MedKoo Cat#: 207208 | Name: HH2853 R-isomer

Description:

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

HH2853 R-isomer is an R-isomer of HH2853. HH-2853 is a potent EZH1/2 inhibitor with potent anti-tumor activities. HH2853 inhibited the enzymatic activities of wild-type and mutant EZH2 with IC50 values of 2.21-5.36 nM, which was similar to that of tazemetostat. In addition, HH2853 inhibited EZH1 enzymatic activity with an IC50 of 9.26 nM, which was stronger than tazemetostat (IC50: 58.43 nM). In contrast, HH2853 up to 10 μM exhibited only marginal or minor inhibitory activity against 36 histone modification enzymes. At cellular level, HH2853 potently inhibited H3K27 mono-, di- and tri-methylation in multiple cancer cell lines with wild-type or mutant EZH2. In contrast, HH2853 up to 10 μM had no effect on the other types of methylation modifications on histone H3. Moreover, HH2853 potently inhibited the cell viability of multiple cancer cell lines with EZH2 GOF mutation or alterations in SWI/SNF complex, and exhibited superior anti-tumor efficacy in several tumor xenograft models than tazemetostat at a comparable dose level. Furthermore, HH2853 exhibited superior PK property than tazemetostat.

Chemical Structure

HH2853 R-isomer
HH2853 R-isomer
CAS#2202678-06-4 (R-isomer)

Theoretical Analysis

MedKoo Cat#: 207208

Name: HH2853 R-isomer

CAS#: 2202678-06-4 (R-isomer)

Chemical Formula: C31H36F3N7O3

Exact Mass: 611.2832

Molecular Weight: 611.67

Elemental Analysis: C, 60.87; H, 5.93; F, 9.32; N, 16.03; O, 7.85

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
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Synonym
HH2853 R-isomer; HH-2853 R-isomer; HH 2853 R-isomer; (R)-HH2853; (R)-HH2853; (R)HH2853;
IUPAC/Chemical Name
(R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-methyl-1-(6-methylpyridazin-3-yl)-5-(1-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethyl)indolizine-7-carboxamide
InChi Key
BIABSPVTTUDBEO-OAQYLSRUSA-N
InChi Code
InChI=1S/C31H36F3N7O3/c1-18-6-7-25(38-37-18)22-8-9-41-26(22)15-23(29(42)35-16-24-27(44-5)14-19(2)36-30(24)43)20(3)28(41)21(4)40-12-10-39(11-13-40)17-31(32,33)34/h6-9,14-15,21H,10-13,16-17H2,1-5H3,(H,35,42)(H,36,43)/t21-/m1/s1
SMILES Code
O=C(C1=CC2=C(C3=NN=C(C)C=C3)C=CN2C([C@H](N4CCN(CC(F)(F)F)CC4)C)=C1C)NCC5=C(OC)C=C(C)NC5=O
Appearance
To be determined
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
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
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
Polycomb Repressive Complex 2 (PRC2) is a multiprotein complex that catalyzes the methylation of lysine 27 on histone H3 (H3K27), and the histone methyltransferases EZH1/2 are the catalytic subunit of PRC2. Aberrant activation of EZH2 drives H3K27 methylation and plays a critical role in cancer initiation and progression. Meanwhile, loss-of-function mutation in the major components of SWI/SNF complex leads to a loss of its suppression ability against PRC2 and subsequently activates EZH2. Targeting EZH2 has been validated as a promising therapeutic strategy for cancer treatment, especially for those with EZH2 gain-of-function (GOF) mutations or alterations of SWI/SNF complex proteins that act as oncogenic drivers. Although when PRC2 was suppressed by EZH2 inhibition, the activity of EZH1 complementarily increased to replace the role of EZH2 and maintained the function of PRC2. In addition, EZH2 inhibition in hematopoietic stem cells of mice has been shown to facilitate the development of heterogeneous hematologic malignancies in an EZH1-dependent manner. As a result, dual inhibition of EZH1 and EZH2 may be more effective than EZH2 inhibition alone in suppressing PRC2 function, as well as overcoming the issues related to the development of secondary malignancies, which has been observed in the clinical development of EZH2 selective inhibitor. Taken together, HH2853 is a selective EZH1/2 dual inhibitor with potent anti-tumor activities and favorable PK properties. HH2853 is currently in phase I clinical development.

Preparing Stock Solutions

The following data is based on the product molecular weight 611.67 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
1: Yu L, Wang YF, Xiao J, Shen QQ, Chi SS, Gao YL, Lin DZ, Ding J, Fang YF, Chen Y. Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition. Acta Pharmacol Sin. 2023 Oct;44(10):2113-2124. doi: 10.1038/s41401-023-01097-4. Epub 2023 May 25. PMID: 37225847; PMCID: PMC10545686. 2: Dou F, Tian Z, Yang X, Li J, Wang R, Gao J. Valemetostat: First approval as a dual inhibitor of EZH1/2 to treat adult T-cell leukemia/lymphoma. Drug Discov Ther. 2022 Dec 26;16(6):297-299. doi: 10.5582/ddt.2022.01085. Epub 2022 Oct 28. PMID: 36310058. 3. https://aacrjournals.org/cancerres/article/82/12_Supplement/5436/702794/Abstract-5436-HH2853-is-a-selective-small