PF-03814735

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H25F3N6O2
Molecular Weight	474.4788
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)NCC(=O)N1[C@H]2CC[C@@H]1C3=C2C=CC(NC4=NC=C(C(NC5CCC5)=N4)C(F)(F)F)=C3

InChI

InChIKey=RYYNGWLOYLRZLK-RBUKOAKNSA-N

InChI=1S/C23H25F3N6O2/c1-12(33)27-11-20(34)32-18-7-8-19(32)16-9-14(5-6-15(16)18)30-22-28-10-17(23(24,25)26)21(31-22)29-13-3-2-4-13/h5-6,9-10,13,18-19H,2-4,7-8,11H2,1H3,(H,27,33)(H2,28,29,30,31)/t18-,19+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H25F3N6O2
Molecular Weight	474.4788
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20354118 | https://www.ncbi.nlm.nih.gov/pubmed/21852114
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22222631

Pfizer was developing PF-03814735, an orally administered, reversible inhibitor of the Aurora A and Aurora B kinases. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1 (Thr 232, a sensitive marker of Aurora1 activity, with IC50 ~ 20 nM), phosphohistone H3 (with IC50 50 nM), and phospho-Aurora2 (with IC50 150 nM). PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. A recent research indicates small cell lung cancer (SCLC) and, to a lesser extent, colon cancer lines are very sensitive to PF-03814735. The status of the Myc gene family and retinoblastoma pathway members significantly correlates with the efficacy of PF-03814735. PF-03814735 was under Phase I trials for patients with advanced solid tumors, but later this research was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20354118	Inhibitor 8297	0.8 nM [IC50]
Serine/threonine-protein kinase Aurora-B 28 Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20354118	Inhibitor 8297	5.0 nM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20354118	Inhibitor 8297	10.0 nM [IC50]
Focal adhesion kinase 1 15 Target ID: CHEMBL2695 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20354118	Inhibitor 8297	22.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: http://adisinsight.springer.com/drugs/800025628 https://clinicaltrials.gov/ct2/show/NCT00424632	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
2.79 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.77 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.11 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.81 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.49 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
37.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
49.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
58 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
64.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
84.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
20.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
21.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21852114	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-03814735 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUM1	https://www.1pchem.com/search?query=1P00GUM1
AK Scientific	2639AH	https://aksci.com/item_detail.php?cat=2639AH
Axon MedChem	2023	https://www.axonmedchem.com/product/2023
BLD Pharm	BD631046	http://www.bldpharm.com/search/Search.html?keyword=BD631046
BOC Sciences	942487-16-3	http://www.bocsci.com/description.asp?cas=942487-16-3
Cayman Chemical	15015	http://www.caymanchem.com/app/template/Product.vm/catalog/15015
Chem Scene	CS-0684	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0684
ChemShuttle	141612	https://www.chemshuttle.com/catalogsearch/result/?q=141612
MedChem Express	HY-14574	https://www.medchemexpress.com/search.html?q=HY-14574&ft=&fa=&fp=
MolPort	MolPort-035-395-702	https://www.molport.com/shop/molecule-link/MolPort-035-395-702
Molnova	M17679	https://www.molnova.com/en/serch-list.html?keywords=M17679
Ryan Scientific	101-94012	https://ryansci.com/products?q=101-94012&list_q=&search_type=exact
Tocris	4821	https://www.tocris.com/search.php?Type=QuickSearch&Value=4821
eMolecules	44811507	https://orderbb.emolecules.com/search/#?query=44811507
eMolecules	95705502	https://orderbb.emolecules.com/search/#?query=95705502
eNovation Chemicals	D395273	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395273&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1931894334	https://mcule.com/MCULE-1931894334/
mcule	MCULE-8111261136	https://mcule.com/MCULE-8111261136/

PubMed

Title	Date	PubMed
PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy.	2010 Apr	20354118
Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours.	2011 Oct	21852114

Patents

Sample Use Guides

In Vivo Use Guide

Patients with advanced solid tumours received oral, once-daily (QD) PF-03814735 on Schedule A: days 1-5 (5-100mg); or Schedule B: days 1-10 (40-60mg) of 21-day cycles.

Route of Administration: Oral

In Vitro Use Guide

Of 220 kinases evaluated, 19 others showed >90% inhibition at 100 nmol/L of PF-03814735

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:09:30 GMT 2023` Edited by `admin` on `Sat Dec 16 08:09:30 GMT 2023`
Record UNII	6V5T4O5758
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-03814735

Common Name

English

PF 3814735

Code

English

PF-3814735

Code

English

N-(2-((1S,4R)-6-((4-(CYCLOBUTYLAMINO)-5-(TRIFLUOROMETHYL)PYRIMIDIN-2-YL)AMINO)-1,2,3,4-TETRAHYDRO-1,4-EPIMINONAPHTHALEN-9-YL)-2-OXOETHYL)ACETAMIDE

Systematic Name

English

PF 03814735

Code

English

PF 03814735 [WHO-DD]

Common Name

English

Code System Code Type Description

FDA UNII

6V5T4O5758