Tizaterkib | 2097416-76-5 | ERK1/2 inhibitor

MedKoo Cat#: 206951 | Name: Tizaterkib free base

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Description:

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

Tizaterkib, also known asAZD0364 and ATG-017, is a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and kinase selectivity. In vitro, AZD0364 treatment resulted in inhibition of proximal and distal biomarkers and reduced proliferation in sensitive BRAF-mutant and KRAS-mutant cell lines. In multiple in vivo xenograft models, AZD0364 showed dose- and time-dependent modulation of ERK1/2-dependent signaling biomarkers resulting in tumor regression in sensitive BRAF- and KRAS-mutant xenografts.

Chemical Structure

Tizaterkib free base

CAS#2097416-76-5 (free base)

Theoretical Analysis

MedKoo Cat#: 206951

Name: Tizaterkib free base

CAS#: 2097416-76-5 (free base)

Chemical Formula: C24H24F2N8O2

Exact Mass: 494.1990

Molecular Weight: 494.51

Elemental Analysis: C, 58.29; H, 4.89; F, 7.68; N, 22.66; O, 6.47

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 590.00	2 Weeks
50mg	USD 1,650.00
100mg	USD 2,650.00
200mg	USD 3,950.00	2 Weeks
500mg	USD 5,450.00	2 Weeks

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Related CAS #

2097416-77-6 (ethanesulonate) 2097416-76-5 (free base) 2097416-93-6 (hemiadipate) Tizaterkib HCl

Synonym

AZD0364; AZD-0364; AZD 0364, ATG-017; ATG 017; ATG017; Tizaterkib

IUPAC/Chemical Name

(6R)-7-(3,4-Difluorobenzyl)-6-(methoxymethyl)-2-{5-methyl-2-[(1-methyl-1H-pyrazol-5-yl)amino]-4-pyrimidinyl}-6,7-dihydroimidazo[1,2-a]pyrazin-8(5H)-one

InChi Key

HVIGNZUDBVLTLU-MRXNPFEDSA-N

InChi Code

InChI=1S/C24H24F2N8O2/c1-14-9-27-24(30-20-6-7-28-32(20)2)31-21(14)19-12-33-11-16(13-36-3)34(23(35)22(33)29-19)10-15-4-5-17(25)18(26)8-15/h4-9,12,16H,10-11,13H2,1-3H3,(H,27,30,31)/t16-/m1/s1

SMILES Code

O=C1C2=NC(C3=NC(NC4=CC=NN4C)=NC=C3C)=CN2C[C@H](COC)N1CC5=CC=C(F)C(F)=C5

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

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

Instruction

View handling instruction

Biological target:

AZD-0364 is a potent and selective ERK2 inhibitor extracted from patent WO2017080979A1, compound example 18, has an IC50 of 0.6 nM.

In vitro activity:

In AZD0364-treated A375, Calu-6, and A549 cells, phosphorylation of the direct ERK1/2 substrate, p90RSK, was reduced in a dose-dependent manner at both 2 and 24 hours, which is consistent with sustained inhibition, as determined by Western blot analysis (Fig. 2). Phosphorylation of another direct ERK1/2 substrate, FRA1, was reduced to a greater extent at 24 hours posttreatment with AZD0364, compared with 2 hours posttreatment. This is coincident with a reduction in total FRA1 levels at 24 hours. Levels of FRA1 expression and stability have been shown to be regulated by ERK1/2. In AZD0364-treated A549 cells, a reduction of p90RSK and FRA1 phosphorylation was evident at both timepoints. However, this was to a lesser extent than in A375 and Calu-6 cells. Reference: Mol Cancer Ther. 2021 Feb;20(2):238-249. https://pubmed.ncbi.nlm.nih.gov/33273059/

In vivo activity:

As a monotherapy treatment, 15 (AZD0364) demonstrated 93% mouse tumor growth inhibition (TGI) at a dose of 15 mg/kg QD and tumor regression (49%) at 50 mg/kg QD. A PK/PD relationship was established, as the reduction in levels of pRSK observed were consistent with the PK (and binding kinetics) of the inhibitor. In this study, almost total knockdown of pRSK was observed at both 0.5 and 6 h time points after the final dose of the compound, with the free concentration of 15 showing a reduction at 6 h. Reference: J Med Chem. 2019 Dec 26;62(24):11004-11018. https://pubmed.ncbi.nlm.nih.gov/31710489/

	Solvent	mg/mL	mM
Solubility
	DMSO	41.7	84.27
	DMF	25.0	50.56
	DMF:PBS (pH 7.2) (1:1)	0.5	1.01
	Ethanol	54.5	110.21

