| Identification | Back Directory | [Name]
2,4-Pyrimidinediamine, N4-(8-methyl-4-cinnolinyl)-N2-[3-(4-morpholinyl)phenyl]- | [CAS]
2785430-90-0 | [Synonyms]
ALK5-IN-34
2,4-Pyrimidinediamine, N4-(8-methyl-4-cinnolinyl)-N2-[3-(4-morpholinyl)phenyl]- | [Molecular Formula]
C23H23N7O | [MOL File]
2785430-90-0.mol | [Molecular Weight]
413.48 |
| Chemical Properties | Back Directory | [Boiling point ]
688.9±65.0 °C(Predicted) | [density ]
1.341±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
5.12±0.40(Predicted) | [color ]
Light yellow to green yellow |
| Hazard Information | Back Directory | [Uses]
ALK5-IN-34 is an selective orally active activin receptor-like kinase (ALK) inhibitor. ALK5-IN-34 can inhibit the activity of ALK5-IN-34 with an IC50 value of ≤10 nM. ALK5-IN-34 also has inhibitory of tumor growth and can be used for the research of proliferative diseases, such as cancer[1]. | [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.
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| 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. |
| [IC 50]
ALK5: <10 nM (IC50) | [References]
[1] Bettina FRANZ, et al. Alk-5 inhibitors and uses thereof. Patent. WO2022126133A1. |
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