Basic information Overview Synthetic Methods Pharmacological Function Pharmacology Pharmacokinetics Adverse Effect Taboo Safety Related Supplier
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TMC-207

Basic information Overview Synthetic Methods Pharmacological Function Pharmacology Pharmacokinetics Adverse Effect Taboo Safety Related Supplier
TMC-207 Basic information
TMC-207 Chemical Properties
  • Melting point:104 °C
  • Boiling point:702.7±60.0 °C(Predicted)
  • Density 1.322±0.06 g/cm3(Predicted)
  • pka13.05±0.29(Predicted)
  • CAS DataBase Reference843663-66-1
Safety Information
TMC-207 Usage And Synthesis
  • OverviewBedaquiline, formally called (1R, 2S)-1-(6-Bromo-2-methoxy-3-quinolinyl)-4-(dimethylamino)-2-(1-naphthyl)-1-phenyl-2-butanol in chemistry and known as Sirturo in commercial, is a new anti-mycobacterial medicine of diarylquinolines. It impinges on the
    ATP synthesis of Mycobacterium tuberculosis by inhibiting the activity of proton pump on the cell’s ATP synthetase, and thereby eliminates M. tuberculosis (TB). It’s used for adult multi-drug resistant tuberculosis (MDR-PTB).
  • Synthetic MethodsSynthetic route of Bedaquiline
    Fig: Synthetic route of Bedaquiline
  • Pharmacological FunctionBedaquinoline has the same bactericidal activity against both sensitive and resistant strains of mycobacterium tuberculosis as well as on dormant bacteria.
  • PharmacologyThe proton pump on the cell’s ATP synthetase, which is a crucial enzyme for M. tuberculosis (TB) to synthesize ATP, is the unique and specific locus of Bedaquinoline.
    After the combination onto the oligomer and lipoprotein subunit c, Bedaquinoline can inhibit the synthesis of ATP and bring the death to the bacterium cell. Compared with those existing anti-TB medicines, it presents a novel pharmacology and no cross resistance effect was found between Bedaquinoline and other anti-TB medicines. The gene sequence of the subunit c of ATP synthetase is named as atpE, whose amino acid sequence is highly conservative. The resistance of TB to Bedaquinoline comes from its reduced combination onto subunit c of ATP synthetase due to the mutation of the 63rd or 66th on atpE.
  • PharmacokineticsBedaquinoline is easy for oral assimilation. The bioavailability of Bedaquinoline taken with food is twice higher than when taken with an empty stomach. It reaches its blood concentration in 5 hours after taken and has a plasma protein binding rate of 99.9% as well as a plasma half-life of 173 hours. Bedaquinoline can be widely distributed in human body with a homeostasis distribution volume of 1000L. Its clearance rate is low enough and the elimination half-life is 5.5 months. Bedaquinoline is metabolize into metabolite 1~8 in the demethylation mainly through CYP3A4 and partly though CYP2C8 and CYP2C19. Metabolite 2 (M2), the most important metabolite,  which has only 1/3-1/6 the activity of Bedaquinoline, yet present a more strong cytotoxicity and is more likely to cause the drug-induced phospholipidosis. Bedaquinoline and its metabolites are mostly excreted by feces, only 1% to 4% by urine.
  • Adverse EffectCommon adverse reactions are nausea, headache, arthralgia, loss of appetite, vomiting and rash, dizziness, elevated transaminase, increased hemodiastase, muscle pain, diarrhea and prolonged TQ interval.
  • Taboo1.The allergic to this product;
    2.Patients suffer serious dysfunction of heart, liver, kidney (relative contraindication);
    3.Pregnant women, lactating women, children, the old and co-infected HIV sufferers (relative contraindication).
  • DescriptionIn December 2012, the US FDA approved bedaquiline as part of combination therapy for the treatment of multi-drug resistant tuberculosis (MDRTB). Bedaquiline is the first drug approved for MDR-TB and is the first approval from a new class of antituberculosis agents in the past 40 years. Due to the high unmetmedical need for treating MDR-TB, the FDA granted bedaquiline accelerated approval based on Phase II results, providing patients access to the drug while additional clinical studies are carried out. Bedaquiline (also known as TMC207 and R207910) is a diarylquinoline that was discovered from a high-throughput, whole-cell screening strategy with Mycobacterium smegmatis used as a surrogate for M. tuberculosis. Bedaquiline is a single enantiomer of an initial screening hit. Bedaquiline has potent and selective activity against mycobacteria, and is active against both drug-sensitive and drug-resistant M. tuberculosis. The mechanism of action of bedaquiline is unique amongst anti-TB drugs and involves inhibition of mycobacterial ATP synthase; it is not active against human ATP synthase. Bedaquiline has in vivo activity in numerous preclinical models of TB infection, alone and in combination with other anti-TB agents, and has bactericidal activity in established TB infection models. Bedaquiline is synthesized in five steps from 3-phenylpropionic acid and para-bromoaniline. Following amide formation, treatment with POCl3 and DMF under Vilsmeier–Hack conditions gave a 2-chloroquinoline product. Treatment with sodium methoxide, followed by condensation with 3-(dimethylamino)-1-(naphthalen-1-yl)propan-1-one, and separation of isomers gave bedaquiline.
  • OriginatorJanssen (Belgium)
  • Uses(αS,βR)-Bedaquiline is a diarylquinoline derivative that acts as a mycobacterial inhibitor. Bedaquiline shows promise as potential drug in the treatment of tuberculosis.
  • UsesLabeled Bedaquiline, intended for use as an internal standard for the quantification of Bedaquiline by GC- or LC-mass spectrometry.
  • brand nameSirturo
TMC-207(843663-66-1)Related Product Information
TMC-207SupplierMore
  • Company Name:Jiaxing Novartis Chemical Co., Ltd. Gold
  • Tel:18957373295
  • Email:sales@novamedicals.com
  • Products Intro:Product Name:TMC-207
    CAS:843663-66-1
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  • Company Name:ChongQing Conscience Pharmaceuticals Ltd. Gold
  • Tel:+86-023- 68549356 023-68548079
  • Email:clive.yang@consciencepharma.com
  • Products Intro:Product Name:bedaquinline
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    Purity:99.5%(single purtiy<0.1%) optical purity >99.9% Package:1g---100g
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  • Company Name:Shanghai Xiang Xin Industrial Co., Ltd. Gold
  • Tel:13651607026
  • Email:sales@xxgmpharm.com;
  • Products Intro:Product Name:bedaquinline
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    Purity:99% Package:25mg,50mg,100mg.
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  • Company Name:Shanghai SynFarm Pharmaceutical Technology Co., Ltd. Gold
  • Tel:18917198199 021-50793966
  • Email:info@synfarm.com
  • Products Intro:Product Name:Bedaquiline
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    Purity:98%Min Package:10Mg,50Mg,100Mg,1g,10g
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  • Company Name:Twochem Co.Ltd. Gold
  • Tel:15800915896 021-58111628-
  • Email:sales@azbiochem.com
  • Products Intro:Product Name:TMC-207
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    Purity:98%+
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