Irpagratinib (ABSK011) is an orally bioactive fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor targeting FGFR4 (IC50<10 nM). Irpagratinib inhibits FGFR4 autophosphorylation and blocks signaling from FGFR4 to downstream pathway activation. Irpagratinib demonstrated high exposure in PK studies in mice, rats, and dogs, and anticancer effect in subcutaneous xenograft tumor models.

Physicochemical Properties

Molecular Formula	C28H32F2N6O5
Molecular Weight	570.587693214417
Exact Mass	570.24
CAS #	2230974-62-4
PubChem CID	135181440
Appearance	Light yellow to yellow solid powder
LogP	2.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	9
Heavy Atom Count	41
Complexity	899
Defined Atom Stereocenter Count	2
SMILES	CC1(CN(C1)C2=C3C(=CC(=N2)C4=C(C(=CC(=C4F)OC)OC)F)C=NC(=N3)N[C@@H]5COCC[C@@H]5NC(=O)C=C)OC
InChi Key	PGRHEHZIRYNZDV-FUHWJXTLSA-N
InChi Code	InChI=1S/C28H32F2N6O5/c1-6-21(37)32-16-7-8-41-12-18(16)34-27-31-11-15-9-17(22-23(29)19(38-3)10-20(39-4)24(22)30)33-26(25(15)35-27)36-13-28(2,14-36)40-5/h6,9-11,16,18H,1,7-8,12-14H2,2-5H3,(H,32,37)(H,31,34,35)/t16-,18+/m0/s1
Chemical Name	N-[(3S,4S)-3-[[6-(2,6-difluoro-3,5-dimethoxyphenyl)-8-(3-methoxy-3-methylazetidin-1-yl)pyrido[3,4-d]pyrimidin-2-yl]amino]oxan-4-yl]prop-2-enamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	FGFR4[1]
References	[1]. Chen Z. Abstract LB-272: Discovery and characterization of a novel FGFR4 Inhibitor for the treatment of hepatocellular carcinoma. Cancer Research, 2018, 78(13_Supplement): LB-272-LB-272.
Additional Infomation	Irpagratinib is an orally bioavailable, selective inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon oral administration, irpagratinib is specifically and irreversibly binds to the cysteine residue at position 552 (Cys 552) that is within the active site of FGFR4. This blocks FGFR4 autophosphorylation and activation of receptor tyrosine kinase activity that would normally occur after binding to its ligand, fibroblast growth factor 19 (FGF19), which both inhibits FGFR4-mediated signaling and leads to the inhibition of tumor cell proliferation in FGF19- and FGFR4-overexpressing cells. FGFR4, a receptor tyrosine kinase, is involved in angiogenesis and in the proliferation, differentiation, and survival of tumor cells. FGFR4 expression is associated with poor prognosis. FGF19 is overexpressed by certain tumor cell types.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7526 mL	8.7629 mL	17.5257 mL
	5 mM	0.3505 mL	1.7526 mL	3.5051 mL
	10 mM	0.1753 mL	0.8763 mL	1.7526 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.