Axitinib

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Cat Number

API319460850

CAS Number

319460-85-0

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Product Detail Description Scientific Support Advanced Innovations Customer Q&A

CAS Number

319460-85-0

EINECS

638-771-6

Storage

Store at room temperature

Synonyms

Inlyta; AG-13736; axitinibum; C9LVQ0YUXG; DTXSID3049049; AG013736; NSC-757441

Molecular Formula

C22H18N4OS

Molecular Weight

386.5

Smiles

CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)/C=C/C4=CC=CC=N4

Appearance

White to tan powder

Melting Point

213-215°C

Boiling Point

668.9±55.0°C at 760 mmHg (Predicted)

Relative Density

1.4±0.1

General Description

Axitinib is a synthetic small-molecule inhibitor of the vascular endothelial growth factor receptors (VEGFR), with a thienopyridine core and an amide side chain. Its chemical structure is N-methyl-2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]benzamide.

Mechanism of Action

Axitinib is a potent and selective inhibitor of VEGFR-1, VEGFR-2, and VEGFR-3, blocking the binding of VEGF to these receptors and inhibiting downstream signaling pathways, including the PI3K/AKT and MAPK pathways. This inhibits angiogenesis, reducing tumor blood supply and tumor growth. The drug has a higher selectivity for VEGFR than for other kinases, such as PDGFR and c-KIT.

Application

Axitinib is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of prior systemic therapy, such as sunitinib or cytokine therapy. It is also used for the treatment of hepatocellular carcinoma and for other solid tumors.

In JAVELIN Renal 101, neither PD-L1 expression nor tumor mutational burden differentiated PFS between avelumab+axitinib and sunitinib in aRCC. FcγR SNPs were unimpactful. However, new immunomodulatory and angiogenesis gene expression signatures, mutational profiles, and HLA types were associated with differential PFS. These findings provide insight into determinants of response to combined PD-1/PD-L1 and angiogenesis inhibition.

Fig. 1 Progression-free survival (PFS) according to (a) programmed cell death ligand 1 (PD-L1) expression and (b) median invasive margin surface area by immunohistochemistry. (Motzer RJ, et al., 2020)

References

Motzer RJ, et al. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial. Nat Med. 2020;26(11):1733-1741.

In a phase II trial (145 patients across four sarcoma subtypes), axitinib demonstrated clinical activity with progression-free survival at 12 weeks rates of 42% (angiosarcoma), 45% (leiomyosarcoma), 57% (synovial sarcoma), and 33% (other subtypes). The safety profile was acceptable, with fatigue and hypertension being the most common grade 3 adverse events. The results support further investigation of axitinib in phase III trials for soft tissue sarcoma.

Fig. 2 Best response of target lesions to axitinib for patients within each sarcoma stratum. (Woll PJ, et al., 2023)

References

Woll PJ, et al. Axitinib in patients with advanced/metastatic soft tissue sarcoma (Axi-STS): an open-label, multicentre, phase II trial in four histological strata. Br J Cancer. 2023;129(9):1490-1499.

Does Axitinib require protection from light during long-term storage?

Yes, it is photosensitive. UV exposure can cause photodegradation and discoloration of the indazole ring. Store in light-resistant containers, preferably original opaque packaging.

What is the recommended storage temperature for Axitinib?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which can accelerate oxidative degradation and sulfoxide formation.

Is Axitinib hygroscopic, and how is this managed?

It is slightly hygroscopic. Under high humidity (>70% RH), it may absorb moisture and clump. Storage in tightly sealed containers with desiccant is recommended.

How is the impurity axitinib N-oxide (an oxidative degradation product) monitored?

This degradation product is quantified using a stability-indicating HPLC method, ensuring it remains within ICH qualification thresholds.