Ipatasertib

Summary

Ipatasertib (CHEMBL2177390) is a phase-3 clinical-stage small molecule targeting AKT1, AKT2, and PRKG1; indicated across 14 conditions including metastatic prostate carcinoma and neoplasm; with CIViC clinical evidence for 2 variant-indication associations (e.g. PTEN Loss in prostate cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (AKT1, AKT2, PRKG1…)
• Indications: 14 conditions
• Clinical trials: 54
• Precision-oncology evidence (CIViC): 2 variant–indication associations
• Chemistry: 458 Da · C24H32ClN5O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2177390
Name	Ipatasertib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	24788740
Molecular formula	C24H32ClN5O2
Molecular weight	458
InChIKey	GRZXWCHAXNAUHY-NSISKUIASA-N

SMILES: C[C@@H]1C[C@H](C2=C1C(=NC=N2)N3CCN(CC3)C(=O)[C@H](CNC(C)C)C4=CC=C(C=C4)Cl)O

IUPAC name: (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one

Also known as: GDC-0068, Ipatasertib, Rg-7440, RG-7440, RG7440, IPATASERTIB, SID174006468, Ipatasertib (GDC-0068)

Patent coverage: 833 distinct patent families (2,231 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,955 (88%) 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
AKT1	AKT serine/threonine kinase 1	Inhibition	9	3.4%	P31749
AKT2	AKT serine/threonine kinase 2	Inhibition	7.74	2.6%	P31751
PRKG1	Protein kinase G (PKG) 1	Inhibition	7.16	0.1%	Q13976
AKT3	AKT serine/threonine kinase 3	Inhibition	8.1	0.2%	Q9Y243

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: RAC-beta serine/threonine-protein kinase, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, cGMP-dependent protein kinase 1, RAC-alpha serine/threonine-protein kinase, RAC-gamma serine/threonine-protein kinase.

Bioactivity

ChEMBL activities: 23 potent at pChembl ≥ 5 of 23 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AKT1	9.19	Kd	0.64	nM	CHEMBL_ACT_24509440
AKT1	8.89	IC50	1.3	nM	CHEMBL_ACT_23246251
AKT1	8.7	IC50	2	nM	CHEMBL_ACT_27884000
AKT3	8.6	Kd	2.5	nM	CHEMBL_ACT_24509450
AKT1	8.59	IC50	2.6	nM	CHEMBL_ACT_27883997
AKT1	8.46	IC50	3.5	nM	CHEMBL_ACT_26316468
AKT2	8.42	IC50	3.8	nM	CHEMBL_ACT_23246261
AKT1	8.42	IC50	3.8	nM	CHEMBL_ACT_24929545
AKT1	8.3	IC50	5	nM	CHEMBL_ACT_12151740
AKT1	8.3	IC50	5	nM	CHEMBL_ACT_25033324
AKT3	8.1	IC50	8	nM	CHEMBL_ACT_12151799
AKT3	8.1	IC50	8	nM	CHEMBL_ACT_25033328
AKT2	7.75	IC50	18	nM	CHEMBL_ACT_12151730
AKT2	7.75	IC50	18	nM	CHEMBL_ACT_25033326
AKT3	7.66	IC50	22	nM	CHEMBL_ACT_24929631
AKT3	7.58	IC50	26	nM	CHEMBL_ACT_22470525
AKT2	7.5	IC50	32	nM	CHEMBL_ACT_22470519
AKT2	7.46	Kd	35	nM	CHEMBL_ACT_24509445
AKT2	7.32	IC50	48	nM	CHEMBL_ACT_24929588
PRKG1	7.16	IC50	69	nM	CHEMBL_ACT_12151806
PRKG1	7.01	IC50	98	nM	CHEMBL_ACT_12151805
AKT1	6.8	IC50	157	nM	CHEMBL_ACT_12151789
PIK3CA	5.85	IC50	1400	nM	CHEMBL_ACT_29205884

Target pathways

Aggregated over 4 target gene(s): AKT1, AKT2, PRKG1, AKT3.

