Axitinib | AG013736 | CAS#319460-85-0

MedKoo Cat#: 200400 | Name: Axitinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Axitinib, also known as AG013736, is an orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect. A xitinib has received FDA (27 January 2012), EMA (13 September 2012), MHRA (3 September 2012) and TGA (26 July 2012) approval for use as a treatment for renal cell carcinoma.

Chemical Structure

Axitinib

CAS#319460-85-0

Theoretical Analysis

MedKoo Cat#: 200400

Name: Axitinib

CAS#: 319460-85-0

Chemical Formula: C22H18N4OS

Exact Mass: 386.1201

Molecular Weight: 386.47

Elemental Analysis: C, 68.37; H, 4.69; N, 14.50; O, 4.14; S, 8.30

Price and Availability

Size	Price	Availability
10mg	USD 55.00	Ready to Ship
25mg	USD 90.00	Ready to ship
100mg	USD 150.00	Ready to ship
500mg	USD 450.00	Ready to ship
1g	USD 750.00	Ready to ship
2g	USD 1,250.00	Ready to ship
5g	USD 2,750.00	Ready to ship

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Related CAS #

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Synonym

AG013736; AG 013736; AG-013736; Axitinib; Brand name: Inlyta.

IUPAC/Chemical Name

(E)-N-methyl-2-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)benzamide

InChi Key

RITAVMQDGBJQJZ-FMIVXFBMSA-N

InChi Code

InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+

SMILES Code

O=C(NC)C1=CC=CC=C1SC2=CC3=C(C=C2)C(/C=C/C4=NC=CC=C4)=NN3

Appearance

white to off-white 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, not in water

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

More Info

Axitinib (also known as AG013736) is a small molecule tyrosine kinase inhibitor under development by Pfizer. It inhibits multiple targets, including VEGFR-1, VEGFR-2, VEGFR-3, platelet derived growth factor receptor (PDGFR), and cKIT (CD117). It has been shown to significantly inhibit growth of breast cancer in xenograft models and has been successful in trials with renal cell carcinoma (RCC) and several other tumor types. Axitinib is a white to light-yellow powder with a pKa of 4.8. The solubility of axitinib in aqueous media over the range pH 1.1 to pH 7.8 is in excess of 0.2 μg/mL. The partition coefficient (n-octanol/water) is 3.5. A Phase II clinical trial showed good response in combination chemotherapy with Gemcitabine for advanced pancreatic cancer. However, Pfizer reported on January 30, 2009 that Phase III clinical trials of the drug when used in combination with Gemcitabine showed no evidence of improved survival rates over treatments using Gemcitabine alone for advanced pancreatic cancer and halted the trial. see http://en.wikipedia.org/wiki/Axitinib.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A9T03K15

View CoA: current batch, Lot#YYP20323

QC Data

View QC data: current batch, Lot#YYP20323

View QC data: current batch, Lot# A9T03K15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Axitinib is a multi-targeted tyrosine kinase inhibitor with IC50s of 0.1, 0.2, 0.1-0.3, 1.6 nM for VEGFR1, VEGFR2, VEGFR3 and PDGFRβ, respectively.

In vitro activity:

In an in vitro study, axitinib significantly inhibited proliferation and migration, and increased apoptosis, of EOC cells in a dose-dependent manner. Initially, cell viability experiments presented that axitinib showed cytotoxic activity in all EOC cells. In addition, axitinib-induced apoptosis was confirmed in EOC cell lines. However, in Western blot confirming expression of VEGFR and its downstream signaling in EOC cell lines, axitinib-induced inhibitory effects in VEGFR2, phosphorylation of AKT, and ERK were not observed in HeyA8-MDR. Unlike A2780 and HeyA8, the migration assay showed no effect of axitinib on HeyA8-MDR. Based on these results, it is hypothesized that axitinib inhibits EOC cells by targeting multiple pathways including angiogenesis, AKT, and ERK signaling pathways. Reference: Sci Rep. 2020; 10: 4904. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078214/

In vivo activity:

In the GIST-T1 xenograft mouse model, axitinib exhibited dose-dependent tumor growth suppression and the TGI (tumor inhibition rate) was 53% at 100 mg/kg/day dosage [Figure 5(a)]. In the GIST-5R xenograft mouse model, 100 mg/kg/day dosage of axitinib could almost completely block the tumor progression and showed a TGI of 88%, whereas the same dosage of imatinib showed limited effect on tumor growth [Figure 5(b)]. As expected, reduced phosphorylation of cKIT and related downstream mediators such as STAT3, AKT, and ERK in tumors were observed compared with the vehicle-treated controls (Supplemental Figure 4). Furthermore, this study found that at 100 mg/kg dosage, aurora kinase started to be inhibited, which might help to enhance the antitumor efficacy of axitinib in vivo (Supplemental Figure 4). These data were also consistent with the results observed in the cell cycle arrest assays and centrosome separation experiments [Figure 4(b) and Supplemental Figure 2]. Reference: Ther Adv Med Oncol. 2019; 11: 1758835919849757. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535728/

