Derazantinib | ARQ-087 | CAS#1234356-69-4 | pan FGFR inhibitor

MedKoo Cat#: 205946 | Name: Derazantinib

Description:

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

Derazantinib, 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.

Chemical Structure

Derazantinib

CAS#1234356-69-4

Theoretical Analysis

MedKoo Cat#: 205946

Name: Derazantinib

CAS#: 1234356-69-4

Chemical Formula: C29H29FN4O

Exact Mass: 468.2325

Molecular Weight: 468.58

Elemental Analysis: C, 74.34; H, 6.24; F, 4.05; N, 11.96; O, 3.41

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 500.00	Ready to ship
50mg	USD 850.00	Ready to ship
100mg	USD 1,450.00	Ready to ship
200mg	USD 2,450.00	Ready to ship
500mg	USD 4,250.00	Ready to ship

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Related CAS #

1821329-75-2 (dihydrochloride) 1234356-69-4

Synonym

ARQ 087; ARQ087; ARQ-087; Derazantinib

IUPAC/Chemical Name

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

InChi Key

KPJDVVCDVBFRMU-AREMUKBSSA-N

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)/t26-/m1/s1

SMILES Code

COCCNCCC1=CC(NC2=NC=C3C[C@@H](C4=CC=CC=C4F)C5=CC=CC=C5C3=N2)=CC=C1

Appearance

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R08B22

QC Data

View QC data: current batch, Lot#C8R08B22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Derazantinib (ARQ-087) is an inhibitor of the fibroblast growth factor receptor (FGFR) with IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3.

In vitro activity:

FGFR pathway inhibition was examined in three solid tumor lines, the colorectal cancer cell line (NCI-H716), and gastric cancer cell lines (SNU-16 and KATO-III). As shown in Fig 3A, ARQ 087 inhibited the phosphorylation of FGFRs in all three cell lines. The mechanism by which ARQ 087 inhibits the growth of FGFR kinase dependent cell lines was also investigated. Treatment with ARQ 087 led to an accumulation of cells in the G1 phase cell cycle in a dose- and time-dependent manner (Fig 4A and Table 4). The sub-G1 population (Fig 4A) of NCI-H716 cells, increased after treatment with 1 μM of ARQ 087 (Fig 4A and Table 4). To investigate whether the disruption of the cell cycle correlated with an increase in apoptosis SNU-16 cells were treated with 1 μM of ARQ 087 for 0, 24, 48, and 72 hours, and X-linked inhibitor of apoptosis protein (XIAP), cleaved PARP, activated caspase 3, phospho-p53 were assessed by Western blotting analysis. A decrease in XIAP, and an increase in cleaved-PARP, activated-caspase 3, and pP53 were observed (Fig 4B). Taken together, these data suggest that ARQ 087 inhibits the proliferation of FGFR amplified cells by inducing G1 cell cycle arrest and apoptosis. Reference: PLoS One. 2016 Sep 14;11(9):e0162594. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023172/

In vivo activity:

The in vivo anti-tumor effect of ARQ 087 was assessed in athymic mice bearing Ba/F3-FGFR2, Ba/F3-INSR, SNU-16, and NCI-H716 cell line-derived tumors. ARQ 087 demonstrated potent tumor growth inhibition in the Ba/F3-FGFR2 model, while failing to inhibit the growth of the Ba/F3-INSR model (Fig 6A and 6B). Meaningful (>50 TGI vs. control) tumor inhibition was observed both cancer cell line derived xenograft models. In the SNU-16 xenograft study, treatment with 75 mg/kg and 50 mg/kg achieved 83% (p = 0.002) and 69% (p = 0.013) TGI, respectively (Fig 6C). Partial (PR) and complete (CR) regressions also were observed in both dose groups. In the NCI-H716 human cecum model, 50 mg/kg and 75 mg/kg on a Q1Dx14 schedule demonstrated significant TGI of 68% (p = 0.0001) and 96% (p = 0.0001), respectively (Fig 6D). Reference: PLoS One. 2016 Sep 14;11(9):e0162594. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023172/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.7	101.73
	DMF	30.0	64.02
	DMF:PBS (pH 7.2) (1:3)	0.3	0.53

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 468.58 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. Hall TG, Yu Y, Eathiraj S, Wang Y, Savage RE, Lapierre JM, Schwartz B, Abbadessa G. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. PMID: 27627808; PMCID: PMC5023172.