Top Reactome pathways

132 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	4	AKT1, AKT2, AKT3, PRKG1
Apoptosis	3	AKT1, AKT2, AKT3
Intrinsic Pathway for Apoptosis	3	AKT1, AKT2, AKT3
Activation of BAD and translocation to mitochondria	3	AKT1, AKT2, AKT3
Activation of BH3-only proteins	3	AKT1, AKT2, AKT3
Signaling by ERBB2	3	AKT1, AKT2, AKT3
PIP3 activates AKT signaling	3	AKT1, AKT2, AKT3
Developmental Biology	3	AKT1, AKT2, AKT3
Cytokine Signaling in Immune system	3	AKT1, AKT2, AKT3
Adaptive Immune System	3	AKT1, AKT2, AKT3
Downregulation of ERBB2:ERBB3 signaling	3	AKT1, AKT2, AKT3
Cell Cycle	3	AKT1, AKT2, AKT3
Disease	3	AKT1, AKT2, AKT3
MTOR signalling	3	AKT1, AKT2, AKT3
Inhibition of TSC complex formation by AKT (PKB)	3	AKT1, AKT2, AKT3
Immune System	3	AKT1, AKT2, AKT3
Regulation of beta-cell development	3	AKT1, AKT2, AKT3
Signaling by VEGF	3	AKT1, AKT2, AKT3
Signaling by WNT	3	AKT1, AKT2, PRKG1
AKT phosphorylates targets in the cytosol	3	AKT1, AKT2, AKT3
AKT phosphorylates targets in the nucleus	3	AKT1, AKT2, AKT3
Negative regulation of the PI3K/AKT network	3	AKT1, AKT2, AKT3
Membrane Trafficking	3	AKT1, AKT2, AKT3
Regulation of gene expression in beta cells	3	AKT1, AKT2, AKT3
AKT-mediated inactivation of FOXO1A	3	AKT1, AKT2, AKT3
Generic Transcription Pathway	3	AKT1, AKT2, AKT3
PI3K/AKT Signaling in Cancer	3	AKT1, AKT2, AKT3
Cellular responses to stress	3	AKT1, AKT2, AKT3
Transcriptional Regulation by TP53	3	AKT1, AKT2, AKT3
Signaling by GPCR	3	AKT1, AKT2, AKT3

Dominant GO biological processes

GO term	Targets
protein phosphorylation	4
signal transduction	4
insulin receptor signaling pathway	3
positive regulation of cell migration	3
intracellular signal transduction	3
negative regulation of apoptotic process	3
positive regulation of blood vessel endothelial cell migration	3
negative regulation of PERK-mediated unfolded protein response	3
positive regulation of endothelial cell proliferation	2
glycogen biosynthetic process	2
glucose metabolic process	2
regulation of translation	2
negative regulation of long-chain fatty acid import across plasma membrane	2
positive regulation of glucose metabolic process	2
regulation of cell migration	2

Indications & clinical

Indications

14 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
metastatic prostate carcinoma	3	MONDO:0004956	EFO:0000196
neoplasm	3	MONDO:0005070	EFO:0000616
breast neoplasm	3	MONDO:0021100	EFO:0003869
triple-negative breast carcinoma	3	MONDO:0005494	EFO:0005537
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
gastric adenocarcinoma	2	MONDO:0005036	EFO:0000503
ovarian neoplasm	2	MONDO:0021068	EFO:0003893
ovarian carcinoma	2	MONDO:0005140	EFO:0001075
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
endometrium neoplasm	1	MONDO:0021251	MONDO:0011962

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 54.

