BLU9931 | CAS#1538604-68-0 | FGFR4 inhibitor

MedKoo Cat#: 206192 | Name: BLU9931

Description:

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

BLU9931 is a potent and irreversible small-molecule inhibitor of FGFR4, as a targeted therapy to treat patients with HCC whose tumors have an activated FGFR4 signaling pathway. BLU9931 is exquisitely selective for FGFR4 versus other FGFR family members and all other kinases. BLU9931 shows remarkable antitumor activity in mice bearing an HCC tumor xenograft that overexpresses FGF19 due to amplification as well as a liver tumor xenograft that overexpresses FGF19 mRNA but lacks FGF19 amplification. Approximately one third of patients with HCC whose tumors express FGF19 together with FGFR4 and its coreceptor klotho β (KLB) could potentially respond to treatment with an FGFR4 inhibitor.

Chemical Structure

BLU9931

CAS#1538604-68-0

Theoretical Analysis

MedKoo Cat#: 206192

Name: BLU9931

CAS#: 1538604-68-0

Chemical Formula: C26H22Cl2N4O3

Exact Mass: 508.1069

Molecular Weight: 509.38

Elemental Analysis: C, 61.31; H, 4.35; Cl, 13.92; N, 11.00; O, 9.42

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to Ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

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Synonym

BLU9931; BLU-9931; BLU 9931.

IUPAC/Chemical Name

N-(2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-3-methylphenyl)acrylamide

InChi Key

TXEBNKKOLVBTFK-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H22Cl2N4O3/c1-5-21(33)30-18-8-6-7-14(2)25(18)32-26-29-13-16-11-15(9-10-17(16)31-26)22-23(27)19(34-3)12-20(35-4)24(22)28/h5-13H,1H2,2-4H3,(H,30,33)(H,29,31,32)

SMILES Code

C=CC(NC1=CC=CC(C)=C1NC2=NC=C3C=C(C4=C(Cl)C(OC)=CC(OC)=C4Cl)C=CC3=N2)=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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC50826

QC Data

View QC data: current batch, Lot#TZC50826

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BLU9931 is an irreversible fibroblast growth factor receptor 4 (FGFR4) inhibitor with an IC50 of 3 nM and a Kd of 6 nM.

In vitro activity:

PK-1 cells exhibited a dose-dependent decrease in proliferation in the presence of BLU9931 (Figure 3A). An inhibitory effect on proliferation was also observed in T3M-4 cells (Figure S3A). By contrast, BLU9931 did no inhibit proliferation in PK-45P cells (Figure 3A), which expressed very low FGFR4 levels (Figure 1). Next, this study examined whether BLU9931 exerts toxic effects in PDAC cells. Incubation of PK-1 cells with 2 μM BLU9931 followed by fluorescence activated cell sorter (FACS) analysis using annexin V and propidium iodide (PI) showed that ~2% of the cells underwent apoptosis, necrosis, or cell injury (Figure 3B). Higher concentration (>10 μM) of BLU9931 revealed dead and floating cells suggestive of a toxic effect at these very high concentrations of the drug. Reference: Cancers (Basel). 2020 Oct; 12(10): 2976. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602396/

In vivo activity:

Mice with YTN16 s.c. transplanted or peritoneally transplanted mice were treated for 3 weeks with BLU9931, a potent, selective, and irreversible FGFR4 inhibitor. Growth of s.c. tumor in BLU9931‐treated mice was slightly blunted compared to non‐treated mice (Figure 7A,B). However, the growth of peritoneal dissemination was remarkably different. Only very small spots of peritoneal dissemination were detected macroscopically and microscopically in BLU9931‐treated mice (Figure 7C,D,E,G). Surprisingly, the histology of s.c. tumor after BLU9931 treatment was remarkably different from that of the original tumor, even though the difference in growth rate was small (Figure 7F,H). YTN16 tumor formed glands, whereas BLU9931‐treated YTN16 tumor formed few glands in all 3 transplanted mice. After activation of FGFR, signaling of Stat3, Erk, and Akt is known to be activated downstream. Staining for all 3 markers was weaker in BLU9931‐treated tumor compared to the original YTN16 tumor. Reference: Cancer Sci. 2018 May; 109(5): 1480–1492. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980194/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	67.8	133.06

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 509.38 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. Sasaki N, Gomi F, Yoshimura H, Yamamoto M, Matsuda Y, Michishita M, Hatakeyama H, Kawano Y, Toyoda M, Korc M, Ishiwata T. FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer. Cancers (Basel). 2020 Oct 14;12(10):2976. doi: 10.3390/cancers12102976. PMID: 33066597; PMCID: PMC7602396. 2. Hagel M, Miduturu C, Sheets M, Rubin N, Weng W, Stransky N, Bifulco N, Kim JL, Hodous B, Brooijmans N, Shutes A, Winter C, Lengauer C, Kohl NE, Guzi T. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37. doi: 10.1158/2159-8290.CD-14-1029. Epub 2015 Mar 16. PMID: 25776529. 3. Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, Saito T, Matsushita H, Uchida E, Seto Y, Goldenring JR, Kakimi K, Tatematsu M, Tsukamoto T. Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018 May;109(5):1480-1492. doi: 10.1111/cas.13569. Epub 2018 Apr 15. PMID: 29532565; PMCID: PMC5980194.

In vitro protocol:

In vivo protocol:

1. Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, Saito T, Matsushita H, Uchida E, Seto Y, Goldenring JR, Kakimi K, Tatematsu M, Tsukamoto T. Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018 May;109(5):1480-1492. doi: 10.1111/cas.13569. Epub 2018 Apr 15. PMID: 29532565; PMCID: PMC5980194. 2. Hagel M, Miduturu C, Sheets M, Rubin N, Weng W, Stransky N, Bifulco N, Kim JL, Hodous B, Brooijmans N, Shutes A, Winter C, Lengauer C, Kohl NE, Guzi T. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37. doi: 10.1158/2159-8290.CD-14-1029. Epub 2015 Mar 16. PMID: 25776529.

1: Packer LM, Pollock PM. Paralog-Specific Kinase Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR Agents. Cancer Discov. 2015 Apr;5(4):355-7. doi: 10.1158/2159-8290.CD-15-0246. PubMed PMID: 25847957. 2: Hagel M, Miduturu C, Sheets M, Rubin N, Weng W, Stransky N, Bifulco N, Kim JL, Hodous B, Brooijmans N, Shutes A, Winter C, Lengauer C, Kohl NE, Guzi T. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37. doi: 10.1158/2159-8290.CD-14-1029. Epub 2015 Mar 16. PubMed PMID: 25776529.