	Solvent	mg/mL	mM
Solubility
	DMSO	14.8	38.17
	DMF	0.3	0.65

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 386.47 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. Paik ES, Kim TH, Cho YJ, Ryu J, Choi JJ, Lee YY, Kim TJ, Choi CH, Kim WY, Sa JK, Lee JK, Kim BG, Bae DS, Han HD, Ahn HJ, Lee JW. Preclinical assessment of the VEGFR inhibitor axitinib as a therapeutic agent for epithelial ovarian cancer. Sci Rep. 2020 Mar 17;10(1):4904. doi: 10.1038/s41598-020-61871-w. PMID: 32184452; PMCID: PMC7078214. 2. Kerr LT, Donoghue JF, Wilding AL, Johns TG. Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma. Sarcoma. 2016;2016:3484673. doi: 10.1155/2016/3484673. Epub 2016 Oct 16. PMID: 27822137; PMCID: PMC5086398. 3. Liu F, Zou F, Chen C, Yu K, Liu X, Qi S, Wu J, Hu C, Hu Z, Liu J, Liu X, Wang L, Ge J, Wang W, Ren T, Bai M, Cai Y, Xiao X, Qian F, Tang J, Liu Q, Liu J. Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors. Ther Adv Med Oncol. 2019 May 17;11:1758835919849757. doi: 10.1177/1758835919849757. PMID: 31205508; PMCID: PMC6535728. 4. Van der Veken B, De Meyer GRY, Martinet W. Axitinib attenuates intraplaque angiogenesis, haemorrhages and plaque destabilization in mice. Vascul Pharmacol. 2018 Jan;100:34-40. doi: 10.1016/j.vph.2017.10.004. Epub 2017 Oct 31. PMID: 29079346.

In vitro protocol:

In vivo protocol:

1. Liu F, Zou F, Chen C, Yu K, Liu X, Qi S, Wu J, Hu C, Hu Z, Liu J, Liu X, Wang L, Ge J, Wang W, Ren T, Bai M, Cai Y, Xiao X, Qian F, Tang J, Liu Q, Liu J. Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors. Ther Adv Med Oncol. 2019 May 17;11:1758835919849757. doi: 10.1177/1758835919849757. PMID: 31205508; PMCID: PMC6535728. 2. Van der Veken B, De Meyer GRY, Martinet W. Axitinib attenuates intraplaque angiogenesis, haemorrhages and plaque destabilization in mice. Vascul Pharmacol. 2018 Jan;100:34-40. doi: 10.1016/j.vph.2017.10.004. Epub 2017 Oct 31. PMID: 29079346.

