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Zoldonrasib

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Chemical compound

Pharmaceutical compound
Zoldonrasib
Clinical data
Pronunciation/ˌzɒldɒnˈræsɪb/
ZOL-don-RAS-ib
Other namesRMC-9805
Drug class Antineoplastic agents
Identifiers
  • (2S)-2-cyclopentyl-2-{(5S)-7-[(2R,3R)-3-cyclopropyl-1-methylaziridine-2-carbonyl]-2,7-diazaspiro[4.4]nonan-2-yl}-N-[(12M,22S,4S,63S)-12-{5-(4-cyclopropylpiperazin-1-yl)-2-[(1S)-1-methoxyethyl]pyridin-3-yl}-10,10-dimethyl-5,7-dioxo-11-(2,2,2-trifluoroethyl)-11H-8-oxa-1(5,3)-indola-2(4,2)-morpholina-6(1,3)-[1,2]diazinanacycloundecaphan-4-yl]acetamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C63H88F3N11O7
Molar mass 1168.462g·mol−1
3D model (JSmol)
  • O=C(N1CCC[C@@H]2N1)[C@H](C[C@@H](C3)OCCN3C4=CC5=C(N(CC(F)(F)F)[C@]([C@]6=C([C@H](C)OC)N=CC(N7CCN(C8CC8)CC7)=C6)=C5CC(C)(C)COC2=O)C=C4)NC([C@@H](N9C[C@]%10(CN(C([C@@H]%11N(C)[C@@H]%11C%12CC%12)=O)CC%10)CC9)C%13CCCC%13)=O
  • InChI=InChI=1S/C63H88F3N11O7/c1-39(82-5)52-47(30-44(33-67-52)72-25-23-71(24-26-72)42-14-15-42)55-48-32-61(2,3)38-84-60(81)49-11-8-20-77(69-49)58(79)50(31-45-34-73(27-28-83-45)43-16-17-51(46(48)29-43)76(55)37-63(64,65)66)68-57(78)54(40-9-6-7-10-40)74-21-18-62(35-74)19-22-75(36-62)59(80)56-53(70(56)4)41-12-13-41/h16-17,29-30,33,39-42,45,49-50,53-54,56,69H,6-15,18-28,31-32,34-38H2,1-5H3,(H,68,78)/t39?,45-,49-,50-,53+,54-,56+,62-,70?/m0/s1
  • Key:VKNNQJWNUPSOEK-QFVODIEJSA-N

Zoldonrasib, also known as RMC-9805, is an investigational drug that selectively targets the G12D mutation in KRAS dependent cancers.[1] [2] [3] Zoldonrasib functions as molecular glue that forms a non-covalent ligand-mediated protein-protein interaction between cyclophilin A and GTP-bound RAS. Subsequent covalent modification of the mutant Asp12 residue affords selectivity over wild-type RAS.[4] [5]

As of 2025, zoldonrasib is in a phase 1/1b clinical trial for the treatment of KRAS G12D-mutant solid tumors.[6] Preliminary data indicated that KRAS G12D–mutant PDAC patients dosed at 1200 mg daily or 600 mg twice daily achieved a 30% objective response rate (n = 12) and 80% disease control rate (n = 32).[7]

See also

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References

[edit ]
  1. ↑ "RMC-9805". AdisInsight. Springer Nature Switzerland AG.
  2. ↑ "KRAS G12D inhibitor RMC-9805". NCI Drug Dictionary. National Cancer Institute. Retrieved 2024年12月03日.
  3. ↑ Zeissig MN, Ashwood LM, Kondrashova O, Sutherland KD (November 2023). "Next batter up! Targeting cancers with KRAS-G12D mutations". Trends in Cancer. 9 (11): 955–967. doi:10.1016/j.trecan.2023年07月01日0 . PMID 37591766.
  4. ↑ de Jesus VH, Mathias-Machado MC, de Farias JP, Aruquipa MP, Jácome AA, Peixoto RD (October 2023). "Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure". Cancers. 15 (20): 5015. doi:10.3390/cancers15205015 . PMC 10605759 . PMID 37894382.
  5. ↑ Bannoura SF, Khan HY, Azmi AS (November 2022). "KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?". Frontiers in Oncology. 12 1013902: 1–9. doi:10.3389/fonc.2022.1013902 . PMC 9749787 . PMID 36531078.
  6. ↑ Clinical trial number NCT06040541 for "Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors" at ClinicalTrials.gov
  7. ↑ Seymour C (2024年10月28日). "RMC-9805 Triggers Tumor Regressions in KRAS G12D–Mutant Pancreatic Cancer". OncLive. Retrieved 2024年12月03日.
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