Giredestrant
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Also known as Gdc-9545RO-7197597RO7197597
Summary
Giredestrant (CHEMBL4650316) is a phase-3 clinical-stage small molecule targeting ESR1; indicated across 3 conditions including breast neoplasm and endometrium neoplasm.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (ESR1)
- Indications: 3 conditions
- Clinical trials: 20
- Chemistry: 522.6 Da · C27H31F5N4O
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4650316 |
| Name | Giredestrant |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 121410806 |
| Molecular formula | C27H31F5N4O |
| Molecular weight | 522.6 |
| InChIKey | GQCXHIKRWBIQMD-AKJBCIBTSA-N |
SMILES: C[C@@H]1CC2=C([C@H](N1CC(CO)(F)F)C3=C(C=C(C=C3F)NC4CN(C4)CCCF)F)NC5=CC=CC=C25
IUPAC name: 3-[(1R,3R)-1-[2,6-difluoro-4-[[1-(3-fluoropropyl)azetidin-3-yl]amino]phenyl]-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]-2,2-difluoropropan-1-ol
Also known as: Gdc-9545, GDC-9545, Giredestrant, RO-7197597, RO7197597, GIREDESTRANT
Patent coverage: 213 distinct patent families (548 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 476 (87%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| ESR1 | Estrogen receptor-α | Antagonist | 10.3 | 1.7% | P03372 |
Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Estrogen receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Cytochrome P450 3A4.
Bioactivity
ChEMBL activities: 4 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| ESR1 | 10.3 | IC50 | 0.05 | nM | CHEMBL_ACT_23232676 |
| ESR1 | 9.37 | IC50 | 0.43 | nM | CHEMBL_ACT_29106418 |
| KCNH2 | 5.21 | IC50 | 6100 | nM | CHEMBL_ACT_23233008 |
| CYP3A4 | 5.19 | IC50 | 6500 | nM | CHEMBL_ACT_23232988 |
Target pathways
Aggregated over 1 target gene(s): ESR1.
Top Reactome pathways
17 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Nuclear signaling by ERBB4 | 1 | ESR1 |
| PIP3 activates AKT signaling | 1 | ESR1 |
| Constitutive Signaling by Aberrant PI3K in Cancer | 1 | ESR1 |
| Nuclear Receptor transcription pathway | 1 | ESR1 |
| SUMOylation of intracellular receptors | 1 | ESR1 |
| Ovarian tumor domain proteases | 1 | ESR1 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1 | ESR1 |
| TFAP2 (AP-2) family regulates transcription of growth factors and their receptors | 1 | ESR1 |
| RUNX1 regulates estrogen receptor mediated transcription | 1 | ESR1 |
| ESR-mediated signaling | 1 | ESR1 |
| RUNX1 regulates transcription of genes involved in WNT signaling | 1 | ESR1 |
| Regulation of RUNX2 expression and activity | 1 | ESR1 |
| Extra-nuclear estrogen signaling | 1 | ESR1 |
| Estrogen-dependent gene expression | 1 | ESR1 |
| Mitochondrial unfolded protein response (UPRmt) | 1 | ESR1 |
| Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 1 | ESR1 |
| Developmental Lineage of Mammary Gland Alveolar Cells | 1 | ESR1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| negative regulation of transcription by RNA polymerase II | 1 |
| antral ovarian follicle growth | 1 |
| epithelial cell development | 1 |
| chromatin remodeling | 1 |
| regulation of DNA-templated transcription | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| signal transduction | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| positive regulation of cytosolic calcium ion concentration | 1 |
| androgen metabolic process | 1 |
| male gonad development | 1 |
| negative regulation of gene expression | 1 |
| nuclear receptor-mediated steroid hormone signaling pathway | 1 |
| estrogen receptor signaling pathway | 1 |
| response to estradiol | 1 |
Indications & clinical
Indications
3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| breast neoplasm | 3 | MONDO:0021100 | MONDO:0007254 |
| endometrium neoplasm | 2 | MONDO:0021251 | MONDO:0011962 |
| neoplasm | 1 | MONDO:0005070 | EFO:0000616 |
Clinical trials
Total trials: 20.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 7 |
| PHASE3 | 6 |
| PHASE1 | 4 |
| PHASE1/PHASE2 | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04546009 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer) |
| NCT04961996 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician’s Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) |
| NCT05296798 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer) |
| NCT05306340 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician’s Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) |
| NCT06065748 | PHASE3 | RECRUITING | A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) |
| NCT07541079 | PHASE3 | NOT_YET_RECRUITING | A Study Evaluating Adherence, Tolerability, and Patient Reported Outcomes of Giredestrant in Participants With ER+/HER2- Early Breast Cancer Who Are Intolerant to Adjuvant Aromatase Inhibitor Therapy (novERA Breast Cancer) |
| NCT04486352 | PHASE1/PHASE2 | RECRUITING | A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer |
| NCT04576455 | PHASE2 | ACTIVE_NOT_RECRUITING | A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician’s Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer) |
| NCT04802759 | PHASE1/PHASE2 | RECRUITING | A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer |
| NCT04931342 | PHASE2 | ACTIVE_NOT_RECRUITING | A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors |
| NCT05634499 | PHASE2 | ACTIVE_NOT_RECRUITING | A Study of Giredestrant in Participants With Grade 1 Endometrial Cancer |
