Lerociclib

Summary

Lerociclib (CHEMBL3904602) is a phase-3 clinical-stage small molecule targeting CDK4 and CDK6; indicated across 5 conditions including breast neoplasm and endometrial carcinoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (CDK4, CDK6)
• Indications: 5 conditions
• Clinical trials: 4
• Chemistry: 474.6 Da · C26H34N8O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3904602
Name	Lerociclib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	86269224
Molecular formula	C26H34N8O
Molecular weight	474.6
InChIKey	YPJRHEKCFKOVRT-UHFFFAOYSA-N

SMILES: CC(C)N1CCN(CC1)C2=CN=C(C=C2)NC3=NC=C4C=C5C(=O)NCC6(N5C4=N3)CCCCC6

IUPAC name: 4-[[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one

Also known as: G1T-38, G1t38, G1T38, G1T38 FREE BASE, Lerociclib, LEROCICLIB

Patent coverage: 390 distinct patent families (1,012 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,010 (100%) 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
CDK4	cyclin dependent kinase 4	Inhibition	9	58%	P11802
CDK6	cyclin dependent kinase 6	Inhibition	8.33	52.1%	Q00534

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Cyclin-dependent kinase 4/cyclin D1, Receptor-type tyrosine-protein kinase FLT3, CDK9/cyclin T1, CDK6/cyclin D3, Cyclin-dependent kinase 6, Cyclin-dependent kinase 2, Serine/threonine-protein kinase Nek10, Cyclin-dependent kinase 9, Cyclin-dependent kinase 4, Dual specificity protein kinase TTK.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 20 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NEK10	9.7	Kd	0.2	nM	CHEMBL_ACT_19279485
NUAK2	9.15	Kd	0.7	nM	CHEMBL_ACT_19279486
CDK4	9	IC50	1	nM	CHEMBL_ACT_17801306
CDK4	9	IC50	1	nM	CHEMBL_ACT_24993235
CDK4	9	IC50	1	nM	CHEMBL_ACT_29144569
CDK4	8.97	IC50	1.06	nM	CHEMBL_ACT_17801488
CDK2	8.82	IC50	1.51	nM	CHEMBL_ACT_17801497
CDK6	8.7	IC50	2	nM	CHEMBL_ACT_24993239
CCND3	8.7	IC50	2	nM	CHEMBL_ACT_29144575
CDK2	8.45	IC50	3.58	nM	CHEMBL_ACT_17801493
TTK	8.38	Kd	4.2	nM	CHEMBL_ACT_19279487
CCND3	8.33	IC50	4.7	nM	CHEMBL_ACT_17801501
ULK2	8.26	Kd	5.5	nM	CHEMBL_ACT_19279488
FLT3	8.19	Kd	6.5	nM	CHEMBL_ACT_19279490
FLT3	7.66	Kd	22	nM	CHEMBL_ACT_19279489
CDK9	7.55	IC50	28	nM	CHEMBL_ACT_24993247
CCNT1	7.55	IC50	28	nM	CHEMBL_ACT_29144580
CDK9	6.55	IC50	280	nM	CHEMBL_ACT_19279491
CDK2	5.82	IC50	1510	nM	CHEMBL_ACT_17801457
CDK2	5.45	IC50	3580	nM	CHEMBL_ACT_17801382

Target pathways

Aggregated over 2 target gene(s): CDK4, CDK6.

Top Reactome pathways

52 total, by targets touching each:

Pathway	Targets	Genes
Cell Cycle	2	CDK4, CDK6
Disease	2	CDK4, CDK6
Generic Transcription Pathway	2	CDK4, CDK6
Cellular responses to stress	2	CDK4, CDK6
Oxidative Stress Induced Senescence	2	CDK4, CDK6
Senescence-Associated Secretory Phenotype (SASP)	2	CDK4, CDK6
Cellular Senescence	2	CDK4, CDK6
Oncogene Induced Senescence	2	CDK4, CDK6
Mitotic G1 phase and G1/S transition	2	CDK4, CDK6
Cyclin D associated events in G1	2	CDK4, CDK6
G1 Phase	2	CDK4, CDK6
Cell Cycle, Mitotic	2	CDK4, CDK6
RNA Polymerase II Transcription	2	CDK4, CDK6
Gene expression (Transcription)	2	CDK4, CDK6
Cellular responses to stimuli	2	CDK4, CDK6
Diseases of Cellular Senescence	2	CDK4, CDK6
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	2	CDK4, CDK6
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	CDK4, CDK6
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	2	CDK4, CDK6
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	CDK4, CDK6
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	2	CDK4, CDK6
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	2	CDK4, CDK6
Diseases of mitotic cell cycle	2	CDK4, CDK6
Diseases of cellular response to stress	2	CDK4, CDK6
Aberrant regulation of mitotic cell cycle due to RB1 defects	2	CDK4, CDK6
Drug-mediated inhibition of CDK4/CDK6 activity	2	CDK4, CDK6
Developmental Biology	1	CDK4
Reproduction	1	CDK4
Meiosis	1	CDK4
Signal Transduction	1	CDK4

Dominant GO biological processes

GO term	Targets
G1/S transition of mitotic cell cycle	2
signal transduction	2
regulation of G2/M transition of mitotic cell cycle	2
regulation of gene expression	2
positive regulation of fibroblast proliferation	2
cell division	2
regulation of cell cycle	2
protein phosphorylation	2
positive regulation of cell population proliferation	1
response to xenobiotic stimulus	1
positive regulation of G2/M transition of mitotic cell cycle	1
regulation of transcription initiation by RNA polymerase II	1
regulation of type B pancreatic cell proliferation	1
cellular response to lipopolysaccharide	1
cellular response to interleukin-4	1

