| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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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.
| Targets |
FGFR4 (IC50 <1.2 nM)
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| ln Vitro |
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| ln Vivo |
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| 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.
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| Animal Protocol |
BALB/c nu/nu female mice
30, 100, and 300 mg/kg orally |
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| References | ||
| Additional Infomation |
H3B-6527 is under investigation in clinical trial NCT03424577 (A Study to Evaluate the Food-Effect of H3B-6527).
FGFR4 Inhibitor H3B-6527 is an orally bioavailable inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, H3B-6527 specifically binds to and blocks FGFR4. This prevents the activation of FGFR4, inhibits FGFR4-mediated signaling and leads to an inhibition of cell proliferation in FGFR4-overexpressing tumor cells. FGFR4, a receptor tyrosine kinase overexpressed by certain tumor cell types, is involved in tumor cell proliferation, differentiation, angiogenesis, and survival; FGFR4 expression is associated with poor prognosis. |
| Molecular Formula |
C29H34CL2N8O4
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| Molecular Weight |
629.54
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| Exact Mass |
628.208
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| Elemental Analysis |
C, 55.33; H, 5.44; Cl, 11.26; N, 17.80; O, 10.17
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| CAS # |
1702259-66-2
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| Related CAS # |
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| PubChem CID |
118029202
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| Appearance |
White to khaki solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
832.1±65.0 °C at 760 mmHg
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| Flash Point |
457.0±34.3 °C
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| Vapour Pressure |
0.0±3.1 mmHg at 25°C
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| Index of Refraction |
1.665
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| LogP |
4.76
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
43
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| Complexity |
913
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=CC(=C(C=1NC(N(C)C1C=C(N=CN=1)NC1C=CC(=CC=1NC(C=C)=O)N1CCN(CC)CC1)=O)Cl)OC)OC
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| InChi Key |
MBWRLLRCTIYXDW-UHFFFAOYSA-N
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| 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)
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| 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
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| 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.
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.
(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.
| 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 |
Biochemical and structural characterization of H3B-6527.Cancer Res.2017 Dec 15;77(24):6999-7013. |
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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. |
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H3B-6527 antitumor effect in four HCC PDX models grown in female nude mice.Cancer Res.2017 Dec 15;77(24):6999-7013. |
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. |
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