H3B-6527
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MedKoo CAT#: 407449

CAS#: 1702259-66-2

Description: 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

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H3B-6527
CAS# 1702259-66-2

Theoretical Analysis

MedKoo Cat#: 407449
Name: H3B-6527
CAS#: 1702259-66-2
Chemical Formula: C29H34Cl2N8O4
Exact Mass: 628.208
Molecular Weight: 629.543
Elemental Analysis: C, 55.33; H, 5.44; Cl, 11.26; N, 17.80; O, 10.17

Price and Availability

Size Price Availability Quantity
5.0mg USD 95.0 Same day
10.0mg USD 165.0 Same day
25.0mg USD 350.0 Same day
50.0mg USD 550.0 Same day
100.0mg USD 950.0 Same day
200.0mg USD 1450.0 2 Weeks
500.0mg USD 2850.0 2 Weeks
1.0g USD 3850.0 2 weeks
2.0g USD 5950.0 2 weeks
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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

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 79.42

Preparing Stock Solutions

The following data is based on the product molecular weight 629.543 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.

Recalculate based on batch purity %
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: 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 vivo 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.

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Additional Information

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.