PBTZ169 | CAS#1377239-83-2 | DprE1 inhibitor

PBTZ169
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 522563

CAS#: 1377239-83-2

Description: PBTZ169, 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 PBTZ169 ranged from 0.03 μg/mL to 0.0037 μg/mL. The MIC50 and MIC90 values of PBTZ169 were 0.0075 and 0.030 μg/mL, respectively. The MIC for PBTZ169 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.

Chemical Structure

PBTZ169

CAS# 1377239-83-2

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522563
Name: PBTZ169
CAS#: 1377239-83-2
Chemical Formula: C20H23F3N4O3S
Exact Mass: 456.14
Molecular Weight: 456.480
Elemental Analysis: C, 52.62; H, 5.08; F, 12.49; N, 12.27; O, 10.51; S, 7.02

Price and Availability

Size	Price	Availability
10mg	USD 150	Ready to ship
25mg	USD 250	Ready to ship
50mg	USD 450	Ready to ship
100mg	USD 750	Ready to ship
200mg	USD 1350	Ready to ship
500mg	USD 2650	Ready to ship
1g	USD 3850	Ready to ship
2g	USD 6450	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: PBTZ169; PBTZ-169; PBTZ 169; macozinone;

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

InChi Key: BJDZBXGJNBMCAV-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: O=C1N=C(N2CCN(CC3CCCCC3)CC2)SC4=C([N+]([O-])=O)C=C(C(F)(F)F)C=C14

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Note: 1. As of 1/6/2016, Sci-finder listed BTZ043 and PBTZ169 the same identity. It's CAS# was listed as 1161233-85-7 2. Our structure listed for BTZ043 was based on below publication, which has CAS# 1377239-83-2. Design, Syntheses, and Anti-TB Activity of 1,3-Benzothiazinone Azide and Click Chemistry Products Inspired by BTZ043 Rohit Tiwari, Patricia A. Miller, Laurent R. Chiarelli, Giorgia Mori, Michal Šarkan, Ivana Centárová, Sanghyun Cho, Katarína Mikušová, Scott G. Franzblau, llen G. Oliver, and Marvin J. Miller Publication Date (Web): January 4, 2016 (Letter) DOI: 10.1021/acsmedchemlett.5b00424

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#A7K10C31

QC Data:

View QC data: current batch, Lot#A7K10C31

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	Macozinone (PBTZ169) is a bactericidal benzothiazinone and a potent DprE1 (decaprenylphosphoryl-β-d-ribose 2’-oxidase) inhibitor.
In vitro activity:	The most important finding of this study is that PBTZ169 exhibits excellent in vitro activity against MDR-TB and XDR-TB. All M. tuberculosis isolates tested have an MIC of less than 0.25 mg/liter, the MIC90 of which is significantly lower than those of moxifloxacin (16.0 mg/liter), linezolid (1.0 mg/liter), and clofazimine (1.0 mg/liter), while similar to those of bedaquiline (0.031 mg/liter) and delamanid (0.031 mg/liter) (18). Despite the limited data regarding plasma concentration of PBTZ169, the extremely low MICs against MDR-TB and XDR-TB highlight the promising efficacy of this anti-TB agent as part of a treatment for pulmonary MDR-TB and XDR-TB. Reference: Antimicrob Agents Chemother. 2018 Nov; 62(11): e01314-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201125/
In vivo activity:	Thus, the in vivo activity of these two drugs was evaluated in a mouse TB model (Fig. 2). At the concentrations tested, all drugs alone and in combinations significantly decreased the bacterial burden by more than 2.18 log10 in the lungs and 1.71 log10 in the spleens compared to the level on day 0, thus indicating a bactericidal effect. Although no combinatory effect was observed in these organs when MCZ (macozinone), DMD (delamanid), and STZ (sutezolid) were combined in two-drug combinations, the triple combination MCZ-DMD-STZ was more active in the lungs of M. tuberculosis-infected mice than DMD-STZ (the most active of the two-drug combinations) with bactericidal activity of more than 0.69 log10 CFU (P = 0.014). Reference: Antimicrob Agents Chemother. 2018 Nov; 62(11): e00840-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201121/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	4.6	10.10

