PKI-166

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H18N4O
Molecular Weight	330.3831
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](NC1=NC=NC2=C1C=C(N2)C3=CC=C(O)C=C3)C4=CC=CC=C4

InChI

InChIKey=XRYJULCDUUATMC-CYBMUJFWSA-N

InChI=1S/C20H18N4O/c1-13(14-5-3-2-4-6-14)23-19-17-11-18(24-20(17)22-12-21-19)15-7-9-16(25)10-8-15/h2-13,25H,1H3,(H2,21,22,23,24)/t13-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H18N4O
Molecular Weight	330.3831
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850439
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16203782 | http://en.pharmacodia.com/web/drug/1_14094.html | https://www.ncbi.nlm.nih.gov/pubmed/23528611

PKI166 is a potent and selective EGFR kinase inhibitor (IC50 = 0.7 nM). PKI166 was tested in phase I clinical trials in patients with advanced solid malignancies, where the recommended dose for further studies was 750 mg once daily for 2 weeks every 4 weeks. In preclinical model, PKI166 was tested in pancreatic, prostate, renal cell, colorectal and other types of cancer. The development of PKI166 was discontinued in 2002 after phase II clinical trials. PKI166 possess antihypertensive properties demonstrated in rat hypertensive chronic kidney disease model.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epidermal growth factor receptor 49 Target ID: P00533\|\|\|Q9GZX1 Gene ID: 1956.0 Gene Symbol: EGFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850439	Inhibitor 8504		0.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23528611	Preventing		Preclinical	Unknown Approved Use Unknown
Cancer 609 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16203782	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
403 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1319 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
273 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2159 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	900 mg 1 times / day steady-state, oral dose: 900 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3555 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13727 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3334 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18853 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	900 mg 1 times / day steady-state, oral dose: 900 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16203782/	900 mg 1 times / day steady-state, oral dose: 900 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	PKI-166 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
900 mg 1 times / day multiple, oral Highest studied dose Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	DLT: Alanine aminotransferase increase, rash... Other AEs: Fatigue, Anorexia... Dose limiting toxicities: Alanine aminotransferase increase (grade 3, 1 pt) rash (grade 3, 1 pt) diarrhea (grade 3, 1 pt) Other AEs: Fatigue (grades 3-4, 1 pt) Anorexia (grade 1-2, 2 patients) Nausea (grade 1-2, 4 patients) Vomiting (grade 1-2, 3 patients) Aspartate aminotransferase increase (grade 1-2, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/
750 mg 1 times / day multiple, oral MTD Dose: 750 mg, 1 times / day Route: oral Route: multiple Dose: 750 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	Other AEs: Alanine aminotransferase increase, Myalgia... Other AEs: Alanine aminotransferase increase (grade 3-4, 1 pt) Myalgia (grade 3-4, 1 pt) Anorexia (grade 1-2, 1 pt) Nausea (grade 1-2, 7 patients) vomiting (grade 1-2, 6 patients) Diarrhea (grade 1-2, 11 patient) abdominal pain (grade 1-2, 3 patients) Rash (grade 1-2, 5 patients) Aspartate aminotransferase increase (grade 1-2, 4 patients) Fatigue (grade 1-2, 1 pt) Dry mouth (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	DLT: Alanine aminotransferase increase... Other AEs: Vomiting, Nausea... Dose limiting toxicities: Alanine aminotransferase increase (grade 3, 2 patients) Other AEs: Vomiting (grade 1-2, 3 patients) Nausea (grade 1-2, 4 patients) Anorexia (grade 1-2, 1 pt) Diarrhea (grade 1-2, 2 patients) Rash (grade 1-2, 1 pt) Aspartate aminotransferase increase (grade 1-2, 3 patients) Fatigue (grade 1-2, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/
50 mg 1 times / day multiple, oral Studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/	DLT: Alanine aminotransferase increase, Aspartate aminotransferase increase... Other AEs: Nausea, vomiting... Dose limiting toxicities: Alanine aminotransferase increase (grade 3, 1 pt) Aspartate aminotransferase increase (grade 3, 2 patients) Other AEs: Nausea (grade 1-2, 5 patients) vomiting (grade 1-2, 3 patients) Abdominal pain (grade 1-2, 1 pt) Rash (grade 3-4, 1 pt) Anorexia (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/16203782/

AEs

PubMed

Title	Date	PubMed
Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats.	2013-06	23528611
Phase I and pharmacologic study of PKI166, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies.	2005-10-01	16203782
Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma.	2000-06-01	10850439

Patents

Sample Use Guides

In Vivo Use Guide

In phase I clinical trials in patients with advanced solid malignancies, PKI166 was first given orally once daily continuously and in the second part of the study once daily for 2 weeks every 4 weeks to establish the maximum tolerated dose. The recommended dose for further studies was 750 mg once daily for 2 weeks every 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

In vitro enzyme assays using EGF-R protein tyrosine kinase was performed in 96-well plates as a filter binding assay. The rate of kinase reaction was measured by a transfer of [γ-33P]ATP to a substrate. PKI166 inhibits EGFR with IC50 of 0.7 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:11:54 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:54 GMT 2025`
Record UNII	9RIE5HW38P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CGP-75166

Preferred Name

English

PKI-166

Common Name

English

PKI 166 [WHO-DD]

Common Name

English

4-(4-((1-PHENYLETHYL)AMINO)-7H-PYRROLO(2,3-D)PYRIMIDIN-6-YL)-PHENOL, R-

Common Name

English

NVP-PKI166

Code

English

Code System Code Type Description

PUBCHEM

6918403