In vitro protocol:

In vivo protocol:

1: Braun S, McSheehy P, Litherland K, McKernan P, Forster-Gross N, Bachmann F, El-Shemerly M, Dimova-Dobreva M, Polyakova I, Häckl M, Zhou P, Lane H, Kellenberger L, Engelhardt M. Derazantinib: an investigational drug for the treatment of cholangiocarcinoma. Expert Opin Investig Drugs. 2021 Nov;30(11):1071-1080. doi: 10.1080/13543784.2021.1995355. Epub 2021 Nov 9. PMID: 34698609. 2: Gourd E. Derazantinib for intrahepatic cholangiocarcinoma. Lancet Oncol. 2019 Jan;20(1):e11. doi: 10.1016/S1470-2045(18)30891-X. Epub 2018 Nov 22. PMID: 30473470. 3: Kommalapati A, Tella SH, Borad M, Javle M, Mahipal A. FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice. Cancers (Basel). 2021 Jun 13;13(12):2968. doi: 10.3390/cancers13122968. PMID: 34199304; PMCID: PMC8231807. 4: Liu YN, Chen J, Xu X, Hu Y, Hu JY, Xu RA, Lin G. Lack of pharmacokinetic interaction between derazantinib and naringin in rats. Pharm Biol. 2023 Dec;61(1):514-519. doi: 10.1080/13880209.2023.2185641. PMID: 36891628; PMCID: PMC10013357. 5: Mazzaferro V, El-Rayes BF, Droz Dit Busset M, Cotsoglou C, Harris WP, Damjanov N, Masi G, Rimassa L, Personeni N, Braiteh F, Zagonel V, Papadopoulos KP, Hall T, Wang Y, Schwartz B, Kazakin J, Bhoori S, de Braud F, Shaib WL. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019 Jan;120(2):165-171. doi: 10.1038/s41416-018-0334-0. Epub 2018 Nov 13. PMID: 30420614; PMCID: PMC6342954. 6: El Shemerly M, Zanini E, Lecoultre M, Walker PR, Kellenberger L, Lane HA, McSheehy PMJ. Derazantinib, a fibroblast growth factor receptor inhibitor, inhibits colony-stimulating factor receptor-1 in macrophages and tumor cells and in combination with a murine programmed cell death ligand-1-antibody activates the immune environment of murine syngeneic tumor models. Anticancer Drugs. 2023 Oct 1;34(9):1035-1045. doi: 10.1097/CAD.0000000000001480. Epub 2022 Dec 19. PMID: 36729099. 7: Kotini MP, Bachmann F, Spickermann J, McSheehy PM, Affolter M. Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos. Pharmaceuticals (Basel). 2020 Dec 30;14(1):25. doi: 10.3390/ph14010025. PMID: 33396726; PMCID: PMC7824571. 8: McSheehy PMJ, Forster-Gross N, El Shemerly M, Bachmann F, Roceri M, Hermann N, Spickermann J, Kellenberger L, Lane HA. The fibroblast growth factor receptor inhibitor, derazantinib, has strong efficacy in human gastric tumor models and synergizes with paclitaxel in vivo. Anticancer Drugs. 2023 Apr 1;34(4):532-543. doi: 10.1097/CAD.0000000000001469. Epub 2022 Dec 2. PMID: 36729959. 9: Lacouture ME, Sibaud V, Anadkat MJ, Kaffenberger B, Leventhal J, Guindon K, Abou-Alfa G. Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines. Oncologist. 2021 Feb;26(2):e316-e326. doi: 10.1002/onco.13552. Epub 2020 Oct 28. PMID: 33021006; PMCID: PMC7873330. 