Avitinib maleate (formerly also known as AC-0010, AC0010MA; Abivertinib), the maleate salt of avitinib, is an orally bioavailable and covalent/irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for T790M resistance mutations. It has anticancer activity and currently in clinical trials. AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib.

Physicochemical Properties

Molecular Formula	C30H30FN7O6
Molecular Weight	603.61
Exact Mass	603.224
CAS #	1557268-88-8
Related CAS #	Avitinib;1557267-42-1
PubChem CID	121596128
Appearance	Light yellow to yellow solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	9
Heavy Atom Count	44
Complexity	871
Defined Atom Stereocenter Count	0
SMILES	CN1CCN(CC1)C2=C(C=C(C=C2)NC3=NC4=C(C=CN4)C(=N3)OC5=CC=CC(=C5)NC(=O)C=C)F.C(=C\C(=O)O)\C(=O)O
InChi Key	VRHPZWLHPIENFW-BTJKTKAUSA-N
InChi Code	InChI=1S/C26H26FN7O2.C4H4O4/c1-3-23(35)29-17-5-4-6-19(15-17)36-25-20-9-10-28-24(20)31-26(32-25)30-18-7-8-22(21(27)16-18)34-13-11-33(2)12-14-34;5-3(6)1-2-4(7)8/h3-10,15-16H,1,11-14H2,2H3,(H,29,35)(H2,28,30,31,32);1-2H,(H,5,6)(H,7,8)/b;2-1-
Chemical Name	N-(3-((2-((3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenyl) acrylamide maleate
Synonyms	AC0010; AC0010MA;AC-0010; AC 0010 maleate; AC-0010MA; AC 0010MA; Abivertinib maleate
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, avoid exposure to moisture.
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	In NCI-H1975 and NIH/3T3_TC32T8 cells, avitinib (AC0010; 0.13 nM-2 μM; 2 h) maleate selectively inhibits the phosphorylation of mutant EGFR with IC50 values of 7.3 and 2.8 nM, respectively. These values are approximately 115 and 298 times more sensitive than inhibition. EGFR times wild-type in A431. In NCI-H1975 cells, avitinib efficiently inhibits EGFR-Tyr1068 phosphorylation, and NCI-H1975 cells have 65 times greater selectivity than A431 cells. Apart from preventing EGFR-Tyr1068 phosphorylation, avitinib also prevents Akt and ERK1/2, which are downstream targets, from becoming phosphorylated in NCI-H1975 and HCC827 cells [1].
ln Vivo	In xenograft models, long-term avitinib (AC0010; 12.5-500 mg/kg; oral; once daily; for 14 days) slows the growth of EGFR mutant tumors but not wild-type EGFR tumors [1].
Cell Assay	Western Blot Analysis[1] Cell Types: NCI-H1975, HCC827, A431 cells Tested Concentrations: 0.13 nM, 0.64 nM, 3.2 nM, 16 nM, 80 nM, 0.4 μM, 2 μM Incubation Duration: 2 h Experimental Results: Selectively inhibits mutant EGFR phosphorylation with IC50 values of 7.3 and 2.8 nM in NCI-H1975 and NIH/3T3_TC32T8 cells.
Animal Protocol	Animal/Disease Models: Nu/Nu nude mice (Six- to 8weeks old) injected with NCI-H1975 and A431 cells[1] Doses: 12.5, 50, and 500 mg/kg Route of Administration: Orally administration; one time/day; for 14 days Experimental Results: Inhibited EGFR-mutant tumor growth but not wild-type EGFR tumor growth.
References	[1]. AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients. Mol Cancer Ther. 2016 Nov;15(11):2586-2597. [2]. Promising efficacy of novel BTK inhibitor AC0010 in mantle cell lymphoma. J Cancer Res Clin Oncol. 2018;144(4):697-706.
Additional Infomation	Abivertinib Maleate is the maleate salt form of abivertinib, an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, abivertinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR. Abivertinib Maleate Anhydrous is the maleate salt form of abivertinib, an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, abivertinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 300 mg/mL (497.02 mM) Water: NA Ethanol: NA

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 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 (4.14 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 (4.14 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	1.6567 mL	8.2835 mL	16.5670 mL
	5 mM	0.3313 mL	1.6567 mL	3.3134 mL
	10 mM	0.1657 mL	0.8283 mL	1.6567 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.