Home Angiogenesis Target Protein Ligand chemical Ibrutinib (PCI-32765)

연구용

Ibrutinib (PCI-32765) Btk inhibitor

제품 번호: S2680

Ibrutinib is a potent and highly selective Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM in cell-free assays, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. Ibrutinib is applicable as a Btk ligand in the synthesis of a series of PROTACs including P13I.
Ibrutinib (PCI-32765) Target Protein Ligand chemical Chemical Structure

화학 구조

분자량: 440.5

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
human Rec1 cells Function assay 2.5 μM 6 h Inhibition of Lyn phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method 25222877
human WSU-NHL cells Cytotoxic assay 72 h Cytotoxicity against human WSU-NHL cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=1.09 μM 24915291
human SU-DHL6 cells Cytotoxic assay 72 h Cytotoxicity against human SU-DHL6 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=0.58 μM. 24915291
human DOHH2 cells Cytotoxic assay 72 h Cytotoxicity against human DOHH2 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=0.41 μM. 24915291
Sf9 cells Function assay 1 h Inhibition of LYN-A expressed in Sf9 cells after 60 mins by TR-FRET Assay, IC50=0.2 μM. 21958547
human Ramos cells Function assay 1 h Inhibition of Btk in human Ramos cells assessed as inhibition of PLC-gamma2 phosphorylation at Tyr1217 after 1 hr by Western blot analysis, IC50=14 nM. 24915291
human Pfeiffer cells Function assay 72 h Cytotoxicity against human Pfeiffer cells assessed as growth inhibition after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50=2 nM. 24915291
Sf9 cells Function assay 1 h Inhibition of human full-length BTK expressed in Sf9 cells using FAM-Srctide peptide as substrate after 60 mins by TR-FRET Assay， IC50=0.5 nM. 21958547
Sf9 insect cells Function assay 60 mins IC50 = 0.0003 μM 29146136
sf9 cells Function assay IC50 = 0.0003 μM 27994736
Sf9 insect cells Function assay 60 mins IC50 = 0.00034 μM 27912175
Sf9 insect cells Function assay 60 mins IC50 = 0.00034 μM 28432946
Sf9 insect cells Function assay 60 mins IC50 = 0.00034 μM 27956037
Sf9 cells Function assay 60 mins IC50 = 0.0004 μM 30006143
Sf9 cells Function assay 60 mins IC50 = 0.0005 μM 21958547
Ramos cells Function assay 1 h IC50 = 0.0005 μM 28280261
Sf9 cells Function assay 60 mins IC50 = 0.001 μM 30077608
Pfeiffer cells Cytotoxicity assay 72 h GI50 = 0.002 μM 24915291
B cells Function assay 1 h IC50 = 0.0046 μM 30290988
Sf9 insect cells Function assay 2 to 60 mins Ki = 0.0048 μM 28315597
Ramos cells Function assay 1 h IC50 = 0.0075 μM 24915291
Sf9 insect cells Function assay 60 mins IC50 = 0.008 μM 28315597
TMD8 cells Antiproliferative activity assay 72 h IC50 = 0.01 μM 29715023
CD19+ B cells Function assay 1 h IC50 = 0.012 μM 29457982
Sf9 insect cells Function assay 60 mins IC50 = 0.012 μM 28315597
Ramos cells Function assay 1 h IC50 = 0.014 μM 24915291
Sf9 insect cells Function assay 1 h IC50 = 0.0144 μM 29715023
Sf9 insect cells Function assay 60 mins IC50 = 0.0161 μM 29146136
HCC827 cells Antiproliferative activity assay 72 h IC50 = 0.039 μM 28734581
PC9 cells Function assay 72 h GI50 = 0.05 μM 28282122
Sf9 cells Function assay 60 mins IC50 = 0.1 μM 30006143
H3255 cells Function assay 72 h GI50 = 0.11 μM 28282122
BaF3 cells Function assay 72 h GI50 = 0.12 μM 26630553
BAF3 cells Antiproliferative activity assay 72 h GI50 = 0.12 μM 28956923
Sf9 insect cells Function assay 60 mins IC50 = 0.123 μM 28315597
Sf9 insect cells Function assay 60 mins IC50 = 0.146 μM 28315597
BAF3 cells Function assay 72 h GI50 = 0.16 μM 28282122
