inavolisib   Click here for help

GtoPdb Ligand ID: 9636

Synonyms: GDC-0077 | GDC0077 | RG6114 | Ro7113755
Compound class: Synthetic organic
Comment: Inavolisib (GDC-0077) is a potent and selective, orally available PI3K-p110α (PIK3CA) inhibitor, with potential antineoplastic activity. 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. A preprint from May 2021 suggests that inavolisib's mechanism of action includes the ability to target oncogenic mutant PI3K-p110α for degradation, in addition to its enzyme inhibitory activity [2].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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
No information available.
Summary of Clinical Use Click here for help
Inavolisib (GDC-0077) has advanced to Phase 2/3 clinical evaluation in advanced solid tumours. It is being used to target tumours (principally breast cancers) that harbour PIK3CA mutations that are predictive of a clinical response.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
GDC-0077 binds to and inhibits PI3K family kinases, including activating mutations in the catalytic alpha isoform PIK3CA (PI3Kα). PIK3CA is frequently mutated in a variety of cancer cell types and this underlies the dysregulation of the PI3K pathway that plays a key role in cancer cell growth and invasion. Pharmacological inactivation of the PI3K pathway inhibits growth and survival of PI3K-overexpressing tumour cells
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03006172 To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer Phase 1 Interventional Genentech, Inc.
NCT04632992 A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response Phase 2 Interventional Genentech, Inc.
NCT04191499 A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer Phase 2/Phase 3 Interventional Hoffmann-La Roche