Phase distribution

Phase	Trials
PHASE2	23
PHASE1	16
PHASE1/PHASE2	10
PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04650581	PHASE3	ACTIVE_NOT_RECRUITING	Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor
NCT05862285	PHASE3	RECRUITING	A Rollover Study for Participants Previously Enrolled in a Genentech and/or F. Hoffman-La Roche Sponsored Study
NCT03072238	PHASE3	COMPLETED	Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer
NCT03337724	PHASE3	COMPLETED	A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
NCT04177108	PHASE3	COMPLETED	A Study of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer
NCT02465060	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT03385655	PHASE2	ACTIVE_NOT_RECRUITING	Prostate Cancer Biomarker Enrichment and Treatment Selection
NCT03424005	PHASE1/PHASE2	RECRUITING	A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
NCT03673787	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Ipatasertib in Combination With Atezolizumab
NCT04486352	PHASE1/PHASE2	RECRUITING	A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer
NCT04589845	PHASE2	ACTIVE_NOT_RECRUITING	Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
NCT04802759	PHASE1/PHASE2	RECRUITING	A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
NCT04920708	PHASE2	ACTIVE_NOT_RECRUITING	Fulvestrant, Ipatasertib and CDK4/6 Inhibition in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression
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
NCT05172258	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
NCT05332561	PHASE2	RECRUITING	Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE)
NCT05498896	PHASE2	ACTIVE_NOT_RECRUITING	Investigate the Contribution of Ipatasertib to Neoadjuvant Chemotherapy Plus Atezolizumab in TNBC
NCT05538897	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers
NCT05564377	PHASE2	RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
NCT06400251	PHASE2	ACTIVE_NOT_RECRUITING	Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K)
NCT01485861	PHASE1/PHASE2	COMPLETED	Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
NCT01896531	PHASE2	COMPLETED	A Study of Ipatasertib (GDC-0068) in Combination With Fluoropyrimidine Plus Oxaliplatin in Participants With Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
NCT02162719	PHASE2	COMPLETED	A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors
NCT02301988	PHASE2	COMPLETED	A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer
NCT03280563	PHASE1/PHASE2	COMPLETED	A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
NCT03337698	PHASE1/PHASE2	TERMINATED	A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
NCT03395899	PHASE2	COMPLETED	Pre-operative Immunotherapy Combination Strategies in Breast Cancer
NCT03498521	PHASE2	COMPLETED	A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site
NCT03853707	PHASE1/PHASE2	COMPLETED	Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Treating Patients With Metastatic Triple Negative Breast Cancer
NCT04464174	PHASE2	COMPLETED	Ipatasertib Plus Non-Taxane Chemotherapy for Advanced or Metastatic Triple-Negative Breast Cancer
NCT04467801	PHASE2	UNKNOWN	Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy
NCT04551521	PHASE2	COMPLETED	CRAFT: The NCT-PMO-1602 Phase II Trial
NCT04561817	PHASE2	WITHDRAWN	To Evaluate the Safety and Efficacy of Ipatasertib (GDC-0068) in Combination With Paclitaxel in Platinum-resistant Recurrent Epithelial Ovarian Cancer
NCT04591431	PHASE2	UNKNOWN	The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT04632992	PHASE2	COMPLETED	A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response
NCT04737109	PHASE1/PHASE2	TERMINATED	Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer
NCT04739202	PHASE2	UNKNOWN	Personalized Targeted IMMUNOtherapy-based Regimens in Recurrent GASTric Adenocarcinoma (IMMUNOGAST)
NCT05554380	PHASE2	SUSPENDED	Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With PTEN/AKT Mutations, A ComboMATCH Treatment Trial
NCT03959891	PHASE1	ACTIVE_NOT_RECRUITING	AKT Inhibitor, Ipatasertib, With Endocrine and CDK 4/6 Inhibitor for Patients With Metastatic Breast Cancer (TAKTIC)
NCT05172245	PHASE1	RECRUITING	Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
PTEN Loss	Prostate Cancer	Sensitivity/Response	Ipatasertib	CIViC B	EID10876 +1
PTEN Mutation	Cancer	Sensitivity/Response	Ipatasertib	CIViC D	EID1491

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.

