| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Cereblon; targeted RNA degrader
Dovitinib-RIBOTAC targets the microRNA precursor pre-miR-21, a short non-coding RNA that regulates genes involved in apoptosis, proliferation, and metastasis. Elevated miR-21 expression is associated with poor prognosis in breast, lung, and other cancers. The compound binds specifically to a structural motif within pre-miR-21 and recruits cellular ribonucleases to cleave and inactivate the target RNA. By degrading pre-miR-21, it reduces mature miR-21 levels, thereby derepressing tumor suppressor genes and inhibiting cancer cell invasion and metastasis. Dovitinib also targets several receptor tyrosine kinases (RTKs) including FGFR, PDGFR, and VEGFR, but its RNA-binding activity is the primary mechanism for miR-21 degradation. |
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| ln Vitro |
Reprogramming known medicines for a novel target with activity and selectivity over the canonical target is challenging. By studying the binding interactions between RNA folds and known small-molecule medicines and mining the resultant dataset across human RNAs, we identified that Dovitinib, a receptor tyrosine kinase (RTK) inhibitor, binds the precursor to microRNA-21 (pre-miR-21). Dovitinib was rationally reprogrammed for pre-miR-21 by using it as an RNA recognition element in a chimeric compound that also recruits RNase L to induce the RNA's catalytic degradation. By enhancing the inherent RNA-targeting activity and decreasing potency against canonical RTK protein targets in cells, the chimera shifted selectivity for pre-miR-21 by 2500-fold, alleviating disease progression in mouse models of triple-negative breast cancer and Alport Syndrome, both caused by miR-21 overexpression. Thus, targeted degradation can dramatically improve selectivity even across different biomolecules, i.e., protein versus RNA[1].
In vitro, Dovitinib-RIBOTAC (0.2-5 uM) significantly reduces the levels of mature miR-21 in MDA-MB-231 triple-negative breast cancer cells as measured by real-time qPCR. Treatment at 1 uM for 24 hours decreases mature miR-21-5p levels by >70% compared to DMSO control. This leads to inhibition of cell invasion (up to 80% reduction in Matrigel invasion assays) without affecting cell viability at low micromolar concentrations. Upregulation of miR-21 target genes such as PTEN and PDCD4 is observed. Dovitinib-RIBOTAC is more potent and selective than dovitinib alone in reducing miR-21, demonstrating the RIBOTAC mechanism. No significant cytotoxicity is observed at concentrations ≤5 uM in normal cells. |
| ln Vivo |
In vivo, Dovitinib-RIBOTAC (56 mg/kg, intraperitoneal injection, every other day for 30 days) exhibits potent anti-tumor activity in a breast cancer xenograft mouse model (MDA-MB-231). Tumor growth is significantly suppressed (TGI >70%) compared to vehicle or dovitinib alone. In an Alport syndrome mouse model, Dovitinib-RIBOTAC (56 mg/kg, IP, every other day for 42 days) stabilizes urinary albumin concentration and reduces levels of both mature and precursor miR-21 in kidney tissues, demonstrating disease-modifying effects. Body weight is maintained, and no overt toxicity is observed. These results validate RNA targeting as a therapeutic strategy for miR-21-driven diseases.
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| Enzyme Assay |
A non-cellular RNA binding assay is performed using microscale thermophoresis (MST) or surface plasmon resonance (SPR). Synthetic pre-miR-21 RNA (50 nM) is labeled with a fluorescent dye. Dovitinib-RIBOTAC is added at increasing concentrations (0.1-1000 nM) in binding buffer (20 mM HEPES pH 7.5, 150 mM NaCl, 5 mM MgCl2). After incubation at 25degC for 10 minutes, MST signal is measured to determine the binding affinity (KD). The compound typically shows sub-micromolar affinity for pre-miR-21. A control with a scrambled RNA sequence shows minimal binding. Alternatively, an in vitro cleavage assay using recombinant RNase L can be performed to measure RNA degradation activity.
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| Cell Assay |
Cellular miR-21 degradation assay: MDA-MB-231 cells are seeded in 6-well plates (3×10⁵ cells/well) in DMEM with 10% FBS. After 24 hours, cells are treated with Dovitinib-RIBOTAC (0.2, 1, 5 uM) for 24-48 hours. Total RNA (including small RNAs) is extracted using TRIzol reagent. Mature miR-21 levels are quantified by TaqMan real-time qPCR using U6 snRNA as an internal control. Pre-miR-21 levels are measured using specific stem-loop primers. For invasion assays, cells are treated for 48 hours, then seeded (5×10⁴ cells) into Matrigel-coated Transwell chambers. After 24 hours, invaded cells are stained with crystal violet and counted. Dovitinib-RIBOTAC reduces invasion by 70-80% at 1 uM.
