Palbociclib

Summary

Palbociclib (CHEMBL189963) is an approved small-molecule EC 2.7.11.22 (cyclin-dependent kinase) inhibitor (ATC L01EF01) targeting CDK4 and CDK6; indicated across 53 conditions including breast carcinoma and breast neoplasm; with CIViC clinical evidence for 83 variant-indication associations (e.g. PIK3CA E453K OR PIK3CA E453Q OR PIK3CA E453A OR PIK3CA E453D OR PIK3CA E453G OR PIK3CA E453V in breast cancer).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EF01
• Targets: 2 (CDK4, CDK6)
• Indications: 53 conditions
• Clinical trials: 322
• Precision-oncology evidence (CIViC): 83 variant–indication associations
• Chemistry: 447.5 Da · C24H29N7O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL189963
Name	Palbociclib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5330286
ChEBI	CHEBI:85993
ATC	L01EF01
Molecular formula	C24H29N7O2
Molecular weight	447.5
InChIKey	AHJRHEGDXFFMBM-UHFFFAOYSA-N

SMILES: CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C

IUPAC name: 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one

ChEBI definition: A member of the class of pyridopyrimidines that is 2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7-one bearing additional methyl, acetyl and cyclopentyl substituents at positions 5, 6 and 8 respectively. It is used in combination with letrozole for the treatment of metastatic breast cancer.

Pharmacological roles (ChEBI): EC 2.7.11.22 (cyclin-dependent kinase) inhibitor, antineoplastic agent.

Also known as: Ibrance, Palbociclib, PD-0332991, PD0332991, PFE-PKIS 32, PALBOCICLIB, PF-0008066573, PALBOCICLIB ISETHIONATE, PD-03329910054, PFE-PKIS_32, PD 0332991, IBRANCE

Parent form; salt/anhydrous children: CHEMBL2364621, CHEMBL3962672

Patent coverage: 5,635 distinct patent families (13,102 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 12,666 (97%) 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	7.36	58%	P11802
CDK6	cyclin dependent kinase 6	Inhibition	7.44	52.1%	Q00534

Broader ChEMBL bioactivity targets: 88 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Serine/threonine-protein kinase TAO2, Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma, Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha, cGMP-specific 3’,5’-cyclic phosphodiesterase, Alpha-2A adrenergic receptor, Neuronal acetylcholine receptor subunit alpha-4, Cyclin-dependent kinase 5/CDK5 activator 1, Cyclin-dependent kinase 4/cyclin D1, Cyclin-dependent kinase 1/cyclin B1.

Bioactivity

ChEMBL activities: 224 potent at pChembl ≥ 5 of 254 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CCND1	9.7	Ki	0.2	nM	CHEMBL_ACT_25011955
CDK4	9.59	Ki	0.26	nM	CHEMBL_ACT_25789144
CCND1	9.59	Ki	0.26	nM	CHEMBL_ACT_25789164
CCND1	9.37	IC50	0.43	nM	CHEMBL_ACT_26333770
CDK4	9.1	Ki	0.8	nM	CHEMBL_ACT_25011932
CDK4	9.01	IC50	0.98	nM	CHEMBL_ACT_25789145
CCNT1	9	IC50	1	nM	CHEMBL_ACT_25789193
CCND1	9	IC50	0.99	nM	CHEMBL_ACT_25993927
CDK4	8.89	IC50	1.3	nM	CHEMBL_ACT_26333767
CDK4	8.7	IC50	2	nM	CHEMBL_ACT_14584743
CCND1	8.7	IC50	2	nM	CHEMBL_ACT_25789168
CDK4	8.52	Ki	3	nM	CHEMBL_ACT_18020966
CCND1	8.52	IC50	3	nM	CHEMBL_ACT_24964305
CCND1	8.52	IC50	3	nM	CHEMBL_ACT_25993906
CDK4	8.49	IC50	3.2	nM	CHEMBL_ACT_22960036
CDK4	8.49	IC50	3.2	nM	CHEMBL_ACT_22960062
CDK4	8.46	IC50	3.44	nM	CHEMBL_ACT_23206362
PARP1	8.46	IC50	3.5	nM	CHEMBL_ACT_29321628
CCND1	8.43	IC50	3.76	nM	CHEMBL_ACT_13917508
CCND3	8.4	IC50	4	nM	CHEMBL_ACT_25789165
CDK4	8.31	IC50	4.84	nM	CHEMBL_ACT_25993915
CCND3	8.3	IC50	5	nM	CHEMBL_ACT_20606447
CCND3	8.29	IC50	5.1	nM	CHEMBL_ACT_26333774
CDK4	8.27	IC50	5.36	nM	CHEMBL_ACT_13917486
STING1	8.22	Kd	6.01	nM	CHEMBL_ACT_26023207
CDK4	8.18	IC50	6.6	nM	CHEMBL_ACT_24964291
CDK4	8.16	IC50	6.9	nM	CHEMBL_ACT_25993903
CDK4	8.15	IC50	7	nM	CHEMBL_ACT_26333772
CDK4	8.09	IC50	8.2	nM	CHEMBL_ACT_22420546
CCND2	8.05	IC50	9	nM	CHEMBL_ACT_15678945

