Cerdulatinib hydrochloride (PRT062070) 是一种选择性，具有口服活性和可逆的 ATP 竞争性的SYK和JAK的双重抑制剂，抑制SYK和Tyk2、JAK1、2、3的IC50值分别为 32 nM、0.5 nM、12 nM、6 nM 和 8 nM。Cerdulatinib hydrochloride 可用于研究自身免疫性疾病和B细胞恶性肿瘤。
| 生物活性 | Cerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dualSYKandJAK, withIC50s of 32 nM, 0.5 nM, 12 nM, 6 nM and 8 nM forSYKandTyk2,JAK1,2,3, respectively. Cerdulatinib hydrochloride could be used to research autoimmune disease and B-cell malignancies[1][2]. |
| IC50& Target | Tyk2 0.5 nM (IC50) | JAK1 12 nM (IC50) | JAK2 6 nM (IC50) | JAK3 8 nM (IC50) | SYK 32 nM (IC50) | MST1 4 nM (IC50) | ARK5 4 nM (IC50) | MLK1 5 nM (IC50) | FMS 5 nM (IC50) | AMPK 6 nM (IC50) | TBK1 10 nM (IC50) | MARK1 10 nM (IC50) | PAR1B-a 13 nM (IC50) | TSSK 14 nM (IC50) | MST2 15 nM (IC50) | GCK 18 nM (IC50) | JNK3 18 nM (IC50) | Rsk2 20 nM (IC50) | Rsk4 28 nM (IC50) | CHK1 42 nM (IC50) | Flt4 51 nM (IC50) | Flt3 90 nM (IC50) | Ret 105 nM (IC50) | Itk 194 nM (IC50) |
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体外研究
(In Vitro) | Cerdulatinib (0.03-4 μM) inhibits ERK Y204 phosphorylation with anIC50of 0.5 μM and reduces the ability to upregulate cellsurface expression of the early activation marker CD69 with anIC50of 0.11 μM in B cells in human whole blood[1].
Cerdulatinib (0.015-2 μM) inhibits FcεRI-mediated basophil degranulation with anIC50of 0.12 μM[1].
Cerdulatinib (0.5-4 μM) exhibits differential potency against cytokine JAK/STAT signaling pathways[1].
Cerdulatinib (0-15 μM; 72 hours) results in viability effects similar to that of the combines SYK plus JAK-selective inhibition[1].
Cerdulatinib (1-3 μM; 48 hours) induces apoptosis in BCR-signaling competent non-Hodgkin lymphoma (NHL) cell lines[1].
Cell Viability Assay[1] | Cell Line: | SU-DHL4; SU-DHL6; Ramosand and Daudi cells | | Concentration: | 0, 1, 3 μM | | Incubation Time: | 48 hours | | Result: | Inhibits cells viability with theIC50s of 0.73-1.39 μM. |
Apoptosis Analysis[1] | Cell Line: | SU-DHL4, SU-DHL6, and Ramos cells | | Concentration: | 0, 1.6, 5.0, 15 μM | | Incubation Time: | 72 hours | | Result: | Induced SU-DHL4, SU-DHL6, and Ramos cells apoptosis. |
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体内研究
(In Vivo) | Cerdulatinib (0.5-5 mg/kg; twice daily p.o. for 2 weeks) elicits dose-dependent efficacy in the rat collagen-induced arthritis (CIA) model[1].
Cerdulatinib ( mg/kg; twice daily p.o. for 5 days) blocks BCR-induced B-cell activation and splenomegaly in mice[1].
| Animal Model: | Female Lewis rats (7-8 weeks old; 159-187 g) are immunized[1] | | Dosage: | 0, 0.5, 1.5, 3, 5 mg/kg | | Administration: | Oral gavage twice daily for 2 weeks | | Result: | Modulated inflammation in the rat CIA treatment model.
Affected anticollagen antibody formation. |
| Animal Model: | Balb/c mice are received BCR stimulation[1] | | Dosage: | 0, 1, 5, 15, 20, 30 mg/kg | | Administration: | Oral gavage twice daily for 5 days | | Result: | Suppressed upregulation of splenic B-cell surface CD80/86 and CD69 by＞60%.
Inhibited mouse splenomegaly in a dose- and concentration-dependent manner. |
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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 : 20 mg/mL(41.49 mM;ultrasonic and warming and heat to 80℃) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 | 1 mM | 2.0747 mL | 10.3734 mL | 20.7469 mL | | 5 mM | 0.4149 mL | 2.0747 mL | 4.1494 mL | | 10 mM | 0.2075 mL | 1.0373 mL | 2.0747 mL |
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此方案可获得 ≥ 2 mg/mL (4.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 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 mg/mL (4.15 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (4.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 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 mg/mL (4.15 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (4.15 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 20.0 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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