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Purity: ≥98%
R1530 is a small-molecule inducer of polyploidy which interferes with tubulin polymerization and mitotic checkpoint function in cancer cells, leading to abortive mitosis, endoreduplication and polyploidy. R1530 may possess antineoplastic and antiangiogenesis properties. Polyploid cancer cells experienced apoptosis or turned senescent when exposed to R1530, which resulted in strong in vitro and in vivo activity. The idea of using R1530-induced polyploidy as a cancer therapy is supported by the fact that normal proliferating cells were resistant to it. As a possible result of PLK4 inhibition, the mitotic checkpoint kinase BubR1 was found to be downregulated during the R1530-induced exit from mitosis. An R1530-like phenotype was produced by BubR1 knockdown in the presence of nocodazole, indicating that BubR1 is important for the induction of polyploidy by R1530 and may be used as a target to create more specialized polyploidy inducers.
| Targets |
KDR (IC50 = 10 nM); FGFR1 (IC50 = 28 nM)
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| ln Vitro |
BLU-554 emonstrates strong in vitro antiproliferative efficacy against all tumor cell lines (IC50 = 0.2−3.4 μM)[1].
R1530 suppresses FGFr1, PDGFr-β, and vascular endothelial growth factor receptor 2 (VGFr2) kinase activities. R1530 inhibits VEGF, and bFGF stimulates the proliferation of HUVECs (IC50 = 49 and 118 nM)[1]. |
| ln Vivo |
R1530 (1.56, 25, and 50 mg/kg; p.o.; daily, for 28 days) has low toxicity and significant antitumor activity in a variety of human xenograft models[1].
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| Enzyme Assay |
With potential antiangiogenesis and antineoplastic properties, R1530 is a multikinase inhibitor. Moreover, R1530 is a mitosis-angiogenesis inhibitor (MAI) that blocks a number of receptor tyrosine kinases implicated in angiogenesis, including platelet-derived growth factor receptor (PDGFR) beta, fibroblast growth factor receptor (FGFR) -1, -2, and MEGFR-1, -2, and platelet-derived growth factor receptor (VEGFR)-1, -2, and 3. This agent also causes apoptosis and initiates mitotic arrest, which both demonstrate anti-proliferative activity.
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| Cell Assay |
Polyploid cancer cells experienced senescence or apoptosis in the presence of R1530, which resulted in strong in vivo and in vitro activity. Normal proliferating cells demonstrated resistance to R1530-induced polyploidy, thereby bolstering the case for using polyploidy to induce cancer therapy. The downregulation of mitotic checkpoint kinase BubR1 was observed during the R1530-induced exit from mitosis, which is most likely the result of PLK4 inhibition. The growth of human tumor cells was significantly inhibited by R1530. Additionally, growth factor-driven endothelial and fibroblast cell proliferation was suppressed.
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| Animal Protocol |
Human tumor xenograft models[1]
1.56, 25 and 50 mg/kg Oral administration; daily, for 28 days. |
| References |
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| Molecular Formula |
C18H14CLFN4O
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| Molecular Weight |
356.08
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| Exact Mass |
356.08
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| Elemental Analysis |
C, 60.60; H, 3.96; Cl, 9.94; F, 5.32; N, 15.70; O, 4.48
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| CAS # |
882531-87-5
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| Appearance |
white solid powder
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| SMILES |
CC1=C2C(=NN1)NC3=CC(=C(C=C3C(=N2)C4=CC=CC=C4Cl)F)OC
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| InChi Key |
UOVCGJXDGOGOCZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14ClFN4O/c1-9-16-18(24-23-9)21-14-8-15(25-2)13(20)7-11(14)17(22-16)10-5-3-4-6-12(10)19/h3-8H,1-2H3,(H2,21,23,24)
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| Chemical Name |
5-(2-chlorophenyl)-7-fluoro-8-methoxy-3-methyl-2,10-dihydropyrazolo[3,4-b][1,4]benzodiazepine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8084 mL | 14.0418 mL | 28.0836 mL | |
| 5 mM | 0.5617 mL | 2.8084 mL | 5.6167 mL | |
| 10 mM | 0.2808 mL | 1.4042 mL | 2.8084 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00493155 | Completed | Drug: RG1530 | Neoplasms | Hoffmann-La Roche | October 2005 | Phase 1 |
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