Abivertinib maleate
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MedKoo CAT#: 206774

CAS#: 1557268-88-8 (maleate)

Description: Abivertinib, also known as avitinib, AC0010 or AC0010MA, is an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib 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.


Chemical Structure

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Abivertinib maleate
CAS# 1557268-88-8 (maleate)

Theoretical Analysis

MedKoo Cat#: 206774
Name: Abivertinib maleate
CAS#: 1557268-88-8 (maleate)
Chemical Formula: C30H30FN7O6
Exact Mass:
Molecular Weight: 603.6114
Elemental Analysis: C, 59.70; H, 5.01; F, 3.15; N, 16.24; O, 15.90

Price and Availability

Size Price Availability Quantity
50.0mg USD 190.0 2 Weeks
100.0mg USD 350.0 2 Weeks
200.0mg USD 550.0 2 Weeks
500.0mg USD 1250.0 2 Weeks
1.0g USD 2250.0 2 Weeks
2.0g USD 3950.0 2 Weeks
5.0g USD 6950.0 2 Weeks
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Related CAS #: 1557267-42-1 (free base)   1557268-88-8 (maleate)   1822357-78-7 (maleate hydrate)   1557268-90-2 (2HCl)   1801879-16-2 (HCl)    

Synonym: Avitinib maleate; AC0010MA; AC-0010MA; AC 0010MA; AC0010; AC-0010; AC 0010; Abivertinib maleate

IUPAC/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

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-

SMILES Code: C=CC(NC1=CC=CC(OC2=C3C(NC=C3)=NC(NC4=CC=C(N5CCN(C)CC5)C(F)=C4)=N2)=C1)=O.O=C(O)/C=C\C(O)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: Avitinib maleate is a pyrrolopyrimidine-based irreversible epidermal growth factor receptor (EGFR) inhibitor with an IC50 of 7.68 nM.
In vitro activity: A proliferation assay with an appropriate concentration of Apigenin in combination with low-dose Abivertinib was examined in U2932 and OCI-LY10 for 48 hours. The results indicate that the cell viability of the combined group is significantly lower than either of the single drug groups (Fig. 3A, B). Next, the results of soft agar colony formation experiments further confirmed that the colony forming ability of the combined group in U2932 is sufficiently inhibited (Fig. 3D). In order to further explore the mechanism of the combination effect, apoptosis was detected in combination and single treatment groups. The results are shown in Fig. 3E and and 3F: the combination of two drugs at a lower concentration can significantly induce apoptosis and is more than any single drug group. In the search for apoptotic mechanisms, it was concluded that the combination of two drugs can down-regulate the anti-apoptotic proteins of BCL2 and BCL-XL (Fig. 4A), while the cleaved-PARP, cleaved-C3, cleaved-C8 were also captured (Fig. 4B). Meanwhile, the expression level of BCL-2 and BCL-XL of different treatment groups was studied by Westernblot assay of tumor tissue moved from DLBCL xenograft and turned out the similar result to cell lines (Fig. 4D). According to the results, it was concluded that Apigenin synergizes with Abivertinib to induce apoptosis in diffuse large B-cell lymphoma by down-regulating BCL2, BCL-XL and activating the caspase family. Reference: J Cancer. 2020 Feb 3;11(8):2123-2132. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32127939/
In vivo activity: All mice were treated as described in methods. Representative tumors in the xenograft mice treated in different groups are shown in Fig. 5A, the treatments of Apigenin and Abivertinib or their combination significantly reduced tumor mass compared to vehicle. In details, Apigenin, Abivertinib, COM decreased by 32.5%, 48%, 80% the tumor weight compared to vehicle group respectively (Fig. 5B).The similar results were found when refer to tumor size(Fig. 5C). Next, the tumor progression was analyzed by measuring the size of tumors in each group every 2 days, the result shown in Fig. 5D, the treatments effectively inhibit the growing of tumors. In order to measure the apoptosis induced by drugs, tunnel assay was played, the results showed increase in combination group (Fig. 5E and F). When the tumor burden on spleen and liver of mice was analyzed, the HE staining showed no significant difference among groups on liver while decreasing extramedullary hematopoiesis in combination group (Fig. 5G). All the results unveiled the fact that Apigenin can inhibit the DLBCL progression and can cooperate with Abivertinib to achieve better anti-lymphoma function. Reference: J Cancer. 2020 Feb 3;11(8):2123-2132. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32127939/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 165.67

Preparing Stock Solutions

The following data is based on the product molecular weight 603.6114 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Huang S, Yu M, Shi N, Zhou Y, Li F, Li X, Huang X, Jin J. Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro. J Cancer. 2020 Feb 3;11(8):2123-2132. doi: 10.7150/jca.34981. PMID: 32127939; PMCID: PMC7052937. 2. Huang S, Li C, Zhang X, Pan J, Li F, Lv Y, Huang J, Ling Q, Ye W, Mao S, Huang X, Jin J. Abivertinib synergistically strengthens the anti-leukemia activity of venetoclax in acute myeloid leukemia in a BTK-dependent manner. Mol Oncol. 2020 Oct;14(10):2560-2573. doi: 10.1002/1878-0261.12742. Epub 2020 Jul 3. PMID: 32519423; PMCID: PMC7530784.
In vitro protocol: 1. Huang S, Yu M, Shi N, Zhou Y, Li F, Li X, Huang X, Jin J. Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro. J Cancer. 2020 Feb 3;11(8):2123-2132. doi: 10.7150/jca.34981. PMID: 32127939; PMCID: PMC7052937. 2. Huang S, Li C, Zhang X, Pan J, Li F, Lv Y, Huang J, Ling Q, Ye W, Mao S, Huang X, Jin J. Abivertinib synergistically strengthens the anti-leukemia activity of venetoclax in acute myeloid leukemia in a BTK-dependent manner. Mol Oncol. 2020 Oct;14(10):2560-2573. doi: 10.1002/1878-0261.12742. Epub 2020 Jul 3. PMID: 32519423; PMCID: PMC7530784.
In vivo protocol: 1. Huang S, Yu M, Shi N, Zhou Y, Li F, Li X, Huang X, Jin J. Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro. J Cancer. 2020 Feb 3;11(8):2123-2132. doi: 10.7150/jca.34981. PMID: 32127939; PMCID: PMC7052937. 2. Huang S, Li C, Zhang X, Pan J, Li F, Lv Y, Huang J, Ling Q, Ye W, Mao S, Huang X, Jin J. Abivertinib synergistically strengthens the anti-leukemia activity of venetoclax in acute myeloid leukemia in a BTK-dependent manner. Mol Oncol. 2020 Oct;14(10):2560-2573. doi: 10.1002/1878-0261.12742. Epub 2020 Jul 3. PMID: 32519423; PMCID: PMC7530784.

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1: Xu X. Parallel phase 1 clinical trials in the US and in China: accelerating the test of avitinib in lung cancer as a novel inhibitor selectively targeting mutated EGFR and overcoming T790M-induced resistance. Chin J Cancer. 2015 Jul 8;34(7):285-7. doi: 10.1186/s40880-015-0029-3. PubMed PMID: 26152224; PubMed Central PMCID: PMC4593347.

2: Xu X, Mao L, Xu W, Tang W, Zhang X, Xi B, Xu R, Fang X, Liu J, Fang C, Zhao L, Wang X, Jiang J, Hu P, Zhao H, Zhang L. 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. PubMed PMID: 27573423.