Name: Ripretinib
Brand: Selleck Chemicals
SKU: S8757
Rating: 5 (10 reviews)

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품질 관리

배치: 순도: 99.82%

99.82

관련 타겟	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
기타 c-Kit 억제제	Masitinib Amuvatinib (MP-470) OSI-930 Sitravatinib (MGCD516) PDGFR inhibitor 1 ISCK03 AZD3229 Masitinib mesylate Bezuclastinib Elenestinib phosphate

세포 배양, 처리 및 작업 농도

세포주	분석 유형	배양 시간	활성 설명	PMID
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.003 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.006 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.013 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.014 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.023 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.031 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.04 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.045 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.048 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.075 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.078 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.098 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.13 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.188 μM.	30204441
Growth inhibition assay	BA/F3	72 hrs	Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.205 μM.	30204441
Cytotoxicity assay	BA/F3	72 hrs	Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 8.037 μM.	30204441
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화학 정보, 보관 및 안정성

분자량	510.36	화학식	C₂₄H₂₁BrFN₅O₂	보관 (수령일로부터)	3 years -20°C powder
CAS 번호	1442472-39-0	--		원액 보관	1년-80°C용매에 보관 1개월-20°C용매에 보관
동의어	DCC-2618			Smiles	CCN1C2=CC(=NC=C2C=C(C1=O)C3=CC(=C(C=C3Br)F)NC(=O)NC4=CC=CC=C4)NC

용해도

In vitro
배치:

DMSO : 100 mg/mL (195.94 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (195.94 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량	농도	부피	분자량
=	×	×

희석 계산기 분자량 계산기

In vivo 배치:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

투여량: mg/kg 동물 평균 체중: g 동물당 투여량:μL 동물 수:

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH₂O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘

Targets/IC₅₀/Ki	PDGFR WT KIT (Cell-free assay) 4 nM D816H KIT (Cell-free assay) 5 nM V654A KIT (Cell-free assay) 8 nM D816V KIT (Cell-free assay) 14 nM T670I KIT (Cell-free assay) 18 nM
시험관 내(In vitro)	DCC-2618은 활성화 돌연변이(예: KIT D816V)와 관계없이 KIT을 비활성 상태로 정지시키는 스위치 제어 유형 II KIT 억제제입니다. 단일 및 이중(1차/2차) KIT 돌연변이로 일시적으로 형질감염된 CHO 세포에서 DCC-2618은 exon 17, exon 9/13, exon 9/14 및 exon 9/17 KIT 돌연변이는 물론 exon 11/17 KIT 돌연변이(exon 17 D816V, D816G, D820A, D820E, D820Y, N822K, N822Y, N822H 및 Y823D 1차 또는 2차 돌연변이 포함)를 강력하게 억제합니다. DCC-2618은 다양한 인간 비만세포주(HMC-1, ROSA, MCPV-1) 및 진행성 전신 비만세포증 환자로부터 얻은 1차 신생물성 비만세포의 증식 및 생존을 억제합니다(IC50 <1 µM). DCC-2618은 전신 비만세포증 또는 호산구 백혈병 환자로부터 얻은 1차 신생물성 호산구, 동반 전신 비만세포증 유무에 관계없이 만성 골수단핵구 백혈병 환자로부터 얻은 백혈병 단핵구, 급성 골수성 백혈병 환자로부터 얻은 모세포의 성장 및 생존을 감소시킵니다. 또한 DCC-2618은 내피세포의 증식을 억제하고 전신 비만세포증 관련 혈관신생에 추가적인 약물 효과를 가질 수 있습니다. DCC-2618은 비만세포에서 IgE 매개 히스타민 방출과 비만세포에서 트립타아제 방출을 하향 조절합니다.
생체 내(In vivo)	생체 내에서 50 mg/kg의 DCC-2618 투여는 GIST T1 이종이식 모델에서 KIT 인산화 억제에 대한 ED90을 제공하며, 이는 약 470 ng/mL의 EC90 농도에 해당합니다. 하루 두 번 투여하면 이 경구 용량은 거의 완전한 종양 정체를 유발합니다. 이 DCC-2618 용량은 KIT exon 11 delW557K558/exon 17 Y823D를 발현하는 환자 유래 이종이식(PDX) GIST 및 KIT exon 17 N822K AML 이종이식 모델에서도 종양 퇴행을 유발합니다. 이종이식 연구에서 DCC-2618은 GIST (Y823D), AML (N822K) 및 비만세포증 (D816V) 모델에서 발견되는 KIT exon 17 돌연변이를 포함하여 KIT 및 PDGFRA 유도 종양 성장을 차단합니다.
참조	[1] http://cancerres.aacrjournals.org/content/75/15_Supplement/2690 [2] https://pubmed.ncbi.nlm.nih.gov/29439183/ [3] https://www.deciphera.com/wp-content/uploads/2018/04/DCC-2618-Pre-Clinical-AACR-2018.pdf

적용 분야

방법	바이오마커	이미지	PMID
Western blot	KIT / BTK STAT5 / AKT / ERK		29439183

임상시험 정보

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호	모집	조건	스폰서/협력자	시작일	단계
NCT05080621	Withdrawn	Gastrointestinal Stromal Tumors	Deciphera Pharmaceuticals LLC	November 2021	Phase 1\|Phase 2
NCT04633122	Completed	Gastrointestinal Stromal Tumor(GIST)	Zai Lab (Shanghai) Co. Ltd.\|Zai Lab (Hong Kong) Ltd.	November 25 2020	Phase 2
NCT02571036	Completed	Gastrointestinal Stromal Tumors\|Advanced Systemic Mastocytosis\|Advanced Cancers	Deciphera Pharmaceuticals LLC	November 2015	Phase 1

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Ripretinib c-Kit 억제제

화학 구조

분자량: 510.36