H3B-6545 hydrochloride

Name: H3B-6545 hydrochloride
Brand: MedChemExpress
SKU: HY-112596A
Rating: 5.0 (3 reviews)

Cat. No.: HY-112596A Purity: 99.16%: FAQs
Data Sheet SDS COA Handling Instructions

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H3B-6545 hydrochloride is an oral, selective estrogen receptor covalent antagonist (SERCA) for the research of metastatic ER-positive, HER2-negative breast cancer.

For research use only. We do not sell to patients.

H3B-6545 hydrochloride Chemical Structure

CAS No. : 2052132-51-9

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 465	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 465	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 350	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 600	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 1800	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 3050	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 3 publication(s) in Google Scholar

Other Forms of H3B-6545 hydrochloride:

H3B-6545 Get quote

3 Publications Citing Use of MCE H3B-6545 hydrochloride

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•Related Screening Libraries:

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View All Estrogen Receptor/ERR Isoform Specific Products:

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Estrogen receptor ERα ERβ ERRα ERRβ ERRγ

Biological Activity
Purity & Documentation
References
Customer Review

Description

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 GI₅₀s 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].

MedChemExpress (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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

604.04

Formula

C₃₀H₃₀ClF₄N₅O₂

CAS No.

2052132-51-9

Appearance

Solid

Color

White to yellow

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

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

In Vitro:

DMSO : 83.33 mg/mL (137.95 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (3.44 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (3.44 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (3.44 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.16%

Select Batch:

Data Sheet (275 KB) SDS (251 KB)

COA (249 KB) HNMR (244 KB) LCMS (100 KB)

Handling Instructions (2659 KB)

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.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.6555 mL	8.2776 mL	16.5552 mL	41.3880 mL
	5 mM	0.3311 mL	1.6555 mL	3.3110 mL	8.2776 mL
	10 mM	0.1656 mL	0.8278 mL	1.6555 mL	4.1388 mL
	15 mM	0.1104 mL	0.5518 mL	1.1037 mL	2.7592 mL
	20 mM	0.0828 mL	0.4139 mL	0.8278 mL	2.0694 mL
	25 mM	0.0662 mL	0.3311 mL	0.6622 mL	1.6555 mL
	30 mM	0.0552 mL	0.2759 mL	0.5518 mL	1.3796 mL
	40 mM	0.0414 mL	0.2069 mL	0.4139 mL	1.0347 mL
	50 mM	0.0331 mL	0.1656 mL	0.3311 mL	0.8278 mL
	60 mM	0.0276 mL	0.1380 mL	0.2759 mL	0.6898 mL
	80 mM	0.0207 mL	0.1035 mL	0.2069 mL	0.5173 mL
	100 mM	0.0166 mL	0.0828 mL	0.1656 mL	0.4139 mL