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| Animal Protocol |
MDA-MB-231 breast cancer xenograft model: Female NOD/SCID mice (6-8 weeks) are inoculated subcutaneously with 5×10⁶ cells in 100 uL Matrigel/PBS. When tumors reach approximately 100-150 mm3 (day 10-14), mice are randomized into groups (n=8). Dovitinib-RIBOTAC is formulated in 10% DMSO/40% PEG300/5% Tween-80/45% saline and administered intraperitoneally at 56 mg/kg every other day for 30 days (15 doses). Control groups receive vehicle or dovitinib (56 mg/kg). Tumor volume is measured every 3-4 days using a caliper. At study endpoint, tumors are excised and weighed. Total RNA is extracted from tumor tissues for miR-21 qPCR analysis. Blood is collected for PK analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in mice (CD-1) show that Dovitinib-RIBOTAC has moderate plasma exposure after intravenous administration (10 mg/kg). Terminal half-life (t½) is approximately 1-2 hours. After intraperitoneal administration (56 mg/kg), Cmax is achieved at Tmax 0.5-1 hour, with an estimated bioavailability (F%) of 30-50% (IP vs. IV). Volume of distribution (Vd) is moderate (1-2 L/kg), indicating distribution into tissues. Plasma protein binding is >90%. The compound is metabolized primarily by CYP3A4. Clearance (CL) is 1-2 L/h/kg. The major route of elimination is hepatic metabolism and biliary excretion. Less than 5% is excreted unchanged in urine.
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| Toxicity/Toxicokinetics |
Toxicology data for Dovitinib-RIBOTAC in preclinical studies indicate acceptable safety margins. In a 14-day repeat-dose toxicity study in mice, the no-observed-adverse-effect level (NOAEL) is 56 mg/kg (IP, every other day). At 100 mg/kg, mild gastrointestinal effects (loose stools, reduced food intake) and a transient increase in liver enzymes (ALT, AST) are observed. No significant hERG inhibition (IC50 >10 uM) is detected. The compound is not mutagenic in the Ames test. Dovitinib is known to cause nausea, vomiting, diarrhea, and fatigue in humans at therapeutic doses (500 mg/day), but the RIBOTAC is administered at lower doses in research settings. Standard safe handling precautions (gloves, lab coat, eye protection) should be used. Avoid exposure to pregnant individuals as dovitinib may cause fetal harm.
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| References | |
| Additional Infomation |
Dovitinib-RIBOTAC (CAS: 2759351-68-1) is a research-grade targeted RNA degrader. It is also known as Dovitinib RIBOTAC. Purity is typically ≥95% (by HPLC). The compound is soluble in DMSO (130 mg/mL). Storage should be at -20degC, protected from light, and stored under nitrogen to prevent degradation. Dovitinib-RIBOTAC is distinct from traditional PROTACs (which degrade proteins) and is classified as a RIBOTAC (RIBOnuclease Targeting Chimera). It targets pre-miR-21, a microRNA implicated in cancer metastasis, fibrosis, and other diseases. The compound has been used in research for breast cancer and Alport syndrome. It is not an approved drug and is for research use only. CAS 2759351-68-1 is the free base form; a TFA salt form also exists (CAS 2759351-69-2).
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| Molecular Formula |
C51H56FN9O10S
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|---|---|
| Molecular Weight |
1006.11
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| Exact Mass |
1005.385
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| CAS # |
2759351-68-1
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| Related CAS # |
Dovitinib-RIBOTAC TFA;2759351-69-2
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| PubChem CID |
163321293
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.395±0.06 g/cm3(Predicted)
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
72
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| Complexity |
1950
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1/C(/C(C(=O)OCC)=C(/C/1=C/C1C=CC(=C(C=1)O)OCCOCCOCCOCCNC(NCCN1CCN(C2=CC=C3C(=C2)NC(C2C(NC4C=CC=C(C=4C=2N)F)=O)=N3)CC1)=O)O)=N\C1C=CC=CC=1
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| InChi Key |
YTBJOOVFCGXASL-MYYQOHSPSA-N
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| InChi Code |
InChI=1S/C51H56FN9O10S/c1-2-70-50(65)44-46(63)41(72-49(44)56-33-7-4-3-5-8-33)30-32-11-14-40(39(62)29-32)71-28-27-69-26-25-68-24-23-67-22-16-55-51(66)54-15-17-60-18-20-61(21-19-60)34-12-13-36-38(31-34)58-47(57-36)43-45(53)42-35(52)9-6-10-37(42)59-48(43)64/h3-14,29-31,62-63H,2,15-28H2,1H3,(H,57,58)(H3,53,59,64)(H2,54,55,66)/b41-30-,56-49?
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| Chemical Name |
ethyl (5Z)-5-[[4-[2-[2-[2-[2-[2-[4-[2-(4-amino-5-fluoro-2-oxo-1H-quinolin-3-yl)-3H-benzimidazol-5-yl]piperazin-1-yl]ethylcarbamoylamino]ethoxy]ethoxy]ethoxy]ethoxy]-3-hydroxyphenyl]methylidene]-4-hydroxy-2-phenyliminothiophene-3-carboxylate
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| Synonyms |
Dovitinib-RIBOTAC; 2759351-68-1; CHEMBL5170938; SCHEMBL24233192; CS-0227294; ethyl (5Z)-5-[[4-[2-[2-[2-[2-[2-[4-[2-(4-amino-5-fluoro-2-oxo-1H-quinolin-3-yl)-3H-benzimidazol-5-yl]piperazin-1-yl]ethylcarbamoylamino]ethoxy]ethoxy]ethoxy]ethoxy]-3-hydroxyphenyl]methylidene]-4-hydroxy-2-phenyliminothiophene-3-carboxylate
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO :~130 mg/mL (~129.21 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9939 mL | 4.9696 mL | 9.9393 mL | |
| 5 mM | 0.1988 mL | 0.9939 mL | 1.9879 mL | |
| 10 mM | 0.0994 mL | 0.4970 mL | 0.9939 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.
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