77 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CAPIVASERTIB	ChEMBL + PubChem	Phase 4 (approved)	AKT1, AKT2, AKT3, PRKG1
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	AKT1, AKT2, AKT3, PRKG1
LESTAURTINIB	ChEMBL	Phase 3	AKT1, AKT2, AKT3, PRKG1
Afatinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Binimetinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Crizotinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
dacomitinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Fostamatinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Idelalisib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Pazopanib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
regorafenib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Selumetinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
Trametinib	PubChem	Approved	AKT1, AKT2, AKT3, PRKG1
AFURESERTIB	ChEMBL	Phase 3	AKT1, AKT2, AKT3
MIRANSERTIB	ChEMBL	Phase 2	AKT1, AKT2, AKT3
MK-2206	ChEMBL	Phase 2	AKT1, AKT2, AKT3
SOTRASTAURIN	ChEMBL	Phase 2	AKT1, AKT2, PRKG1
UPROSERTIB	ChEMBL	Phase 2	AKT1, AKT2, AKT3
belumosudil	PubChem	Approved	AKT1, AKT2, AKT3
Gefitinib	PubChem	Approved	AKT2, AKT3, PRKG1
FEDRATINIB	ChEMBL + PubChem	Phase 4 (approved)	AKT3, PRKG1
SUNITINIB	ChEMBL + PubChem	Phase 4 (approved)	AKT2, PRKG1
ENZASTAURIN	ChEMBL	Phase 3	AKT3, PRKG1
FASUDIL	ChEMBL	Phase 3	AKT1, AKT3
LINIFANIB	ChEMBL	Phase 3	AKT1, PRKG1
RUBOXISTAURIN	ChEMBL	Phase 3	AKT2, AKT3
LAUROGUADINE	ChEMBL	Phase 2	AKT1, AKT2
Belzutifan	PubChem	Approved	AKT2, PRKG1
Cobimetinib	PubChem	Approved	AKT3, PRKG1
PACRITINIB	ChEMBL + PubChem	Phase 4 (approved)	PRKG1
MILTEFOSINE	ChEMBL	Phase 4 (approved)	AKT1
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	AKT1
NINTEDANIB	ChEMBL	Phase 4 (approved)	PRKG1
PERIFOSINE	ChEMBL	Phase 3	AKT1
QUERCETIN	ChEMBL	Phase 3	AKT1
CENISERTIB	ChEMBL	Phase 2	PRKG1
EDELFOSINE	ChEMBL	Phase 2	AKT1
ELLAGIC ACID	ChEMBL	Phase 2	AKT1
KALAFUNGIN	ChEMBL	Phase 2	AKT1
PF-04691502	ChEMBL	Phase 2	AKT1
PICTILISIB	ChEMBL	Phase 2	AKT1
RUPITASERTIB	ChEMBL	Phase 2	AKT1
SAR-407899 FREE BASE	ChEMBL	Phase 2	PRKG1
SULFAETHIDOLE	ChEMBL	Phase 2	AKT1
Abemaciclib	PubChem	Approved	PRKG1
Alectinib	PubChem	Approved	PRKG1
Alpelisib	PubChem	Approved	PRKG1
Aprepitant	PubChem	Approved	PRKG1
Baricitinib	PubChem	Approved	PRKG1
Bosutinib	PubChem	Approved	PRKG1
Cabozantinib	PubChem	Approved	PRKG1
Capmatinib	PubChem	Approved	PRKG1
Ceritinib	PubChem	Approved	PRKG1
Dabrafenib	PubChem	Approved	PRKG1
Duvelisib	PubChem	Approved	PRKG1
Encorafenib	PubChem	Approved	PRKG1
Entrectinib	PubChem	Approved	PRKG1
Erlotinib	PubChem	Approved	PRKG1
Gilteritinib	PubChem	Approved	PRKG1
Ibrutinib	PubChem	Approved	PRKG1