| NCT05708235 | PHASE2 | RECRUITING | A PoC Study to Evaluate Treatments’ Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population |
| NCT07100106 | PHASE1/PHASE2 | RECRUITING | A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer |
| NCT04436744 | PHASE2 | COMPLETED | A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Giredestrant Plus Palbociclib Compared With Anastrozole Plus Palbociclib for Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Untreated Early Breast Cancer (coopERA Breast Cancer) |
| NCT05659563 | PHASE2 | COMPLETED | Preoperative Window Opportunity Study With Giredestrant or Tamoxifen in Premenopausal Women With ER+/HER2[-] & Ki67≥10% |
| NCT05896566 | PHASE2 | COMPLETED | A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer |
| NCT03332797 | PHASE1 | ACTIVE_NOT_RECRUITING | A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer |
| NCT07214662 | PHASE1 | RECRUITING | A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer |
| NCT03916744 | PHASE1 | COMPLETED | A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer |
| NCT04680273 | PHASE1 | COMPLETED | Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-GDC-9545 Following a Single Oral Dose (Part 1) and to Evaluate the Absolute and Relative Bioavailability of Oral Capsule Formulations of GDC-9545 (Part 2) in Healthy Female Subjects of Non-Childbearing Potential |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
173 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| FULVESTRANT | ChEMBL + PubChem | Phase 4 (approved) | ESR1 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | ESR1 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| ASPIRIN | ChEMBL | Phase 4 (approved) | ESR1 |
| AZTREONAM | ChEMBL | Phase 4 (approved) | ESR1 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | ESR1 |
| BELINOSTAT | ChEMBL | Phase 4 (approved) | ESR1 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | ESR1 |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | ESR1 |
| BISACODYL | ChEMBL | Phase 4 (approved) | ESR1 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ESR1 |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| BUTOCONAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | ESR1 |
| CASPOFUNGIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFADROXIL | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFEPIME | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFTAZIDIME | ChEMBL | Phase 4 (approved) | ESR1 |
| CERIVASTATIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CHLOROTRIANISENE | ChEMBL | Phase 4 (approved) | ESR1 |
| CISPLATIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | ESR1 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | ESR1 |
| CYCLOFENIL | ChEMBL | Phase 4 (approved) | ESR1 |
| DANAZOL | ChEMBL | Phase 4 (approved) | ESR1 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | ESR1 |
| DEQUALINIUM | ChEMBL | Phase 4 (approved) | ESR1 |
| DESOGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| DIENESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| DINOPROSTONE | ChEMBL | Phase 4 (approved) | ESR1 |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | ESR1 |
| DRONEDARONE | ChEMBL | Phase 4 (approved) | ESR1 |
| ELACESTRANT | ChEMBL | Phase 4 (approved) | ESR1 |
| ERGOCALCIFEROL | ChEMBL | Phase 4 (approved) | ESR1 |
| ERTAPENEM | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTETROL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL CYPIONATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL VALERATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRAMUSTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRONE | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHINYL ESTRADIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHYLESTRENOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHYNODIOL DIACETATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ETONOGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETRAVIRINE | ChEMBL | Phase 4 (approved) | ESR1 |
| FLUPIRTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| HEXACHLOROPHENE | ChEMBL | Phase 4 (approved) | ESR1 |
| HEXESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| IBUPROFEN | ChEMBL | Phase 4 (approved) | ESR1 |
| ISOCONAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| LASOFOXIFENE | ChEMBL | Phase 4 (approved) | ESR1 |
| LENVATINIB | ChEMBL | Phase 4 (approved) | ESR1 |
| LEVONORGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| LUSUTROMBOPAG | ChEMBL | Phase 4 (approved) | ESR1 |
| LYMECYCLINE | ChEMBL | Phase 4 (approved) | ESR1 |
Related Atlas pages
- Genes: ESR1
- Diseases: breast neoplasm
- Drugs: Fulvestrant, Acetophenazine, Alectinib, Apomorphine, Aripiprazole, Aspirin, Aztreonam, Bazedoxifene, Belinostat, Benzbromarone, Bexarotene, Bisacodyl, Bithionol, Bromocriptine, Butoconazole, Candesartan Cilexetil, Caspofungin, Cefadroxil, Cefepime, Ceftazidime, Cerivastatin, Chlorotrianisene, Cisplatin, Clofazimine, Clomiphene, Cyclofenil, Danazol, Daunorubicin, Dequalinium, Desogestrel, Dienestrol, Diethylstilbestrol, Dinoprostone, Doxorubicin, Dronedarone, Elacestrant, Ergocalciferol, Ertapenem, Estetrol, Estradiol, Estradiol Cypionate, Estradiol Valerate, Estramustine, Estriol, Estrone, Ethinyl Estradiol, Ethylestrenol, Ethynodiol Diacetate, Etonogestrel, Etravirine, Flupirtine, Hexachlorophene, Hexestrol, Ibuprofen, Isoconazole, Lasofoxifene, Lenvatinib, Levonorgestrel, Lusutrombopag, Lymecycline