Eltanexor Z-isomer | CAS#1642300-78-4 | KPT-8602 isomer | XPO1 inhibitor

MedKoo Cat#: 462461 | Name: Eltanexor Z-isomer

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Description:

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

Eltanexor Z-isomer is the less active isomer of KPT-8602.

Chemical Structure

Eltanexor Z-isomer

CAS#1642300-78-4

Theoretical Analysis

MedKoo Cat#: 462461

Name: Eltanexor Z-isomer

CAS#: 1642300-78-4

Chemical Formula: C17H10F6N6O

Exact Mass: 428.0820

Molecular Weight: 428.30

Elemental Analysis: C, 47.67; H, 2.35; F, 26.61; N, 19.62; O, 3.74

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 650.00	2 Weeks
10mg	USD 1,050.00	2 Weeks

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Synonym

Eltanexor Z-isomer; KPT-8602 Z-isomer; KPT 8602 Z-isomer; KPT8602 Z-isomer

IUPAC/Chemical Name

(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-2-(pyrimidin-5-yl)acrylamide

InChi Key

JFBAVWVBLRIWHM-MLPAPPSSSA-N

InChi Code

InChI=1S/C17H10F6N6O/c18-16(19,20)11-1-9(2-12(3-11)17(21,22)23)15-27-8-29(28-15)6-13(14(24)30)10-4-25-7-26-5-10/h1-8H,(H2,24,30)/b13-6-

SMILES Code

O=C(N)/C(C1=CN=CN=C1)=C\N2N=C(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)N=C2

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

>3 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:

Eltanexor Z-isomer (KPT-8602 Z-isomer) is the less active isomer of KPT-8602. KPT-8602 is a potent CRM1 inhibitor.

In vitro activity:

Eltanexor inhibits the production of HCMV progeny virions in a dose-dependent manner, and the half-maximal inhibitory concentration (IC50 or EC50) is determined at 0.03762 μM (Figure 1D). Selectivity of Index (SI) of Eltanxor is calculated as 374. Western-blotting assays also show Eltanexor treatment inhibits the expression of IE2/86 (encoded by UL122), early protein pp52 (UL44), and late proteins pp71 and pp65 (UL82 and UL83) in a dose-dependent manner (Figure 1E). Taken together, these results demonstrate that Eltanexor inhibits HCMV replication in a dose-dependent manner. Reference: Front Microbiol. 2021; 12: 675112. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126617/

In vivo activity:

After 2 weeks of treatment, this study observed a significant reduction in leukemic burden in the mice treated with the combination of KPT-8602 + dexamethasone (Fig. 2A and B). Reference: Clin Cancer Res. 2020 Nov 1;26(21):5747-5758. https://pubmed.ncbi.nlm.nih.gov/32826328/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	116.74

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 428.30 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. Liao Y, Ke X, Deng T, Qin Q. The Second-Generation XPO1 Inhibitor Eltanexor Inhibits Human Cytomegalovirus (HCMV) Replication and Promotes Type I Interferon Response. Front Microbiol. 2021 May 3;12:675112. doi: 10.3389/fmicb.2021.675112. PMID: 34012430; PMCID: PMC8126617. 2. Uddin MH, Li Y, Khan HY, Muqbil I, Aboukameel A, Sexton RE, Reddy S, Landesman Y, Kashyap T, Azmi AS, Heath EI. Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells. Int J Mol Sci. 2021 Jun 22;22(13):6676. doi: 10.3390/ijms22136676. PMID: 34206543; PMCID: PMC8268282. 3. Verbeke D, Demeyer S, Prieto C, de Bock CE, De Bie J, Gielen O, Jacobs K, Mentens N, Verhoeven BM, Uyttebroeck A, Boeckx N, De Keersmaecker K, Maertens J, Segers H, Cools J. The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia. Clin Cancer Res. 2020 Nov 1;26(21):5747-5758. doi: 10.1158/1078-0432.CCR-20-1315. Epub 2020 Aug 21. PMID: 32826328.

