Telaglenastat
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MedKoo CAT#: 206153

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

Description: 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

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Telaglenastat
CAS# 1439399-58-2 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206153
Name: Telaglenastat
CAS#: 1439399-58-2 (free base)
Chemical Formula: C26H24F3N7O3S
Exact Mass: 571.16
Molecular Weight: 571.570
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 Quantity
10mg USD 90 Ready to ship
25mg USD 200 Ready to ship
50mg USD 325 Ready to ship
100mg USD 585 Ready to ship
200mg USD 950 Ready to ship
500mg USD 2050 Ready to ship
1g USD 3450 Ready to ship
2g USD 5850 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:         

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/

Solubility Data

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

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.

Recalculate based on batch purity %
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: 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.
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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1: Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, Janes JR, Laidig GJ, Lewis ER, Li J, Mackinnon AL, Parlati F, Rodriguez ML, Shwonek PJ, Sjogren EB, Stanton TF, Wang T, Yang J, Zhao F, Bennett MK. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901. doi: 10.1158/1535-7163.MCT-13-0870. PubMed PMID: 24523301.

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7: Zimmermann SC, Wolf EF, Luu A, Thomas AG, Stathis M, Poore B, Nguyen C, Le A, Rojas C, Slusher BS, Tsukamoto T. Allosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2-yl)butane Scaffold. ACS Med Chem Lett. 2016 Mar 13;7(5):520-4. doi: 10.1021/acsmedchemlett.6b00060. PubMed PMID: 27200176; PubMed Central PMCID: PMC4868099.

8: Katt WP, Lukey MJ, Cerione RA. A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis. Future Med Chem. 2017 Jan;9(2):223-243. doi: 10.4155/fmc-2016-0190. PubMed PMID: 28111979.

9: Lorendeau D, Rinaldi G, Boon R, Spincemaille P, Metzger K, Jäger C, Christen S, Dong X, Kuenen S, Voordeckers K, Verstreken P, Cassiman D, Vermeersch P, Verfaillie C, Hiller K, Fendt SM. Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors. Metab Eng. 2016 Nov 12. pii: S1096-7176(16)30217-8. doi: 10.1016/j.ymben.2016.11.005. [Epub ahead of print] PubMed PMID: 27847310.

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