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

53 indications (6 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 carcinoma	4	MONDO:0004989	EFO:0000305
breast neoplasm	4	MONDO:0021100	EFO:0003869
neoplasm	4	MONDO:0005070	EFO:0000616
HER2 positive breast carcinoma	4	MONDO:0006244	EFO:1000294
squamous cell lung carcinoma	3	MONDO:0005097	EFO:0000708
head and neck squamous cell carcinoma	3	MONDO:0010150	EFO:0000181
squamous cell carcinoma	3	MONDO:0005096	EFO:0000707
soft tissue sarcoma	3	MONDO:0018078	EFO:1001968
sarcoma	3	MONDO:0005089	EFO:0000691
mantle cell lymphoma	2	MONDO:0018876	EFO:1001469
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
liposarcoma	2	MONDO:0005060	EFO:0000569
adenocarcinoma	2	MONDO:0004970	EFO:0000228
oligoastrocytoma	2	MONDO:0016702	EFO:0000630
oligodendroglioma	2	MONDO:0016695	EFO:0000632
melanoma	2	MONDO:0005105	EFO:0000756
thymus neoplasm	2	MONDO:0005197	EFO:0002626
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
pancreatic neuroendocrine tumor	2	MONDO:0019954	EFO:1000045
Ewing sarcoma	2	MONDO:0012817	EFO:0000174
urothelial carcinoma	2	MONDO:0040679	EFO:0008528
colon carcinoma	2	MONDO:0002032	EFO:1001950
ovarian cancer	2	MONDO:0008170	MONDO:0008170
endometrium neoplasm	2	MONDO:0021251	MONDO:0011962
lymphoma	2	MONDO:0005062	EFO:0000574
clear cell renal carcinoma	2	MONDO:0005005	EFO:0000349
osteosarcoma	2	MONDO:0009807	EFO:0000637
renal cell carcinoma	2	MONDO:0005086	EFO:0000681
chordoma	2	MONDO:0008978	MONDO:0008978
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
ovarian carcinoma	2	MONDO:0005140	EFO:0001075
dedifferentiated liposarcoma	2	MONDO:0020563	EFO:0003085
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
ductal breast carcinoma in situ	2	MONDO:0005023	EFO:0000432
nasopharyngeal carcinoma	2	MONDO:0015459	MONDO:0015459
non-Hodgkin lymphoma	1	MONDO:0018908	EFO:0005952
glioblastoma	1	MONDO:0018177	EFO:0000519
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
acute lymphoblastic leukemia	1	MONDO:0004967	EFO:0000220
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
hereditary breast ovarian cancer syndrome	1	MONDO:0003582	Orphanet:145
kidney disorder	1	MONDO:0005240	EFO:0003086
breast ductal adenocarcinoma	1	MONDO:0005590	EFO:0006318
lung neoplasm	1	MONDO:0021117	MONDO:0008903
breast disorder	1	MONDO:0002657	EFO:0009483
undifferentiated pleomorphic sarcoma	1	MONDO:0002142	EFO:1001972
pancreatic ductal adenocarcinoma	1	MONDO:0005184	MONDO:0005184

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

Clinical trials

Total trials: 322.

