Bedaquiline fumarate
[CAS# 845533-86-0]

Identification

• Classification: API >> Other chemicals
• Name: Bedaquiline fumarate
• Synonyms: R 403323
• Molecular Formula: C₃₂H₃₁BrN₂O₂.C₄H₄O₄
• Molecular Weight: 671.58
• CAS Registry Number: 845533-86-0
• EC Number: 805-637-5
• SMILES: CN(C)CC[C@@](C1=CC=CC2=CC=CC=C21)([C@H](C3=CC=CC=C3)C4=C(N=C5C=CC(=CC5=C4)Br)OC)O.C(=C/C(=O)O)C(=O)O

Properties

• Solubility: 0.8 mg/mL (ethanol, DMSO, DMF, PBS pH=7.2), 2 mg/mL (0.1 M Na2CO3) (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H302-H315-H319-H335-H410
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

Bedaquiline fumarate is a novel drug that plays a crucial role in the treatment of multidrug-resistant tuberculosis (MDR-TB). It was first discovered in the early 2000s by researchers at Janssen Pharmaceutica, a subsidiary of Johnson & Johnson, and was approved by the U.S. Food and Drug Administration (FDA) in 2012. Bedaquiline is a member of the class of diarylquinolines and works by targeting the mycobacterial ATP synthase enzyme, an essential enzyme for the survival of Mycobacterium tuberculosis. By inhibiting ATP synthase, bedaquiline disrupts the bacterium’s energy production, leading to its death.

The drug was developed specifically to address the growing problem of drug-resistant tuberculosis, which has become a significant global health threat. MDR-TB, caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin (the two most commonly used first-line drugs), is challenging to treat due to limited therapeutic options. Bedaquiline represents a breakthrough in this area, providing a new treatment option for patients with MDR-TB.

Bedaquiline fumarate is typically used as part of a combination therapy regimen, as monotherapy is not recommended due to the potential for resistance development. It is often administered alongside other anti-tuberculosis drugs, such as linezolid and clofazimine, to increase its effectiveness and prevent resistance. Clinical studies have demonstrated that when used in combination with other drugs, bedaquiline significantly reduces the time to sputum culture conversion, an important marker of treatment efficacy.

While bedaquiline has shown promising results in treating MDR-TB, its use is not without challenges. The drug can cause side effects such as hepatotoxicity and QT interval prolongation, which can lead to serious heart-related issues. As a result, patients receiving bedaquiline must be monitored regularly for liver function and cardiac health. Despite these risks, bedaquiline has been hailed as a life-saving treatment for patients with MDR-TB, especially in areas where other treatment options are limited.

In addition to its approved use for MDR-TB, ongoing research is exploring the potential of bedaquiline in the treatment of other forms of drug-resistant tuberculosis, as well as in combination with newer drugs to improve treatment outcomes and reduce the duration of therapy.

References

2024. A non-randomized pragmatic historically controlled trial evaluating the effectiveness and safety of a bedaquiline or a linezolid-based short regimen for rifampicin-resistant tuberculosis. The Journal of infection, 149.
DOI: 10.1016/j.jinf.2024.106291

2024. A sensitive, rapid and cost-effective RP-HPLC-UV method for detection and quantification of bedaquiline in physiological fluid (pH 7.4). Analytical methods : advancing methods and applications, 16(31).
DOI: 10.1039/d4ay01143k

2024. Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial. The Lancet. Infectious diseases, 24(9).
DOI: 10.1016/s1473-3099(24)00223-8