Danvatirsen
Based on 1 Customer Validation
Danvatirsen (AZD9150) is an antisense oligonucleotide targeting STAT3. Danvatirsen reduces the viability and promotes apoptosis of leukemia cell lines. Danvatirsen inhibits the expression of endogenous STAT3 and its downstream target genes, and reduces the proliferation and tumorigenicity of neuroblastoma and lymphoma cells. Danvatirsen inhibited tumor growth in mouse models of neuroblastoma, lymphoma, and non-small cell lung cancer. Danvatirsen achieves STAT3 mRNA and protein depletion in a mouse model of epidermoid carcinoma. Danvatirsen can be used in research related to lymphoma, myelodysplastic syndrome, acute myeloid leukemia, neuroblastoma and non-small cell lung cancer.
For research use only. We do not sell to patients.
- Purity: 99.12%
- CAS No.: 1402357-06-5
- Molecular Weight:5422.00
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Storage:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Danvatirsen (2.5-10 μM) significantly reduces STAT3 mRNA levels in KG1a, CMK, MOLM13 and KT1 leukemia cell lines[2].
Danvatirsen (1-10 μM; 24-72 h) significantly reduces the viability of leukemia/myelodysplastic syndrome (MDS) cell lines including NB4, MOLM14, MDS-L, MV411, KG1a, MOLM13, KT1 and CMK[2].
Danvatirsen (5 μM for CMK, 10 μM for KT1 and U937; 48 h) significantly increases the apoptosis levels of CMK, KT1 and U937 leukemia cell lines[2].
Danvatirsen (2.5-10 μM; 24 h) significantly reduces STAT3 mRNA levels in primary MDS/AML stem cells[2].
Danvatirsen (10 μM; 14 days) enhances erythroid and myeloid differentiation of primary myelodysplastic syndrome (MDS) stem/progenitor cells[2].
Danvatirsen (10 μM; 24 h) downregulates STAT3 and its downstream oncogenic target genes (IL1RAP, MSI2, MCL1, IL8, CXCR2) at the mRNA level, and reduces the protein levels of STAT3, phosphorylated STAT3 and MCL1 in CMK leukemia cells[2].
Danvatirsen induces dose-dependent apoptosis in primary TP53-mutant MDS/AML stem/progenitor cells and reduces the replating efficiency of primary AML stem and progenitor cells in colony-forming assays[2].
Danvatirsen (0.25-10 μM; 6 days) dose-dependently inhibits STAT3 mRNA expression in SK-N-AS, NGP and IMR32 neuroblastoma cells, with IC50 values of 0.69, 0.64 and 0.76 μM, respectively[3].
Danvatirsen (0.25-10 μM; 6 days) dose-dependently inhibits the expression of total STAT3 protein and phosphorylated STAT3 protein in SK-N-AS, NGP and IMR32 neuroblastoma cells, with IC50 values of 0.99 μM, 0.97 μM and 0.98 μM, respectively[3].
Danvatirsen (1 μM; 6 days) significantly reduces the mRNA and protein expression levels of multiple STAT3 target genes in SK-N-AS, NGP and IMR32 neuroblastoma cells[3].
Danvatirsen (1 μM; 4 weeks) significantly inhibits the proliferation of SK-N-AS, NGP and IMR32 neuroblastoma cells, reducing the maximum cell confluence by up to 38%, 37% and 34% respectively during continuous incubation. It also suppresses the anchorage-independent colony formation of the cells, decreasing the number of colonies by 20%, 43% and 67% respectively[3].
Danvatirsen (1 μM; 6 days) significantly enhances the sensitivity of SK-N-AS, NGP and IMR32 neuroblastoma cells to Cisplatin (HY-17394), reduces the IC50 value of Cisplatin by up to 2-fold, and attenuates the activation of Cisplatin-induced DNA damage response pathways[3].
Danvatirsen (0.005-5 μM; 5 days) dose-dependently inhibits the proliferation of STAT3-dependent human lymphoma cell lines KARPAS299 and SUP-M2 via free uptake[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NB4, MOLM14, MDS-L, MV411, KG1a, MOLM13, KT1, CMK leukemic/MDS cell lines
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Concentration:10 μM
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Incubation Time:24 h, 48 h, 72 h
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Result:Induced a significant, dose-dependent decrease in cell viability across all tested cell lines.
Showed greater inhibition at higher concentrations.
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Cell Line:CMK, KT1, U937 leukemic cell lines
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Concentration:5 μM (CMK cells); 10 μM (KT1 and U937 cells)
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Incubation Time:48 h
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Result:Induced a significant increase in early apoptotic, late apoptotic, and necrotic cell populations compared with controls.
