| Identification | Back Directory | [Name]
N-[(3R)-3-(2-chloro-5-fluorophenyl)-6-(5-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-oxo-2,3-dihydroisoindol-4-yl]-3-fluoro-5-(trifluoromethyl)benzamide | [CAS]
2733573-94-7 | [Synonyms]
RLY2608
N-[(3R)-3-(2-chloro-5-fluoro-phenyl)-6-(5-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-oxo-isoindolin-4-yl]-3-fluoro-5-(trifluoromethyl)benzamide
N-[(3R)-3-(2-chloro-5-fluorophenyl)-6-(5-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-oxo-2,3-dihydroisoindol-4-yl]-3-fluoro-5-(trifluoromethyl)benzamide | [Molecular Formula]
C29H14ClF5N6O2 | [MOL File]
2733573-94-7.mol | [Molecular Weight]
608.91 |
| Chemical Properties | Back Directory | [density ]
1.61±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
11.06±0.40(Predicted) | [color ]
White to off-white | [InChIKey]
VYWRYBZVVSPTQN-SANMLTNESA-N | [SMILES]
C(NC1=CC(C2=C(C#N)N3N=CN=C3C=C2)=CC2=C1[C@H](C1=CC(F)=CC=C1Cl)NC2=O)(=O)C1=CC(C(F)(F)F)=CC(F)=C1 |
| Hazard Information | Back Directory | [Uses]
RLY-2608 is an orally active first-in-class allosteric mutant-selective inhibitor of PI3Ka with anti-tumor activity. RLY-2608 inhibits tumor growth in PIK3CA-mutant xenograft mice models with minimal impact on insulin[1][2][3]. | [in vivo]
RLY-2608 (25-100 mg/kg, p.o., twice a day for 50 days) inhibits tumors in tumor xenograft mice models with reduced impact on insulin levels[1].
RLY-2608 (12.5-100 mg/kg, p.o., a single dose for 4 days) demonstrates potent tumor growth inhibition in Balb/c nude female mice bearing HSC-2 tumors[2].
| Animal Model: | Tumor xenograft mice models[1] | | Dosage: | 25-100 mg/kg | | Administration: | p.o., twice a day for 50 days | | Result: | Potentiated tumor regression in tumor xenograft mice models. |
| [References]
[1] Andreas Varkaris, et al. Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Ka inhibitor that decouples anti-tumor activity from hyperinsulinemia. Cancer Discov. 2023 Nov 2. DOI:10.1158/2159-8290.CD-23-0944
[2] Pazolli E, et al. RLY-2608: the first allosteric mutant-and isoform-selective inhibitor of PI3Kα, is efficacious as a single agent and drives regressions in combination with standard of care therapies in PIK3CA mutant breast cancer models[J]. Cancer Res., 2022, 82.
[3] Perez C A, et al. First-in-human global multi-center study of RLY-2608, a pan-mutant and isoform-selective PI3Kα inhibitor, as a single agent in patients with advanced solid tumors and in combination with fulvestrant in patients with advanced breast cancer[J]. 2022. |
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