elironrasib   Click here for help

GtoPdb Ligand ID: 12622

Synonyms: RMC-6291 | RMC6291
Compound class: Synthetic organic
Comment: RMC-6291 is a KRASG12C(ON) inhibitor [2], that inhibits active, GTP-bound RAS. It is designed to bind to the immunophilin cyclophilin A (PPIA) via a moiety containing a minimal cyclophilin A-binding motif of the naturally ocurring immunosuppressive (cyclophilin inhibiting) polyketide Sanglifehrin A. It also contains a cysteine-reactive warhead to mediate covalent tethering to KRAS. The resulting RMC-6291:cyclophilin A structure has high affinity for the active state of KRASG12C and forms a RMC-6291:cyclophilin A:KRASG12C tri-complex that causes steric hindrance for RAS effector binding thus blocking oncogenic signalling. The chemical structure of RMC-6291 was disclosed during the 'First Disclosures of New Drug Candidates' session at the April 2023 meeting of the AACR in Orlando. The chemical structure of RMC-6291 is identical to that for the INN elironrasib (proposed list 132, Feb. 2025) and as disclosed in Cregg et al. (2025) [1].
RMC-6291 was developed for anti-tumour potential.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 17
Hydrogen bond donors 2
Rotatable bonds 13
Topological polar surface area 168.9
Molecular weight 1012.26
XLogP 5.49
No. Lipinski's rules broken 3

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCN1C2=CC=C3C=C2C(=C1C4=C([C@H](C)OC)N=CC=C4)CC(C)(C)COC(=O)[C@@H]5CCCN(C(=O)[C@@H](C[C@H]6CN3CCO6)NC(=O)[C@H](C(C)C)N(C)C(=O)C7(CCN(CC7)C(=O)C#CC(C)(C)N(C)C)F)N5
Isomeric SMILES CCN1C2=C3C=C(C=C2)N4CCO[C@H](C4)C[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)C5(F)CCN(CC5)C(=O)C#CC(C)(C)N(C)C)C(=O)N6CCC[C@H](N6)C(=O)OCC(C)(C)CC3=C1C7=C(N=CC=C7)[C@H](C)OC
InChI InChI=1S/C55H78FN9O8/c1-13-64-44-19-18-37-30-40(44)41(48(64)39-16-14-24-57-46(39)36(4)71-12)32-53(5,6)34-73-51(69)42-17-15-25-65(59-42)50(68)43(31-38-33-63(37)28-29-72-38)58-49(67)47(35(2)3)61(11)52(70)55(56)22-26-62(27-23-55)45(66)20-21-54(7,8)60(9)10/h14,16,18-19,24,30,35-36,38,42-43,47,59H,13,15,17,22-23,25-29,31-34H2,1-12H3,(H,58,67)/t36-,38-,42-,43+,47-/m0/s1
InChI Key HJNFYLSFWYRSHS-JVFAQLKDSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
RMC-6291 has been advanced to early stage clinical evaluation.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05462717 Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors Phase 1 Interventional Revolution Medicines, Inc.