Home DNA Damage/DNA Repair Topoisomerase inhibitor Mitoxantrone Dihydrochloride (NSC 301739)

연구용

Mitoxantrone Dihydrochloride (NSC 301739) PKC/Topoisomerase II Inhibitor

제품 번호: S2485

Mitoxantrone 2HCl is a dihydrochloride salt of Mitoxantrone. Mitoxantrone is an inhibitor of type II topoisomerase and protein kinase C (PKC) with IC50 of 8.5 μM for PKC. Mitoxantrone inhibits cell proliferative growth of MCF-7/wt cells with IC50 of 0.42 μM. Mitoxantrone also induces apoptosis.
Mitoxantrone Dihydrochloride (NSC 301739) Topoisomerase inhibitor Chemical Structure

화학 구조

분자량: 517.4

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품질 관리 (Quality Control)

배치: 순도: 99.94%
99.94

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
L1210 cell Cytotoxicity assay 48 h Cytotoxic potency required to inhibit L1210 cell growth by 50% after cell drug contact for 48 hrs, IC50=4e-05 μM
HL60 cells Cytotoxicity assay 48 h Cytotoxicity against human HL60 cells after 48 hrs by MTT assay, GI50=0.33 μM
MDA435/LCC6 cells Proliferation assay Antiproliferative activity against MDA435/LCC6 cells by ELISA, IC50=0.35 nM
A2780-cell Growth inhibition assay Concentration required to inhibit A2780-cell growth by 50%, IC50=0.55 nM
G-361 cell Growth inhibition assay Cytotoxic potency required to inhibit G-361 cell growth by 50%, IC50=0.65 nM
human HL60 cells Proliferation assay 72 h Antiproliferative activity against human HL60 cells after 72 hrs by SRB assay, IC50=2.5 nM
human K562 cells Cytotoxicity assay 5 days Cytotoxicity against human K562 cells after 5 days by XTT assay, IC50=2.6 nM
CH1 cell Cytotoxicity assay Cytotoxic potency required to inhibit CH1 cell growth by 50%, IC50=2.65 nM
MES-SA cells Proliferation assay 72 h Antiproliferative activity against MES-SA cells by MTT assay after 72 hrs, IC50=3 nM
A549 cells Function assay Activity against A549 cancer cell line, IC50=3.1 nM
LoVo cells Cytotoxicity assay 144 h Cytotoxicity against human LoVo cancer cell line was determined after 144 hr, IC50=3.3 nM
P388 cells Proliferation assay Antiproliferative activity against P388 cells by ELISA, IC50=4.3 nM
human Daudi cells Proliferation assay 72 h Antiproliferative activity against human Daudi cells after 72 hrs by MTT assay, IC50=5 nM
SKOV-3 cell Cytotoxicity assay Cytotoxic potency required to inhibit SKOV-3 cell growth 50%, IC50=5.3 nM
OVCAR-3 cell Function assay Antitumor activity against human ovarian OVCAR-3 cell lines, IC50=5.8 nM
human MES-SA cells Proliferation assay 72 h Antiproliferative activity against human MES-SA cells after 72 hrs by MTT assay, IC50=6 nM
PC3 cancer cell Cytotoxicity assay 144 h Cytotoxicity against human PC3 cancer cell line was determined after 144 hr, IC50=7 nM
MXF7 breast cell Function assay Antitumor activity against human mammary carcinoma sensitive MXF7 breast cell line, IC50=8.7 nM
HT-29 cell Cytotoxicity assay 144 h Cytotoxic potency required to inhibit HT-29 cell growth by 50% after cell drug contact for 144 hrs, IC5=0.01 μM
HEK293 cells Cytotoxicity assay 72 h Cytotoxicity against HEK293 cells after 72 hrs by MTT assay, IC50=0.01 μM
MKN45 cells Cytotoxicity assay 144 h Cytotoxicity against human MKN45 cancer cell line was determined after 144 hr, IC50=0.012 μM
MES-SA cells Cytotoxicity assay 72 h Cytotoxicity against human MES-SA cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.012 μM
FM3 cells Proliferation assay 72 h Antiproliferative activity against human FM3 cells after 72 hrs by MTT assay, IC50=0.013 μM
MCF-7 cells Growth inhibition assay Inhibitory activity against human tumor cell line MCF-7 breast adenocarcinoma, IC50=0.02 μM
human small-cell lung cancer Cytotoxicity assay Cytotoxicity against human small-cell lung cancer (SCLC), IC50=0.02 μM
human HCT116 cells Cytotoxicity assay 72 h Cytotoxicity against human HCT116 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.022 μM
human HCT116 cells Proliferation assay 72 h Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50=0.025 μM
NCI-H460 cells Cytotoxicity assay 48 h Cytotoxicity against human NCI-H460 cells after 48 hrs by resazurin dye assay, EC50=0.03 μM
CCRF-CEM cells Cytotoxicity assay 48 h Cytotoxicity against human CCRF-CEM cells assessed as cell viability after 48 hrs by celltiter-blue assay, IC50=0.036 μM
HeLa cells Proliferation assay 72 h Antiproliferative activity against human HeLa cells after 72 hrs by MTT assay, IC50=0.044 μM
NCI60 cells Function assay 48 h Antitumor activity against human NCI60 cells after 48 hrs by SRB assay, GI50=47.86 nM
UACC375 cell Function assay Antitumor activity against human melanoma UACC375 cell line, IC50=0.048 μM
HT1080 cell Growth inhibition assay Inhibitory activity against human tumor cell line HT1080, IC50=0.066 μM
MES-SA/Dx5 cells Proliferation assay 72 h Antiproliferative activity against human MES-SA/Dx5 cells after 72 hrs by MTT assay, IC50=0.073 μM
SF268 cells Proliferation assay 48 h Antiproliferative activity against human SF268 cells after 48 hrs, EC50=0.32 μM
KB/HeLa cells Proliferation assay 48 h Antiproliferative activity against human KB/HeLa cells after 48 hrs, EC50=0.36 μM
K562 cells Growth inhibition assay 72 h Growth inhibition of human K562 cells after 72 hrs by MTS method, IC50=0.42 μM
MDA-MB-231 cells Proliferation assay 72 h Antiproliferative activity against human MDA-MB-231 cells by WST-1 method after 72 hrs, IC50=0.96 μM
SF268 cells Cytotoxicity assay 48 h Cytotoxicity against human SF268 cells after 48 hrs by SRB assay, GI50=0.97 μM
HCT116 cells Cytotoxicity assay Cytotoxicity against human HCT116 cells by MTT assay, IC50=3.96 μM
U937 cells Cytotoxicity assay Cytotoxicity against human U937 cells by MTT assay, IC50=6.2 μM
HepG2 cells Proliferation assay 48 h Antiproliferative activity against human HepG2 cells after 48 hrs by MTT assay, IC50=11.05 μM
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 517.4 화학식

