Home JAK/STAT JAK inhibitor Momelotinib (CYT387)

연구용

Momelotinib (CYT387) JAK inhibitor

제품 번호: S2219

Momelotinib (CYT387, LM-1149, CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. This compound induces apoptosis and autophagy. Phase 3.
Momelotinib (CYT387) JAK inhibitor Chemical Structure

화학 구조

분자량: 414.46

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품질 관리 (Quality Control)

배치: 순도: 99.75%
99.75

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
SET2 Antiproliferative assay 72 hrs Antiproliferative activity against human SET2 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=0.232μM. 19762238
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK2 kinase after 72 hrs by alamar blue assay, IC50=0.798μM. 19762238
CTLL-2 Antiproliferative assay 72 hrs Antiproliferative activity against IL-2-stimulated mouse CTLL-2 cells expressing JAK1/JAK3 after 72 hrs by alamar blue assay, IC50=1.249μM. 19762238
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing wild type JAK2 kinase after 72 hrs by alamar blue assay in presence of IL-3, IC50=1.43μM. 19762238
HEL 92.1.7 Antiproliferative assay 72 hrs Antiproliferative activity against human HEL 92.1.7 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=1.804μM. 19762238
HEL Antiproliferative assay 48 hrs Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay, IC50=2.3μM. 29940115
BAF3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK3 kinase after 72 hrs by alamar blue assay, IC50=2.425μM. 19762238
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs by CCK-8 assay, IC50=6.5μM. 29940115
HL60 Antiproliferative assay 48 hrs Antiproliferative activity against human HL60 cells after 48 hrs by CCK-8 assay, IC50=8.3μM. 29940115
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
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
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
BAF3 Function assay Inhibition of JAK2 V617F mutant in mouse BAF3 cells, IC50=1.5μM. ChEMBL
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 414.46 화학식

C23H22N6O2

 보관 (수령일로부터) 3 years -20°C(in the dark) powder
CAS 번호 1056634-68-4 SDF 다운로드 원액 보관

동의어 LM-1149 , CYT11387 Smiles C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N

용해도 (Solubility)

In vitro
배치:

DMSO : 83 mg/mL (200.26 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:

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
JAK1
(Cell-free assay)
11 nM
JAK2
(Cell-free assay)
18 nM
JAK3
(Cell-free assay)
155 nM
시험관 내(In vitro)
Momelotinib (CYT387) inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, it also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, this compound has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2μ-4 μM. A recent study shows that it inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, it induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells.
키나아제 분석
Cell-free kinase activity assays
곤충 세포에서 발현된 Glutathione-S-transferase (GST) 태그가 붙은 JAK 키나아제 도메인은 Momelotinib (CYT387)을 이용한 펩타이드 기질 인산화 분석에 사용되기 전에 정제됩니다. 분석은 Alphascreen Protein Tyrosine Kinase P100 검출 키트와 PerkinElmer Fusion Alpha 장비를 사용하여 384-웰 옵티플레이트에서 수행됩니다.
생체 내(In vivo)
In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-JAK2 / JAK2 / p-STAT3 / STAT3 p-Src / Src
S2219-WB1
26625308
Immunofluorescence p62 / pS6
S2219-IF1
29138276
Growth inhibition assay Cell viability
S2219-viability1
20385788

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT01236638 Completed
Primary Myelofibrosis|Post-Polycythemia Vera Myelofibrosis|Post-Essential Thrombocythemia Myelofibrosis
Sierra Oncology LLC - a GSK company
 November 2010 Phase 2
NCT00935987 Completed
Primary Myelofibrosis|Post-Polycythemia Vera Myelofibrosis|Post-Essential Thrombocythemia Myelofibrosis
Sierra Oncology LLC - a GSK company
 November 2009 Phase 1|Phase 2