| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
Ripretinib HCl (DCC2618; DCC-2618; Qinlock), the hydrochloride salt of DCC-2618, is an orally bioactive pan KIT and PDGFRA inhibitor approved in 2020 for the treatment of adults with advanced gastrointestinal stromal tumor. It functions by obstructing several additional kinase targets associated with systemic mastocytosis, including KIT D816V.
| Targets |
KIT (wild-type IC50=14 nM; V560G mutant IC50=12 nM; D816V mutant IC50=16 nM; V560G/D816V double mutant IC50=15 nM); PDGFRα (wild-type IC50=21 nM; D842V mutant IC50=19 nM) [1]
KIT and PDGFRα kinases ( focuses on activity against drug-resistant mutants) [2] |
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| ln Vivo |
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| Enzyme Assay |
In order to assess KIT and BTK signaling, ROSAKIT WT, ROSAKIT D816V, HMC-1.1, and HMC-1.2 cells were incubated for 4 hours at 37°C in either control medium or DCC-2618 (0.5–5 μM). Western blotting was done essentially according to other instructions. In order to assess the downstream signaling pathways of KIT, HMC-1.1, HMC-1.2, ROSAKIT WT, and ROSAKIT D816V cells were initially pre-cultured for an entire night in Iscove-modified Dulbecco medium that was devoid of stem cell factor and fetal calf serum. DCC-2618 (0.001–10 μM) was then applied to 106 cells from each line for 90 minutes at 37°C. Following treatment, 10% stem cell factor-containing supernatants of Chinese hamster ovary cells transfected with the murine scf (kl) gene (CHO-KL) were added to ROSAKIT WT cells and incubated for 10 minutes at room temperature. After that, Western blotting was carried out essentially as previously mentioned.
Recombinant KIT kinase activity assay: Purified recombinant KIT kinase domains (wild-type, V560G, D816V, V560G/D816V) were incubated with ATP (10 μM) and a biotinylated peptide substrate in the presence of serial dilutions of DCC-2618 HCl (0.1 nM-1 μM). Phosphorylated substrate was detected using a homogeneous time-resolved fluorescence (HTRF) assay, with streptavidin-conjugated europium and anti-phosphotyrosine antibody. IC50 values were calculated by nonlinear regression analysis of dose-response curves [1] - Recombinant PDGFRα kinase activity assay: The same HTRF-based method was used for PDGFRα kinase domains (wild-type, D842V). Reaction conditions included ATP (10 μM) and PDGFRα-specific biotinylated peptide substrate. DCC-2618 HCl was tested at concentrations ranging from 0.1 nM to 1 μM, and IC50 values were determined as described for KIT [1] - Kinase selectivity assay: DCC-2618 HCl (1 μM) was screened against a panel of 403 human kinases using a radiometric ATP incorporation assay. Inhibition rates were calculated relative to vehicle control, and selectivity was defined as the ratio of IC50 for off-target kinases to IC50 for KIT D816V [1] |
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| Cell Assay |
The survival and proliferation of drug-exposed cells—primary or cell line—were examined. In the Online Supplementary Methods, the bioassays used are described.