1: Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T; KEYNOTE-426 Investigators. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16. PMID: 30779529. 2: Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, Lee JL, Vasiliev A, Miller WH Jr, Gurney H, Schmidinger M, Larkin J, Atkins MB, Bedke J, Alekseev B, Wang J, Mariani M, Robbins PB, Chudnovsky A, Fowst C, Hariharan S, Huang B, di Pietro A, Choueiri TK. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1103-1115. doi: 10.1056/NEJMoa1816047. Epub 2019 Feb 16. PMID: 30779531; PMCID: PMC6716603. 3: Powles T, Plimack ER, Soulières D, Waddell T, Stus V, Gafanov R, Nosov D, Pouliot F, Melichar B, Vynnychenko I, Azevedo SJ, Borchiellini D, McDermott RS, Bedke J, Tamada S, Yin L, Chen M, Molife LR, Atkins MB, Rini BI. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open- label, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1563-1573. doi: 10.1016/S1470-2045(20)30436-8. Epub 2020 Oct 23. Erratum in: Lancet Oncol. 2020 Dec;21(12):e553. PMID: 33284113. 4: Motzer RJ, Robbins PB, Powles T, Albiges L, Haanen JB, Larkin J, Mu XJ, Ching KA, Uemura M, Pal SK, Alekseev B, Gravis G, Campbell MT, Penkov K, Lee JL, Hariharan S, Wang X, Zhang W, Wang J, Chudnovsky A, di Pietro A, Donahue AC, Choueiri TK. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial. Nat Med. 2020 Nov;26(11):1733-1741. doi: 10.1038/s41591-020-1044-8. Epub 2020 Sep 7. PMID: 32895571; PMCID: PMC8493486. 5: Choueiri TK, Motzer RJ, Rini BI, Haanen J, Campbell MT, Venugopal B, Kollmannsberger C, Gravis-Mescam G, Uemura M, Lee JL, Grimm MO, Gurney H, Schmidinger M, Larkin J, Atkins MB, Pal SK, Wang J, Mariani M, Krishnaswami S, Cislo P, Chudnovsky A, Fowst C, Huang B, di Pietro A, Albiges L. Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020 Aug;31(8):1030-1039. doi: 10.1016/j.annonc.2020.04.010. Epub 2020 Apr 25. PMID: 32339648; PMCID: PMC8436592. 6: Kelly RJ, Rixe O. Axitinib (AG-013736). Recent Results Cancer Res. 2010;184:33-44. doi: 10.1007/978-3-642-01222-8_3. PMID: 20072829. 7: Wilky BA, Trucco MM, Subhawong TK, Florou V, Park W, Kwon D, Wieder ED, Kolonias D, Rosenberg AE, Kerr DA, Sfakianaki E, Foley M, Merchan JR, Komanduri KV, Trent JC. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol. 2019 Jun;20(6):837-848. doi: 10.1016/S1470-2045(19)30153-6. Epub 2019 May 8. PMID: 31078463. 8: Tomita Y, Motzer RJ, Choueiri TK, Rini BI, Miyake H, Uemura H, Albiges L, Fujii Y, Umeyama Y, Wang J, Mariani M, Schmidinger M. Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101. ESMO Open. 2022 Apr;7(2):100450. doi: 10.1016/j.esmoop.2022.100450. Epub 2022 Apr 6. PMID: 35397432; PMCID: PMC9058903. 9: Sheng X, Yan X, Chi Z, Si L, Cui C, Tang B, Li S, Mao L, Lian B, Wang X, Bai X, Zhou L, Kong Y, Dai J, Wang K, Tang X, Zhou H, Wu H, Feng H, Yao S, Flaherty KT, Guo J. Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial. J Clin Oncol. 2019 Nov 10;37(32):2987-2999. doi: 10.1200/JCO.19.00210. Epub 2019 Aug 12. PMID: 31403867; PMCID: PMC6839911. 10: Spisarová M, Melichar B, Vitásková D, Študentová H. Pembrolizumab plus axitinib for the treatment of advanced renal cell carcinoma. Expert Rev Anticancer Ther. 2021 Jul;21(7):693-703. doi: 10.1080/14737140.2021.1903321. Epub 2021 Apr 2. PMID: 33794744. 11: Chen Y, Suzuki A, Tortorici MA, Garrett M, LaBadie RR, Umeyama Y, Pithavala YK. Axitinib plasma pharmacokinetics and ethnic differences. Invest New Drugs. 2015 Apr;33(2):521-32. doi: 10.1007/s10637-015-0214-x. Epub 2015 Feb 8. PMID: 25663295. 12: Parekh H, Griswold J, Rini B. Axitinib for the treatment of metastatic renal cell carcinoma. Future Oncol. 2016 Feb;12(3):303-11. doi: 10.2217/fon.15.322. Epub 2016 Jan 15. PMID: 26769075. 13: Grünwald V, Voss MH, Rini BI, Powles T, Albiges L, Giles RH, Jonasch E. Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Br J Cancer. 2020 Sep;123(6):898-904. doi: 10.1038/s41416-020-0949-9. Epub 2020 Jun 26. PMID: 32587360; PMCID: PMC7492460. 14: Albiges L, Gizzi M, Carton E, Escudier B. Axitinib in metastatic renal cell carcinoma. Expert Rev Anticancer Ther. 2015 May;15(5):499-507. doi: 10.1586/14737140.2015.1033408. PMID: 25907705. 15: Keating GM. Axitinib: a review in advanced renal cell carcinoma. Drugs. 2015 Nov;75(16):1903-13. doi: 10.1007/s40265-015-0483-x. PMID: 26487541. 16: Tamada S, Kondoh C, Matsubara N, Mizuno R, Kimura G, Anai S, Tomita Y, Oyama M, Masumori N, Kojima T, Matsumoto H, Chen M, Li M, Matsuda K, Tanaka Y, Rini BI, Uemura H. Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Int J Clin Oncol. 2022 Jan;27(1):154-164. doi: 10.1007/s10147-021-02014-7. Epub 2021 Nov 20. PMID: 34800178; PMCID: PMC8732816. 17: Yang Y, Huang H, Li T, Gao Q, Song Y, Wang Z. Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma. Front Immunol. 2021 Oct 26;12:728750. doi: 10.3389/fimmu.2021.728750. PMID: 34764951; PMCID: PMC8576543. 18: Li S, Wu X, Yan X, Zhou L, Chi Z, Si L, Cui C, Tang B, Mao L, Lian B, Wang X, Bai X, Dai J, Kong Y, Tang X, Feng H, Yao S, Flaherty KT, Guo J, Sheng X. Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis. J Immunother Cancer. 2022 Feb;10(2):e004036. doi: 10.1136/jitc-2021-004036. PMID: 35193932; PMCID: PMC9066368. 19: Swiecicki PL, Spector M, Worden FP. Axitinib in the Treatment of Head and Neck Malignancies. Curr Clin Pharmacol. 2016;11(2):72-6. doi: 10.2174/1574884711666160518120622. PMID: 27188575. 20: Sonpavde G, Hutson TE, Rini BI. Axitinib for renal cell carcinoma. Expert Opin Investig Drugs. 2008 May;17(5):741-8. doi: 10.1517/13543784.17.5.741. Erratum in: Expert Opin Investig Drugs. 2008 Sep;17(9):1405. PMID: 18447599.