Chemical Structure : RP03707
CAS No.:
3030493-05-8
RP03707
Catalog No.: PC-24575Not For Human Use, Lab Use Only.
RP03707 is a CRBN-involving, highly potent, and selective KRAS G12D PROTAC degrader with DC50 of 0.7 nM in PK-59 cells (Dmax=96%).
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Purity & Documentation Purity:
>98% (HPLC)
Biological Activity
RP03707 is a CRBN-involving, highly potent, and selective KRAS G12D PROTAC degrader with DC50 of 0.7 nM in PK-59 cells (Dmax=96%).
RP03707 has a DC50 value of 0.6 nM for KRASG12D degradation, and pERK inhibition IC50 of 2.5 nM in AsPC-1 cells.
RP03707 exhibits no degradation activity against other RAS isoforms, including NRAS and HRAS, KRAS WT.
RP03707 also exhibits no degradation of IKZF1/3, in stark contrast to the positive control pomalidomide that showed expected IKZF1/3 depletion.
RP03707 exhibits a generally stronger antiproliferative effect against cancer cell lines carrying the KRASG12D mutant relative to MRTX1133.
RP03707 induces the degradation of both the active form and inactive forms of KRASG12D proteins concurrently in cells.
RP03707 (0.1-3 mg/kg, i.v.) exhibited significant antitumor effects with tumor growth inhibition (TGI >90%) in KRASG12D tumor-bearing mice.
Physicochemical Properties
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M.Wt
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994.14
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Formula
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C55H58F3N11O4
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Appearance
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Solid
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CAS No.
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Storage
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- Solide Powder
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-20°C 12 Months; 4°C 6 Months
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- In Solvent
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-80°C 6 Months; -20°C 6 Months
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Shipping
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Solubility
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10 mM in DMSO
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Chemical Name/SMILES
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1-[6-[1-[7-[[1-[[4-(3,8-Diazabicyclo[3.2.1]octan-3-yl)-7-(8-ethynyl-7-fluoro-3-hydroxy-1-naphthyl)-8-fluoro-pyrido[4,3-d]pyrimidin-2-yl]oxymethyl]cyclopropyl]methyl]-7-azaspiro[3.5]nonan-2-yl]-4-piperidyl]-5-fluoro-1-methyl-indazol-3-yl]hexahydropyrimidine-2,4-dione
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References
1. Ji X, et al. J Med Chem. 2025 May 8. doi: 10.1021/acs.jmedchem.5c00428.
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