PBTZ-169

PBTZ-169, also known as macozinone, is a new drug candidate that inhibits decaprenyl-phosphoribose-epimerase (DprE1), an essential enzyme involved in the cell wall biosynthesis of Corynebacterineae. The MIC values of PBTZ-169 ranged from 0.03 μg/mL to 0.0037 μg/mL. The MIC50 and MIC90 values of PBTZ-169 were 0.0075 and 0.030 μg/mL, respectively. The MIC for PBTZ-169 for N. brasiliensis HUJEG-1 was 0.0037 μg/mL. The MICs of SXT, DA-7218, and BTZ043 for this strain were 9.5/0.5, 8, and 0.125 μg/mL, respectively.

Product information

CAS Number: 1377239-83-2

Molecular Weight: 456.48

Formula: C20H23F3N4O3S

Synonym:

macozinone

PBTZ 169

PBTZ169

PBTZ-169

Chemical Name: 2-(4-(cyclohexylmethyl)piperazin-1-yl)-8-nitro-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one

Smiles: [O-][N+](=O)C1=CC(=CC2=C1SC(=NC2=O)N1CCN(CC2CCCCC2)CC1)C(F)(F)F

InChiKey: BJDZBXGJNBMCAV-UHFFFAOYSA-N

InChi: InChI=1S/C20H23F3N4O3S/c21-20(22,23)14-10-15-17(16(11-14)27(29)30)31-19(24-18(15)28)26-8-6-25(7-9-26)12-13-4-2-1-3-5-13/h10-11,13H,1-9,12H2

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 5 mg/mL(10.95 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

PBTZ-169, inhibit decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro.

In Vivo:

PBTZ-169 can be suspend in 0.25% hydroxy-propylmethyl-cellulose. The administertration for PBTZ-169 is 100 mg/kg by gavage. The MIC50 and MIC90 values were 0.0075 and 0.030 μg/mL, respectively. The MIC for PBTZ-169 for N. brasiliensis HUJEG-1 was 0.0037 μg/mL. PBTZ-169 has improved potency, safety and efficacy in zebrafish and mouse models of tuberculosis (TB).

References:

1. Makarov V et al. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Aug;59(8):4446-52.
2. González-Martínez NA et al. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022.
3. Makarov V et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones.EMBO Mol Med. 2014 Mar;6(3):372-83.

Products are for research use only. Not for human use.