Valemetostat free base | CAS#1809336-39-7 | EZH1/2 inhibitor

MedKoo Cat#: 558285 | Name: Valemetostat free base

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Description:

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

Valemetostat, also known as DS-3201 is a potent, selective and orally active EZH1/2 inhibitor. DS-3201 selectively inhibits the activity of both wild-type and mutated forms of EZH1 and EZH2. Inhibition of EZH1/2 specifically prevents the methylation of lysine 27 on histone H3 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways, enhances transcription of certain target genes, and results in decreased proliferation of EZH1/2-expressing cancer cells.

Chemical Structure

Valemetostat free base

CAS#1809336-39-7 (free base)

Theoretical Analysis

MedKoo Cat#: 558285

Name: Valemetostat free base

CAS#: 1809336-39-7 (free base)

Chemical Formula: C26H34ClN3O4

Exact Mass: 487.2238

Molecular Weight: 488.02

Elemental Analysis: C, 63.99; H, 7.02; Cl, 7.26; N, 8.61; O, 13.11

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00	2 Weeks
10mg	USD 950.00	2 Weeks

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Related CAS #

1809336-39-7 (free base) 1809336-93-3 (tosylate) 1809336-92-2 (mesylate) 1809336-94-4 (fumarate) 1809336-95-5 (tartrate)

Synonym

Valemetostat; DS-3201; DS 3201; DS3201; DS-3201b

IUPAC/Chemical Name

(2R)-7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide

InChi Key

SSDRNUPMYCFXGM-UYPAYLBCSA-N

InChi Code

InChI=1S/C26H34ClN3O4/c1-14-11-15(2)29-25(32)20(14)13-28-24(31)19-12-21(27)23-22(16(19)3)33-26(4,34-23)17-7-9-18(10-8-17)30(5)6/h11-12,17-18H,7-10,13H2,1-6H3,(H,28,31)(H,29,32)/t17-,18-,26-/m1/s1

SMILES Code

O=C(C1=CC(Cl)=C(O[C@](C)([C@H]2CC[C@H](N(C)C)CC2)O3)C3=C1C)NCC4=C(C)C=C(C)NC4=O

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

EZH1/2, histone lysine methyltransferase (HMT) class enzymes and catalytic subunits of the polycomb repressive complex 2 (PRC2), are overexpressed or mutated in a variety of cancer cells and play key roles in tumor cell proliferation, progression, stem cell self-renewal and migration

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 488.02 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

