VS-4718 HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H26F3N5O3.ClH
Molecular Weight	537.962
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CNC(=O)C1=C(NC2=C(C=NC(NC3=CC=C(C=C3OC)N4CCOCC4)=C2)C(F)(F)F)C=CC=C1

InChI

InChIKey=OWQFAUOQRRIFLB-UHFFFAOYSA-N

InChI=1S/C25H26F3N5O3.ClH/c1-29-24(34)17-5-3-4-6-19(17)31-21-14-23(30-15-18(21)25(26,27)28)32-20-8-7-16(13-22(20)35-2)33-9-11-36-12-10-33;/h3-8,13-15H,9-12H2,1-2H3,(H,29,34)(H2,30,31,32);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

Molecular Formula	C25H26F3N5O3
Molecular Weight	501.5008
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20234191 | https://www.ncbi.nlm.nih.gov/pubmed/27786412 | http://www.ecmcnetwork.org.uk/sites/default/files/5.%2020151221%20Verastem%20CRUK%20VS4718.pdfhttps://web.archive.org/web/20170502234142/http://www.verastem.com/products/vs-4718.aspx
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20234191 | http://www.ecmcnetwork.org.uk/sites/default/files/5.%2020151221%20Verastem%20CRUK%20VS4718.pdf

PND-1186, also known as SR-2156 and VS-4718, is a potent FAK inhibitor with a 50% inhibitory concentration (IC50) of 1.5 nM in vitro. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. PND-1186 is currently being evaluated in a Phase 1 trial in patients with advanced solid tumors. In addition, an ongoing collaboration with Wash U is evaluating PND-1186 in combination with gemcitabine and Abraxane in 1st line pancreatic cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Focal adhesion kinase 1 15 Target ID: CHEMBL2695 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20234191	Inhibitor 8297		1.5 nM [IC50]
Focal adhesion kinase 1 15 Target ID: CHEMBL2695 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20234191	Inhibitor 8297		1.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT01849744 http://adisinsight.springer.com/drugs/800038256	Primary		Phase I 428	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT01849744 http://adisinsight.springer.com/drugs/800038256 https://www.ncbi.nlm.nih.gov/pubmed/25316657	Primary		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 MRP1 106

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678126	inconclusive [IC50 21.3174 uM]
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30425643/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678126	yes [IC50 2.1317 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678126	yes [IC50 4.2534 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30425643/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30425643/	yes

PubMed

Title	Date	PubMed
		252161011
PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments.	2010 May 15	20234191
FAK Inhibition disrupts a β5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth.	2014 Aug	24899686

Patents

Sample Use Guides

In Vivo Use Guide

Mice: VS-4718 was tested in vivo against the PPTP xenograft models using a dose of 50 mg/kg administered by the oral route twice daily for 21 days.

Route of Administration: Oral

In Vitro Use Guide

0.1 uM PND-1186 is sufficient to promote 4T1 breast carcinoma and ID8 ovarian carcinoma cell apoptosis when grown under suspended, spheroid, or soft-agar conditions.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:41:48 GMT 2023` Edited by `admin` on `Sat Dec 16 09:41:48 GMT 2023`
Record UNII	S803K9N9TL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VS-4718 HYDROCHLORIDE

Code

English

SR-2516 HYDROCHLORIDE

Code

English

2-(2-(2-METHOXY-4-MORPHOLINOPHENYLAMINO)-5-(TRIFLUOROMETHYL)PYRIDINE-4-YLAMINO)-N-METHYLBENZAMIDE HYDROCHLORIDE

Systematic Name

English

PND-1186 HYDROCHLORIDE

Code

English

BENZAMIDE, 2-((2-((2-METHOXY-4-(4-MORPHOLINYL)PHENYL)AMINO)-5-(TRIFLUOROMETHYL)-4-PYRIDINYL)AMINO)-N-METHYL-, HYDROCHLORIDE (1:1)

Systematic Name

English

Code System Code Type Description

PUBCHEM

56654067

Created by admin on Sat Dec 16 09:41:48 GMT 2023 , Edited by admin on Sat Dec 16 09:41:48 GMT 2023

PRIMARY

CAS

1356154-94-3

Created by admin on Sat Dec 16 09:41:48 GMT 2023 , Edited by admin on Sat Dec 16 09:41:48 GMT 2023

PRIMARY

FDA UNII

S803K9N9TL

Created by admin on Sat Dec 16 09:41:48 GMT 2023 , Edited by admin on Sat Dec 16 09:41:48 GMT 2023

PRIMARY

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					L2BD0MW4OL

VS-4718

ACTIVE MOIETY

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Overview

OverviewOther

Drug as perpetrator​

PubMed

Patents

Sample Use Guides

Drug as perpetrator