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Details

Stereochemistry ACHIRAL
Molecular Formula C22H27N5O4
Molecular Weight 425.4817
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-04691502

SMILES

Cc1c2cc(-c3ccc(nc3)OC)c(=O)n([C@@]4([H])CC[C@@]([H])(CC4)OCCO)c2nc(=N)[nH]1

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 425.4817
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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

Curator's Comment:: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.8 nM [Ki]
16.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
102.3 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
1287 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9 h
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

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
Low
unlikely
PubMed

PubMed

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

Sample Use Guides

In clinical trials against endometrium cancer PF-04691502 was administred orally once daily (QD) at doses 6-8 mg
Route of Administration: Oral
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 Jun 26 00:18:26 UTC 2021
Edited
by admin
on Sat Jun 26 00:18:26 UTC 2021
Record UNII
4W39NS61KI
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Sat Jun 26 00:18:26 UTC 2021 , Edited by admin on Sat Jun 26 00:18:26 UTC 2021
PRIMARY
DRUG BANK
DB11974
Created by admin on Sat Jun 26 00:18:26 UTC 2021 , Edited by admin on Sat Jun 26 00:18:26 UTC 2021
PRIMARY
ChEMBL
CHEMBL1234354
Created by admin on Sat Jun 26 00:18:26 UTC 2021 , Edited by admin on Sat Jun 26 00:18:26 UTC 2021
PRIMARY
CAS
1013101-36-4
Created by admin on Sat Jun 26 00:18:26 UTC 2021 , Edited by admin on Sat Jun 26 00:18:26 UTC 2021
PRIMARY
FDA UNII
4W39NS61KI
Created by admin on Sat Jun 26 00:18:26 UTC 2021 , Edited by admin on Sat Jun 26 00:18:26 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY