연구용

R406 Syk/FLT3 억제제

Name: R406
Brand: Selleck Chemicals
SKU: S2194
Rating: 5 (126 reviews)

제품 번호: S2194

R406(R406 besylate)는 무세포 분석에서 41 nM의 IC50을 가진 강력한 Syk 억제제로, Syk를 강력하게 억제하지만 Lyn은 억제하지 않으며, Flt3에 대해서는 5배 낮은 효능을 보입니다. R406은 Apoptosis related를 유도합니다. 1상.

화학 구조

분자량: 628.63

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품질 관리 (Quality Control)

배치: 순도: 99.43%

99.43

관련 타겟	EGFR VEGFR JAK FGFR PDGFR Src HIF HER2 FLT3 FLT
기타 Syk 억제제	R406 (free base) PRT062607 (P505-15) HCl Entospletinib (GS-9973) Piceatannol BAY 61-3606 dihydrochloride PRT-060318 2HCl TAK-659 Hydrochloride Lanraplenib (GS-SYK) RO9021 R112

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주	분석 유형	농도	배양 시간	제형	활성 설명	PMID
AMO-1	Function Assay	1 μM	3 h		reduces migration	26251761
U266	Function Assay	1 μM	3 h		reduces migration	26251761
Jeko-1	Growth Inhibition Assay		48 h		IC50=5.06826 μM	25835755
Mino	Growth Inhibition Assay		48 h		IC50=5.70854 μM	25835755
Jeko-1	Apoptosis Assay	5 μM	24 h		induces 25.1 ± 3.2 % apoptosis	25835755
primary MCL	Apoptosis Assay	2 µM	24 h		increases significantly apoptosis	25388373
PBMCs	Cell Viability Assay	0-50 μM	24 h	DMSO	inhibits cell viability dose dependently	25127862
PBMCs	Function Assay	5 μM	1 h	DMSO	decreases the cell migration	25127862
CFSE-CD4+ T	Growth Inhibition Assay	0.0625-1 μM	4 d		blocks proliferation of GVHD-derived CD4+ T cells and CD11b+ cells	24679982
CFSE-CD11b+	Growth Inhibition Assay	0.0625-1 μM	8 d		blocks proliferation of GVHD-derived CD4+ T cells and CD11b+ cells	24679982
HMECs	Function Assay	0-10 μM	20 min		inhibits VEGF-stimulated release of NO	24329544
AB5	Apoptosis Assay	0-2.5 μM	48 h	DMSO	induces apoptosis	23398911
JB7	Apoptosis Assay	0-2.5 μM	48 h	DMSO	induces apoptosis	23398911
AB5	Growth Inhibition Assay	0-2.5 μM	48 h	DMSO	induces cell cycle arrest	23398911
JB7	Growth Inhibition Assay	0-2.5 μM	48 h	DMSO	induces cell cycle arrest	23398911
RL	Function Assay	2.5/5 μM	24/48 h	DMSO	induces a potent decrease in MMP-9 mRNA expression	21926965
RL	Function Assay	1/2.5 μM	24 h	DMSO	reduces the activation of Akt and p70S6K	21926965
platelet	Function Assay	1 μm	5 min		inhibits FcγRIIA-mediated platelet aggregation	21848694
platelet	Function Assay	0.05/1/2.5 μM	5 min		inhibits the signaling mechanisms downstream of FcγRIIA	21848694
DoHH2	Apoptosis Assay	0/3/10 μM	48 h		induces cell death significantly	20875408
Jeko-1	Apoptosis Assay	0/3/10 μM	48 h		induces cell death significantly	20875408
Raji	Apoptosis Assay	0/3/10 μM	48 h		induces cell death significantly	20875408
DHL4	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
LY7	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
LY3	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
DHL6	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
LY10	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
DHL10	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
Wsu-NHL	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
LY18	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
LY1	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
DHL8	Apoptosis Assay	0/1/4 μM	96 h		induces apoptosis dose dependently	18006696
DHL4	Apoptosis Assay	4 μM	96 h		induces cleavage of caspases 9 and 3, but not caspase 8	18006696
DHL6	Apoptosis Assay	4 μM	96 h		induces cleavage of caspases 9 and 3, but not caspase 8	18006696
LY3	Apoptosis Assay	4 μM	96 h		induces cleavage of caspases 9 and 3, but not caspase 8	18006696
LY7	Apoptosis Assay	4 μM	96 h		induces cleavage of caspases 9 and 3, but not caspase 8	18006696
DHL4	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
LY7	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
