Trilaciclib

Summary

Trilaciclib (CHEMBL3894860) is an approved small molecule (ATC V03AF12) targeting CDK2, CDK4, and CDK6; indicated across 10 conditions including small cell lung carcinoma and triple-negative breast carcinoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: V03AF12
• Targets: 5 (CDK2, CDK4, CDK6…)
• Indications: 10 conditions
• Clinical trials: 36
• Chemistry: 446.5 Da · C24H30N8O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3894860
Name	Trilaciclib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	68029831
ATC	V03AF12
Molecular formula	C24H30N8O
Molecular weight	446.5
InChIKey	PDGKHKMBHVFCMG-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)C2=CN=C(C=C2)NC3=NC=C4C=C5C(=O)NCC6(N5C4=N3)CCCCC6

IUPAC name: 4-[[5-(4-methylpiperazin-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: G1T28, Trilaciclib, TRILACICLIB

Parent form; salt/anhydrous children: CHEMBL4650272

Patent coverage: 859 distinct patent families (2,086 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,877 (90%) 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
CDK2	cyclin dependent kinase 2	Inhibition	5.89	71.1%	P24941
CDK4	cyclin dependent kinase 4	Inhibition	10	58%	P11802
CDK6	cyclin dependent kinase 6	Inhibition	8.4	52.1%	Q00534
CDK7	cyclin dependent kinase 7	Inhibition	5.33	99.9% (common-essential)	P50613
CDK9	cyclin dependent kinase 9	Inhibition	7.3	99.3% (common-essential)	P50750

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Cyclin-dependent kinase 4/cyclin D1, Cyclin-dependent kinase 2/cyclin E1, CDK9/cyclin T1, CDK6/cyclin D3, Cyclin-dependent kinase 6, Cyclin-dependent kinase 2.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CDK4	9.1	IC50	0.8	nM	CHEMBL_ACT_17801293
CDK4	9.09	IC50	0.82	nM	CHEMBL_ACT_17801486
CDK4	9	IC50	1	nM	CHEMBL_ACT_19279497
CDK4	9	IC50	1	nM	CHEMBL_ACT_29144568
CDK2	8.78	IC50	1.66	nM	CHEMBL_ACT_17801491
CDK2	8.78	IC50	1.67	nM	CHEMBL_ACT_17801495
CCND3	8.4	IC50	4	nM	CHEMBL_ACT_19279495
CCND3	8.4	IC50	4	nM	CHEMBL_ACT_29144574
CDK6	8.3	IC50	5	nM	CHEMBL_ACT_29145185
CCND3	8.25	IC50	5.64	nM	CHEMBL_ACT_17801499
CCNT1	7.3	IC50	50	nM	CHEMBL_ACT_29144579
CDK2	5.78	IC50	1660	nM	CHEMBL_ACT_17801369
CDK2	5.78	IC50	1670	nM	CHEMBL_ACT_17801444

Target pathways

Aggregated over 5 target gene(s): CDK2, CDK4, CDK6, CDK7, CDK9.

Top Reactome pathways

152 total, by targets touching each:

Pathway	Targets	Genes
Disease	5	CDK2, CDK4, CDK6, CDK7, CDK9
Generic Transcription Pathway	5	CDK2, CDK4, CDK6, CDK7, CDK9
RNA Polymerase II Transcription	5	CDK2, CDK4, CDK6, CDK7, CDK9
Gene expression (Transcription)	5	CDK2, CDK4, CDK6, CDK7, CDK9
Cell Cycle	4	CDK2, CDK4, CDK6, CDK7
Mitotic G1 phase and G1/S transition	4	CDK2, CDK4, CDK6, CDK7
Cyclin D associated events in G1	4	CDK2, CDK4, CDK6, CDK7
G1 Phase	4	CDK2, CDK4, CDK6, CDK7
Cell Cycle, Mitotic	4	CDK2, CDK4, CDK6, CDK7
Signal Transduction	3	CDK2, CDK4, CDK9
Cellular responses to stress	3	CDK2, CDK4, CDK6
Senescence-Associated Secretory Phenotype (SASP)	3	CDK2, CDK4, CDK6
Cellular Senescence	3	CDK2, CDK4, CDK6
Transcriptional Regulation by TP53	3	CDK2, CDK7, CDK9
Cyclin E associated events during G1/S transition	3	CDK2, CDK4, CDK7
G1/S Transition	3	CDK2, CDK4, CDK7
S Phase	3	CDK2, CDK4, CDK7
Cyclin A:Cdk2-associated events at S phase entry	3	CDK2, CDK4, CDK7
Cellular responses to stimuli	3	CDK2, CDK4, CDK6
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	3	CDK2, CDK4, CDK6
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	3	CDK2, CDK4, CDK6
Diseases of mitotic cell cycle	3	CDK2, CDK4, CDK6
Aberrant regulation of mitotic cell cycle due to RB1 defects	3	CDK2, CDK4, CDK6
Formation of RNA Pol II elongation complex	2	CDK7, CDK9
Developmental Biology	2	CDK2, CDK4
Reproduction	2	CDK2, CDK4
Meiosis	2	CDK2, CDK4
HIV Life Cycle	2	CDK7, CDK9
Late Phase of HIV Life Cycle	2	CDK7, CDK9
HIV Infection	2	CDK7, CDK9