C22H29ClN4O6.2HCl

 보관 (수령일로부터) 3 years-20°C(in the dark) powder
CAS 번호 70476-82-3 SDF 다운로드 원액 보관

동의어 NSC-301739 2HCl, Mitozantrone 2HCl Smiles C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO.Cl.Cl

용해도 (Solubility)

In vitro
배치:

DMSO : 104 mg/mL (201.0 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : 104 mg/mL

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
Topoisomerase II
PKC
(Cell-free assay)
8.5 μM
시험관 내(In vitro)

Mitoxantrone Dihydrochloride (NSC 301739)은 연구된 모든 환자에서 caspases 활성화의 지표인 poly(ADP-ribose) polymerase (PARP)의 단백질 분해 절단 및 DNA 파편화를 유도하며, 이는 Mitoxantrone Dihydrochloride (NSC 301739)의 세포 독성 효과가 Apoptosis related 유도에 기인함을 보여줍니다. Mitoxantrone Dihydrochloride (NSC 301739)은 전골수성 백혈병 세포주인 HL60에서는 NFkappaB를 활성화하고 IkappaBalpha 분해를 자극하지만, Topoisomerase II의 베타 이성질체가 결핍되어 있고 세포 내 분포가 변경된 절단된 알파 이성질체를 발현하는 변이 세포인 HL60/MX2 세포에서는 그렇지 않습니다. Mitoxantrone Dihydrochloride (NSC 301739)은 APCs에서 자극된 활성화된 PBMCs, B 림프구 또는 항원 특이적 T-cell lines (TCLs)의 증식을 용량 의존적으로 억제합니다. Mitoxantrone Dihydrochloride (NSC 301739)은 낮은 농도에서 PBMCs, 단핵구 및 DCs의 Apoptosis related을 유도하는 반면, 더 높은 용량에서는 세포 용해를 유발합니다.

생체 내(In vivo)

Mitoxantrone은 생쥐의 HID 이종이식편 성장 속도를 일시적으로 감소시키지만 PAC120 이종이식편에는 영향을 미치지 않습니다. Mitoxantrone은 자연발생적 고혈압 쥐에서 심장 병변, 신병증 및 장 독성의 심각성을 유발합니다. Mitoxantrone과 철(III)은 강력한 2:1 착물을 형성하며, 여기서 mitoxantrone은 세자리 리간드(tridentate ligand)로 작용할 수 있습니다.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/2476134/
  • [5] https://pubmed.ncbi.nlm.nih.gov/9664073/
  • [6] https://pubmed.ncbi.nlm.nih.gov/8254024/
  • [7] https://pubmed.ncbi.nlm.nih.gov/1295884/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-ROS1 / ROS1 / p-STAT3 / STAT3 / p-AKT / AKT / p-ERK / ERK
S2485-WB1
30108778
Growth inhibition assay Cell number
S2485-viability1
24349321

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06156761 Not yet recruiting
Breast Cancer
Cancer Institute and Hospital Chinese Academy of Medical Sciences|CSPC Ouyi Pharmaceutical Co. Ltd.
 November 28 2023 Not Applicable
NCT05875428 Recruiting
Diffuse Large B-Cell Lymphoma
CSPC ZhongQi Pharmaceutical Technology Co. Ltd.
 July 10 2023 Phase 2
NCT05496894 Withdrawn
Relapsing Multiple Sclerosis
CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co. Ltd.
 August 2022 Phase 2