Showed a dose-dependent effect observed across tested concentrations.
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Cell Line:CMK leukemic cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Downregulated expression of STAT3 and oncogenic/stem cell-associated genes including IL1RAP, MSI2, MCL1, IL8, and CXCR2 at the mRNA level.
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Cell Line:CMK leukemic cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Reduced STAT3 protein, phospho-STAT3, and MCL1 protein levels.
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Cell Line:SK-N-AS, NGP, IMR32 human neuroblastoma cell lines
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Concentration:0.25-10 μM
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Incubation Time:6 days
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Result:Inhibited STAT3 mRNA levels in a dose-dependent manner.
Achieved IC50 values of 0.69 μM in SK-N-AS cells, 0.64 μM in NGP cells, and 0.76 μM in IMR32 cells.
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Cell Line:SK-N-AS, NGP, IMR32 human neuroblastoma cell lines
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Concentration:0.25-10 μM
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Incubation Time:6 days
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Result:Decreased both total and phosphorylated STAT3 (Ser727, Tyr705) protein levels in a dose-dependent manner.
Achieved IC50 values of 0.99 μM in SK-N-AS cells, 0.97 μM in NGP cells, and 0.98 μM in IMR32 cells.
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Cell Line:SK-N-AS, NGP, IMR32 human neuroblastoma cell lines
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Concentration:1 μM
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Incubation Time:continuous incubation (up to 240 hours)
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Result:Caused a significant decrease in cell growth: up to 38% decrease in SK-N-AS cells, up to 37% decrease in NGP cells, and up to 34% decrease in IMR32 cells.
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Cell Line:SK-N-AS, NGP, IMR32 human neuroblastoma cell lines
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Concentration:1 μM
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Incubation Time:3 days pre-incubation, followed by 3 days co-incubation with cisplatin
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Result:Significantly increased cisplatin sensitivity, resulting in a 2-fold decrease in cisplatin IC50 in NGP cells and IMR32 cells, and a smaller decrease in SK-N-AS cells.
Attenuated cisplatin-induced activation of the ATM and ATR DNA damage response pathways, as shown by reduced phosphorylation of ATM, Chk2, ATR, Chk1, and γH2AX.
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Cell Line:KARPAS299, SUP-M2 (human lymphoma cell lines)
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Concentration:0.005-5 μM
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Incubation Time:5 days
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Result:Induced dose-dependent inhibition of cell proliferation in KARPAS299 and SUP-M2 cells.
Showed antiproliferative effects that correlated with the degree of STAT3 depletion.
Combination of Danvatirsen (100 mg/kg; s.c.; 5 times per week for 3 consecutive weeks) with Cisplatin results in a maximum growth inhibition rate of 38% in neuroblastoma xenografts and significantly prolongs the survival of tumor-bearing mice[3].
Danvatirsen (25-50 mg/kg; s.c.; 5 times per week; for 3 consecutive weeks) induces potent, dose-dependent depletion of STAT3 mRNA and protein in human epidermoid carcinoma A431 xenografts, with the 25 mg/kg dose reducing tumor STAT3 mRNA levels by 90%[4].
Danvatirsen (50 mg/kg, s.c., 5 times per week for 5 weeks) inhibits the growth of human lymphoma SUP-M2 xenografts with an inhibition rate of 62%, and reduces tumor STAT3 mRNA levels by approximately 40%. It exhibits systemic anti-lymphoma activity in the disseminated SUP-M2 model, reducing tumor STAT3 mRNA by approximately 50% and decreasing plasma concentrations of sIL-2Rα and sCD30[4].
Danvatirsen (25 mg/kg; s.c.; 5 times per week; for approximately 5 weeks) inhibits the growth of PC-9 human non-small cell lung cancer xenografts by 90%, and reduces STAT3 activity and the expression of its downstream target genes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nonobese Diabetic Scid Gamma (NSG) (irradiated, engrafted with primary human MDS/AML peripheral blood mononuclear cells)[2]
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Dosage:50 mg/kg
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Administration:s.c.; 5 days per week; 4 weeks
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Result:Reduced MDS/AML burden, with greatly decreased fold change of human CD45+ cells in bone marrow compared with controls.
Achieved complete loss of detectable human CD45+ cells in some treated mice.
Exerted effects in both low-risk and high-risk MDS patient-derived xenografts.
