Home DNA Damage/DNA Repair DNA/RNA Synthesis inhibitor CX-5461 (Pidnarulex)

연구용

CX-5461 (Pidnarulex) RNA Polymerase I inhibitor

제품 번호: S2684

Pidnarulex (CX-5461) is an inhibitor of rRNA synthesis, selectively inhibits Pol I-driven transcription of rRNA with IC50 of 142 nM in HCT-116, A375, and MIA PaCa-2 cells, has no effect on Pol II, and possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA replication and protein translation.
CX-5461 (Pidnarulex) DNA/RNA Synthesis inhibitor Chemical Structure

화학 구조

분자량: 513.61

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품질 관리 (Quality Control)

배치: 순도: 99.07%
99.07

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
MNNG Cell viability assay 72 h IC50=0.5-1.5 µM 27729807
U2-OS Cell viability assay 72 h IC50=0.5-1.5 µM 27729807
RS4;11 Proliferation assay 250 nM 24 h time dependent decrease in proliferation relative to their DMSO treated controls 26472108
SEM Proliferation assay 250 nM 24 h time dependent decrease in proliferation relative to their DMSO treated controls 26472108
KOPN-8 Proliferation assay 250 nM 24 h time dependent decrease in proliferation relative to their DMSO treated controls 26472108
NALM-6 Proliferation assay 250 nM 24 h time dependent decrease in proliferation relative to their DMSO treated controls 26472108
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 513.61 화학식

C27H27N7O2S

 보관 (수령일로부터) 3 years-20°C(in the dark) powder
CAS 번호 1138549-36-6 SDF 다운로드 원액 보관

동의어 N/A Smiles CC1=CN=C(C=N1)CNC(=O)C2=C3N(C4=CC=CC=C4S3)C5=C(C2=O)C=CC(=N5)N6CCCN(CC6)C

용해도 (Solubility)

In vitro
배치:

DMSO : Insoluble
(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
Pol I-driven transcription of rRNA
(HCT-116, A375, MIA PaCa-2 cells)
142 nM
시험관 내(In vitro)

CX-5461 (Pidnarulex) is found to selectively inhibit rRNA synthesis (Pol I IC50=142 nM; Pol II IC50 > 25 μM; selectivity ~200-fold) in the HCT-116 cells. This selective inhibition is confirmed in two other human solid tumor cell lines; melanoma A375 (Pol I IC50 = 113 nM; Pol II IC50 > 25 μM) and pancreatic carcinoma MIA PaCa-2 (Pol I IC50=54 nM; Pol II IC50 ~25 mM). It possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA replication and protein translation. The compound exhibits broad antiproliferative potency in a panel of cancer cell lines in human cancer cell lines, but has minimal effect on viability of nontransformed human cells. The median EC50 across all tested cell lines is 147 nM, yet all normal cell lines have EC50 values of approximately 5, 000 nM. Evaluation of the antiproliferative dose response for HCT-116, A375, and MIA PaCa-2 cell lines yield EC50 values of 167, 58, and 74 nM. It induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process.

키나아제 분석
Pol I and Pol II Transcription Assay
Two short-lived RNA transcripts (half-lives ~20-30 minutes), one produced by Pol I and another by Pol II, are quantitated by qRT-PCR as a measure of CX-5461 (Pidnarulex)-related effects on transcription. The 45S pre-rRNA served as the Pol I transcript and the mRNA for the protooncogene c-myc served as the comparator Pol II transcript. Both Pol I and Pol II transcription are known to be affected by general cellular stress. To minimize the potential effects of such stress, cells are exposed to test agents for only a short period of time (2 hours). This is sufficient time for these transcripts to be reduced by greater than 90% if this compound affects their synthesis.
생체 내(In vivo)

CX-5461 (Pidnarulex) is orally bioavailable and demonstrates in vivo antitumor activity against human solid tumors in murine xenograft models. This compound demonstrates significant MIA PaCa-2 TGI with TGI equal to 69% on day 31. Likewise, it demonstrates significant A375 TGI with TGI equal to 79% on day 32.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Cyclin D1 / p53 / p16 53BP1 / γ-H2AX / p-ATM Bcl-2 / Bax / Caspase3 cleaved PARP / cleaved Caspase-9 / cleaved caspase-3 p-AMPK / AMPK / p-mTOR / mTOR EG5 / Histone H3 / p-Histone H3 (S10)
S2684-WB1
29631594
Immunofluorescence Vimentin / Phalloidin / Snail1 Rictor / Calnexin Fibrillarin LC3 γH2AX / 53BP1 / RPA / RAD51 chromosome / telomere F-actin / Aurora B
S2684-IF1
31068593
Growth inhibition assay Cell viability
S2684-viability1
26061708

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT02719977 Completed
Cancer
Canadian Cancer Trials Group|Senhwa Biosciences Inc.|Stand Up To Cancer
 June 13 2016 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
I want to make it for further in vivo treatment.

답변:
This compound has poor solubility in common vehicles. It can be dissolved in DMF at 3 mg/ml with warming.