Rezivertinib (BPI-7711) is an orally bioactive, selective and irreversible third-generation EGFR tyrosine kinase inhibitor (TKI). Rezivertinib has high potency against common EGFR activating and resistant T790M mutations. Rezivertinib has excellent central nervous system/CNS penetration and has anti-tumor activity.

Physicochemical Properties

Molecular Formula	C27H30N6O3
Molecular Weight	486.57
Exact Mass	486.237
CAS #	1835667-12-3
PubChem CID	118912975
Appearance	White to yellow solid powder
Density	1.2±0.1 g/cm3
Index of Refraction	1.617
LogP	3.53
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	36
Complexity	724
Defined Atom Stereocenter Count	0
InChi Key	BPMZUKYFIDPLEA-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H30N6O3/c1-6-26(34)29-22-15-21(24(35-5)16-25(22)36-14-13-32(2)3)31-27-28-12-11-20(30-27)19-17-33(4)23-10-8-7-9-18(19)23/h6-12,15-17H,1,13-14H2,2-5H3,(H,29,34)(H,28,30,31)
Chemical Name	N-[2-[2-(dimethylamino)ethoxy]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]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	EGFR
ln Vitro	In cell lines with GI50 values of 13.3 nM (PC9, del19), 6.8 nM (HCC827, L858R), 22 nM (NCI-H1975, del19/T790M), and > 1000 nM (A431, EGFR WT), rezivertinib (BPI-7711) specifically inhibits the cellular proliferation of EGFR mutations[1].
ln Vivo	Significant tumor regression is observed when rezivertinib (BPI-7711; 6.25–25 mg/kg/day; oral; 14 days) is used[2]. The H1975-luc human NSCLC mouse model had an average survival time of 112% longer when rezivertinib (12.5 mg/kg/day; oral; 14 days) is administered[2]. The anti-tumor activity of rezivertinib (50 mg/kg/day; oral) has been linked to an increase in the animals' average overall survival of 115% (28 days vs. 13 days)[2].
References	[1]. Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC. J Thorac Oncol. 2021 May;16(5):740-763. [2]. Preclinical evidence of BPL-7711 activity in Egfr-mutant non-smallcell lung cancer ( NSCLC ) in orthotopically implanted human tumorxenografts in the lung and brain.
Additional Infomation	Rezivertinib is an orally available third-generation and selective inhibitor of certain epidermal growth factor receptor (EGFR) activating mutations, including the resistance mutations T790M and L858R, as well as exon 19 deletion, with potential antineoplastic activity. Upon administration, rezivertinib specifically and covalently binds to and inhibits selective EGFR mutations, with particularly high selectivity against the T790M mutation, which prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. Compared to some other EGFR inhibitors, BPI-7711 may have therapeutic benefits in tumors with T790M-mediated drug resistance. This agent shows minimal activity against wild-type EGFR (wt EGFR), and does not cause dose-limiting toxicities that occur during the use of non-selective EGFR inhibitors, which also inhibit wt EGFR. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.

Solubility Data

Solubility (In Vitro)

DMSO: 125 mg/mL (256.90 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.27 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 20.8 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: ≥ 2.08 mg/mL (4.27 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 20.8 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	2.0552 mL	10.2760 mL	20.5520 mL
	5 mM	0.4110 mL	2.0552 mL	4.1104 mL
	10 mM	0.2055 mL	1.0276 mL	2.0552 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.