Lomeguatrib

製品コードS8056 バッチS805601

化学情報

	Synonyms	PaTrin-2	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₀H₈BrN₅OS
	分子量	326.17	CAS No.	192441-08-0
Solubility (25°C)*	体外	DMSO	65 mg/mL (199.28 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Lomeguatrib (PaTrin-2) is a potent inhibitor of O⁶-alkylguanine-DNA-alkyltransferase with IC50 of 5 nM.
in vitro	Lomeguatrib inactivates O⁶-alkylguanine-DNA-alkyltransferase (ATase) with a IC50 10-fold lower than O⁶-Benzylguanine. Lomeguatrib inhibits the activity of ATase in Raji cells with IC50 of 10 nM. ^[1] Lomeguatrib effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM ). Lomeguatrib (10 μM ) substantially increases the growth inhibitory effects of temozolomide in MCF-7 cells (D60= 10 μM with Lomeguatrib vs 400 μM without). ^[2]
in vivo	Lomeguatrib (20 mg/kg/day for 5 days) combined with temozolomide (100 mg/kg/day for 5 days) produces a substantial tumour growth delay: median tumour quintupling time is increased by 22 days without any significant increase in toxicity, while neither of the two drugs administrated along show any antitumor activity. ^[2] Lomeguatrib inactivates ATase and enhances the anti-tumour effect of temozolomide in A375M human melanoma xenografts model. Lomeguatrib, at a single dose of 20 mg/kg i.p., produces complete ATase depletion in tumor within 2 hr. Temozolomide (100 g/kg/day) significantly delays growth of the A375M tumour xenograft with an estimated delay in the time for tumour to quintuple in size of 9.6 days. Addition of Lomeguatrib to temozolomide significantly enhances the latter’s effect, delaying the quintupling time a further 8.7 days. Moreover, the Lomeguatrib combination results in considerably less toxicity (0/9 vs. 2/9 deaths; 6.84% weight loss vs. 9.48%). Lomeguatrib alone has no significant effect on tumour growth. ^[3]

プロトコル(参考用のみ)

キナーゼアッセイ	ATases activity assay
キナーゼアッセイ	The cDNA cloning and overexpression of the human ATase are performed. Purification of the recombinant proteins is achieved by DEAE-cellulose ion-exchange chromatography. The ATase protein is partially purified by ammonium sulfate precipitation (30-60%) and dialyzed against 10 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol (DTT), 2 mM EDTA, 10% glycerol, before loading onto a DEAE-cellulose column. The ATase is then eluted with a 0-0.1 M NaCl gradient. The purified human ATase protein retains activity for more than 1 year when stored at high concentration at -20 ℃ in buffer I [50 mM Tris-HCl (pH 8.3)/3 mM DTT/1 mM EDTA] and could be thawed and refrozen several times without substantial loss of activity. Compounds to be tested are dissolved in DMSO to a final concentration of 10 mM and diluted just before use in buffer I containing 1 mg/mL bovine serum albumin (IBSA). Recombinant ATase is diluted in IBSA and titrated in order that the reaction be conducted under ATase, and not substrate, limiting conditions. In each assay, fixed amounts of ATase (50 -60 fmol) are incubated with varying amounts of O⁶-benzylguanine, or test compound, in a total volume of 200 μL of IBSA containing 10 μg of calf thymus DNA at 37 ℃ for 1 h. The ³H-methylated DNA substrate (100 μL containing 4 μg of DNA and 100 fmol of O⁶-benzylguanine is added and incubation continued at 37 ℃for 1 h, until the reaction is completed. Following acid hydrolysis of the DNA, the ³H-methylated protein is recovered and quantitated by liquid scintillation counting. Samples are typically assayed in duplicate and experiments repeated several times.

参考

カスタマーフィードバック

: , , Mol Cancer Ther, 2015, 14(5):1236-46.

: Data from [Data independently produced by , , Onco Targets Ther, 2018, 11:3671-3684]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy [ Neurooncol Adv, 2024, 6(1):vdad165]	PubMed: 38213834
Epigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status [ Int J Mol Sci, 2023, 24(20)15179]	PubMed: 37894860
Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters [ Pharmaceuticals (Basel), 2021, 14(2)107]	PubMed: 33573093
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143]	PubMed: 33067904
MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP. [ Nucleic Acids Res, 2018, 46(20):10888-10904]	PubMed: 30304478
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740]	PubMed: 30135193
CAT3, a prodrug of 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine, circumvents temozolomide-resistant glioblastoma via the Hedgehog signaling pathway, independently of O6-methylguanine DNA methyltransferase expression [Ji M Onco Targets Ther, 2018, 11:3671-3684]	PubMed: 29983575
MGMT Expression Predicts PARP-Mediated Resistance to Temozolomide. [Erice O, et al. Mol Cancer Ther, 2015, 14(5):1236-46]	PubMed: 25777962

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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