Ripretinib free base | DCC-2618 | CAS#1442472-39-0 | KIT/PDGFR inhibitor

MedKoo Cat#: 206497 | Name: Ripretinib free base

Description:

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

Ripretinib, also known as DCC-2618, is a potent, orally active and selective KIT/PDGFR inhibitor with potential antineoplastic activity. DCC-2618 targets and binds to both wild-type and mutant forms of KIT and PDGFRa specifically at their switch pocket binding sites, thereby preventing the switch from inactive to active conformations of these kinases and inactivating their wild-type and mutant forms. In May 2020, FDA Approves Qinlock (ripretinib) for the Treatment of Fourth-Line Gastrointestinal Stromal Tumor

Chemical Structure

Ripretinib free base

CAS#1442472-39-0 (free base)

Theoretical Analysis

MedKoo Cat#: 206497

Name: Ripretinib free base

CAS#: 1442472-39-0 (free base)

Chemical Formula: C24H21BrFN5O2

Exact Mass: 509.0863

Molecular Weight: 510.37

Elemental Analysis: C, 56.48; H, 4.15; Br, 15.66; F, 3.72; N, 13.72; O, 6.27

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,650.00	Ready to ship

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Related CAS #

1442472-39-0 (free base) Ripretinib HCl 1225278-16-9 (wrong structure for DCC-2618)

Synonym

DCC-2618; DCC 2618; DCC2618; DP 2618; DP-2618; DP2618; Ripretinib;

IUPAC/Chemical Name

1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea

InChi Key

CEFJVGZHQAGLHS-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33)

SMILES Code

O=C(NC1=CC(C2=CC3=C(C=C(NC)N=C3)N(CC)C2=O)=C(Br)C=C1F)NC4=CC=CC=C4

Appearance

White to off-white 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

Note: Many vendors listed wrong structure with CAS#1225278-16-9

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S20S06C20

QC Data

View QC data: current batch, Lot#S20S06C20

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ripretinib (DCC-2618) is a KIT and PDGFRA switch-control inhibitor.

In vitro activity:

Based on this safety profile, ripretinib was formulated into a mouse diet to achieve approximate levels of 100 and 25 mg/kg/day in mouse efficacy studies. In the GIST T1 model treated with ripretinib, significant tumor regression was observed at both doses (Figure 3A). At the high dose, 6/10 mice had complete tumor regression, with the remaining 4/10 mice having partial tumor regression during the dosing period. At the low dose, 2/10 mice had complete tumor regression, and 6/10 had partial tumor regression. Tumors exhibited slow regrowth after the end of the dosing period. Survival to study endpoint (day 68) was 100% for ripretinib-treated mice and 25% for vehicle-treated mice (Figure 3B). Body weight changes for ripretinib-treated groups were similar to vehicle (Figure S4D). Reference: Cancer Cell. 2019 May 13;35(5):738-751.e9. https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30201-6

In vivo activity:

DCC-2618 and its active metabolite, DP-5439 were found to inhibit 3H-thymidine uptake and thus proliferation in a dose-dependent manner in all MC lines tested, with slightly lower IC50 values obtained in HMC-1.1 cells lacking KIT D816V and ROSAKIT WT cells compared to the KIT D816V-positive cell lines HMC-1.2 and ROSAKIT D816V (Figure 1A and Table 2). In addition, DCC-2618 and DP-5439 were found to inhibit proliferation of ROSAKIT K509I cells with lower IC50 values (DCC-2618, IC50: 34±10 nM) compared to ROSAKIT D816V cells (Figure 1A). Unexpectedly, DCC-2618 and its metabolite also produced growth-inhibition in the multi-resistant MC lines MCPV-1.1, MCPV-1.2, MCPV-1.3 and MCPV-1.4 (Figure 1B and Table 2). Finally, DCC-2618 and DP- 5439 induced dose-dependent inhibition of growth of primary neoplastic bone marrow cells obtained from patients suffering from various forms of SM, including ASM and MCL (Figure 1C, Table 1). Interestingly, the effects of DCC-2618 on primary neoplastic BM cells and the related IC50 values obtained in different SM variants were comparable (Figure 1C, Table 1). Reference: Haematologica. 2018 May; 103(5): 799–809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927976/

	Solvent	mg/mL	mM
Solubility
	DMSO	25.0	49.00

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 510.37 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. Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, Rutkoski TJ, Ahn YM, Al-Ani G, Bulfer SL, Caldwell TM, Chun L, Ensinger CL, Hood MM, McKinley A, Patt WC, Ruiz-Soto R, Su Y, Telikepalli H, Town A, Turner BA, Vogeti L, Vogeti S, Yates K, Janku F, Abdul Razak AR, Rosen O, Heinrich MC, Flynn DL. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell. 2019 May 13;35(5):738-751.e9. doi: 10.1016/j.ccell.2019.04.006. PMID: 31085175. 2. Schneeweiss M, Peter B, Bibi S, Eisenwort G, Smiljkovic D, Blatt K, Jawhar M, Berger D, Stefanzl G, Herndlhofer S, Greiner G, Hoermann G, Hadzijusufovic E, Gleixner KV, Bettelheim P, Geissler K, Sperr WR, Reiter A, Arock M, Valent P. The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis. Haematologica. 2018 May;103(5):799-809. doi: 10.3324/haematol.2017.179895. Epub 2018 Feb 8. PMID: 29439183; PMCID: PMC5927976.

In vitro protocol:

In vivo protocol:

1: Baird JH, Gotlib J. Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis. Curr Hematol Malig Rep. 2018 Oct;13(5):407-416. doi: 10.1007/s11899-018-0469-3. Review. PubMed PMID: 30155614. 2: Schneeweiss M, Peter B, Bibi S, Eisenwort G, Smiljkovic D, Blatt K, Jawhar M, Berger D, Stefanzl G, Herndlhofer S, Greiner G, Hoermann G, Hadzijusufovic E, Gleixner KV, Bettelheim P, Geissler K, Sperr WR, Reiter A, Arock M, Valent P. The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis. Haematologica. 2018 May;103(5):799-809. doi: 10.3324/haematol.2017.179895. Epub 2018 Feb 8. PubMed PMID: 29439183; PubMed Central PMCID: PMC5927976. 3: BLU-285, DCC-2618 Show Activity against GIST. Cancer Discov. 2017 Feb;7(2):121-122. doi: 10.1158/2159-8290.CD-NB2016-165. Epub 2017 Jan 11. PubMed PMID: 28077435.