General
Preferred name
PALBOCICLIB
Synonyms
PD0332991 ()
PD-0332991 ()
PALBOCICLIB ISETHIONATE ()
PFE-PKIS 32 ()
PD-0332991, PF-0008066573, Palbociclib Isethionate, PD-03329910054 ()
PD 0332991 hydrochloride ()
Palbociclib hydrochloride ()
Palbociclib (PD-0332991) HCl ()
Palbociclib (PD0332991) Isethionate ()
PD 0332991 isethionate ()
PD 0332991 HCl ()
IBRANCE ()
Palbociclib (monohydrochloride) ()
Palbociclib (isethionate) ()
PD 0332991 (monohydrochloride) ()
PD 0332991 ()
Ibrance, PD 0332991 ()
PFE-PKIS_32 ()
PD0332991 isethionate ()
Palbociclib monohydrochloride ()
PalbociclibPD-0332991PD0332991IbranceCS-0019A-1030 ()
PD 0332991 (hydrochloride) ()
PF-00080665-73 ()
PD-0332991-0054 ()
PD-03329910054 ()
PD 0332991-0054 ()
Palbociclib isethiolate ()
PF-0008066573 ()
PD 0332991-d8 ()
P&D ID
PD003263
CAS
571190-30-2
827022-33-3
1279034-84-2
827022-32-2
1628752-83-9
571189-11-2
Tags
available
probe
drug
drug candidate
Approved by
FDA
PMDA
EMA
First approval
2015
Drug indication
Breast cancer
Schizophrenia
Neoplasm
Solid tumour/cancer
breast carcinoma
Drug Status
approved
investigational
Max Phase
2.0
4.0
Probe info
Probe type
calculated probe
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
7
No orthogonal probes found
Similar probes
3
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PRICE
62
PHARMACODYNAMICS
Due to its mechanism of action, palbociclib inhibits cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB) proficient cancer cells. As expected, these RB cells present a significant increase in the proportion of cells in G1 state and the presence of palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest.[A176810]; ; In vitro studies showed the potential for palbociclib to reduce cellular proliferation of estrogen receptor-positive breast cancer cell lines through the inhibition of the cell-cycle progression from G1 to S phase. In this study, it was demonstrated that the sensitivity of the cells significantly increased with the expression of _RB1_ and _CCND1_ and low expression of _CDKN2A_. As well, palbociclib, combined with antiestrogens, enhanced _in vivo_ antitumor activity in estrogen receptor-positive breast cancer mouse models.[A176792]; ; In clinical trials, palbociclib, in combination with letrozole, was shown to significantly increase the progression-free survival (PFS) in patients with metastatic breast cancer without prior endocrine treatment. In the results, the PFS increased from 4.5 to 9.5 months with an overall response rate (ORR) of 24.6%.[A176789]
MOA
Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor[A176783] that acts by binding to the ATP pocket with an IC50 in the range of 9-15 nmol/L. It is important to consider that it presents low to absent activity against other kinases.[A176798] ; ; The CDK4/6 kinase is involved, with coregulatory partner cyclin D, in the G1-S transition. Hence, inhibition of this step prevents cell cycle progression in cells in whose this pathway is functioning. This step includes the pathways of the phosphorylation of retinoblastoma protein and the E2F family of transcription factors.[A176798]
ROE
The main route of elimination of palbociclib is through feces after hepatic metabolism while renal clearance seems to play a minor role accounting only for 17.5% of the eliminated dose.[A176792]
HALF-LIFE
The mean plasma elimination half-life of palbociclib is 29 hours.[A176792]
TOXICITY
The reported oral Ld50 is of 100 mg/kg.[MSDS] In cases of overdosage, only supportive measures are considered.[FDA label]; ; Palbociclib was showed to present clastogenic activities in _in vitro_ and _in vivo_ assays. As well, it has been reported to produce fetal harm due to its mechanism of action.[A176792] Lastly, it was shown to increase the incidence of microglial cell tumors in the central nervous system at high doses.[FDA label]
METABOLISM
Palbociclib is mainly hepatically transformed.[A176792] the metabolism is mainly performed by the activities of the cytochrome P450 isoenzyme 3A and the sulfotransferase 2A1.[A176798] The metabolism of palbociclib is represented mainly by reactions of oxidation and sulfonation followed by acylation and glucuronidation as minor reactions. After its metabolism, palbociclib forms mainly inactive glucuronide and sulfamic acid conjugates. The major circulating metabolite, accounting for 1.5% of the dose in excreta is is the glucuronide conjugate.[F4265]
ABSORPTION
Palbociclib presents a linear pharmacokinetic profile and its peak plasma concentration was observed 6-12 hours after oral administration. The oral bioavailability is reported to be of 46% with a steady-state reached after 8 days and a median accumulation ratio of 2.4.[A176792]; ; The absorption of palbociclib is significantly reduced under fasting conditions and hence, food intake is recommended when this drug is administered.[A176792]
COMMENT
PD0332991 leads to complete tumor stasis in a MDA-MB-435 xenograft at 150 mg/kg. Jun 30 2016 - 12:37am; Additional kinase selectivity data can be found on the MRC website (http://www.kinase-screen.mrc.ac.uk/screening-compounds/348821). Cellular target- engagement studies would strengthen support for using this as a probe and would further link the target to the phenotype. Sep 4 2016 - 1:58pm
DESCRIPTION
Palbociclib is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 . This kinase inhibitor has anti-tumour activity in several tumour models .
