ARQ-087 free base · Synonyms: Derazantinib

Derazantinib (ARQ-087) is an orally bioavailable, ATP competitive tyrosine kinase inhibitor; exhibits potent activity against FGFR1-3 chondrocytes…

For research use only. Not for human or veterinary use.

Target FGFR

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

ARQ-087 structure

CAS No.: 1234356-69-4

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
250 mg	USD 380.00	BP-01858-250mg	In stock	Get quote
500 mg	USD 630.00	BP-01858-500mg	In stock	Get quote
1 g	USD 980.00	BP-01858-1g	In stock	Get quote
5 g	Inquire	BP-01858-5g	Inquire	Inquire

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Related forms

BP-01858A — Derazantinib hydrochloride

Description

Derazantinib (ARQ-087) is an orally bioavailable, ATP competitive tyrosine kinase inhibitor; exhibits potent activity against FGFR1-3 chondrocytes with IC50s of 4.5, 1.8, and 4.5 nM, respectively.

Biological activity

In Vitro In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2α, AKT, ERK) is evident by the response to Derazantinib treatment. Cell proliferation studies demonstrate Derazantinib has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein show a positive relationship between Derazantinib induced G1 cell cycle arrest and subsequent induction of apoptosis. Derazantinib rescues the FGF2-mediated growth arrest with EC50 at about 100 nM, with no significant toxicity detected for up to 500 nM. The concentration range at which Derazantinib significantly suppresses the FGF2 effect is between 70-500 nM. Derazantinib inhibits FGF-mediated loss of extracellular matrix and induction of chondrocyte premature senescence. Derazantinib rescues FGF-mediated inhibition of chondrocyte differentiation in tibia cultures. Derazantinib inhibits FGFR1-4 but no other receptor tyrosine kinases in cell-free kinase assay. Derazantinib inhibits FGFR1 and FGFR2 mutants associated with craniosynostoses. Derazantinib rescues FGFR-mediated bone differentiation in mouse limb bud micromass cultures and ex vivo mouse calvarial organ cultures. In Vivo Derazantinib is effective at inhibiting tumor growth in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions. Most of the embryos exhibit abnormal external phenotype (81.3%) in Derazantinib-injected wings, possibly due to inhibition of proliferation of limb bud mesenchyme. The wings are shorter and thinner, with skeletal phenotype typical for FGFR inhibition, where ulna and radius are shorter or smaller in size, or occasionally missing completely.

Identifiers

SMILES: COCCNCCC1=CC(NC2=NC=C3C[C@@H](C4=CC=CC=C4F)C4=CC=CC=C4C3=N2)=CC=C1
InChIKey: KPJDVVCDVBFRMU-AREMUKBSSA-N

Specifications

MW (average): 468.5652
Formula: C₂₉H₂₉FN₄O
CAS No.: 1234356-69-4
Physical state: Solid
Color: White to yellow
Shipping: 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: Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1]. Hall TG, et al. Preclinical Activity of ARQ-087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594.

[2]. Balek L, et al. ARQ-087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3. Bone. 2017 Dec;105:57-66

Same target

Search FGFR

Same research area

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