1: Wang MS, Sussman J, Xu JA, Patel R, Elghawy O, Rawla P. Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review. Life (Basel). 2024 Dec 11;14(12):1645. doi: 10.3390/life14121645. PMID: 39768352; PMCID: PMC11678550. 2: Zinzani PL, Izutsu K, Mehta-Shah N, Barta SK, Ishitsuka K, Córdoba R, Kusumoto S, Bachy E, Cwynarski K, Gritti G, Prica A, Jacobsen E, Feldman T, Guillermin Y, Ennishi D, Yoon DH, Domenech ED, Zain J, Wang J, Kim JS, Poel MV, Jin J, Wu S, Chen Y, Moriyama T, Inoue A, Nakajima K, Horwitz SM. Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE- PTCL01): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2024 Dec;25(12):1602-1613. doi: 10.1016/S1470-2045(24)00503-5. Epub 2024 Oct 29. PMID: 39486433. 3: Maruyama D, Jacobsen E, Porcu P, Allen P, Ishitsuka K, Kusumoto S, Narita T, Tobinai K, Foss F, Tsukasaki K, Feldman T, Imaizumi Y, Izutsu K, Morishima S, Yamauchi N, Yuda J, Brammer JE, Kawamata T, Ruan J, Nosaka K, Utsunomiya A, Wang J, Zain J, Kakurai Y, Yamauchi H, Hizukuri Y, Biserna N, Tachibana M, Inoue A, Horwitz SM. Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study. Lancet Oncol. 2024 Dec;25(12):1589-1601. doi: 10.1016/S1470-2045(24)00502-3. Epub 2024 Oct 29. PMID: 39486432. 4: Braunstein Z, Brammer JE. Maintenance Therapy Post-Stem Cell Transplantation for Patients with T-Cell Lymphomas. Curr Hematol Malig Rep. 2024 Dec;19(6):276-284. doi: 10.1007/s11899-024-00743-w. Epub 2024 Oct 19. PMID: 39425756; PMCID: PMC11568030. 5: Osada N, Kikuchi J, Okada Y, Matsuoka S, Morishita K, Nakasone H, Furukawa Y. Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells. PLoS One. 2024 Sep 30;19(9):e0309533. doi: 10.1371/journal.pone.0309533. PMID: 39348376; PMCID: PMC11441677. 6: Gonnella R, Collura F, Corrado V, Di Crosta M, Santarelli R, Cirone M. EZH2 Inhibition by DS3201 Triggers the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle and Potentiates the Effects Induced by SAHA in Primary Effusion Lymphoma Cells. Viruses. 2024 Sep 20;16(9):1490. doi: 10.3390/v16091490. PMID: 39339966; PMCID: PMC11437442. 7: Obama K, Yamamoto H, Inoue H. Sequential treatment with valemetostat and conventional anti-cancer drugs for refractory aggressive adult T-cell leukemia/lymphoma: A case report. EJHaem. 2024 Jun 17;5(4):851-854. doi: 10.1002/jha2.963. PMID: 39157624; PMCID: PMC11327715. 8: Fukae M, Rogers J, Garcia R, Tachibana M, Shimizu T. Bayesian sparse regression for exposure-response analyses of efficacy and safety endpoints to justify the clinical dose of valemetostat for adult T-cell leukemia/lymphoma. CPT Pharmacometrics Syst Pharmacol. 2024 Oct;13(10):1655-1669. doi: 10.1002/psp4.13203. Epub 2024 Aug 18. PMID: 39155584; PMCID: PMC11494914. 9: Fukae M, Baron K, Tachibana M, Mondick J, Shimizu T. Population pharmacokinetics of total and unbound valemetostat and platelet dynamics in healthy volunteers and patients with non-Hodgkin lymphoma. CPT Pharmacometrics Syst Pharmacol. 2024 Oct;13(10):1641-1654. doi: 10.1002/psp4.13201. Epub 2024 Jul 30. PMID: 39077926; PMCID: PMC11494923. 10: Toho M, Yasunaga M, Masuda Y, Shimura A, Masamoto Y, Sumi K, Muramatsu K, Tsujita M, Mitsuchi S, Yoshioka R, Baba Y, Maekawa H, Kimura T, Hamada M, Toda T, Kurokawa M. Adult T-cell leukemia-lymphoma with neurolymphomatosis successfully controlled by valemetostat: a case report and review of literature. Leuk Lymphoma. 2024 Dec;65(12):1891-1895. doi: 10.1080/10428194.2024.2381646. Epub 2024 Jul 25. PMID: 39052853. 