Hydroxyurea Ribonucleotide Reductase Inhibitor

제품 번호S1896

Hydroxyurea is an antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxyurea activates apoptosis and autophagy. Hydroxyurea is used to treat HIV infection.
Hydroxyurea DNA/RNA Synthesis inhibitor Chemical Structure

화학 구조

분자량: 76.05

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품질 관리 (Quality Control)

배치: 순도: 99.95%
99.95

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
L1210 Leukemia cells Growth inhibition assay Concentration required for 50% inhibition of cell growth (L1210 Leukemia), IC50=21.3796 μM 2991520
P388 leukemic cell Proliferation assay 24-48 h Antiproliferative activity of compound expressed as concentration that inhibits 50% of growth of P388 leukemic cell suspension from 24 to 48 hr after compound addition, IC50=32 μM 2709372
L1210 Function assay 48 h Activity against cultured L1210 leukemic cells was determined in vitro, after 48 h of incubation. Compound dose that causes 16 % inhibition was reported, ID16 = 1.99 μM. 6319702
U373-MAGI Function assay 500 uM 2 hrs Potentiation of 5-Aza-C-induced antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as 5-Aza-C EC50 at 500 uM preincubated for 2 hrs followed by 5-Aza-C addition for 2 hrs and subsequent viral infection meas, EC50 = 25.8 μM. 27117260
Burkitt's lymphoma cells Function assay Inhibition of [14C]-cytidine incorporation into DNA in Burkitt's lymphoma cells, IC50 = 37.15 μM. 11405653
U373-MAGI Antiviral assay 500 uM Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in viral infectivity at 500 uM incubated for 4 hrs prior to viral infection measured at 72 hrs post infection by flow cytometric analysis 27117260
U373-MAGI Function assay 0.5 mM 2 hrs Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 0.5 mM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-C 27117260
U373-MAGI Function assay 2 mM 6 hrs Reduction in dATP level in human U373-MAGI cells at 2 mM after 6 hrs by LC-MS/MS analysis 27117260
U373-MAGI Function assay 0.5 mM 2 hrs Reduction in dCTP level in human U373-MAGI cells at 0.5 mM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis 27117260
U373-MAGI Function assay 2 mM 2 hrs Reduction in dCTP level in human U373-MAGI cells at 2 mM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-C 27117260
U373-MAGI Function assay 0.5 mM 2 hrs Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 0.5 mM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC 27117260
U373-MAGI Function assay 2 mM 2 hrs Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 2 mM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC 27117260
U373-MAGI Function assay 0.5 mM 2 hrs Reduction in dCTP level in human U373-MAGI cells at 0.5 mM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC 27117260
U373-MAGI Function assay 2 mM 2 hrs Reduction in dCTP level in human U373-MAGI cells at 2 mM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC 27117260
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
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
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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS 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
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
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 76.05 화학식

CH4N2O2

보관 (수령일로부터)
CAS 번호 127-07-1 SDF 다운로드 원액 보관

동의어 NCI-C04831, Hydroxycarbamide,NSC-32065 Smiles C(=O)(N)NO

용해도 (Solubility)

In vitro
배치:

DMSO : 15 mg/mL (197.23 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : 15 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
ribonucleoside diphosphate reductase
시험관 내(In vitro)
hydroxyurea can inhibit HIV-1 replication. In vitro experiments have shown that the 90% inhibitory concentration (IC90) of this compound for laboratory strains of HIV-1 in activated PBMC is 0.4 mM. It was also found to be synergistic with the nucleoside reverse transcriptase inhibitor didanosine and to inhibit HIV-1 replication in activated PBMC; this inhibition may be due to a reduction in deoxynucleoside triphosphate pool sizes. This chemical has been shown to sensitize didanosine-resistant mutants. It has demonstrated activity in the treatment of sickle cell anemia by increasing the production of fetal hemoglobin, which reduces hemolysis in patients with this disease. This agent exerts its cytostatic effect through inhibition of ribonucleotide reductase—the rate-limiting enzyme responsible for the conversion of ribonucleotides to deoxyribonucleotides, which are essential for DNA synthesis. As a result, cellular division is arrested in the S phase.
참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/12101433/

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06171217 Recruiting
Sickle Cell Disease|Children
Children''s Hospital Medical Center Cincinnati|National Heart Lung and Blood Institute (NHLBI)
October 27 2023 Phase 2
NCT05909657 Recruiting
Sickle Cell Disease
The University of The West Indies
July 1 2023 --
NCT05548062 Recruiting
Polycythemia Vera
Novartis Pharmaceuticals|Novartis
March 2 2023 --
NCT05662098 Recruiting
Sickle Cell Disease
Children''s Hospital Medical Center Cincinnati|Jinja Regional Referral Hospital (JRRH) Sickle Cell Clinic Jinja Uganda
June 16 2022 Early Phase 1