ALK5-IN-34 是一种选择性的激活素受体样激酶 (ALK) 抑制剂，具有口服活性。ALK5-IN-34 可以抑制激活素受体样激酶的活性，IC50值 ≤10 nM。ALK5-IN-34 还具有抑制肿瘤生长的作用，可用于癌症等增殖性疾病的研究。
| 生物活性 | ALK5-IN-34 is an selective orally activeactivin receptor-like kinase (ALK)inhibitor. ALK5-IN-34 can inhibit the activity of ALK5-IN-34 with anIC50value of ≤10 nM. ALK5-IN-34 also has inhibitory of tumor growth and can be used for the research of proliferative diseases, such ascancer[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | ALK5-IN-34 (EX-11) has kinase inhibition of ALK5 with an IC50value of ≤10 nM[1].
ALK5-IN-34 has kinase selectivity of ALK2/ALK5 with an IC50value of ＜100 nM[1].
ALK5-IN-34 shows TGFB-RI inhibition (RD-SMAD receptor activity) with an IC50value of ≤100 nM[1].
ALK5-IN-34 (1 μM-10 nM) inhibits the expression of TGF-β-mediated alpha-SMA in a full concentration-dependent[1].
ALK5-IN-34 (30, 300 and 3000 nM) suppresses the Treg frequency in a dose dependent manner[1].
ALK5-IN-34 (0-0.1 μM; for 6 days or 7 days) inhibits FOXL2CI34W-driven growth in KGN and COV434 cells with IC50 values of 140 nM and﹥10 μM, respectively[1].
ALK5-IN-34 (10, 100 and 1000 nM; 2 h) shows a dose-dependent decrease in pSmad2 in KGN cell line[1].
ALK5-IN-34 (30, 300 nM; 24 h) reverses the upregulation of gene expression in dose dependentent[1].
ALK5-IN-34 (30, 300 nM; 24 h) increases HLA class I expression in dose-dependent[1].
Cell Viability Assay[1] | Cell Line: | KGN and COV434 cell lines | | Concentration: | 0-0.1 μM | | Incubation Time: | for 6 days or 7 days | | Result: | Inhibited FOXL2CI34W-driven growth. |
RT-PCR[1] | Cell Line: | Human primary dermal fibroblasts | | Concentration: | 30, 300 nM | | Incubation Time: | 24 h | | Result: | Reversed the upregulation of gene expression with TGFB stimulation. |
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体内研究
(In Vivo) | ALK5-IN-34 (EX-11) (oral; 10-100 mg/kg) reduces the phopho SMAD2 levels (p-SMAD2) in a dose dependent manner in A549 murine xenograft model[1].
ALK5-IN-34 (oral; 75 mg/kg; 0-24 h) shows reversely correlated between PK and tumor PD (pSMAD2 levels)[1].
ALK5-IN-34 (oral; 150 mg/kg; bid; for 22 days) increases overall survival in ES-2 ovarian cancer mouse xenograft model and can delay progression[1].
ALK5-IN-34 (p.o.; 75, 150 mg/kg; twice a day; for 21days) shows tumor growth inhibition (TGI) and increases the survival when combining with anti-PD-L1/anti-PD-1 in Syngeneic TNBC Model and in Subcutaneous Cloudman S91 melanoma model[1].
ALK5-IN-34 (oral; 300, 1000 mg/kg; bid for 5 days) has good tolerability and safety margin in Tolerability Model[1].
| Animal Model: | A549 murine xenograft model[1] | | Dosage: | 10, 50, 75 and 100 mg/kg | | Administration: | oral gavage | | Result: | Exhibited 92.5% inhibition based upon the average p-SMAD2 levels (75 mg/kg). |
| Animal Model: | EMT6 Syngeneic TNBC Model[1] | | Dosage: | 75, 150 mg/kg | | Administration: | p.o., twice a day, for 21days | | Result: | Resulted significantly tumor growth inhibition (TGI) by 37% at 150 mg/kg.
Result in significant tumor growth inhibition (TGI) with combination of anti-PD-LI and resulted in a significant increase in mean survival by 37%.
Resulted in significant TGI by 34% with combination of anti-PD-1 and resulted in significant increase in mean survival by 26%.
Decreased the intra-tumoral pressure. |
| Animal Model: | Cachexia Model[1] | | Dosage: | 150 mg/kg | | Administration: | oral gavage, twice a day for 22 days | | Result: | Showed reduction in total fluid volume and high whole limb weights. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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