WARNING: This product is for research use only, not for human or veterinary use.
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.
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
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
| 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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 165.67 |
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.
| 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. |
1: Huang J, Huang X, Li Y, Li X, Wang J, Li F, Yan X, Wang H, Wang Y, Lin X, Tu J, He D, Ye W, Yang M, Jin J. Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis. Front Med. 2022 Jun;16(3):416-428. doi: 10.1007/s11684-021-0838-5. Epub 2021 Nov 18. PMID: 34792736.
2: He J, Huang Z, Han L, Gong Y, Xie C. Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer (Review). Int J Oncol. 2021 Nov;59(5):90. doi: 10.3892/ijo.2021.5270. Epub 2021 Sep 24. PMID: 34558640; PMCID: PMC8562388.
3: Wang H, Pan R, Zhang X, Si X, Wang M, Zhang L. Abivertinib in patients with T790M-positive advanced NSCLC and its subsequent treatment with osimertinib. Thorac Cancer. 2020 Mar;11(3):594-602. doi: 10.1111/1759-7714.13302. Epub 2020 Jan 14. PMID: 31943845; PMCID: PMC7049520.
4: Nagasaka M, Zhu VW, Lim SM, Greco M, Wu F, Ou SI. Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC. J Thorac Oncol. 2021 May;16(5):740-763. doi: 10.1016/j.jtho.2020.11.028. Epub 2020 Dec 15. PMID: 33338652.
5: 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.
6: Tang Q, Chen H, Mai Z, Sun H, Xu L, Wu G, Tu Z, Cheng X, Wang X, Chen T. Bim- and Bax-mediated mitochondrial pathway dominates abivertinib-induced apoptosis and ferroptosis. Free Radic Biol Med. 2022 Feb 20;180:198-209. doi: 10.1016/j.freeradbiomed.2022.01.013. Epub 2022 Jan 19. PMID: 35063650.
7: Huang S, Pan J, Jin J, Li C, Li X, Huang J, Huang X, Yan X, Li F, Yu M, Hu C, Jin J, Xu Y, Ling Q, Ye W, Wang Y, Jin J. Abivertinib, a novel BTK inhibitor: Anti-Leukemia effects and synergistic efficacy with homoharringtonine in acute myeloid leukemia. Cancer Lett. 2019 Oct 1;461:132-143. doi: 10.1016/j.canlet.2019.07.008. Epub 2019 Jul 13. PMID: 31310800.
8: Wang L, Guo L, Wang Y, Guo R, Xu Z, Gao Z, Xie L, Chen J, Chen Y, Liu Y, Zhang H, Bao L, Xu W, Zhu M, Shao F, Shu Y. Metabolic disposition of [14 C]-abivertinib, an epidermal growth factor receptor tyrosine kinase inhibitor: Role of glutathione conjugation. Br J Clin Pharmacol. 2021 Mar;87(3):1475-1485. doi: 10.1111/bcp.14555. Epub 2020 Nov 5. PMID: 32959915.
9: Zhou Q, Wu L, Hu P, An T, Zhou J, Zhang L, Liu XQ, Luo F, Zheng X, Cheng Y, Yang N, Li J, Feng J, Han B, Song Y, Wang K, Zhang L, Fang J, Zhao H, Shu Y, Lin XY, Chen Z, Gan B, Xu WH, Tang W, Zhang X, Yang JJ, Xu X, Wu YL. A Novel Third- generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non- Small Cell Lung Cancer: a Multicenter Phase I/II Study. Clin Cancer Res. 2022 Mar 15;28(6):1127-1135. doi: 10.1158/1078-0432.CCR-21-2595. PMID: 34740925; PMCID: PMC9365372.
10: 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.
