Structure of Hydroxyurea
CAS No.: 127-07-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Hydroxyurea is a cell apoptosis inducer that inhibits DNA synthesis by targeting ribonucleotide reductase. It also shows anti-orthopoxvirus activity.
Synonyms: Hydroxycarbamide; NCI C04831; Droxia
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The polySUMOylation axis promotes nucleolar release of Tof2 for mitotic exit
Gutierrez-Morton, Emily ; Haluska, Cory ; Collins, Liam ; Rizkallah, Raed ; Tomko, Robert J ; Wang, Yanchang
Abstract: In budding yeast, the nucleolus serves as the site to sequester Cdc14, a phosphatase essential for mitotic exit. Nucleolar proteins Tof2, Net1, and Fob1 are required for this sequestration. Although it is known that these nucleolar proteins are SUMOylated, how SUMOylation regulates their activity remains unknown. Here, we show that Tof2 exhibits cell-cycle-regulated nucleolar delocalization and turnover. Depletion of the nuclear small ubiquitin-like modifier (SUMO) protease Ulp2 not only causes Tof2 polySUMOylation, nucleolar delocalization, and degradation but also leads to Cdc14 nucleolar release and activation. This outcome depends on polySUMOylation and the activity of downstream enzymes, including SUMO-targeted ubiquitin ligase and Cdc48/p97 segregase. We further developed a system to tether SUMO machinery to Tof2 and generated a SUMO-deficient tof2 mutant, and the results indicate that Tof2 polySUMOylation is necessary and sufficient for its nucleolar delocalization and degradation. Together, our work reveals a polySUMO dependent mechanism that delocalizes Tof2 from the nucleolus to facilitate mitotic exit.
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CAS No. : | 127-07-1 |
Formula : | CH4N2O2 |
M.W : | 76.05 |
SMILES Code : | O=C(N)NO |
Synonyms : |
Hydroxycarbamide; NCI C04831; Droxia
|
MDL No. : | MFCD00007943 |
InChI Key : | VSNHCAURESNICA-UHFFFAOYSA-N |
Pubchem ID : | 3657 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H340-H360-H410 |
Precautionary Statements: | P201-P202-P273-P281-P308+P313-P403-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
In Vitro:
Concentration | Treated Time | Description | References |
hTERT-RPE cells | 10 μM | 2 hours | To study the effect of acute hydroxyurea-induced replication blockade on replication fork stability, results showed that replisome components were disengaged from nascent DNA without compromising fork restart. | PMC11104804 |
hTERT-RPE cells | 10 μM | 14 hours | To study the effect of sustained hydroxyurea-induced replication blockade on replication fork stability, results showed that replisome components were dissociated from nascent DNA and fork collapse occurred. | PMC11104804 |
Xenopus tissue culture cells | 1 μM | 30 minutes | To assess the effect of the DNA synthesis inhibitor on histone H3 and H1C mRNAs, the results showed that the amount of histone mRNA decreased rapidly in response to the inhibitor, but cycloheximide could prevent this response. | PMC322048 |
Mouse embryonic stem (ES) cells | 1 μMol/L | 6, 10, 12 hours | To evaluate the role of Mrad1 in S/M checkpoint control, results showed that Mrad1 deletion leads to S/M checkpoint defect | PMC4875338 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
Mice | Mtarc1 knockout mice and GalNAc-siMtarc1 treated mice | Intravenous injection | 10 mg/kg | pretreatment 2 hours before infection, post-treatment starting 6 hours after infection, every 12 hours for 4 days | To investigate the role of mARC1 in hydroxyurea metabolism, results showed that plasma hydroxyurea levels significantly increased and urea levels significantly decreased after mARC1 knockout or knockdown | PMC11513889 |
Mice | Oral gavage | 3 mg/kg | 2 consecutive days | To investigate the effects of hydroxyurea on testicular architecture and function in male mice, and the resumption of fertility post-treatment withdrawal. Results showed that hydroxyurea significantly reduced testis weight, sperm density, and motility, and increased abnormal sperm morphology. Fertility indices improved after 4 months of withdrawal but remained lower than controls. | PMC10253555 | |
Mice | CBA mice | Tail vein injection | 5 mg/kg | Once daily for 3 weeks | Hydroxyurea significantly decreased bone marrow cellularity, and PTIO failed to reverse this effect | PMC8616001 |
Clinical Trial:
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Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
13.15mL 2.63mL 1.31mL |
65.75mL 13.15mL 6.57mL |
131.49mL 26.30mL 13.15mL |
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Dissolving Methods |
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:
in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
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