WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406182
CAS#: 872573-93-8
Description: RO-3306 is a CDK1 inhibitor with potential anticancer activity. Treatment of growing AML cells with RO-3306 induced G2/M-phase cell cycle arrest and apoptosis in a dose- and time-dependent manner. RO-3306 downregulated expression of the antiapoptotic proteins Bcl-2 and survivin and blocked p53-mediated induction of p21 and MDM2. RO-3306 actively enhances downstream p53 signaling to promote apoptosis.
Hodoodo Cat#: H406182
Name: RO-3306
CAS#: 872573-93-8
Chemical Formula: C18H13N3OS2
Exact Mass: 351.05
Molecular Weight: 351.440
Elemental Analysis: C, 61.52; H, 3.73; N, 11.96; O, 4.55; S, 18.24
Synonym: RO3306; RO 3306; RO-3306
IUPAC/Chemical Name: 5-(6-Quinolinylmethylene)-2-[(2-thienylmethyl)amino]-4(5H)-thiazolone
InChi Key: XOLMRFUGOINFDQ-MHWRWJLKSA-N
InChi Code: InChI=1S/C18H13N3OS2/c22-17-16(24-18(21-17)20-11-14-4-2-8-23-14)10-12-5-6-15-13(9-12)3-1-7-19-15/h1-10H,11H2,(H,20,21,22)/b16-10+
SMILES Code: O=C1N=C(NCC2=CC=CS2)S/C1=C/C3=CC=C4N=CC=CC4=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Ro-3306 is an inhibitor of CDK1, with Kis of 20 nM, 35 nM and 340 nM for CDK1, CDK1/cyclin B1 and CDK2/cyclin E, respectively. |
| In vitro activity: | To analyze the DNA damage and repair processes during RO-3306-induced G2 arrest, this study examined whether irradiated cells undergoing prolonged G2 arrest repaired DSBs or induced damaged DNA to enter M-phase during RO-3306 treatment. Immediate discontinuation of RO-3306 treatment (10 μM) and exchanged treatment (DMSO or 2 μM) after irradiation in HL-60 cells resulted in mitotic entry and DSB levels significantly higher in M-phase cells, compared to in non-irradiated control (Fig. 4A and B). In contrast, persistent 10 μM RO-3306 treatment for 8 h after irradiation dramatically decreased DSB levels in M-phase cells compared to the immediate release of RO-3306 treatment (Fig. 4C and D). This study showed that further DNA-PK inhibition during prolonged G2 arrest delayed DNA repair and inhibited cell proliferation (supplementary Fig. 2). The clonogenic assay demonstrated that persistent treatment with RO-3306 after irradiation resulted in higher fractions of surviving HeLa cells, supporting the resistance of cells to CDK1 inhibition (Fig. 4E). These results show that even higher dose of RO-3306 induced prolonged G2 arrest, allowing irradiated cells to repair DSBs and preventing DNA damage from being carried over into M-phase. Reference: Biochem Biophys Res Commun. 2021 Apr 23;550:56-61. https://www.sciencedirect.com/science/article/pii/S0006291X21003466?via%3Dihub |
| In vivo activity: | Subcutaneous tumor xenografts developed from HEC-1-B cells in BALB/c nude mice were successfully established individually. Consistent with the in vitro results, the tumor growth of xenograft endometrial cancer grafts was significantly blocked with the treatment of RO3306 (Figure (5A-D). As early as day 4 of the treatment, there was a extremely significant difference in tumor volume between the RO3306 treatment group and the control group (p <0.0001) (Figure 5A). At the end of the study, tumor volumes of endometrial cancer grafts in the RO3306 treatment group and the control group were 392.2 ± 24.34 and 689.8 ± 104.3mm3, respectively, with highly significant differences between the two groups (p <0.01) (Figure 5A). As to body weight, there was no significant difference between the two groups (p >0.05) (Figure 5B). The tumor weight of endometrial cancer grafts harvested at the end of the study in the RO3306 treatment group was significantly lower than that in the control group (p <0.05) (Figure 5C). These data suggested that CDK1 played an important role in the growth and proliferation of endometrial cancer cells in vivo and RO3306 can serve as its targeted inhibitor for the treatment of endometrioid endometrial cancer. Reference: J Cancer. 2021; 12(8): 2206–2215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974891/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 16.3 | 46.27 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.71 | |
| DMF | 20.0 | 56.91 |
The following data is based on the product molecular weight 351.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Sunada S, Saito H, Zhang D, Xu Z, Miki Y. CDK1 inhibitor controls G2/M phase transition and reverses DNA damage sensitivity. Biochem Biophys Res Commun. 2021 Apr 23;550:56-61. doi: 10.1016/j.bbrc.2021.02.117. Epub 2021 Mar 5. PMID: 33684621. 2. Kojima K, Shimanuki M, Shikami M, Andreeff M, Nakakuma H. Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis in AML. Cancer Sci. 2009 Jun;100(6):1128-36. doi: 10.1111/j.1349-7006.2009.01150.x. Epub 2009 Mar 10. PMID: 19385969; PMCID: PMC2759356. 3. Ying X, Che X, Wang J, Zou G, Yu Q, Zhang X. CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer. J Cancer. 2021 Feb 22;12(8):2206-2215. doi: 10.7150/jca.51139. PMID: 33758599; PMCID: PMC7974891. 4. Czaplinski S, Hugle M, Stiehl V, Fulda S. Polo-like kinase 1 inhibition sensitizes neuroblastoma cells for vinca alkaloid-induced apoptosis. Oncotarget. 2016 Feb 23;7(8):8700-11. doi: 10.18632/oncotarget.3901. PMID: 26046302; PMCID: PMC4890998. |
| In vitro protocol: | 1. Sunada S, Saito H, Zhang D, Xu Z, Miki Y. CDK1 inhibitor controls G2/M phase transition and reverses DNA damage sensitivity. Biochem Biophys Res Commun. 2021 Apr 23;550:56-61. doi: 10.1016/j.bbrc.2021.02.117. Epub 2021 Mar 5. PMID: 33684621. 2. Kojima K, Shimanuki M, Shikami M, Andreeff M, Nakakuma H. Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis in AML. Cancer Sci. 2009 Jun;100(6):1128-36. doi: 10.1111/j.1349-7006.2009.01150.x. Epub 2009 Mar 10. PMID: 19385969; PMCID: PMC2759356. |
| In vivo protocol: | 1. Ying X, Che X, Wang J, Zou G, Yu Q, Zhang X. CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer. J Cancer. 2021 Feb 22;12(8):2206-2215. doi: 10.7150/jca.51139. PMID: 33758599; PMCID: PMC7974891. 2. Czaplinski S, Hugle M, Stiehl V, Fulda S. Polo-like kinase 1 inhibition sensitizes neuroblastoma cells for vinca alkaloid-induced apoptosis. Oncotarget. 2016 Feb 23;7(8):8700-11. doi: 10.18632/oncotarget.3901. PMID: 26046302; PMCID: PMC4890998. |
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