LY3	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
DHL6	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
LY10	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
Wsu-NHL	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
LY18	Function Assay	4 μM	16 h		inhibits tonic BLNK tyrosine phosphorylation	18006696
MV411	Function assay		72 hrs		Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry, EC50=0.01μM.	24779514
TF1	Function assay		1 hr		Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation, EC50=0.013μM.	24779514
neutrophils	Function assay				Inhibition of SYK in human neutrophils cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.033μM.	22257213
SK-M-MC	Function assay		1 hr		Inhibition of Ret in human SK-M-MC cells assessed as assessed as phosphorylation after 1 hr incubation, EC50=0.036μM.	24779514
mast cells	Function assay		1 hr		Inhibition of cKit in stem cell factor-stimulated bone marrow derived mouse mast cells assessed as phosphorylation after 1 hr incubation, EC50=0.046μM.	24779514
B-cells	Function assay				Inhibition of SYK in human B-cells cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.048μM.	22257213
Ramos	Function assay				Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay, EC50=0.053μM.	24779514
mesangial cells	Function assay				Inhibition of SYK in cultured human mesangial cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.056μM.	22257213
SK-N-SH	Function assay				Inhibition of Ret in human SK-N-SH cells, EC50=0.08μM.	22257213
mouse bone marrow cells	Function assay				Inhibition of IL3 dependent proliferation in C57/B16 mouse bone marrow cells using [3H]thymidine by liquid scintillation counting, IC50=0.147μM.	24726806
B-cells	Function assay		1 hr		Inhibition of Syk in alphaIgM-stimulated human B cells assessed as cell proliferation after 1 hr incubation by flow cytometry, EC50=0.151μM.	24779514
THP1	Function assay				Inhibition of SYK in human THP1 cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.171μM.	22257213
B-cells	Function assay		1 hr		Inhibition of Syk in alphaIgM-stimulated human B cells assessed as CD86 expression after 1 hr incubation by flow cytometry, EC50=0.335μM.	24779514
Ramos	Function assay				Inhibition of Syk in anti IgM-stimulated human Ramos cells assessed as BLNK phosphorylation by cellular assay, IC50=0.457μM.	24726806
Rec1	Function assay	2.5 uM	6 hrs		Inhibition of BTK phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method	25222877
Rec1	Function assay	2.5 uM	6 hrs		Inhibition of Syk phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method	25222877
Rec1	Function assay	2.5 uM	6 hrs		Inhibition of Lyn phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method	25222877
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량	628.63	화학식	C₂₂H₂₃FN₆O₅.C₆H₆O₃S	보관 (수령일로부터)	3년-20°C분말
CAS 번호	841290-81-1	SDF 다운로드		원액 보관	1년-80°C용매에 보관 1개월-20°C용매에 보관
동의어	R406 besylate			Smiles	CC1(C(=O)NC2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)C.C1=CC=C(C=C1)S(=O)(=O)O

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (159.07 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 0 mg/mL

DMSO : 126 mg/mL (200.43 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 8 mg/mL

Water : Insoluble

DMSO : Insoluble
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (159.07 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 38 mg/mL

Water : 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.
Clear solution	5%DMSO 1 Corn oil Selleck 연구소에서 검증되었습니다. 이 제형에 대한 조정이 필요한 경우 맞춤 테스트를 위해 당사 영업팀에 문의하십시오.	0.500mg/ml (0.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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 (Mechanism of Action)