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 494.51 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. Flemington V, Davies EJ, Robinson D, Sandin LC, Delpuech O, Zhang P, Hanson L, Farrington P, Bell S, Falenta K, Gibbons FD, Lindsay N, Smith A, Wilson J, Roberts K, Tonge M, Hopcroft P, Willis SE, Roudier MP, Rooney C, Coker EA, Jaaks P, Garnett MJ, Fawell SE, Jones CD, Ward RA, Simpson I, Cosulich SC, Pease JE, Smith PD. AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity in KRAS-Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib. Mol Cancer Ther. 2021 Feb;20(2):238-249. doi: 10.1158/1535-7163.MCT-20-0002. Epub 2020 Dec 3. PMID: 33273059. 2. Jasek-Gajda E, Jurkowska H, Jasińska M, Lis GJ. Targeting the MAPK/ERK and PI3K/AKT Signaling Pathways Affects NRF2, Trx and GSH Antioxidant Systems in Leukemia Cells. Antioxidants (Basel). 2020 Jul 17;9(7):633. doi: 10.3390/antiox9070633. PMID: 32709140; PMCID: PMC7402140. 3. Ward RA, Anderton MJ, Bethel P, Breed J, Cook C, Davies EJ, Dobson A, Dong Z, Fairley G, Farrington P, Feron L, Flemington V, Gibbons FD, Graham MA, Greenwood R, Hanson L, Hopcroft P, Howells R, Hudson J, James M, Jones CD, Jones CR, Li Y, Lamont S, Lewis R, Lindsay N, McCabe J, McGuire T, Rawlins P, Roberts K, Sandin L, Simpson I, Swallow S, Tang J, Tomkinson G, Tonge M, Wang Z, Zhai B. Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC). J Med Chem. 2019 Dec 26;62(24):11004-11018. doi: 10.1021/acs.jmedchem.9b01295. Epub 2019 Nov 25. PMID: 31710489.

In vitro protocol:

In vivo protocol:

1. Flemington V, Davies EJ, Robinson D, Sandin LC, Delpuech O, Zhang P, Hanson L, Farrington P, Bell S, Falenta K, Gibbons FD, Lindsay N, Smith A, Wilson J, Roberts K, Tonge M, Hopcroft P, Willis SE, Roudier MP, Rooney C, Coker EA, Jaaks P, Garnett MJ, Fawell SE, Jones CD, Ward RA, Simpson I, Cosulich SC, Pease JE, Smith PD. AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity in KRAS-Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib. Mol Cancer Ther. 2021 Feb;20(2):238-249. doi: 10.1158/1535-7163.MCT-20-0002. Epub 2020 Dec 3. PMID: 33273059. 2. Ward RA, Anderton MJ, Bethel P, Breed J, Cook C, Davies EJ, Dobson A, Dong Z, Fairley G, Farrington P, Feron L, Flemington V, Gibbons FD, Graham MA, Greenwood R, Hanson L, Hopcroft P, Howells R, Hudson J, James M, Jones CD, Jones CR, Li Y, Lamont S, Lewis R, Lindsay N, McCabe J, McGuire T, Rawlins P, Roberts K, Sandin L, Simpson I, Swallow S, Tang J, Tomkinson G, Tonge M, Wang Z, Zhai B. Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC). J Med Chem. 2019 Dec 26;62(24):11004-11018. doi: 10.1021/acs.jmedchem.9b01295. Epub 2019 Nov 25. PMID: 31710489.

1: Lutze RD, Ingersoll MA, Thotam A, Joseph A, Fernandes J, Teitz T. ERK1/2 Inhibition Alleviates Noise-Induced Hearing Loss While Tempering Down the Immune Response. bioRxiv [Preprint]. 2023 Oct 20:2023.10.18.563007. doi: 10.1101/2023.10.18.563007. Update in: Int J Mol Sci. 2024 Jun 07;25(12):6305. doi: 10.3390/ijms25126305. PMID: 37905140; PMCID: PMC10614960. 2: Lutze RD, Ingersoll MA, Thotam A, Joseph A, Fernandes J, Teitz T. ERK1/2 Inhibition via the Oral Administration of Tizaterkib Alleviates Noise-Induced Hearing Loss While Tempering down the Immune Response. Int J Mol Sci. 2024 Jun 7;25(12):6305. doi: 10.3390/ijms25126305. PMID: 38928015; PMCID: PMC11204379. 3: Taufeeq M, Choudhury A, Hussain A, Alajmi MF, Mohammad T, Shamsi A, Hassan MI. Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease. J Alzheimers Dis. 2025 Jan 15:13872877241309592. doi: 10.1177/13872877241309592. Epub ahead of print. PMID: 39814427.