In vitro protocol:

In vivo protocol:

1. Verbeke D, Demeyer S, Prieto C, de Bock CE, De Bie J, Gielen O, Jacobs K, Mentens N, Verhoeven BM, Uyttebroeck A, Boeckx N, De Keersmaecker K, Maertens J, Segers H, Cools J. The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia. Clin Cancer Res. 2020 Nov 1;26(21):5747-5758. doi: 10.1158/1078-0432.CCR-20-1315. Epub 2020 Aug 21. PMID: 32826328.

1: Bazinet A, Bravo GM. New Approaches to Myelodysplastic Syndrome Treatment. Curr Treat Options Oncol. 2022 May;23(5):668-687. doi: 10.1007/s11864-022-00965-1. Epub 2022 Mar 23. PMID: 35320468. 2: Otte K, Zhao K, Braun M, Neubauer A, Raifer H, Helmprobst F, Barrera FO, Nimsky C, Bartsch JW, Rusch T. Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide. Biomedicines. 2022 Aug 31;10(9):2145. doi: 10.3390/biomedicines10092145. PMID: 36140245; PMCID: PMC9496210. 3: Lee S, Mohan S, Knupp J, Chamoun K, de Jonge A, Yang F, Baloglu E, Shah J, Kauffman MG, Shacham S, Bhatnagar B. Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. J Hematol Oncol. 2022 Aug 3;15(1):103. doi: 10.1186/s13045-022-01319-y. PMID: 35922861; PMCID: PMC9351096. 4: Pianigiani G, Gagliardi A, Mezzasoma F, Rocchio F, Tini V, Bigerna B, Sportoletti P, Caruso S, Marra A, Peruzzi S, Petito E, Spinozzi G, Shacham S, Landesman Y, Quintarelli C, Gresele P, Locatelli F, Martelli MP, Falini B, Brunetti L. Prolonged XPO1 inhibition is essential for optimal antileukemic activity in NPM1-mutated AML. Blood Adv. 2022 Nov 22;6(22):5938-5949. doi: 10.1182/bloodadvances.2022007563. PMID: 36037515; PMCID: PMC9701620. 5: Liao Y, Ke X, Deng T, Qin Q. The Second-Generation XPO1 Inhibitor Eltanexor Inhibits Human Cytomegalovirus (HCMV) Replication and Promotes Type I Interferon Response. Front Microbiol. 2021 May 3;12:675112. doi: 10.3389/fmicb.2021.675112. PMID: 34012430; PMCID: PMC8126617. 6: Camilli S, Lockey R, Kolliputi N. Nuclear Export Inhibitors Selinexor (KPT-330) and Eltanexor (KPT-8602) Provide a Novel Therapy to Reduce Tumor Growth by Induction of PANoptosis. Cell Biochem Biophys. 2023 Sep;81(3):421-426. doi: 10.1007/s12013-023-01135-2. Epub 2023 May 1. PMID: 37126200. 7: Cornell RF, Baz R, Richter JR, Rossi A, Vogl DT, Chen C, Shustik C, Alvarez MJ, Shen Y, Unger TJ, Ben-Shahar O, Wang H, Baloglu E, Senapedis W, Ma X, Landesman Y, Bai X, Bader J, Xu H, Marshall T, Chang H, Walker CJ, Shah J, Shacham S, Kauffman MG, Hofmeister CC. A phase 1 clinical trial of oral eltanexor in patients with relapsed or refractory multiple myeloma. Am J Hematol. 2022 Feb 1;97(2):E54-E58. doi: 10.1002/ajh.26420. Epub 2021 Nov 30. PMID: 34817872. 8: Chen J, Song D, Xu Y, Wu L, Tang L, Su Y, Xie X, Zhao J, Xu J, Liu Q. Anti- Osteoclast Effect of Exportin-1 Inhibitor Eltanexor on Osteoporosis Depends on Nuclear Accumulation of IκBα-NF-κB p65 Complex. Front Pharmacol. 2022 Aug 30;13:896108. doi: 10.3389/fphar.2022.896108. PMID: 36110547; PMCID: PMC9468713. 9: Yu H, Wu S, Liu S, Li X, Gai Y, Lin H, Wang Y, Edwards H, Ge Y, Wang G. Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia. J Cell Mol Med. 2022 May;26(9):2646-2657. doi: 10.1111/jcmm.17274. Epub 2022 Mar 31. PMID: 35355406; PMCID: PMC9077288. 