits an IC50 of approximately 9 nM and is currently under investigation for its potential in treating cancers that have developed resistance to chemotherapeutic agents such as temozolomide and others.

Uses

Used in Cancer Treatment:
Lomeguatrib is used as an inhibitor of MGMT for enhancing the effectiveness of O6-alkylating agents in cancer treatment. By acting as a pseudosubstrate inactivator of MGMT (IC50 = ~3 nM), lomeguatrib completely inactivates MGMT in human prostate and colorectal tumors when given as a single 120 mg oral dose and in primary central nervous system cancers at 160 mg. This helps overcome resistance to treatments that use O6-alkylating agents to produce cytotoxicity.
Used in Combination Therapy:
Lomeguatrib is used as an enhancer of antitumor activity when combined with temozolomide in both human melanoma and MCF-7 xenografts. By attenuating MGMT activity in vitro and in vivo, lomeguatrib increases the sensitivity of cancer cells to the cytotoxic effects of temozolomide, potentially improving treatment outcomes for patients with resistant cancers.

References

1) Reinhard?et al.?(2001),?Monosaccharide-Linked Inhibitors of O6-Methylguanine-DNA Methyltransferase (MGMT): Synthesis, Molecular Modeling, and Structure-Activity Relationships; J. Med. Chem.?44?4050 2) Barvaux?et al.?(2004),?Sensitization of a human ovarian cancer cell line to temozolomide by simultaneous attenuation of the Bcl-2 antiapoptotic protein and DNA repair by O6-alkylguanine-DNA alkyltransferase: Mol. Cancer Ther.?3?1215 3) Gumbrell?et al.?(2006),?Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors: Clin. Cancer Res.?12?1577 4) Watson?et al.?(2009),?O(6)-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib: Br. J. Cancer?100?1250 5) Taspinar?et al.?(2013),?Effect of lomeguatrib-temozolomide combination of MGMT promoter methylation and expression in primary glioblastoma tumor cells: Tumour Biol.?34?1935 6) Sabharwal?et al.?(2010),?A phase I trial of lomeguatrib and irinotecan in metastatic colorectal cancer: Cancer Chemother. Pharmacol.?66?829 7) Tawbi?et al.?(2011),?Inhibition of DNA repair with MGMT pseudosubstrates: phase I study of lomeguatrib in combination with dacarbazine in patients with advanced melanoma and other solid tumors: Br. J. Cancer?105?773

InChI:InChI=1/C10H8BrN5OS/c11-5-1-6(18-3-5)2-17-9-7-8(14-4-13-7)15-10(12)16-9/h1,3-4H,2H2,(H3,12,13,14,15,16)

Upstream product

• 18791-75-8 4-Bromothiophen-2-aldehyde 
• 79757-77-0 (4-bromothiophen-2-yl)methanol 
• 34798-95-3 2-amino-N,N,N-trimethyl-9H-purine-6-ylammonium chloride 

Downstream Products

• 382607-75-2 6-[O⁶-(4-bromothenyl)-guan-9-yl]-hexyl-β-D-tetra-O-benzoylglucoside 
• 382607-77-4 8-[O⁶-(4-bromothenyl)-guan-9-yl]-octyl-β-D-tetra-O-benzoylglucoside 
• 382607-79-6 10-[O⁶-(4-bromothenyl)-guan-9-yl]-decyl-β-D-tetra-O-benzoylglucoside 
• 382607-78-5 8-[O⁶-(4-bromothenyl)-guan-9-yl]-octyl-β-D-glucoside 

Relevant articles and documents

Low-oxygen activation AGT protein inhibitor and preparation method and application thereof

The invention provides a low-oxygen activation AGT protein inhibitor shown in the general formula (I) (please see the formula in the description) and a preparation method and application thereof. In the formula, R1=R2=H or R1=H and R2=CH3 or R1=R2=CH3 and R3=H, NO2, OCH3, CH2OH or CO2CH3. The composition has a good low-oxygen activation characteristic and good tumor cell targeting performance, can inhibit the activity of AGT in solid tumors in the low-oxygen environment in a targeted mode, and improves the sensitivity of tumor cells to chemotherapy medicine. The composition has an obvious inhibition function on various solid tumor cell systems when used together with ACNU, can obviously improve the sensitivity of tumor cells to anti-cancer medicine when used together with alkylating agent type anti-cancer medicine, and can be used for targeted combined chemotherapy of malignant tumors.