Sf9 cells Function assay 60 mins IC50 = 0.2 μM 21958547
MV411 cells Growth inhibition assay GI50 = 0.25 μM 28315597
MV4-11 cells Antiproliferative activity assay 72 h GI50 = 0.33 μM 26630553
MV4-11 cells Antiproliferative activity assay 72 h GI50 = 0.33 μM 28956923
DOHH2 cells Cytotoxicity assay 72 h GI50 = 0.41 μM 24915291
HCC827 cells Antiproliferative activity assay 96 h EC50 = 0.45 μM 28853575
SU-DHL6 cells Cytotoxicity assay 72 h GI50 = 0.58 μM 24915291
M07e cells Growth inhibition assay GI50 = 0.59 μM 28315597
NCI-H1975 cells Antiproliferative activity assay 96 h EC50 = 0.64 μM 28853575
SU-DHL-2 cells Growth inhibition assay GI50 = 0.64 μM 28315597
HEK293T cells Function assay 1 h IC50 = 0.9 μM 28280261
Ramos cells Antiproliferative activity assay 72 h IC50 = 0.92 μM 29715023
BA/F3 cells Antiproliferative activity assay 72 h IC50 = 1 μM 26258521
WSU-NHL cells Cytotoxicity assay 72 h GI50 = 1.09 μM 24915291
NCI-H1975 cells Function assay 72 h GI50 = 1.2 μM 28282122
NCI-H1975 cells Antiproliferative activity assay 72 h IC50 = 1.27 μM 28734581
Raji cells Antiproliferative activity assay 48 h IC50 = 1.49 μM 29567295
Pfeiffer cells Growth inhibition assay GI50 = 1.6 μM 28315597
A431 cells Antiproliferative activity assay 96 h EC50 = 2.38 μM 28853575
BAF3 cells Antiproliferative activity assay 72 h GI50 = 2.5 μM 28956923
U937 cells Growth inhibition assay GI50 = 2.9 μM 28315597
NB4 cells Growth inhibition assay GI50 = 3 μM 28315597
Ramos cells Growth inhibition assay GI50 = 3.4 μM 28315597
SKM1 cells Growth inhibition assay GI50 = 3.6 μM 28315597
U2932 cells Growth inhibition assay GI50 = 4.4 μM 28315597
Ramos cells Antiproliferative activity assay 72 h IC50 = 5.14 μM 30006143
Ramos cells Antiproliferative activity assay 48 h IC50 = 5.14 μM 27956037
Ramos cells Antiproliferative activity assay 48 h IC50 = 5.88 μM 28432946
Ramos cells Antiproliferative activity assay 72 h IC50 = 6.62 μM 29146136
K562 cells Antiproliferative activity assay 48 h IC50 = 7.5 μM 30077608
HL60 cells Antiproliferative activity assay 48 h IC50 = 8 μM 30077608
Ramos cells Antiproliferative activity assay 48 h IC50 = 8.11 μM 27994736
Ramos cells Antiproliferative activity assay 48 h IC50 = 8.26 μM 29567295
OCI-AML3 cells Growth inhibition assay GI50 = 9.2 μM 28315597
BAF3 cells Cytotoxicity assay 72 h GI50 = 10 μM 26630553
BAF3 cells Antiproliferative activity assay 72 h GI50 = 10 μM 28956923
BAF3 cells Growth inhibition assay 72 h GI50 = 10 μM 28282122
NAMALWA cells Antiproliferative activity assay 72 h IC50 = 10.45 μM 29146136
Ramos cells Antiproliferative activity assay 48 h IC50 = 12.6 μM 27912175
Raji cells Antiproliferative activity assay 48 h IC50 = 14.2 μM 30077608
Raji cells Antiproliferative activity assay 48 h IC50 = 15.2 μM 27994736
MIAPaCa2 cells Cytotoxicity assay 3 days IC50 = 16.6 μM 27077228
HeLa cells Cytotoxicity assay 3 days IC50 = 16.8 μM 27077228
Raji cells Antiproliferative activity assay 48 h IC50 = 19.3 μM 27912175
Raji cells Antiproliferative activity assay 48 h IC50 = 19.3 μM 28432946
Raji cells Antiproliferative activity assay 72 h IC50 = 19.5 μM 30006143
Raji cells Antiproliferative activity assay 48 h IC50 = 19.5 μM 27956037
NAMALWA cells Antiproliferative activity assay 72 h IC50 = 19.6 μM 30006143
A2780 cells Cytotoxicity assay 3 days EC50 = 20.1 μM 27077228
Raji cells Antiproliferative activity assay 72 h IC50 = 20.88 μM 29146136
A549 cells Antiproliferative activity assay 72 h IC50 = 21.79 μM 28734581
SW480 cells Cytotoxicity assay 3 days IC50 = 25.6 μM 27077228
Ramos cells Cytotoxicity assay 24 h IC50 = 28.7 μM 28274675
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 440.5 화학식