10: Richard S, Jagannath S. Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. BioDrugs. 2022 Jan;36(1):13-25. doi: 10.1007/s40259-021-00514-6. Epub 2022 Feb 3. PMID: 35113384. 11: Wang S, Sellner L, Wang L, Sauer T, Neuber B, Gong W, Stock S, Ni M, Yao H, Kleist C, Schmitt A, Müller-Tidow C, Schmitt M, Schubert ML. Combining selective inhibitors of nuclear export (SINEs) with chimeric antigen receptor (CAR) T cells for CD19‑positive malignancies. Oncol Rep. 2021 Aug;46(2):170. doi: 10.3892/or.2021.8121. Epub 2021 Jun 24. PMID: 34165175; PMCID: PMC8250584. 12: Theodoropoulos N, Lancman G, Chari A. Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. Target Oncol. 2020 Dec;15(6):697-708. doi: 10.1007/s11523-020-00758-2. PMID: 33074469; PMCID: PMC7570401. 13: Martin JG, Ward JA, Feyertag F, Zhang L, Couvertier S, Guckian K, Huber KVM, Johnson DS. Chemoproteomic Profiling of Covalent XPO1 Inhibitors to Assess Target Engagement and Selectivity. Chembiochem. 2021 Jun 15;22(12):2116-2123. doi: 10.1002/cbic.202100038. Epub 2021 Apr 22. PMID: 33887086. 14: Cai J, Wang L. [Looking back 2018--focused on colorectal cancer]. Zhonghua Wei Chang Wai Ke Za Zhi. 2019 Jan 25;22(1):9-16. Chinese. PMID: 30703787. 15: Jing CB, Prutsch N, He S, Zimmerman MW, Landesman Y, Look AT. Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors. Br J Haematol. 2023 May;201(3):489-501. doi: 10.1111/bjh.18667. Epub 2023 Feb 6. PMID: 36746437; PMCID: PMC10121884. 16: Turner JG, Cui Y, Bauer AA, Dawson JL, Gomez JA, Kim J, Cubitt CL, Nishihori T, Dalton WS, Sullivan DM. Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma. Cancer Res. 2020 Dec 1;80(23):5344-5354. doi: 10.1158/0008-5472.CAN-19-0677. Epub 2020 Oct 6. PMID: 33023948; PMCID: PMC7718436. 17: Govaerts I, Prieto C, Vandersmissen C, Gielen O, Jacobs K, Provost S, Nittner D, Maertens J, Boeckx N, De Keersmaecker K, Segers H, Cools J. PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia. J Hematol Oncol. 2021 Jun 24;14(1):97. doi: 10.1186/s13045-021-01114-1. PMID: 34167562; PMCID: PMC8223323. 18: Aboukameel A, Muqbil I, Baloglu E, Senapedis W, Landesman Y, Argueta C, Kauffman M, Chang H, Kashyap T, Shacham S, Neggers JE, Daelemans D, Heath EI, Azmi AS. Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression. Oncotarget. 2018 Oct 19;9(82):35327-35342. doi: 10.18632/oncotarget.26239. PMID: 30450161; PMCID: PMC6219671. 19: Yan D, Pomicter AD, Tantravahi S, Mason CC, Senina AV, Ahmann JM, Wang Q, Than H, Patel AB, Heaton WL, Eiring AM, Clair PM, Gantz KC, Redwine HM, Swierczek SI, Halverson BJ, Baloglu E, Shacham S, Khorashad JS, Kelley TW, Salama ME, Miles RR, Boucher KM, Prchal JT, O'Hare T, Deininger MW. Nuclear- Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis. Clin Cancer Res. 2019 Apr 1;25(7):2323-2335. doi: 10.1158/1078-0432.CCR-18-0959. Epub 2018 Dec 18. PMID: 30563936; PMCID: PMC6445677. 20: Sexton R, Mahdi Z, Chaudhury R, Beydoun R, Aboukameel A, Khan HY, Baloglu E, Senapedis W, Landesman Y, Tesfaye A, Kim S, Philip PA, Azmi AS. Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer. Int J Mol Sci. 2019 Sep 28;20(19):4826. doi: 10.3390/ijms20194826. PMID: 31569391; PMCID: PMC6801932.