H3B-6527 | CAS#1702259-66-2 | FGFR4 inhibitor

MedKoo Cat#: 407449 | Name: H3B-6527

Description:

WARNING: This product is for research use only, not for human or veterinary use.

H3B-6527 is a potent and orally active FGFR4 inhibitor 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.

Chemical Structure

H3B-6527

CAS#1702259-66-2

Theoretical Analysis

MedKoo Cat#: 407449

Name: H3B-6527

CAS#: 1702259-66-2

Chemical Formula: C29H34Cl2N8O4

Exact Mass: 628.2080

Molecular Weight: 629.54

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

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship

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Synonym

H3B-6527; H3B 6527; H3B6527

IUPAC/Chemical Name

N-{2-[(6-{[(2,6-Dichloro-3,5-dimethoxyphenyl)carbamoyl](methyl)amino}-4-pyrimidinyl)amino]-5-(4-ethyl-1-piperazinyl)phenyl}acrylamide

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)

SMILES Code

C=CC(NC1=CC(N2CCN(CC)CC2)=CC=C1NC3=NC=NC(N(C(NC4=C(Cl)C(OC)=CC(OC)=C4Cl)=O)C)=C3)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R05B26

QC Data

View QC data: current batch, Lot#C8R05B26

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

H3B-6527 is a 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).

In vitro activity:

H3B-6527 treatment resulted in a GI50 value (concentration of inhibitor that led to a 50% reduction in viability) of 25 nmol/L (Fig. 2E). Furthermore, H3B-6527 treatment of Hep3B cells led 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 (Fig. 2F). In summary, these data show that H3B-6527 inhibits proliferation and leads to apoptosis in a HCC cell line by inhibiting FGFR4 signaling. Reference: Cancer Res. 2017 Dec 15;77(24):6999-7013. https://cancerres.aacrjournals.org/content/77/24/6999.long

In vivo activity:

Furthermore, ESCC tumors in nude mice responded to H3B-6527 treatment with an apparent slowing of growth. At 20 days of H3B-6527 treatment, the speed of ESCC tumor growth was reduced and the tumor volume was significantly smaller. On the contrary, the control group treated with physiological saline exhibited no significant inhibitory effects. These findings indicate that FGFR4 blocking is effective in inhibiting the growth and survival of ESCC cancer cells in xenograft models. A dose-response effect of tumor regression may be achieved with higher doses of H3B-6527 administered for longer periods (20 days). The effectiveness of H3B-6527 in ESCC tumor xenografts may be linked to the blocking of FGFR4 in human ESCC cancers. Therefore, FGFR4 may become a potential target and H3B‐6527 may be useful for ESCC cancer patients with FGFR4 overexpression. Reference: Thorac Cancer. 2018 Dec; 9(12): 1687–1698. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275831/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	79.42

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 629.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Xin Z, Song X, Jiang B, Gongsun X, Song L, Qin Q, Wang Q, Shi M, Liu X. Blocking FGFR4 exerts distinct anti-tumorigenic effects in esophageal squamous cell carcinoma. Thorac Cancer. 2018 Dec;9(12):1687-1698. doi: 10.1111/1759-7714.12883. Epub 2018 Sep 28. PMID: 30267473; PMCID: PMC6275831. 2. Joshi JJ, Coffey H, Corcoran E, Tsai J, Huang CL, Ichikawa K, Prajapati S, Hao MH, Bailey S, Wu J, Rimkunas V, Karr C, Subramanian V, Kumar P, MacKenzie C, Hurley R, Satoh T, Yu K, Park E, Rioux N, Kim A, Lai WG, Yu L, Zhu P, Buonamici S, Larsen N, Fekkes P, Wang J, Warmuth M, Reynolds DJ, Smith PG, Selvaraj A. H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma. Cancer Res. 2017 Dec 15;77(24):6999-7013. doi: 10.1158/0008-5472.CAN-17-1865. PMID: 29247039.

In vitro protocol:

In vivo protocol:

1: Joshi JJ, Coffey H, Corcoran E, Tsai J, Huang CL, Ichikawa K, Prajapati S, Hao MH, Bailey S, Wu J, Rimkunas V, Karr C, Subramanian V, Kumar P, MacKenzie C, Hurley R, Satoh T, Yu K, Park E, Rioux N, Kim A, Lai WG, Yu L, Zhu P, Buonamici S, Larsen N, Fekkes P, Wang J, Warmuth M, Reynolds DJ, Smith PG, Selvaraj A. H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma. Cancer Res. 2017 Dec 15;77(24):6999-7013. doi: 10.1158/0008-5472.CAN-17-1865. PMID: 29247039. 2: Colombo F, Smith S, Lai GW, Nix D, Smith PG, Schindler J, Rioux N. Correlation of the in vitro biotransformation of H3B-6527 in dog and human hepatocytes with the in vivo metabolic profile of ¹⁴C-H3B-6527 in a dog mass balance study. Xenobiotica. 2020 Apr;50(4):458-467. doi: 10.1080/00498254.2019.1643941. Epub 2019 Aug 2. PMID: 31305210. 3: Rioux N, Kim A, Nix D, Bowser T, Warmuth M, Smith PG, Schindler J. Effect of a high-fat meal on the relative bioavailability of H3B-6527, a novel FGFR4 inhibitor, in healthy volunteers. Cancer Chemother Pharmacol. 2019 Jan;83(1):91-96. doi: 10.1007/s00280-018-3708-3. Epub 2018 Oct 27. PMID: 30368584.