| Identification | Back Directory | [Name]
3-Pyridinecarboxamide, N-[(1R,2S)-5-(difluoromethyl)-7-fluoro-2,3-dihydro-2-hydroxy-1H-inden-1-yl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)- | [CAS]
2810747-89-6 | [Synonyms]
BLU2864
3-Pyridinecarboxamide, N-[(1R,2S)-5-(difluoromethyl)-7-fluoro-2,3-dihydro-2-hydroxy-1H-inden-1-yl]-6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)- | [Molecular Formula]
C24H19F3N4O2 | [MOL File]
2810747-89-6.mol | [Molecular Weight]
452.43 |
| Hazard Information | Back Directory | [Uses]
BLU2864 is an orally active, highly selective, ATP-competitive PRKACA inhibitor (IC50=0.3 nM). BLU2864 shows anti-tumor activity. BLU2864 can be used in cancer and polycystic kidney disease research[1][2]. | [in vivo]
BLU2864 (oral gavage; 45 mg/kg; once daily; 5 d) inhibits renal PKA activity in Pkd1RC/RC mice[1].
BLU2864 (oral gavage; 30 mg/kg; once daily; 5 d) inhibits PKA activity and ameliorates PKD in Pkd1RC/RC mice[1].
BLU2864 (oral gavage; 30 mg/kg and 75 mg/kg; once daily; 34 d) reduces FLC tumor growth in vivo[2]. | Animal Model: | Pkd1RC/RC mice[1] | | Dosage: | 45 mg/kg | | Administration: | Oral gavage; 45 mg/kg; once daily; 5 days | | Result: | Suppressed kidney basal and total PKA activities by 74% and 87% at 3 hours and by 46% and 56% at 15 hours, respectively, in the BLU2864-treated mice compared with controls. |
| Animal Model: | Pkd1RC/RC mice[1] | | Dosage: | 30 mg/kg | | Administration: | Oral gavage; 30 mg/kg; once daily; 5 days | | Result: | Showed higher urine outputs at 15 weeks in the BLU2864-treated mice than in the controls. Showed lower kidney weights, kidney volumes as percent of body weights, and cyst indices. Showed renal basal and total PKA activities by 69% and 84% lower in the BLU2864-treated mice compared with controls. |
| Animal Model: | Mice harboring FLC PDX tumors[2] | | Dosage: | 30 mg/kg and 75 mg/kg | | Administration: | Oral gavage; 30 mg/kg and 75 mg/kg; once daily; 34 days | | Result: | Inhibited tumor growth by 48.5% (P=0.003) and by 45.3% (P=0.0005), respectively, at day 34. |
| [References]
[1] Xiaofang Wang, et al. Protein Kinase A Downregulation Delays the Development and Progression of Polycystic Kidney Disease. J Am Soc Nephrol. 2022 Jun;33(6):1087-1104. DOI:10.1681/ASN.2021081125
[2] Stefanie S. Schalm, et al. Evaluation of PRKACA as a Therapeutic Target for Fibrolamellar Carcinoma. bioRxiv 2022.01.31.477690. |
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