Indications & clinical

Indications

5 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
endometrial carcinoma	3	MONDO:0002447	EFO:1001512
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060
breast ductal adenocarcinoma	1	MONDO:0005590	EFO:0006318
lung neoplasm	1	MONDO:0021117	MONDO:0008903

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE1/PHASE2	2
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05712941	PHASE3	WITHDRAWN	Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer
NCT02983071	PHASE1/PHASE2	UNKNOWN	G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
NCT03455829	PHASE1/PHASE2	COMPLETED	G1T38, a CDK 4/6 Inhibitor, in Combination With Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer
NCT05085002	PHASE2	TERMINATED	A Study of Lerociclib in Participants With Advanced Breast Cancer

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.

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

Molecule	Source	Status	Shared targets
ABEMACICLIB	ChEMBL	Phase 4 (approved)	CDK4, CDK6
DABRAFENIB	ChEMBL	Phase 4 (approved)	CDK4, CDK6
PALBOCICLIB	ChEMBL	Phase 4 (approved)	CDK4, CDK6
RIBOCICLIB	ChEMBL	Phase 4 (approved)	CDK4, CDK6
TRILACICLIB	ChEMBL	Phase 4 (approved)	CDK4, CDK6
ALVOCIDIB	ChEMBL	Phase 3	CDK4, CDK6
DALPICICLIB	ChEMBL	Phase 3	CDK4, CDK6
DINACICLIB	ChEMBL	Phase 3	CDK4, CDK6
DOVITINIB	ChEMBL	Phase 3	CDK4, CDK6
LESTAURTINIB	ChEMBL	Phase 3	CDK4, CDK6
QUERCETIN	ChEMBL	Phase 3	CDK4, CDK6
AT-7519	ChEMBL	Phase 2	CDK4, CDK6
AT-9283	ChEMBL	Phase 2	CDK4, CDK6
ATIRMOCICLIB	ChEMBL	Phase 2	CDK4, CDK6
CROZBACICLIB	ChEMBL	Phase 2	CDK4, CDK6
CT-7001	ChEMBL	Phase 2	CDK4, CDK6
CULMERCICLIB	ChEMBL	Phase 2	CDK4, CDK6
EBVACICLIB	ChEMBL	Phase 2	CDK4, CDK6
ECIRUCICLIB	ChEMBL	Phase 2	CDK4, CDK6
INDIRUBIN	ChEMBL	Phase 2	CDK4, CDK6
INIXACICLIB	ChEMBL	Phase 2	CDK4, CDK6
ISTISOCICLIB	ChEMBL	Phase 2	CDK4, CDK6
MILCICLIB	ChEMBL	Phase 2	CDK4, CDK6
NARAZACICLIB	ChEMBL	Phase 2	CDK4, CDK6
RG-547	ChEMBL	Phase 2	CDK4, CDK6
RIVICICLIB	ChEMBL	Phase 2	CDK4, CDK6
SELICICLIB	ChEMBL	Phase 2	CDK4, CDK6
TEGTOCICLIB	ChEMBL	Phase 2	CDK4, CDK6
ULECACICLIB	ChEMBL	Phase 2	CDK4, CDK6
VORUCICLIB	ChEMBL	Phase 2	CDK4, CDK6
ZEMIRCICLIB	ChEMBL	Phase 2	CDK4, CDK6
Afatinib	PubChem	Approved	CDK4, CDK6
Binimetinib	PubChem	Approved	CDK4, CDK6
Crizotinib	PubChem	Approved	CDK4, CDK6
dacomitinib	PubChem	Approved	CDK4, CDK6
Fostamatinib	PubChem	Approved	CDK4, CDK6
Gefitinib	PubChem	Approved	CDK4, CDK6
Idelalisib	PubChem	Approved	CDK4, CDK6
Pazopanib	PubChem	Approved	CDK4, CDK6
Pomalidomide	PubChem	Approved	CDK4, CDK6
regorafenib	PubChem	Approved	CDK4, CDK6
Selumetinib	PubChem	Approved	CDK4, CDK6
Trametinib	PubChem	Approved	CDK4, CDK6
CERITINIB	ChEMBL	Phase 4 (approved)	CDK4
ENCORAFENIB	ChEMBL	Phase 4 (approved)	CDK4
FEDRATINIB	ChEMBL	Phase 4 (approved)	CDK4
GILTERITINIB	ChEMBL	Phase 4 (approved)	CDK4
MOMELOTINIB	ChEMBL	Phase 4 (approved)	CDK6
NINTEDANIB	ChEMBL	Phase 4 (approved)	CDK4
OLAPARIB	ChEMBL	Phase 4 (approved)	CDK6
SORAFENIB	ChEMBL	Phase 4 (approved)	CDK6
SUNITINIB	ChEMBL	Phase 4 (approved)	CDK4
RUBOXISTAURIN	ChEMBL	Phase 3	CDK4
BI-2536	ChEMBL	Phase 2	CDK4
CYC-065	ChEMBL	Phase 2	CDK4
ELLAGIC ACID	ChEMBL	Phase 2	CDK4
FISETIN	ChEMBL	Phase 2	CDK6
LY-2090314	ChEMBL	Phase 2	CDK4
REBASTINIB	ChEMBL	Phase 2	CDK4
RONICICLIB	ChEMBL	Phase 2	CDK4