Phase distribution

Phase	Trials
PHASE2	126
PHASE1	77
Not specified	39
PHASE1/PHASE2	34
PHASE3	32
PHASE4	6
EARLY_PHASE1	5
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02679755	PHASE4	COMPLETED	Palbociclib In Combination With Letrozole As Treatment Of Post-Menopausal Women With HR+, HER2- Advanced Breast Cancer
NCT03220178	PHASE4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03355157	PHASE4	COMPLETED	A Randomized, Open-label, Multi-center Phase IV Study Evaluating Palbociclib Plus Endocrine Treatment Versus a Chemotherapy-based Treatment Strategy in Patients With Hormone Receptor Positive / HER2 Negative Breast Cancer in a Real World Setting (GBG 93 - PADMA Study).
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT06331715	PHASE4	COMPLETED	Bioequivalence Study of Palbociclib 125 mg Capsules of Iclos vs. Ibrance (Palbociclib) Capsules 125 mg
NCT07487129	PHASE4	COMPLETED	Clinical and Pharmacoeconomic Assessment of CDK4/6 Inhibitors for Treatment of Breast Cancer in Egypt
NCT02513394	PHASE3	ACTIVE_NOT_RECRUITING	PALbociclib CoLlaborative Adjuvant Study
NCT02947685	PHASE3	ACTIVE_NOT_RECRUITING	Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
NCT03820830	PHASE3	ACTIVE_NOT_RECRUITING	Palbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer
NCT04191499	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
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)
NCT04711252	PHASE3	ACTIVE_NOT_RECRUITING	A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease
NCT04862663	PHASE3	RECRUITING	Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
NCT04964934	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
NCT04966481	PHASE3	RECRUITING	Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor
NCT05207709	PHASE3	ACTIVE_NOT_RECRUITING	Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
NCT05501886	PHASE3	ACTIVE_NOT_RECRUITING	Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)
NCT05909397	PHASE3	ACTIVE_NOT_RECRUITING	Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced 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)
NCT06377852	PHASE3	RECRUITING	The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
NCT06380751	PHASE3	RECRUITING	Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer
NCT06757634	PHASE3	RECRUITING	Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)
NCT06760637	PHASE3	ACTIVE_NOT_RECRUITING	Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease
NCT07174336	PHASE3	RECRUITING	A Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)
NCT07405164	PHASE3	RECRUITING	Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)
NCT07492641	PHASE3	RECRUITING	BGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease
NCT01740427	PHASE3	COMPLETED	A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)
NCT01864746	PHASE3	COMPLETED	A Study of Palbociclib in Addition to Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After Neoadjuvant Chemotherapy and Surgery
NCT01942135	PHASE3	COMPLETED	Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)
NCT02028507	PHASE3	COMPLETED	Phase III Palbociclib With Endocrine Therapy vs. Capecitabine in HR+/HER2- MBC With Resistance to Aromatase Inhibitors
NCT02297438	PHASE3	COMPLETED	A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]
NCT02600923	PHASE3	COMPLETED	Palbociclib Plus Letrozole For Postmenopausal Women With HR(+) HER2(-) Advanced Breast Cancer For Whom Letrozole Is Deemed Appropriate
NCT02692755	PHASE2/PHASE3	COMPLETED	Palbociclib / Letrozole or Fulvestrant in African American Women With HR+ HER2- Breast Cancer
NCT02785939	PHASE2/PHASE3	COMPLETED	Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer
NCT03079011	PHASE3	COMPLETED	PAlbociclib and Circulating Tumor DNA for ESR1 Mutation Detection
NCT03423199	PHASE3	UNKNOWN	PAlbociclib Plus Tamoxifen for the Treatment of Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Women - Asian studY
NCT03447132	PHASE3	COMPLETED	Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant
NCT03784014	PHASE3	COMPLETED	Molecular Profiling of Advanced Soft-tissue Sarcomas
NCT03969121	PHASE3	COMPLETED	Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer
NCT04047758	PHASE3	UNKNOWN	Palbociclib Combined With an Aromatase Inhibitor in Breast Cancer

Clinical evidence (CIViC)

