Elimusertib HCl | CAS#1876467-74-1 (free base) | ATR inhibitor

MedKoo Cat#: 206822 | Name: Elimusertib HCl

Description:

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

Elimusertib (BAY-1895344) is a potent and selective ATM inhibitor. It exhibits strong inhibitory activity with an IC₅₀ of approximately 0.74 nM against ATM in biochemical assays and demonstrates high selectivity over related kinases such as ATR and DNA-PK. In preclinical studies, elimusertib effectively sensitized tumor cells to DNA-damaging agents, particularly in ATM-deficient or p53-mutant models, leading to enhanced apoptosis and tumor regression. In vivo, it showed tumor growth inhibition and regression in xenograft models, especially when combined with radiotherapy or chemotherapeutics like topoisomerase inhibitors. These data support its potential as a targeted therapy in tumors with defective DNA damage response pathways.

Chemical Structure

Elimusertib HCl

CAS#Elimusertib HCl

Theoretical Analysis

MedKoo Cat#: 206822

Name: Elimusertib HCl

CAS#: Elimusertib HCl

Chemical Formula: C20H22ClN7O

Exact Mass: 0.0000

Molecular Weight: 411.89

Elemental Analysis: C, 58.32; H, 5.38; Cl, 8.61; N, 23.80; O, 3.88

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to Ship
2g	USD 5,250.00	Ready to Ship

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Related CAS #

1876467-74-1 (free base) Elimusertib HCl

Synonym

BAY-1895344 HCl; BAY-1895344 hydrochloride; BAY-1895344; BAY 1895344; BAY1895344; Elimusertib HCl; Elimusertib hydrochloride

IUPAC/Chemical Name

(R)-3-methyl-4-(4-(1-methyl-1H-pyrazol-5-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl)morpholine hydrochloride

InChi Key

KWQNBYGUBHMRPY-BTQNPOSSSA-N

InChi Code

InChI=1S/C20H21N7O.ClH/c1-13-12-28-10-9-27(13)18-11-15(17-5-8-23-26(17)2)14-3-6-21-20(19(14)24-18)16-4-7-22-25-16;/h3-8,11,13H,9-10,12H2,1-2H3,(H,22,25);1H/t13-;/m1./s1

SMILES Code

CN1N=CC=C1C2=CC(N3[C@H](C)COCC3)=NC4=C(C5=CC=NN5)N=CC=C24.[H]Cl

Appearance

Yellow 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

Certificate of Analysis

View CoA: current batch, Lot#A20T10K28

View CoA: current batch, Lot#B7B09C12

QC Data

View QC data: current batch, Lot#B7B09C12

View QC data: current batch, Lot#A20T10K28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Elimusertib (BAY 1895344) hydrochloride is a potent, orally available and selective ATR inhibitor with an IC50 of 7 nM.

In vitro activity:

In vitro, BAY 1895344 is shown to be a very potent and highly selective ATR inhibitor (IC50 = 7 nM), which potently inhibits proliferation of a broad spectrum of human tumor cell lines (median IC50 = 78 nM). In cellular mechanistic assays BAY 1895344 potently inhibits hydroxyurea-induced H2AX phosphorylation (IC50 = 36 nM) Reference: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 983. https://cancerres.aacrjournals.org/content/77/13_Supplement/983

In vivo activity:

BAY 1895344 is an ATR inhibitor that exhibits strong in vivo anti-tumor efficacy in monotherapy in a variety of xenograft models of different indications that are characterized by DDR deficiencies, inducing stable disease in ovarian and colorectal cancer or even complete tumor remission in mantle cell lymphoma models. Reference: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 836. https://cancerres.aacrjournals.org/content/77/13_Supplement/836

	Solvent	mg/mL	mM
Solubility
	Soluble in DMSO	54.0	131.10
	Water	50.0	121.39
	Ethanol	82.0	199.08

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 411.89 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. Lücking U, Wortmann L, Wengner AM, Lefranc J, Lienau P, Briem H, Siemeister G, Bömer U, Denner K, Schäfer M, Koppitz M, Eis K, Bartels F, Bader B, Bone W, Moosmayer D, Holton SJ, Eberspächer U, Grudzinska-Goebel J, Schatz C, Deeg G, Mumberg D, von Nussbaum F. Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models. J Med Chem. 2020 Jul 9;63(13):7293-7325. doi: 10.1021/acs.jmedchem.0c00369. Epub 2020 Jun 28. PMID: 32502336. 2. Antje Margret Wengner, Gerhard Siemeister, Ulrich Luecking, Julien Lefranc, Philip Lienau, Gesa Deeg, Eleni Lagkadinou, Li Liu, Sven Golfier, Christoph Schatz, Arne Scholz, Franz von Nussbaum, Michael Brands, Dominik Mumberg, Karl Ziegelbauer. ATR inhibitor BAY 1895344 shows potent anti-tumor efficacy in monotherapy and strong combination potential with the targeted alpha therapy Radium-223 dichloride in preclinical tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 836. doi:10.1158/1538-7445.AM2017-836