Dominant GO biological processes

GO term	Targets
protein phosphorylation	5
cell division	4
DNA damage response	4
regulation of cell cycle	4
G1/S transition of mitotic cell cycle	3
DNA repair	3
signal transduction	3
regulation of G2/M transition of mitotic cell cycle	3
regulation of gene expression	3
negative regulation of transcription by RNA polymerase II	2
positive regulation of cell population proliferation	2
negative regulation of protein localization to chromatin	2
positive regulation of fibroblast proliferation	2
transcription by RNA polymerase II	2
transcription initiation at RNA polymerase II promoter	2

Indications & clinical

Indications

10 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
small cell lung carcinoma	3	MONDO:0008433	EFO:0000702
triple-negative breast carcinoma	3	MONDO:0005494	EFO:0005537
angiosarcoma	2	MONDO:0016982	EFO:0003968
breast neoplasm	2	MONDO:0021100	MONDO:0007254
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
osteosarcoma	2	MONDO:0009807	EFO:0000637
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
lung neoplasm	2	MONDO:0021117	MONDO:0008903

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

Clinical trials

Total trials: 36.

Phase distribution

Phase	Trials
PHASE2	25
PHASE3	5
PHASE4	2
PHASE1/PHASE2	2
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05874401	PHASE4	RECRUITING	Trilaciclib vs Placebo in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Topotecan
NCT05071703	PHASE4	COMPLETED	Evaluation of TRILACICLIB in Chinese Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC) for Chemotherapy-induced Myelosuppression, Antitumor Effects of Combination Regimens, and Safety in a Real-world Study
NCT06364904	PHASE3	NOT_YET_RECRUITING	A Clinical Trail to Determine the Safety and Efficacy of the Combination of Tislelizumab With Cisplatin and Gemcitabine, With or Without Trilaciclib for Patients With Untreated Unresectable and Metastatic Urothelial Carcinoma.
NCT07473128	PHASE3	NOT_YET_RECRUITING	Effect of Trilaciclib in the Prevention of Myelosupression in Subjects With Limited-stage Small Cell Lung Cancer
NCT04607668	PHASE3	TERMINATED	Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC):
NCT04799249	PHASE3	COMPLETED	Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)
NCT04902885	PHASE3	COMPLETED	Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Small Cell Lung Cancer Patients
NCT05578326	PHASE2	RECRUITING	Study of Trilaciclib and Lurbinectidin
NCT05910034	PHASE2	NOT_YET_RECRUITING	Envafolimab Plus Docetaxel In Combination With or Without Trilaciclib Versus Docetaxel in Advanced NSCLC
NCT05978648	PHASE2	RECRUITING	Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy
NCT06027268	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Metastatic Triple-Negative Breast Cancer
NCT06151262	PHASE2	RECRUITING	A Study of Trilaciclib Combined With mFOLFIRINOX in the Treatment of Patients With Advanced Pancreatic Cancer
NCT06297811	PHASE2	NOT_YET_RECRUITING	Myeloprotection With Trilaciclib in Pan-cancer Population
NCT06370416	PHASE2	ENROLLING_BY_INVITATION	the Prevention of Bone Marrow Suppression Caused by Chemotherapy in Advanced NSCLC With Trilaciclib
NCT06490081	PHASE2	RECRUITING	Trilaciclib Prevents Myelosuppression With Chemoradiotherapy
NCT06569485	PHASE2	RECRUITING	A Study of Trilaciclib Combined With Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma Patients
NCT06698965	PHASE2	RECRUITING	Efficacy and Safety of First-line Treatment for Extensive-stage Small Cell Lung Cancer Using a Combination Therapy of Trilaciclib, Envafolimab, Etoposide, and Carboplatin
NCT06714266	PHASE2	NOT_YET_RECRUITING	Trilaciclib in Preventing Hematopoietic Suppression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
NCT06714383	PHASE2	RECRUITING	Trilaciclib Combing Chemotherapy in the Neoadjuvant Treatment of Osteosarcoma
NCT06752798	PHASE2	RECRUITING	Bone Marrow Protective Effect of Trilaciclib in Postoperative CCRT for LA-HNSCC
NCT06955156	PHASE2	RECRUITING	Trilaciclib Combined With Anti-PD-1 Antibody and Chemotherapy in the Treatment of Locally Advanced TNBC
NCT06992739	PHASE2	RECRUITING	Trilaciclib in Patients Receiving Sacituzumab Tirumotecan for EGFR-mutated, Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT07255612	PHASE2	NOT_YET_RECRUITING	Bone Marrow Protection, Safety, Efficacy of Trilaciclib and Eribulin in Locally Advanced or Metastatic TNBC(Triple-negative Breast Cancer)
NCT02499770	PHASE1/PHASE2	COMPLETED	Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)
NCT02514447	PHASE1/PHASE2	COMPLETED	Trilaciclib (G1T28) in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy
NCT02978716	PHASE2	TERMINATED	Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)
NCT03041311	PHASE2	COMPLETED	Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK4/6 Inhibitor, in Extensive-Stage SCLC
NCT04863248	PHASE2	TERMINATED	Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Docetaxel for Metastatic Non-Small Cell Lung Cancer (NSCLC) (PRESERVE 4)
NCT04887831	PHASE2	TERMINATED	Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
NCT05112536	PHASE2	COMPLETED	Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer
NCT05113966	PHASE2	TERMINATED	Trilaciclib in Patients Receiving Sacituzumab Govitecan-hziy for Triple Negative Breast Cancer
NCT05900921	PHASE2	UNKNOWN	Trilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
NCT06217003	PHASE2	UNKNOWN	Trilaciclib Combined With Chemotherapy for Perioperative Treatment of Osteosarcoma
NCT06328049	PHASE2	UNKNOWN	A Study of Trilaciclib Combined With Chemotherapy in the Treatment of NSCLC
NCT07490236	PHASE1	RECRUITING	Trilaciclib in Combination With Chemotherapy in Patients With CDK4/6-Dependent Solid Tumors
NCT04504513	Not specified	APPROVED_FOR_MARKETING	Expanded Access to Trilaciclib for Patients Receiving Chemotherapy for Small Cell Lung 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.

