[CAS NO. 2052132-51-9] H3B-6545hydrochloride
PRODUCTS SPECIFICATIONS [2052132-51-9]
DESCRIPTION [2052132-51-9]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 604.04 |
| Molecular Formula | C30H30ClF4N5O2 |
| SMILES | O=C(N(C)C)/C=C/CNCCOC1=NC=C(/C(C2=CC3=C(NN=C3F)C=C2)=C(C4=CC=CC=C4)/CC(F)(F)F)C=C1.Cl |
2 Publications Citing Use of MCE
Summary
H3B-6545 hydrochloride is an oral, selective estrogen receptor covalent antagonist ( SERCA ) for the research of metastatic ER-positive, HER2-negative breast cancer [1] [2] .
IC50 & Target
Estrogen receptor [1]
In Vitro
H3B-6545 is a highly selective small molecule that potently antagonizes wild-type and mutant ERα in biochemical and cell based assays. In vitro comparisons with standard of care and other experimental agents confirm increased cell potency of H3B-6545 under continuous as well as washout treatment conditions [1] . H3B-6545, a member of a novel class of ERα antagonists refer to as selective ER covalent antagonist (SERCA), which inactivates both wild-type and mutant ERα by targeting C530 and enforcing a unique antagonist conformation. H3B-6545 is a first-in-class selective ER covalent antagonist (SERCA). H3B-6545 inhibits ERα WT activity and growth of ERα WT -positive breast cancer lines. H3B-6545 potently inhibits ERα WT activity and suppresses proliferation of ERα WT -positive breast cancer lines. With GI 50 s of 0.3-0.4, 1.0, 0.5, 5.2, and 0.2 nM for MCF7, HCC1428, BT483, T47D and CAMA-1 cell lines [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
In vivo, once daily oral dosing of H3B-6545 shows potent activity and superior efficacy to fulvestrant in the MCF-7 xenograft model with maximal antitumor activity at doses >10x below the maximum tolerated dose in mice. In addition, H3B-6545 shows superior antitumor activity to Tamoxifen and Fulvestrant in patient derived xenograft models of estrogen receptor positive breast cancer including models carrying ERα mutations in rat and monkeys, H3B-6545 is well tolerated across a broad dose range and at exposures that significantly exceed those required for efficacy in mouse xenograft models [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03250676 | Eisai Inc. |
Breast Neoplasms|Breast Cancer|Estrogen-receptor Positive Breast Cancer|Cancer, Breast|Breast Cancer Female|Breast Adenocarcinoma|Estrogen Receptor Positive Tumor|ER Positive
|
August 17, 2017 | Phase 1|Phase 2 |
| NCT04288089 | Eisai Inc. |
Receptors, Estrogen|Genes, Erbb-2|Breast Neoplasms
|
April 1, 2020 | Phase 1 |
| NCT04568902 | Eisai Co., Ltd.|Eisai Inc. |
Breast Neoplasms
|
September 30, 2020 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 83.33 mg/mL ( 137.95 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6555 mL | 8.2776 mL | 16.5552 mL |
| 5 mM | 0.3311 mL | 1.6555 mL | 3.3110 mL |
| 10 mM | 0.1656 mL | 0.8278 mL | 1.6555 mL |
References
- [1] Peter G. Smith, et al. Abstract DDT01-04: Discovery and development of H3B-6545: A novel, oral, selective estrogen receptor covalent antagonist (SERCA) for the treatment of breast cancer.AACR Annual Meeting 2017; April 1-5.
- [2] Amy H Kim, et al. H3B-6545, a selective estrogen receptor covalent antagonist, prevents bone loss in ovariectomized Sprague-Dawley rats. J Pharmacol Toxicol Methods. Sep-Oct 2019;99:106595.