TEGLARINAD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H43ClN5O8
Molecular Weight	637.144
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

COCCOCCOCCOCCOC(=O)OC[N+]1=CC=C(NC(NCCCCCCOC2=CC=C(Cl)C=C2)=NC#N)C=C1

InChI

InChIKey=RXXJCNMVVRGOJB-UHFFFAOYSA-O

InChI=1S/C30H42ClN5O8/c1-38-16-17-39-18-19-40-20-21-41-22-23-43-30(37)44-25-36-13-10-27(11-14-36)35-29(34-24-32)33-12-4-2-3-5-15-42-28-8-6-26(31)7-9-28/h6-11,13-14H,2-5,12,15-23,25H2,1H3,(H,33,34)/p+1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25145669 | https://www.ncbi.nlm.nih.gov/pubmed/20103674 | https://clinicaltrials.gov/ct2/show/NCT00724841https://www.ncbi.nlm.nih.gov/pubmed/12231525
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28097126 | https://www.ncbi.nlm.nih.gov/pubmed/15863303

CHS-828 () is a potent and selective inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the biosynthesis of NAD, which may be used to deplete cells of Nicotinamide adenine dinucleotide (NAD). Early preclinical studies revealed a high in vitro activity of CHS 828 in human tumor cell lines, a low cross-reactivity with clinically used anticancer agents, and no significant sensitivity to some of the known mechanisms of resistance. In the subsequent pharmacodynamic evaluation, CHS 828 demonstrated significant antitumor activity in several in vivo tumor models, especially pronounced in a nude mouse model of small cell lung cancer. CHS 828 exerted a high antitumor activity on eight tumor samples derived from patients with ovarian cancer and chronic lymphocytic leukemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nicotinamide phosphoribosyltransferase 8 Target ID: CHEMBL1744525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28097126	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00003979	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1723 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	420 mg 1 times / 3 weeks multiple, oral dose: 420 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3999 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	500 mg 1 times / 3 weeks multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
16063 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	420 mg 1 times / 3 weeks multiple, oral dose: 420 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
54529 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	500 mg 1 times / 3 weeks multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	420 mg 1 times / 3 weeks multiple, oral dose: 420 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15763645	500 mg 1 times / 3 weeks multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CHS-828 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
500 mg 1 times / 3 weeks multiple, oral MTD Dose: 500 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 500 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 3 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	DLT: Mucositis, Thrombocytopenia... Dose limiting toxicities: Mucositis (grade 3, 33.3%) Thrombocytopenia (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704
420 mg 1 times / 3 weeks multiple, oral RP2D Dose: 420 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 420 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	DLT: Leucopenia, Mucositis... Dose limiting toxicities: Leucopenia (grade 4, 25%) Mucositis (grade 4, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704

AEs

AE	Significance	Dose	Population
Mucositis	grade 3, 33.3% DLT	500 mg 1 times / 3 weeks multiple, oral MTD Dose: 500 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 500 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 3 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704
Thrombocytopenia	grade 4, 33.3% DLT	500 mg 1 times / 3 weeks multiple, oral MTD Dose: 500 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 500 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 3 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704
Leucopenia	grade 4, 25% DLT	420 mg 1 times / 3 weeks multiple, oral RP2D Dose: 420 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 420 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704
Mucositis	grade 4, 25% DLT	420 mg 1 times / 3 weeks multiple, oral RP2D Dose: 420 mg, 1 times / 3 weeks Route: oral Route: multiple Dose: 420 mg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704	unhealthy, 56 n = 4 Health Status: unhealthy Condition: Cancer Age Group: 56 Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/15763645 Page: p.704