Variant × indication × effect (83 predictive associations from 87 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
PIK3CA E453K OR PIK3CA E453Q OR PIK3CA E453A OR PIK3CA E453D OR PIK3CA E453G OR PIK3CA E453V	Breast Cancer	Sensitivity/Response	Fulvestrant + Inavolisib + Palbociclib	CIViC A	EID12540
PIK3CA E542K OR PIK3CA E542Q OR PIK3CA E542A OR PIK3CA E542D OR PIK3CA E542G OR PIK3CA E542R OR PIK3CA E542V	Breast Cancer	Sensitivity/Response	Palbociclib + Inavolisib + Fulvestrant	CIViC A	EID12535
PIK3CA E545K OR PIK3CA E545Q OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545V OR PIK3CA E545D OR PIK3CA E545L OR PIK3CA E545R	Breast Cancer	Sensitivity/Response	Palbociclib + Inavolisib + Fulvestrant	CIViC A	EID12534
PIK3CA G1049S OR PIK3CA G1049R OR PIK3CA G106V OR PIK3CA G106R OR PIK3CA G1049A OR PIK3CA G106S OR PIK3CA G106A OR PIK3CA G106D OR PIK3CA G118D OR PIK3CA G1049C OR PIK3CA G1049D	Breast Cancer	Sensitivity/Response	Palbociclib + Inavolisib + Fulvestrant	CIViC A	EID12537
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L OR PIK3CA H1047D OR PIK3CA H1047I OR PIK3CA H1047N OR PIK3CA H1047P OR PIK3CA H1047Q OR PIK3CA H1047T	Breast Cancer	Sensitivity/Response	Palbociclib + Inavolisib + Fulvestrant	CIViC A	EID12533
PIK3CA N345K OR PIK3CA N345D OR PIK3CA N345H OR PIK3CA N345I OR PIK3CA N345S OR PIK3CA N345T OR PIK3CA N345Y	Breast Cancer	Sensitivity/Response	Palbociclib + Inavolisib + Fulvestrant	CIViC A	EID12538
PIK3CA Q546K OR PIK3CA Q546E OR PIK3CA Q546P OR PIK3CA Q546R OR PIK3CA Q546L OR PIK3CA K111E OR PIK3CA K111N OR PIK3CA K111R OR PIK3CA Q546H	Breast Cancer	Sensitivity/Response	Inavolisib + Fulvestrant + Palbociclib	CIViC A	EID12536
PIK3CA R88Q OR PIK3CA C420R OR PIK3CA M1043V OR PIK3CA M1043I OR PIK3CA M1043T	Breast Cancer	Sensitivity/Response	Fulvestrant + Palbociclib + Inavolisib	CIViC A	EID12539
CCND1 Overexpression	Mantle Cell Lymphoma	Sensitivity/Response	Palbociclib	CIViC B	EID1536 +1
CDK4 Amplification	Liposarcoma	Sensitivity/Response	Palbociclib	CIViC B	EID1366 +1
ESR1 Y537N	Breast Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID4817 +1
ESR1 Y537S	Breast Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID4819 +1
CCND1 Amplification	Lung Squamous Cell Carcinoma	Sensitivity/Response	Palbociclib	CIViC B	EID7405
CCND1 Amplification OR CCND2 Amplification OR CCND3 Amplification	Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID11673
CCND2 Amplification	Lung Squamous Cell Carcinoma	Sensitivity/Response	Palbociclib	CIViC B	EID7406
CCND3 Amplification	Lung Squamous Cell Carcinoma	Sensitivity/Response	Palbociclib	CIViC B	EID7407
CCNE1 Underexpression	Breast Cancer	Sensitivity/Response	Fulvestrant + Palbociclib	CIViC B	EID7331
CDK6 Overexpression	Breast Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID11200
CDKN2A Deletion	Gastrointestinal Stromal Tumor	Sensitivity/Response	Palbociclib	CIViC B	EID7311
CDKN2A Loss OR CDKN2A Mutation	Pancreatic Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID11653
CDKN2A Loss OR CDKN2A Mutation	Biliary Tract Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID11654
CDKN2A Mutation	Pancreatic Cancer	Sensitivity/Response	Palbociclib	CIViC B	EID7299
CDKN2A Mutation	Cholangiocarcinoma	Sensitivity/Response	Palbociclib	CIViC B	EID7300
ESR1 Overexpression	Breast Cancer	Sensitivity/Response	Palbociclib + Letrozole	CIViC B	EID1541
RB1 Wildtype AND ( CDKN2A Loss OR CDKN2A Mutation )	Lung Non-small Cell Carcinoma	Sensitivity/Response	Palbociclib	CIViC B	EID11665
CDKN2A Loss	Lung Non-small Cell Carcinoma	Resistance	Palbociclib	CIViC B	EID7444
PIK3CA Mutation OR RB1 Mutation OR ESR1 Mutation	Breast Cancer	Resistance	Fulvestrant + Palbociclib	CIViC B	EID12045
FGFR1 Amplification	Breast Cancer		Palbociclib + Erdafitinib + Fulvestrant	CIViC B	EID12485
CDKN2A Loss	Her2-receptor Negative Breast Cancer	Sensitivity/Response	Letrozole + Palbociclib	CIViC C	EID1765
ESR1 D538G	Breast Cancer	Sensitivity/Response	Palbociclib	CIViC C	EID4813

+53 more predictive associations (showing top 30 by level).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 6 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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
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
LEROCICLIB	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