In vitro protocol:

In vivo protocol:

1. Antje Margret Wengner, Gerhard Siemeister, Ulrich Luecking, Julien Lefranc, Philip Lienau, Gesa Deeg, Eleni Lagkadinou, Li Liu, Sven Golfier, Christoph Schatz, Arne Scholz, Franz von Nussbaum, Michael Brands, Dominik Mumberg, Karl Ziegelbauer. ATR inhibitor BAY 1895344 shows potent anti-tumor efficacy in monotherapy and strong combination potential with the targeted alpha therapy Radium-223 dichloride in preclinical tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 836. doi:10.1158/1538-7445.AM2017-836

1: Pal S, Kaplan JP, Nguyen H, Stopka SA, Savani MR, Regan MS, Nguyen QD, Jones KL, Moreau LA, Peng J, Dipiazza MG, Perciaccante AJ, Zhu X, Hunsel BR, Liu KX, Alexandrescu S, Drissi R, Filbin MG, McBrayer SK, Agar NYR, Chowdhury D, Haas- Kogan DA. A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma. Cancer Cell. 2022 Sep 12;40(9):957-972.e10. doi: 10.1016/j.ccell.2022.07.012. Epub 2022 Aug 18. PMID: 35985342; PMCID: PMC9575661. 2: Harold J, Bellone S, Manavella DD, Mutlu L, McNamara B, Hartwich TMP, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa MS, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz PE, Santin AD. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecol Oncol. 2023 Jan;168:157-165. doi: 10.1016/j.ygyno.2022.11.014. Epub 2022 Nov 25. Erratum in: Gynecol Oncol. 2023 Mar;170:334. PMID: 36442427; PMCID: PMC9797429. 3: Harold J, Bellone S, Manavell DD, Mutlu L, McNamara B, Hartwich TMP, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa MSZ, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz PE, Santin AD. Corrigendum to "Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma". Gynecol Oncol. 2023 Mar;170:334. doi: 10.1016/j.ygyno.2023.01.029. Erratum for: Gynecol Oncol. 2023 Jan;168:157-165. PMID: 36906375; PMCID: PMC10266020. 4: Kiesel BF, Parise RA, Krishnamurthy A, Gore S, Beumer JH. Quantitation of the ataxia-telangiectasia-mutated and Rad3-related inhibitor elimusertib (BAY-1895344) in human plasma using LC-MS/MS. Biomed Chromatogr. 2022 Nov;36(11):e5455. doi: 10.1002/bmc.5455. Epub 2022 Aug 8. PMID: 35876841; PMCID: PMC9731518. 5: Kiesel BF, Deppas JJ, Guo J, Parise RA, Clump DA, Bakkenist CJ, Beumer JH. Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice. Cancer Chemother Pharmacol. 2022 Jun;89(6):795-807. doi: 10.1007/s00280-022-04436-0. Epub 2022 May 4. PMID: 35507041; PMCID: PMC10082586. 6: Haciefendi A, Guney Eskiler G. The suppression of ATR/Chk1 pathway by Elimusertib ATR inhibitor in triple negative breast cancer cells. Am J Transl Res. 2023 Jul 15;15(7):4902-4911. PMID: 37560219; PMCID: PMC10408524. 7: Manavella DD, McNamara B, Harold J, Bellone S, Hartwich TMP, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa MS, Altwerger G, Ratner E, Huang GS, Clark M, Andikyan V, Azodi M, Schwartz PE, Dottino PR, Choi J, Alexandrov LB, Buza N, Hui P, Santin AD. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecol Oncol. 2023 Feb;169:98-105. doi: 10.1016/j.ygyno.2022.12.003. Epub 2022 Dec 14. PMID: 36525930; PMCID: PMC9925406. 8: Sundararajan V, Tan TZ, Lim D, Peng Y, Wengner AM, Ngoi NYL, Jeyasekharan AD, Tan DSP. Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition. J Pathol. 2023 Feb;259(2):194-204. doi: 10.1002/path.6032. Epub 2022 Dec 8. PMID: 36373784; PMCID: PMC10107453. 9: Martin B, Garman T, Laramee M, Wang A, Zhang X, Beck E, Wilson K, Klumpp- Thomas C, McKnight C, Xu X, Hagen N, Holland D, Dahmane N, Thomas CJ, Souweidane M. Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma. J Control Release. 2023 May;357:580-590. doi: 10.1016/j.jconrel.2023.04.016. Epub 2023 Apr 23. PMID: 37054779; PMCID: PMC10174050. 10: Dexheimer TS, Coussens NP, Silvers T, Wright J, Morris J, Doroshow JH, Teicher BA. Multicellular Complex Tumor Spheroid Response to DNA Repair Inhibitors in Combination with DNA-damaging Drugs. Cancer Res Commun. 2023 Aug 25;3(8):1648-1661. doi: 10.1158/2767-9764.CRC-23-0193. PMID: 37637936; PMCID: PMC10452929.