RMC-6291   Click here for help

GtoPdb Ligand ID: 12622

Compound class: Synthetic organic
Comment: RMC-6291 is a KRASG12C(ON) inhibitor [1], 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. 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 CDK toolkit. 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
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.

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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
Classification Click here for help
Compound class Synthetic organic
Database Links Click here for help
GtoPdb PubChem SID 479821412
PubChem CID 167993669
Search Google for chemical match using the InChIKey HJNFYLSFWYRSHS-JVFAQLKDSA-N
Search Google for chemicals with the same backbone HJNFYLSFWYRSHS
UniChem Compound Search for chemical match using the InChIKey HJNFYLSFWYRSHS-JVFAQLKDSA-N
UniChem Connectivity Search for chemical match using the InChIKey HJNFYLSFWYRSHS-JVFAQLKDSA-N