Q203

SKU: orb1226521

Description

A novel potent anti-tuberculosis agent targeting cytochrome b subunit qcrB, inhibits M. tuberculosis H37Rv with MIC50 of of 2.7 nM; does not inhibit any of thecytochrome P450 (CYP450) isoenzymes; targets the respiratory cytochrome bc1 complex and triggers a rapid ATP depletion in M. tuberculosis, also inhibits the growth of MDR and XDR M. tuberculosis; deonstrates potency in mouse model of tuberculosis and displays pharmacokinetic and safety profiles.Bacterial Infection Phase 1 Clinical(In Vitro):Imidazopyridine amide (IPA) compounds block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Telacebec (Q203) inhibits the growth of MDR and XDR Mycobacterium tuberculosis clinical isolates in culture broth medium in the low nanomolar range. Telacebec is active against the reference strain Mycobacterium tuberculosis H37Rv with MIC50s of 2.7 nM in culture broth medium and 0.28 nM inside macrophages.(In Vivo):Telacebec (Q203) is efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight. Telacebec displays pharmacokinetic and safety profiles compatible with once-daily dosing. Telacebec has a bioavailability of 90% and a terminal half-life of 23.4 h. The volume of distribution is moderate (5.27 l per kg body weight), and the systemic clearance is low (4.03 mL/min per kg). After 4 weeks of treatment, reductions of 90%, 99% and 99.9% in M. tuberculosis H37Rv bacterial load is observed in the groups treated with Telacebec at 0.4, 2 and 10 mg per kg body weight, respectively.

Key Properties

• CAS Number: 1334719-95-7
• MW: 557.0064296
• Purity: >98% (HPLC)
• Formula: C₂₉H₂₈ClF₃N₄O₂
• SMILES: CCC1=C(N2C=C(C=CC2=N1)Cl)C(=O)NCC3=CC=C(C=C3)N4CCC(CC4)C5=CC=C(C=C5)OC(F)(F)F
• Target: Antibacterial
• Solubility: DMSO: 10 mM

Bioactivity

• In Vivo:
  Telacebec (Q203) is efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight. Telacebec displays pharmacokinetic and safety profiles compatible with once daily dosing. Telacebec has a bioavailability of 90% and a terminal half-life of 23.4 h. The volume of distribution is moderate (5.27 l per kg body weight), and the systemic clearance is low (4.03 mL/min per kg). After 4 weeks of treatment, reductions of 90%, 99% and 99.9% in M. tuberculosis H37Rv bacterial load is observed in the groups treated with Telacebec at 0.4, 2 and 10 mg per kg body weight, respectively.
• In Vitro:
  Imidazopyridine amide (IPA) compounds block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Telacebec (Q203) inhibits the growth of MDR and XDR Mycobacterium tuberculosis clinical isolates in culture broth medium in the low nanomolar range. Telacebec is active against the reference strain Mycobacterium tuberculosis H37Rv with MIC50s of 2.7 nM in culture broth medium and 0.28 nM inside macrophages.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Q-203 | Q 203 | IAP6 | Telacebec

Quick Database Links

Gene Symbol

Antibacterial