Ripretinib (DCC-2618)

Name: Ripretinib (DCC-2618)
Brand: Selleck Chemicals
SKU: S8757
Rating: 5 (0 reviews)

For research use only.

Catalog No.S8757

Ripretinib (DCC-2618) Chemical Structure

Molecular Weight(MW): 510.36

DCC-2618 is an orally bioavailable switch pocket control inhibitor of wild-type and mutated forms of the tumor-associated antigens (TAA) mast/stem cell factor receptor (SCFR) KIT and PDGFR-alpha, with IC50 values of 4 nM, 8 nM, 18 nM, 5 nM and 14 nM for WT KIT, V654A KIT, T670I KIT, D816H KIT and D816V KIT, respectively.

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Biological Activity

Description

Targets

PDGFR ^[2] ()	WT KIT ^[1] (Cell-free assay)	D816H KIT ^[1] (Cell-free assay)	V654A KIT ^[1] (Cell-free assay)	D816V KIT ^[1] (Cell-free assay)	View More
	4 nM	5 nM	8 nM	14 nM	View More

In vitro

DCC-2618 is a switch-control type II inhibitor of KIT, which arrests KIT in an inactive state, regardless of activating mutations, such as KIT D816V. In CHO cells transiently transfected with both single and double (primary/secondary) KIT mutants, DCC-2618 robustly inhibits exon 17, exon 9/13, exon 9/14, and exon 9/17 KIT mutants, as well as exon 11/17 KIT mutants, including exon 17 D816V, D816G, D820A, D820E, D820Y, N822K, N822Y, N822H, and Y823D primary or secondary mutations^[1]. DCC-2618 inhibits the proliferation and survival of various human mast cell lines (HMC-1, ROSA, MCPV-1) as well as primary neoplastic mast cells obtained from patients with advanced systemic mastocytosis (IC50 <1 μM). DCC-2618 decreases growth and survival of primary neoplastic eosinophils obtained from patients with systemic mastocytosis or eosinophilic leukemia, leukemic monocytes obtained from patients with chronic myelomonocytic leukemia with or without concomitant systemic mastocytosis, and blast cells obtained from patients with acute myeloid leukemia. Furthermore, DCC-2618 suppresses the proliferation of endothelial cells and may have additional drug effects on systemic mastocytosis-related angiogenesis. DCC-2618 downregulates IgE-mediated histamine release from basophils and tryptase release from mast cells^[2].

In vivo

In vivo, DCC-2618 administration at 50 mg/kg affords an ED90 for inhibition of KIT phosphorylation in the GIST T1 xenograft model, corresponding to an EC90 concentration of ∼ 470 ng/mL. When give twice daily, this oral dose results in almost complete tumor stasis. This dose of DCC-2618 produces tumor regressions in a patient derived xenograft (PDX) GIST expressing KIT exon 11 delW557K558/exon 17 Y823D, and also in a KIT exon 17 N822K AML xenograft model^[1]. In xenograft studies, DCC-2618 blocks KIT and PDGFRA-driven tumor growth, including of KIT exon 17 mutants found in GIST (Y823D), AML (N822K), and mastocytosis (D816V) models^[3].

Protocol

Cell Research: ^[2]	- Collapse Cell lines: HMC-1.1, HMC-1.2, ROSA (KIT WT) and ROSA (KIT D816V) cells Concentrations: 0.5-5 μM Incubation Time: 4 h Method: For evaluation of KIT and BTK signaling, HMC-1.1, HMC-1.2, ROSA (KIT WT) and ROSA (KIT D816V) cells are incubated in control medium or in DCC-2618 (0.5–5 μM) for 4 h at 37°C. Western blotting is performed. (Only for Reference)
Animal Research: ^[3]	- Collapse Animal Models: xenograft models (mice) Dosages: 100 mg/kg/day or 25 mg/kg/day or 50 mg/kg BID Administration: oral (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	100 mg/mL (195.94 mM)
	Water	Insoluble
	Ethanol	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight	510.36
Formula	C₂₄H₂₁BrFN₅O₂
CAS No.	1442472-39-0
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A
Smiles	CCN1C(=O)C(=CC2=C1C=C(NC)N=C2)C3=C(Br)C=C(F)C(=C3)NC(=O)NC4=CC=CC=C4

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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