Basic Description

Synonyms	H3B-6527 \| 1702259-66-2 \| N-[2-[[6-[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl-methylamino]pyrimidin-4-yl]amino]-5-(4-ethylpiperazin-1-yl)phenyl]prop-2-enamide \| 4HTE364XIK \| N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(
Specifications & Purity	10mM in DMSO
Biochemical and Physiological Mechanisms	H3B-6527 is a highly selective covalent FGFR4 inhibitor with an IC50 value of <1.2 nM and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nM respectively).
Storage Temp	Store at -80°C
Shipped In	Ice chest + Ice pads This product requires cold chain shipping. Ground and other economy services are not available.
Product Description	Information H3B-6527 H3B-6527 is a highly selective covalent FGFR4 inhibitor with an IC50 value of <1.2 nM and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nM respectively). Targets FGFR4 (Cell-free assay) <1.2 nM In vitro H3B-6527 shows robust inhibition of the target kinase FGFR4 with an IC50 value of <1.2 nmol/L and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nmol/L respectively). TAOK2, JNK2, and CSF1R are also less sensitive to H3B-6527 treatment with IC50 values of 690, >10,000, and >10,000 nmol/L, respectively. H3B-6527 inhibits FGFR4 signaling, proliferation, and leads to apoptosis in a HCC cell line (Hepatocellular carcinoma). Treatment on Hep3B cells leads to robust activation of caspase-3/7, an apoptotic marker, in a concentration-dependent manner, indicating FGFR4 inhibition by H3B-6527 leads to cell death in HCC cell lines. H3B-6527 has the selectivity and the selective dependence on FGFR4 across cancer types. In vivo In the Hep3B human HCC xenograft mouse model, H3B-6527 shows dose-proportional plasma exposures and greater than dose-proportional tumor exposures within the dose range evaluated (30, 100, and 300 mg/kg). The H3B-6527 pharmacodynamic response as measured by CYP7A1 mRNA and pERK1/2 protein levels is dose dependent, with higher doses leading to sustained responses. Oral treatment of H3B-6527, twice daily, inhibits xenograft growth in a dose-dependent manner in nude mice, with the 300 or 100 mg/kg twice daily, significantly inhibiting tumor growth in both Hep3B subcutaneous and orthotopic xenograft model and causing tumor regressions in the subcutaneous xenograft model. Palbociclib can enhance H3B-6527 efficacy and promote tumor regression in JHH-7 model where H3B-6527 as a single agent can only lead to tumor stasis. Cell Research(from reference) Cell lines：Hep3B cells Concentrations：100 and 300 nmol/L Incubation Time：0.5, 1, 2, 4, 8, and 24 hours

Taxonomic Classification

Taxonomy Tree

Kingdom Organic compounds
- Superclass Organoheterocyclic compounds
  - Class Diazinanes
    - Subclass Piperazines

Kingdom	Organic compounds
Superclass	Organoheterocyclic compounds
Class	Diazinanes
Subclass	Piperazines
Intermediate Tree Nodes	Not available
Direct Parent	Phenylpiperazines
Alternative Parents	N-arylpiperazines N-phenylureas Dimethoxybenzenes Methoxyanilines Anilides Phenoxy compounds N-arylamides Dichlorobenzenes Dialkylarylamines Anisoles N-alkylpiperazines Aminopyrimidines and derivatives Alkyl aryl ethers Imidolactams Aryl chlorides Heteroaromatic compounds Acrylic acids and derivatives Ureas Trialkylamines Secondary carboxylic acid amides Amino acids and derivatives Secondary amines Azacyclic compounds Organopnictogen compounds Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
Molecular Framework	Aromatic heteromonocyclic compounds
Substituents	N-arylpiperazine - Phenylpiperazine - M-dimethoxybenzene - Dimethoxybenzene - N-phenylurea - Methoxyaniline - Anilide - Phenoxy compound - Methoxybenzene - Aniline or substituted anilines - Dialkylarylamine - N-arylamide - Tertiary aliphatic/aromatic amine - Phenol ether - 1,3-dichlorobenzene - Anisole - N-alkylpiperazine - Halobenzene - Chlorobenzene - Aminopyrimidine - Alkyl aryl ether - Imidolactam - Benzenoid - Pyrimidine - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Acrylic acid or derivatives - Heteroaromatic compound - Urea - Tertiary aliphatic amine - Tertiary amine - Secondary carboxylic acid amide - Carbonic acid derivative - Carboxamide group - Amino acid or derivatives - Azacycle - Secondary amine - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Carbonyl group - Amine - Aromatic heteromonocyclic compound
Description	This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
External Descriptors	Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61. DOI: 10.1186/s13321-016-0174-y

Product Properties

ALogP	5.16
hba_count	6
HBD Count	3
Rotatable Bond	10

Associated Targets(Human)

FGFR2 Tclin Fibroblast growth factor receptor 2 (3405 Activities)

Discover Target: FGFR2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FGFR1 Tclin Fibroblast growth factor receptor 1 (9149 Activities)

Discover Target: FGFR1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Fgfr4 Fibroblast growth factor receptor 4 (138 Activities)

Discover Target: Fgfr4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Fgfr3 Fibroblast growth factor receptor 3 (21 Activities)

Discover Target: Fgfr3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Mechanism of Action	Action Type	target ID	Target Name	Target Type	Target Organism	Binding Site Name	References

Names and Identifiers

IUPAC 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
INCHI	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)
InChIKey	MBWRLLRCTIYXDW-UHFFFAOYSA-N
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
Isomeric 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
Molecular Weight	629.54
Reaxy-Rn	28151526
Reaxys-RN_link_address	https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=28151526&ln=

Certificates（CoA,COO,BSE/TSE and Analysis Chart)

C of A & Other Certificates(BSE/TSE, COO):

Analytical Chart:

Chemical and Physical Properties

DMSO(mg / mL) Max Solubility	50
DMSO(mM) Max Solubility	79.42307081
Water(mg / mL) Max Solubility	＜1
Molecular Weight	629.500 g/mol
XLogP3	4.400
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	10
Exact Mass	628.208 Da
Monoisotopic Mass	628.208 Da
Topological Polar Surface Area	124.000 Å²
Heavy Atom Count	43
Formal Charge	0
Complexity	913.000
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
The total count of all stereochemical bonds	0
Covalently-Bonded Unit Count	1

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H3B-6527 - 10mM in DMSO, high purity , CAS No.1702259-66-2