Telaglenastat | CB-839 | CAS#1439399-58-2 | glutaminase inhibitor

MedKoo Cat#: 206153 | Name: Telaglenastat

Description:

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

Telaglenastat, also known as CB-839, an is orally bioavailable inhibitor of glutaminase, with potential antineoplastic activity. Telaglenastat selectively and irreversibly inhibits glutaminase. By blocking glutamine utilization, proliferation in rapidly growing cells is impaired. Glutamine-dependent tumors rely on the conversion of exogenous glutamine into glutamate and glutamate metabolites to both provide energy and generate building blocks for the production of macromolecules, which are needed for cellular growth and survival.

Chemical Structure

Telaglenastat

CAS#1439399-58-2 (free base)

Theoretical Analysis

MedKoo Cat#: 206153

Name: Telaglenastat

CAS#: 1439399-58-2 (free base)

Chemical Formula: C26H24F3N7O3S

Exact Mass: 571.1613

Molecular Weight: 571.57

Elemental Analysis: C, 54.63; H, 4.23; F, 9.97; N, 17.15; O, 8.40; S, 5.61

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 200.00	Ready to ship
50mg	USD 325.00	Ready to ship
100mg	USD 585.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 2,050.00	Ready to ship
1g	USD 3,450.00	Ready to ship
2g	USD 5,850.00	2 Weeks

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Related CAS #

1439399-58-2 (free base) 1874231-60-3 (HCl)

Synonym

CB839; CB-839; CB 839, Telaglenastat.

IUPAC/Chemical Name

2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide

InChi Key

PRAAPINBUWJLGA-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H24F3N7O3S/c27-26(28,29)39-20-9-5-6-17(14-20)15-22(37)31-21-12-11-18(33-34-21)7-1-2-10-24-35-36-25(40-24)32-23(38)16-19-8-3-4-13-30-19/h3-6,8-9,11-14H,1-2,7,10,15-16H2,(H,31,34,37)(H,32,36,38)

SMILES Code

O=C(NC1=CC=C(CCCCC2=NN=C(NC(CC3=NC=CC=C3)=O)S2)N=N1)CC4=CC(OC(F)(F)F)=CC=C4

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC51009

QC Data

View QC data: current batch, Lot#BBC51009

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Telaglenastat (CB-839) is a glutaminase 1 (GLS1) inhibitor with an IC50 of 24 nM.

In vitro activity:

The efficacy of ionizing radiation (IR) for head and neck cancer squamous cell carcinoma (HNSCC) is limited by poorly understood mechanisms of adaptive radioresistance. Elevated glutaminase gene expression is linked to significantly reduced survival (p < 0.03). Whether telaglenastat, a glutaminae inhibitor, enhances the cellular response to IR in HNSCC models was investigated. Telaglenastat significantly reduced the Oxygen Consumption Rate/Extracellular Acidification Rate ratio in CAL-27 and HN5 cells in the presence of glucose and glutamine (p ≤ 0.0001). Telaglenastat also increased oxidative stress and DNA damage in irradiated CAL-27 cells. These data suggest that combination treatment with IR and telaglenastat leads to an enhanced anti-tumor response. Reference: Cancer Lett. 2021 Apr 1;502:180-188. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897292/

In vivo activity:

CB-839 efficacy was evaluated in an autochthonous STS model using KP and KPH2 mice. After tumours were initiated with AdCre injection, bi-weekly computed tomography (CT) scans of mouse lower limbs were performed to track tumour growth. As minor limb size differences emerged, animals were treated with vehicle or CB-839 for ~2–3 weeks. CB-839 treatment did not impact mouse weights (Supplementary Fig. 7A, B). However, in marked contrast to previous in vivo studies, CB-839 administration to KP and KPH2 animals substantially inhibited tumour growth, as calculated from the difference in the muscular compartment of tumour-bearing limbs (red) relative to control limbs (green) (Fig. 7a–f). CT-quantified tumour size strongly correlated with tumour mass, and CB-839 treatment significantly reduced final tumour weight in KP and KPH2 animals compared to vehicle-treated mice (Fig. 7g), with stronger effects observed in KPH2 mice, much like allograft studies (Fig. 6a, b). Histological analyses showed CB-839 increased cell cycle arrest, decreased cell proliferation, and increased cell death in established tumours (Fig. 7h; Supplementary Fig. 7C). Reference: Nat Commun. 2020 Jan 24;11(1):498. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981153/

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	17.50
	DMSO	50.0	87.48
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.58

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 571.57 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. Wicker CA, Hunt BG, Krishnan S, Aziz K, Parajuli S, Palackdharry S, Elaban WR, Wise-Draper TM, Mills GB, Waltz SE, Takiar V. Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models. Cancer Lett. 2021 Apr 1;502:180-188. doi: 10.1016/j.canlet.2020.12.038. Epub 2021 Jan 12. PMID: 33450358; PMCID: PMC7897292. 2. Lee P, Malik D, Perkons N, Huangyang P, Khare S, Rhoades S, Gong YY, Burrows M, Finan JM, Nissim I, Gade TPF, Weljie AM, Simon MC. Targeting glutamine metabolism slows soft tissue sarcoma growth. Nat Commun. 2020 Jan 24;11(1):498. doi: 10.1038/s41467-020-14374-1. PMID: 31980651; PMCID: PMC6981153.

In vitro protocol:

In vivo protocol:

1. Lee P, Malik D, Perkons N, Huangyang P, Khare S, Rhoades S, Gong YY, Burrows M, Finan JM, Nissim I, Gade TPF, Weljie AM, Simon MC. Targeting glutamine metabolism slows soft tissue sarcoma growth. Nat Commun. 2020 Jan 24;11(1):498. doi: 10.1038/s41467-020-14374-1. PMID: 31980651; PMCID: PMC6981153.

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