| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Cell lines | CD4+T cells |
Preparation Method | CD4+lymphocytes isolated from healthy donors were incubated with prostratin, OTX-015 or OTX-015/prostratin for 48 h and immunostained with anti-CD25, anti-CD69, anti-HLA-DR, anti-CD4, anti-CCR5 or anti-CXCR4 antibodies for 20 min at 4 ℃. |
Reaction Conditions | 5 μM for 48 hours |
Applications | Primary CD4+T cells were treated with OTX-015 for 48 h and evaluated for the expression of CD4, CCR5 and CXCR4 using flow cytometry. OTX-015 treatment did not cause an increase in the expression of these HIV receptors/co-receptors, suggesting that OTX-015 may not pose the risk of increasing the susceptibility of CD4+T cells to HIV-1 infection during the reactivation of HIV-1 latency. |
Animal models | Female nude Foxn1 mice 6-week-old |
Preparation Method | mice were randomized (nine animals/group) to one of the following experimental groups: vehicle (for OTX-015, water, twice daily, oral; for everolimus vehicle, 5% Tween-80/5% polyethylene glycol 400, thrice weekly, intraperitoneal); 50 mg/kg OTX-015, twice daily, oral; 2 mg/kg everolimus, thrice weekly, intraperitoneal; 50 mg/kg OTX-015 + 2 mg/kg everolimus, according to the single agent dosing schedules. |
Dosage form | 50 mg/kg OTX-015, twice daily, oral |
Applications | OTX-015-treated mice showed a substantial reduction in tumor mass with respect to the control group (p < 0.05) from 7 days after treatment start. The best T/C value was 41.3% recorded on day 23. |
| 产品描述 | OTX-015 inhibits the binding of BRD2, BRD3, and BRD4 to acetylated histone 4 in a concentration-dependent manner, with IC50values from 92-112nM[1]. OTX-015 significant growth inhibition was mesured in six of nine AML cell lines and all four ALL cell lines: HEL IC50value as 248 nM, NB4 IC50value as 233 nM, NOMO-1 IC50value as 229 nM, KG1 IC50value as 198 nM, OCI-AML3 IC50value as 60 nM, Kasumi IC50value as 17 nM, JURKAT IC50value as 249 nM, BV-173 IC50value as 161 nM, TOM-1 IC50value as 133 nM, RS4-11 IC50value as 34 nM[2]. GI50 values obtained with OTX-015 in vitro in glioblastoma cell lines were equivalent to those achieved in plasma from patients treated at nontoxic doses in the ongoing Phase Ib clinical study in patients with hematologic malignancies, as described in a clinical pharmacokinetics evaluation. OTX-015 displayed higher potency (GI50 618.1 nM) in glioblastoma cell line panel. OTX-015 exerted antiproliferative effects and delayed tumor growth in lymphoma and neuroblastoma cells, together with a downregulation of C-MYC, MYCN and genes associated with superenhancers[3]. OTX-015, offering a significant survival advantage in vivo in the orthotopic human glioblastoma model and slowing tumor progression in the heterotopic model with all administration regimens. Furthermore, no toxicity was seen with any of the OTX-015 dosing regimens, in direct contrast to treatment with temozolomide which induced pronounced weight loss. Synergistic and additive activity of OTX-015 in combination with several antitumor agents currently used to manage GBM patients, improving mouse survival with simultaneous combination of OTX-015 and temozolomide in the absence of toxicity, supporting the incorporation of OTX-015 as an epigenetic modulator in combination with temozolomide in glioblastoma[3]. References: |
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