10: Manne A, Woods E, Tsung A, Mittra A. Biliary Tract Cancers: Treatment Updates and Future Directions in the Era of Precision Medicine and Immuno- Oncology. Front Oncol. 2021 Nov 15;11:768009. doi: 10.3389/fonc.2021.768009. PMID: 34868996; PMCID: PMC8634105. 11: Aitcheson G, Mahipal A, John BV. Targeting FGFR in intrahepatic cholangiocarcinoma [iCCA]: leading the way for precision medicine in biliary tract cancer [BTC]? Expert Opin Investig Drugs. 2021 Apr;30(4):463-477. doi: 10.1080/13543784.2021.1900821. Epub 2021 Apr 11. PMID: 33678096. 12: King G, Javle M. FGFR Inhibitors: Clinical Activity and Development in the Treatment of Cholangiocarcinoma. Curr Oncol Rep. 2021 Jul 16;23(9):108. doi: 10.1007/s11912-021-01100-3. PMID: 34269915. 13: Lee PC, Hendifar A, Osipov A, Cho M, Li D, Gong J. Targeting the Fibroblast Growth Factor Receptor (FGFR) in Advanced Cholangiocarcinoma: Clinical Trial Progress and Future Considerations. Cancers (Basel). 2021 Apr 3;13(7):1706. doi: 10.3390/cancers13071706. PMID: 33916849; PMCID: PMC8038487. 14: Raggi C, Fiaccadori K, Pastore M, Correnti M, Piombanti B, Forti E, Navari N, Abbadessa G, Hall T, Destro A, Di Tommaso L, Roncalli M, Meng F, Glaser S, Rovida E, Peraldo-Neia C, Olaizola P, Banales JM, Gerussi A, Elvevi A, Droz Dit Busset M, Bhoori S, Mazzaferro V, Alpini G, Marra F, Invernizzi P. Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma. Am J Pathol. 2019 Oct;189(10):2090-2101. doi: 10.1016/j.ajpath.2019.06.007. Epub 2019 Jul 24. PMID: 31351075. 15: Leroy L, Cousin S, Italiano A. Genetic determinants of response to fibroblast growth factor receptor inhibitors in solid tumours. Eur J Cancer. 2017 Aug;81:102-105. doi: 10.1016/j.ejca.2017.04.011. Epub 2017 Jun 15. PMID: 28623773. 16: Hall TG, Yu Y, Eathiraj S, Wang Y, Savage RE, Lapierre JM, Schwartz B, Abbadessa G. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. PMID: 27627808; PMCID: PMC5023172. 17: Yu Y, Hall T, Eathiraj S, Wick MJ, Schwartz B, Abbadessa G. In-vitro and in- vivo combined effect of ARQ 092, an AKT inhibitor, with ARQ 087, a FGFR inhibitor. Anticancer Drugs. 2017 Jun;28(5):503-513. doi: 10.1097/CAD.0000000000000486. PMID: 28240679; PMCID: PMC5404396. 18: Balek L, Gudernova I, Vesela I, Hampl M, Oralova V, Kunova Bosakova M, Varecha M, Nemec P, Hall T, Abbadessa G, Hatch N, Buchtova M, Krejci P. 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. doi: 10.1016/j.bone.2017.08.016. Epub 2017 Aug 18. PMID: 28826843. 19: Papadopoulos KP, El-Rayes BF, Tolcher AW, Patnaik A, Rasco DW, Harvey RD, LoRusso PM, Sachdev JC, Abbadessa G, Savage RE, Hall T, Schwartz B, Wang Y, Kazakin J, Shaib WL. A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours. Br J Cancer. 2017 Nov 21;117(11):1592-1599. doi: 10.1038/bjc.2017.330. Epub 2017 Oct 3. PMID: 28972963; PMCID: PMC5729432.