Cell viability assay: KIT/PDGFRα-mutant cell lines (HMC-1.1, HMC-1.2, PDGFRα D842V Ba/F3) and control cell lines (MV4-11, HL-60) were seeded in 96-well plates (5×10^3 cells/well) and treated with DCC-2618 HCl (0.1 nM-10 μM) for 72 hours. Cell viability was measured using a colorimetric MTT assay, and IC50 values were calculated from three independent experiments (mean ± SD) [1] - Western blot for signaling analysis: HMC-1.2 cells were seeded in 6-well plates (2×10^5 cells/well) and serum-starved for 16 hours. Cells were treated with DCC-2618 HCl (10-100 nM) for 2 hours, then harvested and lysed in RIPA buffer. Protein lysates (30 μg/lane) were separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against p-KIT (Y703, Y721), total KIT, p-AKT (S473), total AKT, p-ERK1/2 (T202/Y204), total ERK1/2, and GAPDH (loading control). Chemiluminescent detection was used to visualize bands, and densitometric analysis was performed [1] - Apoptosis assay: HMC-1.2 cells (1×10^6 cells/mL) were treated with DCC-2618 HCl (50-200 nM) for 48 hours. Cells were washed with PBS, stained with Annexin V-FITC and propidium iodide (PI) for 15 minutes at room temperature, and analyzed by flow cytometry. The percentage of apoptotic cells (Annexin V-positive, PI-negative or positive) was quantified [1] - Colony formation assay: HMC-1.2 cells were seeded in 6-well plates (200 cells/well) and treated with DCC-2618 HCl (10-50 nM). Medium was changed every 3 days, and after 14 days, colonies were fixed with methanol, stained with crystal violet, and counted. Colony formation efficiency was calculated as (number of colonies in treatment group / number of colonies in vehicle group) × 100% [1] - Primary patient cell assay: Bone marrow-derived mast cells from SM patients (n=3) were isolated and cultured in medium containing cytokines. Cells were treated with DCC-2618 HCl (10-100 nM) for 72 hours, and cell viability was measured using a trypan blue exclusion assay [1] |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Oral bioavailability: In rats, the oral bioavailability of DCC-2618 HCl (10 mg/kg) was 45%, with a Cmax of 1.2 μg/mL and an AUC0-24h of 8.5 μg·h/mL [1]. Terminal half-life: In rats, the terminal half-life (t1/2) of intravenous DCC-2618 HCl (5 mg/kg) was 6.2 hours, and the systemic clearance was 1.8 mL/min/kg [1]. Plasma protein binding: As determined by equilibrium dialysis, DCC-2618 HCl showed high plasma protein binding rates (92-94%) in human, rat, and canine plasmas [1].
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| Toxicity/Toxicokinetics |
In vitro toxicity: At concentrations up to 1 μM, DCC-2618 HCl did not show significant cytotoxicity to normal human peripheral blood mononuclear cells (PBMCs) (cell viability >85% vs solvent control group) [1] - In vivo toxicity: Rats were orally administered DCC-2618 HCl (30 mg/kg/day) for 28 days and did not show significant weight loss, hematological abnormalities (white blood cell count, red blood cell count, platelet count) or histopathological changes in major organs (liver, kidney, heart, lung, spleen) [1] - No significant toxicity was observed in xenotransplantation studies: Mice were orally administered DCC-2618 HCl (30 mg/kg/day) for 21-32 days and maintained normal weight without showing acute toxic symptoms (drowsiness, diarrhea, hair loss) [1]
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| References | |||
| Additional Infomation |
DCC-2618 HCl is a highly bioavailable, efficient, and selective small molecule inhibitor of KIT and PDGFRα kinases with specific activity against clinically relevant resistance mutations such as KIT D816V and PDGFRα D842V [1][2]. This compound targets the oncogenic KIT/PDGFRα signaling pathway, which drives the pathogenesis of systemic mast cell hyperplasia (SM), mast cell leukemia (MCL), acute myeloid leukemia (AML), and gastrointestinal stromal tumor (GIST) [1][2]. DCC-2618 HCl blocks downstream signaling pathways (PI3K/AKT, RAS/ERK) that are crucial for cell proliferation and survival, thereby inhibiting the growth of mutant cells and inducing their apoptosis [1]. Preclinical data support its clinical development. DCC-2618 HCl is used to treat systemic mastocytic (SM)-associated hematologic malignancies, including mantle cell lymphoma (MCL) and acute myeloid leukemia (AML), which are often unresponsive to conventional therapies [2]. DCC-2618 HCl has favorable pharmacokinetic properties (good oral bioavailability, moderate half-life, and high plasma protein binding) and favorable toxicity profiles, supporting its use as an oral therapeutic agent [1].
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| Related CAS # |
1442472-39-0; 1225278-16-9
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| Appearance |
Solid
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| Synonyms |
DCC-2618 hydrochloride; DCC 2618 HCl; DCC2618; Ripretinibhydrochloride
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| HS Tariff Code |
2934.99.9001
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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.) |
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.
 DCC-2618 and its active metabolite DP-5439 inhibit proliferation of neoplastic mast cells.Haematologica.2018 May;103(5):799-809. |
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 DCC-2618 inhibits phosphorylation of KIT and other targets in neoplastic mast cells.Haematologica.2018 May;103(5):799-809. |
Effects of DCC-2618 on anti-IgE-induced histamine release from normal basophils.Haematologica.2018 May;103(5):799-809. |
 DCC-2618 and DP-5439 induce apoptosis in neoplastic mast cells.Haematologica.2018 May;103(5):799-809. |
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 Effects of DCC-2618 and DP-5439 on proliferation and survival of acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML).Haematologica.2018 May;103(5):799-809. |
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