CPL304110 is a potent, orally bioavailable, and selective inhibitor of the fibroblast growth factor receptor FGFR (1-3) with IC50s of 0.75 nM, 0.5 nM, and 3.05 nM for FGFR (1-3). .

Physicochemical Properties

Molecular Formula	C25H30N6O2
Molecular Weight	446.544704914093
Exact Mass	446.243
CAS #	1627826-19-0
PubChem CID	136387462
Appearance	White to light yellow solid powder
LogP	3.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	606
Defined Atom Stereocenter Count	0
SMILES	C(C1NN=C(C2=NC3=CC=C(N4CCN(C)CC4)C=C3N2)C=1)CC1C=C(OC)C=C(OC)C=1
InChi Key	QHCGPJPIPKDWAT-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H30N6O2/c1-30-8-10-31(11-9-30)19-6-7-22-23(15-19)27-25(26-22)24-14-18(28-29-24)5-4-17-12-20(32-2)16-21(13-17)33-3/h6-7,12-16H,4-5,8-11H2,1-3H3,(H,26,27)(H,28,29)
Chemical Name	2-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
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	FGFR1 0.75 nM (IC50) FGFR2 0.5 nM (IC50) FGFR3 3.05 nM (IC50)
ln Vitro	CPL304110 (0-0.6 μM) inhibits downstream signaling (p-ERK) and FGFR2 phosphorylation in a dose-dependent manner[1]. In the SNU-16 proliferation assay, CPL304110 (compound 56q) shows an IC50 of 85.64 nM[1]. In comparison to FGFR2, CPL304110 (compound 56q) exhibits a selectivity over KDR (VEGFR2), Flt3, Aura A, and PDGFRb that is more than 45-fold, 345-fold, 395-fold, and 680-fold, respectively. No discernible inhibitory effects were seen with other tyrosine kinases[1].
ln Vivo	Mice treated with CPL304110 (po, 40 mg/kg) show a t1/2 of 2 h and a Cmax of 3369 ng/mL[1]. In mice, CPL304110 (compound 56q, 2 X 20 mg/kg) dramatically suppresses tumor growth without causing toxicity or appreciable body loss. Tumor growth inhibition (TGI) at day 21 (D21, day of termination) is 64% when dosed twice daily at 20 mg/kg[1].
Cell Assay	Western Blot Analysis[1] Cell Types: SNU-16 cell lines. Tested Tested Concentrations: 0-0.6 μM. Incubation Duration: 1 h. Experimental Results: Suppressed FGFR2 phosphorylation and downstream signaling (p-ERK)
Animal Protocol	Animal/Disease Models: Severe combined immunodeficient (SCID) mice implanted subcutaneously (sc) with SNU-16 (human)[1]. Doses: 20 mg/kg (X2). Route of Administration: Orally, twice (two times) daily for 21 days. Experimental Results: After 6 hrs (hours) of last dosing, concentration of 56q diminished in the plasma (9 %) but increased stepwise in the tumor cells (121%).
References	[1]. Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3). Eur J Med Chem. 2020 Nov 7;112990.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (223.94 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2394 mL	11.1972 mL	22.3944 mL
	5 mM	0.4479 mL	2.2394 mL	4.4789 mL
	10 mM	0.2239 mL	1.1197 mL	2.2394 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.