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Animal Model:athymic nude mice (5-6 week-old female)[3]
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Dosage:100 mg/kg (target reagent); 2 mg/kg (Cisplatin)
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Administration:subcutaneous (target reagent; 5 times per week; 3 weeks); intraperitoneal (cisplatin; 2 times per week; 3 weeks; co-administered starting on day 11 of target reagent treatment)
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Result:Reduced neuroblastoma xenograft growth by up to 38% compared to control-treated mice.
Prolonged survival significantly compared to control-treated mice.
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Animal Model:Immunocompromised mice; NSG mice (disseminated lymphoma model)[4]
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Dosage:25 mg/kg; 37.5 mg/kg; 50 mg/kg
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Administration:5 times per week; 3 weeks (25 mg/kg, 50 mg/kg)
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Result:Reduced tumor STAT3 mRNA by approximately 90% (P=0.0001) and STAT3 protein by 93% (25 mg/kg).
Produced near-complete depletion of STAT3 protein throughout the tumor as measured by immunohistochemistry (50 mg/kg).
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Animal Model:NSG mice, Immunocompromised mice[4]
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Dosage:50 mg/kg
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Administration:5 times per week; 2, 5 weeks
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Result:Reduced STAT3 mRNA by ~50% in tumors isolated from axillary lymph nodes and peritoneal cavity vs control groups.
Reduced plasma sIL-2Rα and sCD30 concentrations.
Reduced tumor burden (and ascites formation.
Achieved 67% tumor growth inhibition (TGI).
Confirmed inhibition of human STAT3 in tumor cells and murine STAT3 in tumor-associated stromal cells via species-specific PCR.
Confirmed reduced phospho-STAT3 protein in both human tumor and mouse stromal cells via immunohistochemistry.
No associated change in body weight was observed.
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Animal Model:Immunocompromised mice[4]
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Dosage:25 mg/kg
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Administration:5 times per week; ~5 weeks
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Result:Achieved 90% tumor growth inhibition (TGI) vs control .
Reduced tumor STAT3 and phospho-STAT3 protein, and reduced expression of STAT3 target genes c-MYC, MCL-1, and VEGF.
Chemical Information
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CAS No. 1402357-06-5
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Appearance Solid
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Molecular Weight 5422.00
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Color White to off-white
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SMILES
[Danvatirsen]
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Synonyms
AZD9150
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Sequence
DNA, d(P-thio)([(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]m5C-(3′→4′)-[(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]m5U-(3′→4′)-[(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]A-T-T-T-G-G-A-T-G-T-m5C-(3′→4′)-[(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]A-(3′→4′)-[(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]G-(3′→4′)-[(5′ξ)-2′,5′-anhydro-6′-deoxy-4′-C-(hydroxymethyl)-α-L-lyxo-hexofurano]m5C)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
H2O : 100 mg/mL (18.44 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (9.22 mM); Clear solution; Need ultrasonic
Purity & Documentation
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Data Sheet (293 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2242 KB)
References
[1]. Reilley MJ, et al. STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial. J Immunother Cancer. 2018;6(1):119. Published 2018 Nov 16. [Content Brief]
[2]. Shastri A, et al. Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells. J Clin Invest. 2018;128(12):5479-5488. [Content Brief]
[3]. Odate S, et al. Inhibition of STAT3 with the Generation 2.5 Antisense Oligonucleotide, AZD9150, Decreases Neuroblastoma Tumorigenicity and Increases Chemosensitivity. Clin Cancer Res. 2017;23(7):1771-1784. [Content Brief]
[4]. Hong D, et al. AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci Transl Med. 2015;7(314):314ra185. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 0.1844 mL | 0.9222 mL | 1.8443 mL | 4.6108 mL |
| 5 mM | 0.0369 mL | 0.1844 mL | 0.3689 mL | 0.9222 mL | |
| 10 mM | 0.0184 mL | 0.0922 mL | 0.1844 mL | 0.4611 mL | |
| 15 mM | 0.0123 mL | 0.0615 mL | 0.1230 mL | 0.3074 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Danvatirsen Related Classifications
HY-145729 Related Classifications
Powered by Bioz
- Danvatirsen
- 1402357-06-5
- AZD9150
- AZD 9150
- AZD-9150
- STAT
- Apoptosis
- STAT3 Inhibitor
- MOLM14 cells
- MDS-L cells
- MV411 cells
- KG1a cells
- MOLM13 cells
- KT1 cells
- CMK leukemic/MDS cell lines
- SK-N-AS cells
- NGP cells
- IMR32 cells
- lymphoma
- myelodysplastic syndrome
- acute myeloid leukemia
- neuroblastoma and non-small cell lung cancer
- Inhibitor
- inhibitor
- inhibit