H3B-6527

Alias: H3B-6527; H3B6527; H3B 6527

Cat No.:V3131 Purity: ≥98%

COA Product Data Instructions for use SDS

H3B-6527 is a potent, highly selective, orally bioavailable, covalent FGFR4 inhibitor with IC50 value of ~1.2 nM.

H3B-6527 Chemical Structure CAS No.: 1702259-66-2
Product category: FGFR

This product is for research use only, not for human use. We do not sell to patients.

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5mg
10mg
25mg
50mg
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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

H3B-6527 is a potent, highly selective, orally bioavailable, covalent FGFR4 inhibitor with IC50 value of ~1.2 nM. The IC50 values for FGFR1/2/3 are 1,290, 320, and 1,060 nM, respectively, indicating that it is at least 250 times more selective for FGFR4 than for FGFR1-3. H3B-6527 may be utilized as an anticancer drug because it is an FGFR4 inhibitor. When administered, H3B-6527 selectively binds to and inhibits FGFR4, preventing FGFR4 from being activated. This stops FGFR4-mediated signaling from occurring, which in turn stops FGFR4-overexpressing tumor cells from proliferating.

Biological Activity I Assay Protocols (From Reference)

Targets

FGFR4 (IC50 <1.2 nM)

ln Vitro

H3B-6527 exhibits at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290, and 1,060 nmol/L, respectively) and strong inhibition of the target kinase FGFR4 with an IC50 value of <1.2 nmol/L. Additionally, with IC50 values of 690, >10,000, and >10,000 nmol/L, respectively, TAOK2, JNK2, and CSF1R are less sensitive to H3B-6527 treatment. In an HCC cell line, H3B-6527 suppresses FGFR4 signaling, promotes cell division, and causes apoptosis. Treatment of Hep3B cells results in concentration-dependent, strong activation of the apoptotic marker caspase-3/7, suggesting that H3B-6527-induced FGFR4 inhibition causes cell death in HCC cell lines. Across all cancer kinds, H3B-6527 exhibits both selectivity and selective dependence on FGFR4[1].

ln Vivo

H3B-6527 exhibits dose-proportional plasma exposures and greater than dose-proportional tumor exposures within the dose range evaluated (30, 100, and 300 mg/kg) in the Hep3B human HCC xenograft mouse model. The CYP7A1 mRNA and pERK1/2 protein levels measure the dose-dependent pharmacodynamic response of H3B-6527, with higher doses producing longer-lasting effects. In nude mice, oral administration of H3B-6527 twice a day inhibits xenograft growth in a dose-dependent manner. In the subcutaneous xenograft model, tumor growth is significantly inhibited and tumor regressions occur when the dose is 300 or 100 mg/kg twice a day. In the JHH-7 model, where H3B-6527 alone can only cause tumor stasis, palbociclib can increase H3B-6527 efficacy and encourage tumor regression[1].

Cell Assay

The levels of pERK1/2 are determined after Hep3B cells are treated with H3B-6527 at 100 and 300 nmol/L for 0.5, 1, 2, 4, 8, and 24 hours.

Animal Protocol

BALB/c nu/nu female mice
30, 100, and 300 mg/kg
orally

References

[1]. Cancer Res . 2017 Dec 15;77(24):6999-7013.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C29H34CL2N8O4

Molecular Weight

629.54

Exact Mass

628.21

Elemental Analysis

C, 55.33; H, 5.44; Cl, 11.26; N, 17.80; O, 10.17

CAS #

1702259-66-2

Related CAS #

1702259-66-2

Appearance

Solid powder

SMILES

CCN1CCN(CC1)C2=CC(=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl)NC(=O)C=C

InChi Key

MBWRLLRCTIYXDW-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H34Cl2N8O4/c1-6-25(40)35-20-14-18(39-12-10-38(7-2)11-13-39)8-9-19(20)34-23-16-24(33-17-32-23)37(3)29(41)36-28-26(30)21(42-4)15-22(43-5)27(28)31/h6,8-9,14-17H,1,7,10-13H2,2-5H3,(H,35,40)(H,36,41)(H,32,33,34)

Chemical Name

N-[2-[[6-[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl-methylamino]pyrimidin-4-yl]amino]-5-(4-ethylpiperazin-1-yl)phenyl]prop-2-enamide

Synonyms

H3B-6527; H3B6527; H3B 6527

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~50 mg/mL (~79.4 mM)

Water: < 1mg/mL

Ethanol: < 1mg/mL

Solubility (In Vivo)

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5885 mL	7.9423 mL	15.8846 mL
	5 mM	0.3177 mL	1.5885 mL	3.1769 mL
	10 mM	0.1588 mL	0.7942 mL	1.5885 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03424577	Completed	Drug: H3B-6527	Healthy Participants	Eisai Inc.	December 27, 2017	Phase 1
NCT02834780	Completed	Drug: H3B-6527	Liver Cancer Liver Neoplasms	H3 Biomedicine Inc.	December 28, 2016	Phase 1

Biological Data

Biochemical and structural characterization of H3B-6527.Cancer Res.2017 Dec 15;77(24):6999-7013.
H3B-6527 effects in the HCC cell line Hep3Bin vitro.Cancer Res.2017 Dec 15;77(24):6999-7013.
H3B-6527 effects in a HCC cell line Hep3B subcutaneous xenografts in female nude mice.Cancer Res.2017 Dec 15;77(24):6999-7013.
FGF19 expression and its correlation to the H3B-6527 sensitivity.Cancer Res.2017 Dec 15;77(24):6999-7013.
H3B-6527 antitumor effect in four HCC PDX models grown in female nude mice.Cancer Res.2017 Dec 15;77(24):6999-7013.

H3B-6527

Antitumor effects and RNA-seq analysis following H3B-6527 and palbociclib as single agents or in combination in JHH-7 HCC cell line xenografts grown in female nude mice.Cancer Res.2017 Dec 15;77(24):6999-7013.