Derazantinib, CAS No. 1234356-69-4, also known as ARQ-087, is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor ARQ 087 binds to and potently inhibits the activity of FGFR subtypes 1, 2 and 3. This may result in the inhibition of FGFR-mediated signal transduction pathways, tumor cell proliferation, tumor angiogenesis and tumor cell death in FGFR-overexpressing tumor cells. FGFR, a receptor tyrosine kinase, is upregulated in many tumor cell types and plays a key role in tumor cellular proliferation, differentiation, angiogenesis and survival.

Product information

CAS Number: 1234356-69-4

Molecular Weight: 468.57

Formula: C29H29FN4O

Synonym:

ARQ 087

ARQ087

ARQ-087

Chemical Name: (6R)-6-(2-fluorophenyl)-N-(3-{2-[(2-methoxyethyl)amino]ethyl}phenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine

Smiles: COCCNCCC1=CC(=CC=C1)NC1N=C2C3=CC=CC=C3[C@@H](CC2=CN=1)C1=CC=CC=C1F

InChiKey: KPJDVVCDVBFRMU-AREMUKBSSA-N

InChi: InChI=1S/C29H29FN4O/c1-35-16-15-31-14-13-20-7-6-8-22(17-20)33-29-32-19-21-18-26(24-10-4-5-12-27(24)30)23-9-2-3-11-25(23)28(21)34-29/h2-12,17,19,26,31H,13-16,18H2,1H3,(H,32,33,34)/t26-/m1/s1

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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

References:

1. Ganguli D, Das N, Saha I, Sanapala KR, Chaudhuri D, Ghosh S, Dey S. Association between inflammatory markers and cardiovascular risk factors in women from Kolkata, W.B, India. Arq Bras Cardiol. 2011 Jan;96(1):38-46. Epub 2010 Dec 22. English, Portuguese, Spanish. PubMed PMID: 21180893.
2. Dantas RO, Alves LM, Cassiani Rde A. Gender differences in proximal esophageal contractions. Arq Gastroenterol. 2009 Oct-Dec;46(4):284-7. PubMed PMID: 20232007.

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