The pharmaceutical formulation contains palbociclib isethionate (PubChem CID 11478676). (GtoPdb)
The pharmaceutical formulation contains palbociclib isethionate (PubChem CID 11478676). (GtoPdb)
INDICATION
Palbociclib is indicated in combination with [letrozole] as initial endocrine-based therapy for the treatment of human epidermal growth factor receptor type 2 (HER2)-negative and hormone receptor(HR)-positive tumors in adult patients with advanced/metastatic breast cancer. It is as well approved in combination with [fulvestrant] in patients with disease progression with prior endocrine therapy.[A176783]; ; In the official labeling, the use of palbociclib should be accompanied with either an aromatase inhibition, no restricted to letrozole, as initial endocrine-based therapy in postmenopausal women or in man.[FDA label]; ; The breast cancer starts as a group of cancer cells that grow into and destroy the nearby breast tissue. This growth can spread into other parts of the body which is called metastasis. According to the location of the cancer cells, it can be categorized in ductal carcinoma and lobular carcinoma. However, other types of breast cancer include inflammatory breast cancer, Paget disease of the breast, triple negative breast cancer non-Hodgkin lymphoma and soft tissue sarcoma.[L5870] In males, breast cancer is usually treated as the cases of postmenopausal women and almost all the cases are ductal carcinoma.[L5873]
PRICE
63
DESCRIPTION
Palbociclib (PD 0332991) is a CDK inhibitor that inhibits CDK4 and CDK6 (IC50=11/16 nM) and is orally active. Palbociclib has anti-tumorigenic activity and has investigational potential for use in ER-positive and HER2-negative breast cancer.
DESCRIPTION
Palbociclib (PD 0332991) isethionate is an orally active selective CDK4 and CDK6 inhibitor with IC50 values of 11 and 16 nM, respectively. Palbociclib isethionate has potent anti-proliferative activity and induces cell cycle arrest in cancer cells, which can be used in the research of HR-positive and HER2-negative breast cancer and hepatocellular carcinoma[1][3][4].
PRICE
67
PRICE
73
DESCRIPTION
Palbociclib hydrochloride (pabociclib hydrochloride) is the salt form of Palbociclib, a selective and orally available CDK4 and CDK6 inhibitor with anti-tumor proliferative activity for use in breast and hepatocellular carcinoma.
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
Palbociclib is indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
(PKIDB)
DESCRIPTION
Palbociclib monohydrochloride (PD 0332991 hydrochloride) is a selective inhibitor of CDK4/6 (IC50s: 11/16 nM). It exhibits no inhibition against a panel of 36 additional protein kinases.
(TargetMol Bioactive Compound Library)
DESCRIPTION
Palbociclib is an endocrine-based chemotherapeutic agent used in combination with other antineoplastic agents to treat HER2-negative and HR-positive advanced or metastatic breast cancer.
(Enamine Bioactive Compounds)
DESCRIPTION
Noncompetitive Epac1 inhibitor
(Tocris Bioactive Compound Library)
DESCRIPTION
Palbociclib Isethionate (PD 0332991 isethionate) is a selective inhibitor of CDK4/6 (IC50s: 11/16 nM). It exhibits no inhibition against a panel of 36 additional protein kinases.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
471
Organisms
2
Compound Sets
45
CDK inhibitor database (CDKiDB)
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors
Clinical kinase drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
Kinase Chemogenomic Set (KCGS 08/2017, in progress)
Kinase Chemogenomic Set (KCGS)
Kinase Inhibitors (best-in-class)
LINCS compound set
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
Tocris Bioactive Compound Library
Tool Compound Set
Welcome Trust Cancer Drugs
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
82
Molecular Weight
447.24
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
2
Rotatable Bonds
5
Ring Count
5
Aromatic Ring Count
3
cLogP
2.97
TPSA
105.04
Fraction CSP3
0.46
Chiral centers
0.0
Largest ring
6.0
QED
0.58
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Cyclin-dependent kinase 4
CDK4, CDK6
CDK4/6
Cyclin-dependent kinase 6
CDK
CDK4/CyclinD1
CDK4/CyclinD3
CDK6/CyclinD2
CDK4, TTK
CDK 4/6 inhibitor
CDK4
CDK6
Pathway
Cell Cycle
Cell Cycle/Checkpoint
Cell Cycle/DNA Damage
Kinase group
CMGC
Targets
CDK4,CDK6
Primary Target
Cyclin-Dependent Protein Kinases
MOA
Inhibitor
CDK6 Inhibitors
CDK4 Inhibitors
CDK inhibitor
Member status
member
Indication
breast cancer
Target class
Protein kinase
Kinase, Kinase
Biosynthetic Origin
Nucleoside
Therapeutic Indication
Anticancer
Therapeutic Class
Anticancer Agents
Target subclass
CMGC, CMGC
Recommended Cell Concentration
100 nM
Source data
