RRx-001 是一种低氧选择性的表观遗传因子，被用作放射或化疗敏感剂，能诱发凋亡，克服骨髓瘤的耐药性。RRx-001 具有有效的抗癌活性且毒性极低。RRx-001是一个免疫检查点的抑制剂，可下调CD47和SIRP-α。RRx-001是G6PD的有效抑制剂，具有较强的抗疟活性。
| 生物活性 | RRx-001, a hypoxia-selective epigenetic agent and studied as a radio- and chem-sensitizer, triggersapoptosisand overcomes drug resistance in myeloma. RRx-001 exhibits potent anti-tumor activity with minimal toxicity[1]. RRx-001 is a dual small molecule checkpoint inhibitor by downregulatingCD47andSIRP-α[2]. RRx-001 is a potent inhibitor ofG6PDand shows potentantimalarialactivity[3]. |
体外研究
(In Vitro) | RRx-001 (0-5 μM, 24 hours) inhibits MM cells growth and overcomes resistance to novel and conventional therapies[1].
RRx-001 blocks migration of MM cells and associated angiogenesis[1].
RRx-001 induces significant G1 phase growth arrest, with concomitant decrease in S phase. RRx-001 triggers significant apoptosis in MM cells[1].
RRx-001 inhibits DNA methylation by downregulating DNA methytransferases[1].
RRx-001 and the supernatant of RRx-001-treated macrophages downregulates CD47 on tumor cells and SIRPα on macrophages[2].
Cell Viability Assay[1] | Cell Line: | Human MM-cell lines (MM.1S, RPMI-8226, H929, ARP1, KMS-11, OPM2, LR5, ANBL6.WT), along with drug resistant cell lines such as (MM.1R, Dox40, LR5, ANBL6.BR, RPMI-8226). | | Concentration: | 0-5 μM. | | Incubation Time: | 24 hours. | | Result: | Induced a dose-dependent significant (p< 0.05) decrease in viability of all cell lines. |
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体内研究
(In Vivo) | RRx-001 (5 mg/kg or 10 mg/kg, I.V., thrice-weekly for 24 days) inhibits tumor growth and prolongs survival in a xenograft mouse model[1].
RRx-001 (10 mg/kg, IP, twice a week and once a day) exhibits potent anti-cancer activity on the A549 lung cancer model dependent on the presence of tumor-associated macrophages (TAMs) in tumor tissue[2].
| Animal Model: | CB-17 SCID-mice were subcutaneously inoculated with 5.0 × 106MM.1S cells in 100 μL of serum-free RPMI 1640 medium[1]. | | Dosage: | 5 mg/kg or 10 mg/kg. | | Administration: | I.V., thrice-weekly for 24 days. | | Result: | Blocked MM tumor growth and enhances survival.
Treatment was well tolerated, suggested by no apparent weight loss. |
| Animal Model: | Female BALB/c nude mice (19.2 ± 1.7 g) based on A549 lung cancer model[2]. | | Dosage: | 10 mg/kg. | | Administration: | IP, twice a week and once a day. | | Result: | Resulted in the most significant tumor growth retardation.
Reduction of resident macrophages in tumor-bearing mice attenuates the antitumor activity of RRx-001. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(373.11 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 3.7311 mL | 18.6553 mL | 37.3107 mL | | 5 mM | 0.7462 mL | 3.7311 mL | 7.4621 mL | | 10 mM | 0.3731 mL | 1.8655 mL | 3.7311 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (9.33 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.33 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (9.33 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.33 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (9.33 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.33 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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