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Purity: ≥98%
Derazantinib Racemate is the racemic mixture of derazantinib which is formerly known as ARQ 087 and is a novel, orally bioavailable, ATP competitive, small molecule, multi-kinase inhibitor with potent in vitro and in vivo activity against FGFR (fibroblast growth factor receptor) addicted cell lines and tumors with IC50s of 4.5, 1.8, and 4.5 nM for FGFR1-3 respectively in biochemical assay, IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3. The response to ARQ 087 treatment demonstrated that it inhibited the auto-phosphorylation of FGFR2 and other proteins downstream in the FGFR pathway (FRS2α, AKT, and ERK) in cells. Research on cell proliferation showed that ARQ 087 exhibited anti-proliferative activity in cell lines with FGFR dysregulation, encompassing mutations, fusions, and amplifications. Research on cell cycles in cell lines expressing high levels of FGFR2 protein revealed a positive correlation between the G1 cell cycle arrest induced by ARQ 087 and the subsequent induction of apoptosis. Furthermore, in FGFR2 modified SNU-16 and NCI-H716 xenograft tumor models with gene amplifications and fusions, ARQ 087 was successful in suppressing tumor growth in vivo. A subcohort of patients with intrahepatic cholangiocarcinoma who have been found to have FGFR2 gene fusions is part of the phase 1/2 clinical trial ongoing research on ARQ 087 (NCT01752920).
| ln Vitro |
Derazantinib, formerly known as ARQ 087, is a novel, orally bioavailable, ATP competitive, small molecule, multi-kinase inhibitor with strong in vivo and in vitro activity against tumors and cell lines addicted to the fibroblast growth factor receptor (FGFR). In a biochemical assay, the inhibitor's IC50 values were 1.8 nM for FGFR2, 4.5 nM for FGFR1, and 4.5 nM for FGFR3. The results of treating cells with ARQ 087 showed that it inhibited the auto-phosphorylation of FGFR2 and other proteins (FRS2α, AKT, and ERK) downstream in the FGFR pathway. ARQ 087 has been shown in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations, to exhibit anti-proliferative activity. A positive correlation was observed between the induction of apoptosis and the G1 cell cycle arrest induced by ARQ 087 in cell lines that had high levels of FGFR2 protein, according to cell cycle studies. Furthermore, FGFR2 modified SNU-16 and NCI-H716 xenograft tumor models with gene amplifications and fusions showed that ARQ 087 was efficacious in suppressing tumor growth in vivo. A subcohort of patients with intrahepatic cholangiocarcinoma who have been found to have FGFR2 gene fusions is part of the phase 1/2 clinical trial ongoing research on ARQ 087 (NCT01752920).
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| ln Vivo |
Derazantinib is efficient in preventing the growth of tumors in xenograft tumor models with gene fusions and amplifications that have FGFR2 altered, SNU-16, and NCI-H716. With Derazantinib-injected wings, the majority of embryos (81.3%) display aberrant external phenotypes, which may be caused by inhibition of limb bud mesenchyme proliferation. The ulna and radius are smaller or absent altogether, and the wings are shorter and thinner, with a skeletal phenotype characteristic of FGFR inhibition.
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| Enzyme Assay |
Derazantinib is titrated in DMSO using a three-fold dilution scheme, and the final DMSO concentration is achieved by diluting the mixture ten times more in deionized water. Each reaction plate well receives a volume (2.5 μL) of these dilutions or vehicle. Assay buffer containing FGFR1 or FGFR2 is added to each well in a volume of 17.5 μL, resulting in a final concentration of 0.50 or 0.25 nM, respectively. Following a 30-minute pre-incubation phase, ATP and substrate are added to assay buffer (5 μL) to achieve final concentrations of 80 nM biotinylated-PYK2 and 0-1,000 μM ATP in a final reaction volume of 25 μL. After incubating the plates for 60 minutes at room temperature, 10 μL of a stop/detection mixture made in assay buffer with EDTA is added to the plates to stop them in the dark.
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| Cell Assay |
Cells are seeded at 3000-5000 cells per well with 130 μL media in 96-well tissue culture treated plates. The cells are incubated overnight and subsequently treated with 3-fold serial dilutions of Derazantinib starting at 100 μM. The cells are returned to a 37°C humidified incubator for 72 hours. Cell proliferation is measured using MTS assay.
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| References |
| Molecular Formula |
C29H29FN4O
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| Molecular Weight |
468.57
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| Exact Mass |
468.23253972
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| CAS # |
2309668-44-6
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| Related CAS # |
Derazantinib;1234356-69-4;Derazantinib dihydrochloride;1821329-75-2
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| Appearance |
Solid
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| SMILES |
COCCNCCC1=CC(=CC=C1)NC2=NC=C3CC(C4=CC=CC=C4C3=N2)C5=CC=CC=C5F
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| InChi Key |
KPJDVVCDVBFRMU-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
6-(2-fluorophenyl)-N-[3-[2-(2-methoxyethylamino)ethyl]phenyl]-5,6-dihydrobenzo[h]quinazolin-2-amine
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| Synonyms |
AR-Q087; ARQ 087; ARQ087; AR-Q087 racemate; Derazantinib Racemate
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1342 mL | 10.6708 mL | 21.3415 mL | |
| 5 mM | 0.4268 mL | 2.1342 mL | 4.2683 mL | |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1342 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Mode of FGFR inhibition for ARQ 087.PLoS One.2016 Sep 14;11(9):e0162594. |
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 Fig 2. ARQ 087 inhibits FGFR phosphorylation.
ARQ 087 arrests cells in the G1 cell cycle phase and induces apoptosis.PLoS One.2016 Sep 14;11(9):e0162594. |
 ARQ 087 inhibits the FGFR pathway in cancer cell lines.
ARQ 087 inhibits the FGFR pathway in xenograft tumors.PLoS One.2016 Sep 14;11(9):e0162594. |
 ARQ 087 activity in tumor growth models.PLoS One.2016 Sep 14;11(9):e0162594. |
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Animal weights in BaF3/FGFR2 animals dosed with ARQ 087.PLoS One.2016 Sep 14;11(9):e0162594. |
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