11: Matsumura N, Mandai M. PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs: approval selpercatinib for solid tumor with RET fusion, gumarontinib for non-small cell lung cancer with MET gene exon 14 skipping mutation, momelotinib for myelofibrosis, bexarotene for adult T-cell leukemia/lymphoma, valemetostat for peripheral T-cell lymphoma, and pirtobrutinib for mantle cell lymphoma in Japan. Int J Clin Oncol. 2024 Sep;29(9):1207-1208. doi: 10.1007/s10147-024-02579-z. PMID: 39007945. 12: Choudhury NJ, Lai WV, Makhnin A, Heller G, Eng J, Li B, Preeshagul I, Santini FC, Offin M, Ng K, Paik P, Larsen C, Ginsberg MS, Lau Y, Zhang X, Baine MK, Rekhtman N, Rudin CM. A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer. Clin Cancer Res. 2024 Sep 3;30(17):3697-3703. doi: 10.1158/1078-0432.CCR-23-3383. PMID: 38940666; PMCID: PMC11371507. 13: Tavakoli Shirazi P, Bywater MJ. Unlocking adult T-cell leukemia/lymphoma's epigenetic secrets: delving into the mechanism and impact of EZH1/2 inhibition. Immunol Cell Biol. 2024 May-Jun;102(5):298-301. doi: 10.1111/imcb.12748. Epub 2024 Apr 12. PMID: 38606590. 14: Hamamura-Yasuno E, Kinoshita J, Goto K, Fujimoto K, Pignatello M, Tsuchiya Y, Mori K. Effective in vitro evaluation of the risk of histamine release related to valemetostat tosylate using MRGPRX2-expressing cells. J Toxicol Sci. 2024;49(4):163-174. doi: 10.2131/jts.49.163. PMID: 38556353. 15: Di Crosta M, Arena A, Benedetti R, Gilardini Montani MS, Cirone M. 5-AZA Upregulates SOCS3 and PTPN6/SHP1, Inhibiting STAT3 and Potentiating the Effects of AG490 against Primary Effusion Lymphoma Cells. Curr Issues Mol Biol. 2024 Mar 14;46(3):2468-2479. doi: 10.3390/cimb46030156. PMID: 38534772; PMCID: PMC10968859. 16: Yamagishi M, Kuze Y, Kobayashi S, Nakashima M, Morishima S, Kawamata T, Makiyama J, Suzuki K, Seki M, Abe K, Imamura K, Watanabe E, Tsuchiya K, Yasumatsu I, Takayama G, Hizukuri Y, Ito K, Taira Y, Nannya Y, Tojo A, Watanabe T, Tsutsumi S, Suzuki Y, Uchimaru K. Mechanisms of action and resistance in histone methylation-targeted therapy. Nature. 2024 Mar;627(8002):221-228. doi: 10.1038/s41586-024-07103-x. Epub 2024 Feb 21. PMID: 38383791; PMCID: PMC10917674. 17: Bagnato G, Stefoni V, Broccoli A, Argnani L, Pellegrini C, Casadei B, Bonifazi F, Zinzani PL. Successful Bridging to Allogeneic Transplantation With Valemetostat in Two Refractory/relapsed Peripheral T-cell lymphoma patients. Mediterr J Hematol Infect Dis. 2024 Jan 1;16(1):e2024004. doi: 10.4084/MJHID.2024.004. PMID: 38223480; PMCID: PMC10786139. 18: Lorenzo-Guerra SL, Codina-Martínez H, Suárez-Fernández L, Cabal VN, García- Marín R, Riobello C, Vivanco B, Blanco-Lorenzo V, Sánchez-Fernández P, López F, Llorente JL, Hermsen MA. Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma. Cells. 2023 Dec 30;13(1):81. doi: 10.3390/cells13010081. PMID: 38201285; PMCID: PMC10778008. 19: Yoshimitsu M. [Adult T-cell leukemia/lymphoma]. Rinsho Ketsueki. 2023;64(9):1032-1040. Japanese. doi: 10.11406/rinketsu.64.1032. PMID: 37899180. 20: Wu G, Yoshida N, Liu J, Zhang X, Xiong Y, Heavican-Foral TB, Mandato E, Liu H, Nelson GM, Yang L, Chen R, Donovan KA, Jones MK, Roshal M, Zhang Y, Xu R, Nirmal AJ, Jain S, Leahy C, Jones KL, Stevenson KE, Galasso N, Ganesan N, Chang T, Wu WC, Louissaint A, Debaize L, Yoon H, Dal Cin P, Chan WC, Ho Sui SJ, Ng SY, Feldman AL, Horwitz SM, Adelman K, Fischer ES, Chen CW, Weinstock DM, Brown M. TP63 fusions drive multicomplex enhancer rewiring, lymphomagenesis, and EZH2 dependence. Sci Transl Med. 2023 Sep 20;15(714):eadi7244. doi: 10.1126/scitranslmed.adi7244. Epub 2023 Sep 20. PMID: 37729434; PMCID: PMC11014717.