Preparing Stock Solutions

The following data is based on the product molecular weight 456.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Spaggiari D, Desfontaine V, Cruchon S, Guinchard S, Vocat A, Blattes E, Pitteloud J, Ciullini L, Bardinet C, Ivanyuk A, Makarov V, Ryabova O, Buclin T, Cole ST, Decosterd LA. Development and validation of a multiplex UHPLC-MS/MS method for the determination of the investigational antibiotic against multi-resistant tuberculosis macozinone (PBTZ169) and five active metabolites in human plasma. PLoS One. 2019 May 31;14(5):e0217139. doi: 10.1371/journal.pone.0217139. PMID: 31150423; PMCID: PMC6544242. 2. Shi J, Lu J, Wen S, Zong Z, Huo F, Luo J, Liang Q, Li Y, Huang H, Pang Y. In Vitro Activity of PBTZ169 against Multiple Mycobacterium Species. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01314-18. doi: 10.1128/AAC.01314-18. PMID: 30150479; PMCID: PMC6201125. 3. Lupien A, Vocat A, Foo CS, Blattes E, Gillon JY, Makarov V, Cole ST. Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169). Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00840-18. doi: 10.1128/AAC.00840-18. PMID: 30126954; PMCID: PMC6201121. 4. González-Martínez NA, Lozano-Garza HG, Castro-Garza J, De Osio-Cortez A, Vargas-Villarreal J, Cavazos-Rocha N, Ocampo-Candiani J, Makarov V, Cole ST, Vera-Cabrera L. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022. doi: 10.1371/journal.pntd.0004022. PMID: 26474057; PMCID: PMC4608729.
In vitro protocol:	1. Spaggiari D, Desfontaine V, Cruchon S, Guinchard S, Vocat A, Blattes E, Pitteloud J, Ciullini L, Bardinet C, Ivanyuk A, Makarov V, Ryabova O, Buclin T, Cole ST, Decosterd LA. Development and validation of a multiplex UHPLC-MS/MS method for the determination of the investigational antibiotic against multi-resistant tuberculosis macozinone (PBTZ169) and five active metabolites in human plasma. PLoS One. 2019 May 31;14(5):e0217139. doi: 10.1371/journal.pone.0217139. PMID: 31150423; PMCID: PMC6544242. 2. Shi J, Lu J, Wen S, Zong Z, Huo F, Luo J, Liang Q, Li Y, Huang H, Pang Y. In Vitro Activity of PBTZ169 against Multiple Mycobacterium Species. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01314-18. doi: 10.1128/AAC.01314-18. PMID: 30150479; PMCID: PMC6201125.
In vivo protocol:	1. Lupien A, Vocat A, Foo CS, Blattes E, Gillon JY, Makarov V, Cole ST. Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169). Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00840-18. doi: 10.1128/AAC.00840-18. PMID: 30126954; PMCID: PMC6201121. 2. González-Martínez NA, Lozano-Garza HG, Castro-Garza J, De Osio-Cortez A, Vargas-Villarreal J, Cavazos-Rocha N, Ocampo-Candiani J, Makarov V, Cole ST, Vera-Cabrera L. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022. doi: 10.1371/journal.pntd.0004022. PMID: 26474057; PMCID: PMC4608729.

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1: González-Martínez NA, Lozano-Garza HG, Castro-Garza J, De Osio-Cortez A, Vargas-Villarreal J, Cavazos-Rocha N, Ocampo-Candiani J, Makarov V, Cole ST, Vera-Cabrera L. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022. doi: 10.1371/journal.pntd.0004022. eCollection 2015 Oct. PubMed PMID: 26474057; PubMed Central PMCID: PMC4608729.

2: Lechartier B, Cole ST. Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Aug;59(8):4457-63. doi: 10.1128/AAC.00395-15. Epub 2015 May 18. PubMed PMID: 25987624; PubMed Central PMCID: PMC4505229.

3: Makarov V, Neres J, Hartkoorn RC, Ryabova OB, Kazakova E, Šarkan M, Huszár S, Piton J, Kolly GS, Vocat A, Conroy TM, Mikušová K, Cole ST. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Aug;59(8):4446-52. doi: 10.1128/AAC.00778-15. Epub 2015 May 18. PubMed PMID: 25987616; PubMed Central PMCID: PMC4505264.

4: Peng CT, Gao C, Wang NY, You XY, Zhang LD, Zhu YX, Xv Y, Zuo WQ, Ran K, Deng HX, Lei Q, Xiao KJ, Yu LT. Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1373-6. doi: 10.1016/j.bmcl.2015.02.061. Epub 2015 Mar 2. PubMed PMID: 25754492.

5: Makarov V, Lechartier B, Zhang M, Neres J, van der Sar AM, Raadsen SA, Hartkoorn RC, Ryabova OB, Vocat A, Decosterd LA, Widmer N, Buclin T, Bitter W, Andries K, Pojer F, Dyson PJ, Cole ST. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med. 2014 Mar;6(3):372-83. doi: 10.1002/emmm.201303575. Epub 2014 Feb 5. PubMed PMID: 24500695; PubMed Central PMCID: PMC3958311.

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