C25H24N6O2

 보관 (수령일로부터)
CAS 번호 936563-96-1 SDF 다운로드 원액 보관

동의어 PCI-32765 Smiles C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N

용해도 (Solubility)

In vitro
배치:

DMSO : 88 mg/mL (199.77 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 8 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

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

mg/kg g μL

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)

Targets/IC50/Ki
BTK
(Cell-free assay)
0.5 nM
BLK
(Cell-free assay)
0.5 nM
Bmx
(Cell-free assay)
0.8 nM
CSK
(Cell-free assay)
2.3 nM
FGR
(Cell-free assay)
2.3 nM
BRK
(Cell-free assay)
3.3 nM
Hck
(Cell-free assay)
3.7 nM
EGFR
(Cell-free assay)
5.6 nM
YES
(Cell-free assay)
6.5 nM
ErbB2
(Cell-free assay)
9.4 nM
ITK
(Cell-free assay)
10.7 nM
JAK3
(Cell-free assay)
16.1 nM
FRK
(Cell-free assay)
29.2 nM
LCK
(Cell-free assay)
33.2 nM
RET
(Cell-free assay)
36.5 nM
시험관 내(In vitro)

Ibrutinib shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. In BCR pathway-activated DOHH2 cell line, this compound inhibits autophosphorylation of Btk, phosphorylation of Btk's physiological substrate PLCγ, and phosphorylation of further downstream kinase, ERK with IC50 of 11 nM, 29 nM and 13 nM, respectively. It exhibits a significant dose-dependent and time-dependent induction of cytotoxicity in chronic lymphocytic leukemia (CLL) cells. In addition, this compound induces cell death depending on caspase pathway activation and antagonizes the ability of CLL cells to proliferate after TLR signaling. A recent study shows that this chemical inhibits BCR-activated primary B cell proliferation with IC50 of 8 nM and results in inhibition of TNFα, IL-1β and IL-6 production in primary monocytes with IC50 of 2.6 nM, 0.5 nM and 3.9 nM, respectively.

키나아제 분석
Kinase Assays
In vitro kinase IC50 values are measured using 33P filtration binding assay after 1 hour incubation of kinase, 33P-ATP, Ibrutinib, and substrate [0.2 mg/mL poly(EY)(4:1]. Assays are performed at Reaction Biology.
생체 내(In vivo)

In a collagen-induced arthritis model, Ibrutinib significantly reduces clinical arthritis scores reflecting paw swelling and joint inflammation by inhibiting B-cell activation. In a MRL-Fas(lpr) lupus model, this compound reduces renal disease and autoantibody production. In an adoptive transfer TCL1 mouse model of CLL, this compound (25 mg/kg/day) causes a transient early lymphocytosis, and delays CLL disease progression.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/22180443/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot pEGFR(Tyr1068) / EGFR pBTK / pPLCγ2 / pAKT / pERK / pJNK
S2680-WB1
28061447
Immunofluorescence CD11b COX-2
S2680-IF1
30231870
ELISA hTNFα IL-10
S2680-ELISA1
26627823

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06084923 Not yet recruiting
Chronic Lymphocytic Leukemia
Gruppo Italiano Malattie EMatologiche dell''Adulto
 May 2024 --
NCT06224452 Not yet recruiting
Hematological Malignancy|Atrial Fibrillation
University Hospital Caen
 March 1 2024 --
NCT05694312 Recruiting
Autoimmune Hemolytic Anemia|Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma|Monoclonal B-Cell Lymphocytosis CLL-Type
Gruppo Italiano Malattie EMatologiche dell''Adulto
 November 24 2023 Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
How to reconstitute it for in vivo studies?

답변:
For in vivo study, we suggest to use 5% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 10mg/ml for it.