특징	Lead drug candidate for rheumatoid arthritis.
Targets/IC₅₀/Ki	Flt3 (Cell-free assay) Syk (Cell-free assay) 41 nM
시험관 내(In vitro)	R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. This compound inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. It inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. This chemical binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with K_i of 30 nM. It blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. This compound significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering. It is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients.
키나아제 분석	In Vitro 형광 편광 키나아제 분석
키나아제 분석	R406을 DMSO로 연속 희석한 후 키나아제 완충액(20 mM HEPES, pH 7.4, 5 mM MgCl₂, 2 mM MnCl₂, 1 mM DTT, 0.1 mg/mL 아세틸화 BGG)으로 1% DMSO가 되도록 희석합니다. 키나아제 완충액 내의 ATP와 기질을 실온에서 첨가하여 최종 DMSO 농도를 0.2%로 맞춥니다. 키나아제 반응은 5mM HS1 펩타이드 기질과 4 mM ATP를 포함하는 20 mL의 최종 부피에서 수행되며, 키나아제 완충액에 담긴 0.125 ng의 Syk을 첨가하여 시작됩니다. 반응은 실온에서 40분 동안 진행됩니다. 반응은 FP 희석 완충액에 희석된 EDTA/항-포스포티로신 항체(최종 1X)/형광 포스포펩타이드 추적자(최종 0.5X)를 포함하는 20 mL의 PTK 퀀치 믹스를 첨가하여 중단됩니다. 플레이트를 실온의 어두운 곳에서 30분간 배양한 후 Polarion 형광 편광 플레이트 판독기로 판독합니다. 데이터는 Tyrosine Kinase Assay Kit에서 제공하는 포스포펩타이드 경쟁자와의 경쟁을 통해 생성된 검량선을 사용하여 존재하는 포스포펩타이드 양으로 변환됩니다. IC50 결정을 위해, 이 화합물은 11가지 농도에서 테스트되며 비선형 회귀 분석을 통해 곡선 맞춤이 수행됩니다.
생체 내(In vivo)	R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. This compound also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. It does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect.
참조	[1] https://pubmed.ncbi.nlm.nih.gov/16946104/ [2] https://pubmed.ncbi.nlm.nih.gov/19491390/ [3] https://pubmed.ncbi.nlm.nih.gov/21848694/ [4] https://pubmed.ncbi.nlm.nih.gov/17490694/

적용 분야 (Applications)

방법	바이오마커	이미지	PMID
Western blot	p-AKT / T-AKT / p-mTOR / T-mTOR p-c-RAF / T-c-RAF p-MEK / T-MEK / p-ERK / T-ERK p-RPS6 / T-RPS6 / p-4E-BP1 / T-4E-BP1		23535559
Growth inhibition assay	Cell viability (GSC lines) Cell viability (U87, U251 cells)		31043589

임상시험 정보 (Clinical Trial Information)

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

NCT 번호	모집	조건	스폰서/협력자	시작일	단계
NCT01725230	Completed	Rheumatoid Arthritis	AstraZeneca	November 2012	Phase 1
NCT01598571	Completed	Healthy	AstraZeneca	May 2012	Phase 1
NCT01387308	Completed	Healthy	AstraZeneca	August 2011	Phase 1
NCT01355354	Completed	Healthy Volunteers\|Rheumatoid Arthritis	AstraZeneca	June 2011	Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
What’s the difference between S1533 and S2194?

답변:
S1533 and S2194 are two different forms of this compound. S1533 is the free base form, containing only its molecule without an acid added to it. S2194 has an additional C6H6O3S acid on it which makes the molecule a salt form. The free base and salt forms have same biology activities. Free base has a lower molecular weight and salt form has a better solubility in DMSO.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

R406 Syk/FLT3 억제제

분자량: 628.63

품질 관리 (Quality Control)

세포 배양, 처리 및 작업 농도 (Cell Culture, Treatment & Working Concentration)

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

용해도 (Solubility)

몰농도 계산기

생체 내 제형 계산기 (투명한 용액)

작용 메커니즘 (Mechanism of Action)

적용 분야 (Applications)

임상시험 정보 (Clinical Trial Information)

자주 묻는 질문 (Frequently Asked Questions)

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)