PF-04691502

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H27N5O4
Molecular Weight	425.4809
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(C=N1)C2=CC3=C(C)N=C(N)N=C3N([C@H]4CC[C@@H](CC4)OCCO)C2=O

InChI

InChIKey=XDLYKKIQACFMJG-WKILWMFISA-N

InChI=1S/C22H27N5O4/c1-13-17-11-18(14-3-8-19(30-2)24-12-14)21(29)27(20(17)26-22(23)25-13)15-4-6-16(7-5-15)31-10-9-28/h3,8,11-12,15-16,28H,4-7,9-10H2,1-2H3,(H2,23,25,26)/t15-,16-

HIDE SMILES / InChI

Molecular Formula	C22H27N5O4
Molecular Weight	425.4809
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/21750219
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27103175 | https://clinicaltrials.gov/ct2/show/NCT01420081

PF-04691502 is a PI3K/mTOR dual inhibitor. It was tested in phase 2 clinical trials against endometrial cancer and breast cancer, but its development was discontinued due to unacceptable toxicity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21750219	Inhibitor 8297		1.8 nM [Ki]
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21750219	Inhibitor 8297		16.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Endometrial cancer 43 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27103175	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT01430585	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24395457	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
102.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24395457	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04691502 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1287 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24395457	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04691502 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24395457	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-04691502 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYPs 33 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681619	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681619	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681619	yes [IC50 4.2534 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24900568/	Low
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25139570/	unlikely

Sourcing

Vendor/Aggregator	ID	URL
Lab Seeker	SC-96618	http://www.labseeker.com/search.php?keywords=SC-96618&category=0
LabSeeker	SC-96618	http://www.labseeker.com/search.php?keywords=SC-96618&category=0
MolPort	MolPort-044-193-824	https://www.molport.com/shop/molecule-link/MolPort-044-193-824
Molcore	MC103042	http://www.molcore.com/CatMC103042.html
MuseChem	I000123	https://www.musechem.com/product/I000123.html
Selleck Chemicals	S2743	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2743
Synthonix	SL100065	http://www.synthon-lab.com/search.php?cas_or_id=SL100065&cas_id_field=1
Synthonix	14324	https://synthonix.com/catalogsearch/result/?q=14324
TargetMol	T6251	https://www.targetmol.com/search?keyword=T6251
Toronto Research Chemicals	C955815	https://www.trc-canada.com/product-detail/?CatNum=C955815
Toronto Research Chemicals	P293985	https://www.trc-canada.com/product-detail/?CatNum=P293985
eMolecules	300565576	https://orderbb.emolecules.com/search/#?query=300565576
eMolecules	45920158	https://orderbb.emolecules.com/search/#?query=45920158

PubMed

Title	Date	PubMed
		252160513
Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity.	2011 Nov 10	24900269
PF-04691502 triggers cell cycle arrest, apoptosis and inhibits the angiogenesis in hepatocellular carcinoma cells.	2013 Jul 4	23639247

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trials against endometrium cancer PF-04691502 was administred orally once daily (QD) at doses 6-8 mg

Route of Administration: Oral

In Vitro Use Guide

BT20, U87MG, and SKOV3 cells were plated at 3,000 cell/well in 96-well culture plates in growth medium with 10% FBS. Cells were incubated overnight and treated with DMSO (0.1% final) or serial diluted compound for 3 days. Resazurin (Sigma-Aldrich) was added to 0.1 mg/mL. Plates were incubated at 37°C in 5% CO2 for 3 hours. Fluorescence signals were read as emission at 590 nm after excitation at 530 nm. IC50 values were calculated by plotting fluorescence intensity to drug concentration in nonlinear curves. PF-04691502 inhibited cell proliferation of BT20, SKOV3, and U87MG with IC50 values of 313, 188, and 179 nmol/L

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:34:49 UTC 2023` Edited by `admin` on `Sat Dec 16 01:34:49 UTC 2023`
Record UNII	4W39NS61KI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-04691502

Common Name

English

PF-4691502

Code

English

PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE, 2-AMINO-8-(TRANS-4-(2-HYDROXYETHOXY)CYCLOHEXYL)-6-(6-METHOXY-3-PYRIDINYL)-4-METHYL-

Systematic Name

English

Code System Code Type Description

PUBCHEM

25033539