XK-469, (R)-

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H12ClN2O4.Na
Molecular Weight	366.731
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].C[C@@H](OC1=CC=C(OC2=NC3=CC(Cl)=CC=C3N=C2)C=C1)C([O-])=O

InChI

InChIKey=OJENKXNXJPNEPU-HNCPQSOCSA-M

InChI=1S/C17H13ClN2O4.Na/c1-10(17(21)22)23-12-3-5-13(6-4-12)24-16-9-19-14-7-2-11(18)8-15(14)20-16;/h2-10H,1H3,(H,21,22);/q;+1/p-1/t10-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C17H12ClN2O4
Molecular Weight	343.741
Charge	-1
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/10518594 | https://www.ncbi.nlm.nih.gov/pubmed/18650079 | https://www.ncbi.nlm.nih.gov/pubmed/10518594

XK-469 (2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid) is a novel synthetic quinoxaline phenoxypropionic acid derivative. The R-isomer of XK-469 was approximately twice as effective as the S-isomer of XK-469R. R( )-isomers induce reversible protein DNA crosslinks in mammalian cells. It acts as a selective topoisomerase IIβ inhibitor. A phase I study was performed to determine the safety and pharmacokinetics of XK-469, (R)- in patients with various neoplasms.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II beta 14 Target ID: CHEMBL3396 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10518594 \| https://www.ncbi.nlm.nih.gov/pubmed/18650079	Inhibitor 8297
Peripheral-type benzodiazepine receptor 6 Target ID: CHEMBL2149 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11403918	Binding Agent 1064		0.35 µM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Refractory hematologic cancer 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18425419	Primary	Phase I 428	Unknown Approved Use Unknown
Advanced neuroblastoma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20860039	Primary	Phase I 428	Unknown Approved Use Unknown
Advanced solid cancer 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18650079	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
27.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	240 mg single, intravenous dose: 240 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
247.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2000 mg single, intravenous dose: 2000 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
293.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2500 mg single, intravenous dose: 2500 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
292.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	3200 mg single, intravenous dose: 3200 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
173.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1400 mg single, intravenous dose: 1400 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
105.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	850 mg single, intravenous dose: 850 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
146.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1100 mg single, intravenous dose: 1100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1.285 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	240 mg single, intravenous dose: 240 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.204 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2000 mg single, intravenous dose: 2000 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.905 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2500 mg single, intravenous dose: 2500 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.445 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	3200 mg single, intravenous dose: 3200 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.473 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1400 mg single, intravenous dose: 1400 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
162 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
347 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.161 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	850 mg single, intravenous dose: 850 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.903 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1100 mg single, intravenous dose: 1100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	240 mg single, intravenous dose: 240 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2000 mg single, intravenous dose: 2000 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	2500 mg single, intravenous dose: 2500 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	3200 mg single, intravenous dose: 3200 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
107 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1400 mg single, intravenous dose: 1400 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	850 mg single, intravenous dose: 850 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18650079	1100 mg single, intravenous dose: 1100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	XK-469, (R)- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
Debye Scientific	DA-09831	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-09831
MuseChem	M138948	https://www.musechem.com/product/M138948.html
NCI Plated 2007	656889

PubMed

Title	Date	PubMed
In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase.	2010 Aug	20444863

Patents

Sample Use Guides

In Vivo Use Guide

850-1100 mg/d on days 1, 3 and 5 of a 21-d cycle and 2500 mg on day 1 of a 21-d cycle.

Route of Administration: Intravenous

In Vitro Use Guide

Exposure of L1210 cells to a 7 uM concentration of the R (+) form of XK469 for 4 h led to a 50% loss of viability.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 04:53:36 GMT 2023` Edited by `admin` on `Sat Dec 16 04:53:36 GMT 2023`
Record UNII	4YM76775EY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

XK-469, (R)-

Common Name

English

R-(+)-XK-469

Common Name

English

XK 469R [WHO-DD]

Common Name

English

PROPANOIC ACID, 2-(4-((7-CHLORO-2-QUINOXALINYL)OXY)PHENOXY)-, SODIUM SALT (1:1), (2R)-

Systematic Name

English

Code System Code Type Description

CAS

157542-89-7

Created by admin on Sat Dec 16 04:53:36 GMT 2023 , Edited by admin on Sat Dec 16 04:53:36 GMT 2023

PRIMARY

FDA UNII

4YM76775EY

Created by admin on Sat Dec 16 04:53:36 GMT 2023 , Edited by admin on Sat Dec 16 04:53:36 GMT 2023

PRIMARY

PUBCHEM

11957724

Created by admin on Sat Dec 16 04:53:36 GMT 2023 , Edited by admin on Sat Dec 16 04:53:36 GMT 2023

PRIMARY

Related Record Type Details


					8VSJ573G09

XK-469 FREE ACID, (R)-

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/10518594 | https://www.ncbi.nlm.nih.gov/pubmed/18650079 | https://www.ncbi.nlm.nih.gov/pubmed/10518594

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10518594 | https://www.ncbi.nlm.nih.gov/pubmed/18650079 | https://www.ncbi.nlm.nih.gov/pubmed/10518594

C_max

T_1/2