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

Molecule	Source	Status	Shared targets
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	CDK2, CDK4, CDK6, CDK7, CDK9
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	CDK2, CDK4, CDK6, CDK7, CDK9
ABEMACICLIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4, CDK6, CDK7, CDK9
ALVOCIDIB	ChEMBL	Phase 3	CDK2, CDK4, CDK6, CDK7, CDK9
DINACICLIB	ChEMBL	Phase 3	CDK2, CDK4, CDK6, CDK7, CDK9
LESTAURTINIB	ChEMBL	Phase 3	CDK2, CDK4, CDK6, CDK7, CDK9
AT-7519	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
CT-7001	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
INDIRUBIN	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
INIXACICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
ISTISOCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
MILCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
NARAZACICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
RG-547	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
SELICICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
ULECACICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
ZEMIRCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK7, CDK9
Afatinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Binimetinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
dacomitinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Fostamatinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Idelalisib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
regorafenib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Selumetinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Trametinib	PubChem	Approved	CDK2, CDK4, CDK6, CDK7, CDK9
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	CDK4, CDK6, CDK7, CDK9
PALBOCICLIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4, CDK6, CDK9
RIBOCICLIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4, CDK6, CDK9
LEROCICLIB	ChEMBL	Phase 3	CDK2, CDK4, CDK6, CDK9
CULMERCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK9
CYC-065	ChEMBL	Phase 2	CDK2, CDK4, CDK7, CDK9
EBVACICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK9
RIVICICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK9
RONICICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK7, CDK9
TEGTOCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK9
VORUCICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6, CDK9
ZOTIRACICLIB	ChEMBL	Phase 2	CDK2, CDK6, CDK7, CDK9
Pomalidomide	PubChem	Approved	CDK4, CDK6, CDK7, CDK9
DABRAFENIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4, CDK6
FEDRATINIB	ChEMBL	Phase 4 (approved)	CDK4, CDK7, CDK9
MOMELOTINIB	ChEMBL	Phase 4 (approved)	CDK2, CDK6, CDK9
NINTEDANIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4, CDK7
SORAFENIB	ChEMBL	Phase 4 (approved)	CDK2, CDK6, CDK7
DEFACTINIB	ChEMBL	Phase 3	CDK2, CDK7, CDK9
DOVITINIB	ChEMBL	Phase 3	CDK4, CDK6, CDK7
ENZASTAURIN	ChEMBL	Phase 3	CDK2, CDK7, CDK9
QUERCETIN	ChEMBL	Phase 3	CDK2, CDK4, CDK6
ASNUCICLIB	ChEMBL	Phase 2	CDK2, CDK7, CDK9
AT-9283	ChEMBL	Phase 2	CDK4, CDK6, CDK9
CROZBACICLIB	ChEMBL	Phase 2	CDK2, CDK4, CDK6
CERITINIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4
GILTERITINIB	ChEMBL	Phase 4 (approved)	CDK2, CDK4
PACRITINIB	ChEMBL	Phase 4 (approved)	CDK2, CDK9
QUIZARTINIB	ChEMBL	Phase 4 (approved)	CDK2, CDK7
SUNITINIB	ChEMBL	Phase 4 (approved)	CDK4, CDK7
CRENOLANIB	ChEMBL	Phase 3	CDK2, CDK9
DALPICICLIB	ChEMBL	Phase 3	CDK4, CDK6
FASUDIL	ChEMBL	Phase 3	CDK7, CDK9
LINIFANIB	ChEMBL	Phase 3	CDK7, CDK9
RUBOXISTAURIN	ChEMBL	Phase 3	CDK4, CDK7