RMC-9805
RMC-9805 (CAS 2922732-54-3) is a covalent inhibitor specifically targeting GTP-bound KRASG12D. It binds to the cellular chaperone cyclophilin A (CypA) to form a binary complex, which subsequently covalently modifies GTP-bound KRASG12D. This CypA-catalyzed reaction achieves greater than 95% modification of GTP-bound KRASG12D (second-order rate constant: 89.9 M⁻¹s⁻¹), while exhibiting negligible modification of KRASWT (<1%), KRASG12C (18%), and KRASG12E (9%). The resulting trimeric complex, comprising CypA, KRASG12D, and RMC-9805, disrupts the interaction between KRASG12D and downstream effectors such as CRAF, RALGDS, and PLCɛ, thereby inhibiting oncogenic RAS signaling.
References:
[1] Weller C, Burnett GL, Jiang L, Chakraborty S, Zhang D, Vita NA, Dilly J, Kim E, Maldonato B, Seamon K, Eilerts DF, Milin A, Marquez A, Spradlin J, Helland C, Gould A, Ziv TB, Dinh P, Steele SL, Wang Z, Mu Y, Chugh S, Feng H, Hennessey C, Wang J, Roth J, Rees M, Ronan M, Wolpin BM, Hahn WC, Holderfield M, Wang Z, Koltun ES, Singh M, Gill AL, Smith JAM, Aguirre AJ, Jiang J, Knox JE, Wildes D. A neomorphic protein interface catalyzes covalent inhibition of RASG12D aspartic acid in tumors. Science. 2025 Jul 24;389(6758):eads0239. doi: 10.1126/science.ads0239. Epub 2025 Jul 24. PMID: 40705880.
| Storage | Store at -20°C |
| M.Wt | 1168.44 |
| Cas No. | 2922732-54-3 |
| Formula | C63H88F3N11O7 |
| Synonyms | Zoldonrasib;KRAS G12D inhibitor 18 |
| Chemical Name | (2S)-2-cyclopentyl-2-((S)-7-((2R,3R)-3-cyclopropyl-1-methylaziridine-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)-N-((22S,63S,4S)-12-(5-(4-cyclopropylpiperazin-1-yl)-2-((S)-1-methoxyethyl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-11-(2,2,2-trifluoroethyl)-61,6 |
| SDF | Download SDF |
| Canonical SMILES | O=C(OCC(C)(C)CC1=[C@@]([C@@]2=C([C@H](C)OC)N=CC(N3CCN(C4CC4)CC3)=C2)N(CC(F)(F)F)C5=C1C=C6C=C5)[C@@H]7CCCN(C([C@H](C[C@H]8CN6CCO8)NC([C@H](C9CCCC9)N%10C[C@]%11(CN(C([C@H]%12[C@@H](C%13CC%13)N%12C)=O)CC%11)CC%10)=O)=O)N7 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Quality Control & MSDS
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Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
Chemical structure
