inavolisib   Click here for help

GtoPdb Ligand ID: 9636

Synonyms: GDC-0077 | GDC0077 | Itovebi® | RG6114 | Ro7113755
Approved drug PDB Ligand
inavolisib is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Inavolisib (GDC-0077) is a potent and selective, orally available PI3K-p110α (PIK3CA) inhibitor, with antineoplastic activity [2,4]. It is example 101 in patent US20170015678 (where it is named (S)-2-((2-((S)-4-(difluoromethyl)- 2-oxooxazolidin-3-yl)-5,6- dihydrobenzo[f]imidazo[1,2- d][1,4]oxazepin-9- yl)amino)propanamide) [1]. GDC-0077 is one of the agents in Genentech's oncology discovery pipeline. Inavolisib's mechanism of action includes the ability to target oncogenic mutant PI3K-p110α for degradation, in addition to its enzyme inhibitory activity [2].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

inavolisib is commercially available from our sponsors

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 7
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 111.71
Molecular weight 407.14
XLogP 2.7
No. Lipinski's rules broken 0

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 NC(=O)C(Nc1ccc2c(c1)OCCn1c2nc(c1)N1C(=O)OCC1C(F)F)C
Isomeric SMILES NC(=O)[C@@H](Nc1ccc2c(c1)OCCn1c2nc(c1)N1C(=O)OC[C@H]1C(F)F)C
InChI InChI=1S/C18H19F2N5O4/c1-9(16(21)26)22-10-2-3-11-13(6-10)28-5-4-24-7-14(23-17(11)24)25-12(15(19)20)8-29-18(25)27/h2-3,6-7,9,12,15,22H,4-5,8H2,1H3,(H2,21,26)/t9-,12-/m0/s1
InChI Key SGEUNORSOZVTOL-CABZTGNLSA-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/)
References
1. Braun M-G, Hanan E, Staben ST, Heald RA, Macleod C, Elliott R. (2017)
Benzoxazepin oxazolidinone compounds and methods of use.
Patent number: US20170015678. Assignee: Genentech, Inc.. Priority date: 02/07/2015. Publication date: 19/01/2017.
2. Hanan EJ, Braun MG, Heald RA, MacLeod C, Chan C, Clausen S, Edgar KA, Eigenbrot C, Elliott R, Endres N et al.. (2022)
Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα.
J Med Chem, 65 (24): 16589-16621. [PMID:36455032]
3. Jhaveri KL, Accordino MK, Bedard PL, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop IE, Oliveira M et al.. (2024)
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer.
J Clin Oncol, 42 (33): 3947-3956. [PMID:39236276]
4. Salphati L, Pang J, Plise EG, Cheong J, Braun MG, Friedman LS, Hong Thibodeau R, Jaochico A, Johnson R, Liu N et al.. (2024)
Preclinical assessment of the PI3Kα selective inhibitor inavolisib and prediction of its pharmacokinetics and efficacious dose in human.
Xenobiotica, 54 (10): 808-820. [PMID:39387185]