BPI-9016M is a potent, orally bioactive, selective dual c-Met and AXL tyrosine kinase inhibitor (TKI). BPI-9016M inhibits tumor cell growth, migration and invasion of lung adenocarcinoma.

Physicochemical Properties

Molecular Formula	C25H18F2N4O3
Molecular Weight	460.43
CAS #	1528546-94-2
PubChem CID	72700713
Appearance	Light yellow to brown solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	34
Complexity	842
Defined Atom Stereocenter Count	0
SMILES	C1C(OC2C=CC(NC(=O)C3C(C(C4C=CC(F)=CC=4)=CNC=3)=O)=CC=2F)=C2C(NC=1)=NCC2
Synonyms	BPI9016M; BPI 9016M
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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

ln Vitro	BPI-9016M suppresses cell growth at 6.3-25 μM for two weeks [2]. In the G1 phase, BPI-9016M (12.5-50 μM; 24 hours) causes an increase in the number of tumor cells [2]. In H1299 and A549 cells, BPI-9016M (3.1-50 μM) dose-dependently decreases the expression of c-Met, pc-Met, p-AKT, and p-ERK [2]. In both primary lung adenocarcinoma cells and several lung adenocarcinoma cell lines (A549, H1299, H1650, H1975, HCC827, and PC-9 cells), the IC50 of BPI-9016M varies from 5.3 μM to 27.1 μM [2].
ln Vivo	BPI-9016M (60 mg/kg; oral; given once daily for 16 or 12 days) dramatically reduces the formation of tumors in NOD/SCID mice's PDX xenografts [2].
Cell Assay	Cell proliferation assay[2] Cell Types: A549 and H1299 Cell Tested Concentrations: 6.3, 12.5, 25 μM Incubation Duration: 2 weeks Experimental Results: Colony formation was Dramatically inhibited in a dose-dependent manner. Cell cycle analysis [2] Cell Types: A549 and H1299 Cell Tested Concentrations: 12.5, 25, 50 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced more tumor cells to accumulate in G1 phase.
Animal Protocol	Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse [2] Doses: 60 mg/kg Route of Administration: Oral; one time/day for 16 or 12 days Experimental Results: Significant inhibition of tumor growth in PDX xenografts in NOD/SCID (severe combined immunodeficient) mouse.
References	[1]. BPI-9016M, a c-Met inhibitor, suppresses tumor cell growth, migration and invasion of lung adenocarcinoma via miR203-DKK1. Theranostics. 2018 Nov 12;8(21):5890-5902. [2]. First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer.J Hematol Oncol. 2020 Jan 16;13(1):6.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~217.19 mM)

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	2.1719 mL	10.8594 mL	21.7188 mL
	5 mM	0.4344 mL	2.1719 mL	4.3438 mL
	10 mM	0.2172 mL	1.0859 mL	2.1719 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.