TELACEBEC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H28ClF3N4O2
Molecular Weight	557.006
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=C(N2C=C(Cl)C=CC2=N1)C(=O)NCC3=CC=C(C=C3)N4CCC(CC4)C5=CC=C(OC(F)(F)F)C=C5

InChI

InChIKey=OJICYBSWSZGRFB-UHFFFAOYSA-N

InChI=1S/C29H28ClF3N4O2/c1-2-25-27(37-18-22(30)7-12-26(37)35-25)28(38)34-17-19-3-8-23(9-4-19)36-15-13-21(14-16-36)20-5-10-24(11-6-20)39-29(31,32)33/h3-12,18,21H,2,13-17H2,1H3,(H,34,38)

HIDE SMILES / InChI

Molecular Formula	C29H28ClF3N4O2
Molecular Weight	557.006
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23913123 | https://www.ncbi.nlm.nih.gov/pubmed/27151308

Q203 (6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide) is an an imidazopyridine antitubercular compound. Q203 targets the cytochrome b subunit (QcrB) of the cytochrome bc1 complex. This complex is an essential component of the respiratory electron transport chain of ATP synthesis. Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ubiquinol-cytochrome c reductase cytochrome b subunit 2 Target ID: P9WP37 Gene ID: 887400.0 Gene Symbol: qcrB Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23913123 \| https://www.ncbi.nlm.nih.gov/pubmed/27151308	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23913123 https://www.ncbi.nlm.nih.gov/pubmed/27151308	Curative		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
0.92 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32205344	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Q-203 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1490 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28527405	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Q-203 plasma	Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
23.91 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32205344	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Q-203 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
44100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28527405	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Q-203 plasma	Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28527405	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		Q-203 plasma	Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32212527 Page: p.2	unhealthy, ADULT Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32212527 Page: p.2	Sources: https://pubmed.ncbi.nlm.nih.gov/32212527 Page: p.2

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2C19 1478	P-gp 1537 HLM 31

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >10 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >10 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no [IC50 >25 uM]
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	no
HLM 31	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/	unlikely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23913123/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009YGV	https://www.1pchem.com/search?query=1P009YGV
AstaTech	43183	http://astatechinc.com/CPSResult.php?CRNO=43183
BLD Pharm	BD00813051	http://www.bldpharm.com/search/Search.html?keyword=BD00813051
Chem Scene	CS-6412	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6412
ChemShuttle	186315	https://www.chemshuttle.com/catalogsearch/result/?q=186315
Enamine	EN300-218150	https://www.enaminestore.com/catalog/EN300-218150
Excenen	EX-A2561	http://www.excenen.com/searchresultlist.php?id=EX-A2561
KeyOrganics	AS-35270	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35270
MedChem Express	HY-101040	https://www.medchemexpress.com/search.html?q=HY-101040&ft=&fa=&fp=
MolPort	MolPort-038-949-455	https://www.molport.com/shop/molecule-link/MolPort-038-949-455
Molnova	M11336	https://www.molnova.com/en/serch-list.html?keywords=M11336
MuseChem	I008935	https://www.musechem.com/product/I008935.html
TargetMol	T5400	https://www.targetmol.com/search?keyword=T5400
eMolecules	54860188	https://orderbb.emolecules.com/search/#?query=54860188
eNovation Chemicals	D621824	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D621824&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7294912765	https://mcule.com/MCULE-7294912765/

PubMed

Title	Date	PubMed
Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis.	2013 Sep	23913123
Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug-resistant anti-tuberculosis agent.	2014 Jun 26	24870926
New agents for the treatment of drug-resistant Mycobacterium tuberculosis.	2016 Jul 1	27151308
Efflux Attenuates the Antibacterial Activity of Q203 in Mycobacterium tuberculosis.	2017 Jul	28416541

Patents

Sample Use Guides

In Vivo Use Guide

The Phase I clinical trial (clinicaltrials.gov identifier: NCT02530710) enrolling healthy patients is a dose-escalation study starting at 100 mg dosing that will be adjusted based on PK analysis.

Route of Administration: Oral

In Vitro Use Guide

Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:30:01 UTC 2023` Edited by `admin` on `Sat Dec 16 08:30:01 UTC 2023`
Record UNII	55G92WGH3X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TELACEBEC

Official Name

English

TELACEBEC [USAN]

Common Name

English

telacebec [INN]

Common Name

English

6-CHLORO-2-ETHYL-N-((4-(4-(4-(TRIFLUOROMETHOXY)PHENYL)-1-PIPERDINYL)PHENYL)METHYL)-IMIDAZO(1,2-A)PYRIDINE-3-CARBOXAMIDE

Systematic Name

English

Q203

Code

English

Telacebec [WHO-DD]

Common Name

English

Q-203

Code

English

IMIDAZO(1,2-A)PYRIDINE-3-CARBOXAMIDE, 6-CHLORO-2-ETHYL-N-((4-(4-(4-(TRIFLUOROMETHOXY)PHENYL)-1-PIPERIDINYL)PHENYL)METHYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C280