vociprotafib   Click here for help

GtoPdb Ligand ID: 12067

Synonyms: compound A-290 [WO2018013597A1] | RMC-4630 | RMC4630 | SAR-442720 | SAR442720 | SHP2-IN-7
Compound class: Synthetic organic
Comment: RMC-4630 (Revolution Medicines) is a clinical stage oral, allosteric SHP2 (PTPN11) inhibitor [1] that is being evaluated for efficacy against advanced solid tumours. SHP2 is a phosphatase whose inhibition blocks activation of the RAS-RAF-MEK-ERK signalling pathway which is often hyperactivated in tumours.
We matched RMC-4630's chemical structure to the INN 'vociprotafib' which was released in the WHO's proposed INN list 127 on 21 July 2022.
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 148.71
Molecular weight 450.16
XLogP 1.76
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES OCc1nc(Sc2ccnc(c2Cl)N)c(nc1N1CCC2(CC1)CO[C@H]([C@H]2N)C)C
Isomeric SMILES C[C@H]1[C@H](C2(CCN(CC2)c2nc(c(nc2CO)Sc2c(c(ncc2)N)Cl)C)CO1)N
InChI InChI=1S/C20H27ClN6O2S/c1-11-19(30-14-3-6-24-17(23)15(14)21)26-13(9-28)18(25-11)27-7-4-20(5-8-27)10-29-12(2)16(20)22/h3,6,12,16,28H,4-5,7-10,22H2,1-2H3,(H2,23,24)/t12-,16+/m0/s1
InChI Key HISJAYUQVHMWTA-BLLLJJGKSA-N
No information available.
Summary of Clinical Use Click here for help
RMC-4630 has entered clinical studies as a monotherapy and in various combinations with other anti-tumour agents such as RAS inhibitors and the MEK inhibitor cobimetinib.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03989115 Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC Phase 1/Phase 2 Interventional Revolution Medicines, Inc.
NCT03634982 Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors Phase 1 Interventional Revolution Medicines, Inc.
NCT05054725 Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies Phase 2 Interventional Revolution Medicines, Inc.