11: Zhang YC, Chen ZH, Zhang XC, Xu CR, Yan HH, Xie Z, Chuai SK, Ye JY, Han- Zhang H, Zhang Z, Bai XY, Su J, Gan B, Yang JJ, Li WF, Tang W, Luo FR, Xu X, Wu YL, Zhou Q. Analysis of resistance mechanisms to abivertinib, a third-generation EGFR tyrosine kinase inhibitor, in patients with EGFR T790M-positive non-small cell lung cancer from a phase I trial. EBioMedicine. 2019 May;43:180-187. doi: 10.1016/j.ebiom.2019.04.030. Epub 2019 Apr 23. PMID: 31027916; PMCID: PMC6558024.
12: Zheng X, Wang W, Zhang Y, Ma Y, Zhao H, Gao H, Hu P, Jiang J. Development of an LC-MS/MS method for quantifying two main metabolites of abivertinib in human plasma. Biomed Chromatogr. 2020 Feb;34(2):e4704. doi: 10.1002/bmc.4704. Epub 2019 Dec 23. PMID: 31629371.
13: Tan S, Lu R, Yao D, Wang J, Gao P, Xie G, Liu H, Yao X. Identification of LRRK2 Inhibitors through Computational Drug Repurposing. ACS Chem Neurosci. 2023 Feb 1;14(3):481-493. doi: 10.1021/acschemneuro.2c00672. Epub 2023 Jan 17. PMID: 36649061.
14: Schein CH. Repurposing approved drugs for cancer therapy. Br Med Bull. 2021 Mar 25;137(1):13-27. doi: 10.1093/bmb/ldaa045. PMID: 33517358; PMCID: PMC7929227.
15: Alizadehmohajer N, Behmardi A, Najafgholian S, Moradi S, Mohammadi F, Nedaeinia R, Haghjooy Javanmard S, Sohrabi E, Salehi R, Ferns GA, Emami Nejad A, Manian M. Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking. Netw Model Anal Health Inform Bioinform. 2022;11(1):11. doi: 10.1007/s13721-021-00341-3. Epub 2022 Feb 4. PMID: 35136710; PMCID: PMC8814570.
16: Jade D, Ayyamperumal S, Tallapaneni V, Joghee Nanjan CM, Barge S, Mohan S, Nanjan MJ. Virtual high throughput screening: Potential inhibitors for SARS- CoV-2 PLPRO and 3CLPRO proteases. Eur J Pharmacol. 2021 Jun 15;901:174082. doi: 10.1016/j.ejphar.2021.174082. Epub 2021 Apr 3. PMID: 33823185; PMCID: PMC8018918.
17: Miao Y, Wang Y, Bi Z, Huang K, Gao J, Li X, Li S, Wei L, Zhou H, Yang C. Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice. BMC Pulm Med. 2023 Mar 22;23(1):94. doi: 10.1186/s12890-023-02385-9. PMID: 36949426; PMCID: PMC10031887.
18: Wu Q, Jiang H, Wang S, Dai D, Chen F, Meng D, Geng P, Tong H, Zhou Y, Pan D, Zhou Q, Wang C. Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats. Thorac Cancer. 2020 Oct;11(10):2775-2781. doi: 10.1111/1759-7714.13587. Epub 2020 Aug 19. PMID: 32812378; PMCID: PMC7529555.
19: Shi Y, Meng D, Wang S, Geng P, Xu T, Zhou Q, Zhou Y, Li W, Chen X. Effects of Avitinib on CYP450 Enzyme Activity in vitro and in vivo in Rats. Drug Des Devel Ther. 2021 Aug 21;15:3661-3673. doi: 10.2147/DDDT.S323186. PMID: 34456561; PMCID: PMC8387736.
20: Attwa MW, Kadi AA, Abdelhameed AS. Reactive intermediates and bioactivation pathways characterization of avitinib by LC-MS/MS: In vitro metabolic investigation. J Pharm Biomed Anal. 2019 Feb 5;164:659-667. doi: 10.1016/j.jpba.2018.11.033. Epub 2018 Nov 17. PMID: 30472584.