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002D99	https://www.1pchem.com/search?query=1P002D99
AChemBlock	O33893	http://www.achemblock.com/catalogsearch/result/?q=O33893
AK Scientific	3544AH	https://aksci.com/item_detail.php?cat=3544AH
AKOS	AKOS028109359	http://akoscompounds.de/catalogue/AKosSamplesiSSretrieval.php?GUID=4e4caa52-3dca-4da0-b75a-caeae59e1096&IDNUMBERS=AKOS028109359
Angene	AGN-PC-0WHA02	http://www.angenechemical.com/productshow/AGN-PC-0WHA02.html
ApexBio Technology	B6031	https://www.apexbt.com/catalogsearch/result/?q=B6031
AstaTech	F15167	http://astatechinc.com/CPSResult.php?CRNO=F15167
BLD Pharm	BD328419	http://www.bldpharm.com/search/Search.html?keyword=BD328419
BOC Sciences	200484-11-3	http://www.bocsci.com/description.asp?cas=200484-11-3
Cayman Chemical	11021	http://www.caymanchem.com/app/template/Product.vm/catalog/11021
Chem Scene	CS-3852	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3852
ChemShuttle	134390	https://www.chemshuttle.com/catalogsearch/result/?q=134390
Combi-Blocks	QV-8047	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-8047
Excenen	EX-A713	http://www.excenen.com/searchresultlist.php?id=EX-A713
KeyOrganics	AS-71873	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-71873
Lab Network	LN01315547	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01315547
Matrix Scientific	153973	http://www.matrixscientific.com/153973.html
MedChem Express	HY-10079	https://www.medchemexpress.com/search.html?q=HY-10079&ft=&fa=&fp=
MolPort	MolPort-039-139-609	https://www.molport.com/shop/molecule-link/MolPort-039-139-609
MolPort	MolPort-044-560-292	https://www.molport.com/shop/molecule-link/MolPort-044-560-292
MolPort	MolPort-044-724-622	https://www.molport.com/shop/molecule-link/MolPort-044-724-622
Molnova	M13128	https://www.molnova.com/en/serch-list.html?keywords=M13128
MuseChem	I002539	https://www.musechem.com/product/I002539.html
Ryan Scientific	Micafungin_sodium	https://ryansci.com/products?q=Micafungin_sodium&list_q=&search_type=exact
Selleck Chemicals	S8117	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8117
ShangHai Biochempartner	BCP15158	http://www.biochempartner.com/search_BCP15158
TargetMol	T1998	https://www.targetmol.com/search?keyword=T1998
Toronto Research Chemicals	G765050	https://www.trc-canada.com/product-detail/?CatNum=G765050
eMolecules	44466617	https://orderbb.emolecules.com/search/#?query=44466617
eMolecules	44850652	https://orderbb.emolecules.com/search/#?query=44850652
eMolecules	45920128	https://orderbb.emolecules.com/search/#?query=45920128
eMolecules	46013678	https://orderbb.emolecules.com/search/#?query=46013678
eMolecules	93429966	https://orderbb.emolecules.com/search/#?query=93429966
mcule	MCULE-7127309331	https://mcule.com/MCULE-7127309331/

PubMed

Title	Date	PubMed
Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical pharmacology.	2001 May 15	11322922
Preclinical development of the nicotinamide phosphoribosyl transferase inhibitor prodrug GMX1777.	2009 Jun	19369827
Efficacy of combining GMX1777 with radiation therapy for human head and neck carcinoma.	2010 Feb 1	20103674
Synergy between the NAMPT inhibitor GMX1777(8) and pemetrexed in non-small cell lung cancer cells is mediated by PARP activation and enhanced NAD consumption.	2014 Nov 1	25145669
Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase.	2015 Mar	25505128

Patents

Sample Use Guides

In Vivo Use Guide

40 or 50 or 62 mg/m2 GMX1777 (TEGLARINAD) with Temozolomide

Route of Administration: Intravenous

In Vitro Use Guide

U251-MG and T98 cells (5 × 10^3) were cultured in 6-well plates and treated with temozolomide alone (25, 50, 100, 200, and 400 μM), temozolomide (25, 50, 100, 200, and 400 μM) plus FK866 (5 nM and 100 nM), and temozolomide plus CHS828 (10 nM and 200 nM). At 24 hours after drug treatment, 10 μL of CCK-8 solution was added to the culture medium for 1 h at 37°C. The absorbing at 450 nm was recorded by a microplate reader and the relative cell viability was calculated.

Name

Type

Language

TEGLARINAD

Common Name

English

Teglarinad [WHO-DD]

Common Name

English

TEGLARINAD CATION

Common Name

English

TEGLARINAD ION

Common Name

English

4-((N'-(6-(4-CHLOROPHENOXY)HEXYL))-N''-CYANOCARBAMIMIDAMIDO)-1-(3-OXO-2,4,7,10,13,16-HEXAOXAHEPTADECYL)PYRIDIN-1-IUM

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C274