HSP-990

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H18FN5O2
Molecular Weight	379.3876
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC(=N1)C2=CC(F)=CC=C2[C@H]3CC4=NC(N)=NC(C)=C4C(=O)N3

InChI

InChIKey=WSMQUUGTQYPVPD-OAHLLOKOSA-N

InChI=1S/C20H18FN5O2/c1-10-18-16(26-20(22)23-10)9-15(25-19(18)27)12-7-6-11(21)8-13(12)14-4-3-5-17(24-14)28-2/h3-8,15H,9H2,1-2H3,(H,25,27)(H2,22,23,26)/t15-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22246440
Curator's Comment: Description was created based on several sources, including https://www.scbt.com/scbt/product/hsp-990-934343-74-5

HSP-990 is an oral Hsp90 inhibitor being developed by Novartis in a collaboration with Vernalis. It is also known by NVP-HSP990. HSP-990 is an inhibitor of human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp-990 binds to and inhibits the activity of Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. Hsp90, upregulated in a variety of tumor cells, is a molecular chaperone that plays a key role in the conformational maturation, stability and function of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation and/or immune responses.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP 90-alpha 12 Target ID: CHEMBL3880 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22246440	Inhibitor 8504		0.6 nM [IC50]
Heat shock protein HSP 90-beta 14 Target ID: CHEMBL4303 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22246440	Inhibitor 8504		0.8 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced solid cancer 30 Sources: https://clinicaltrials.gov/ct2/show/NCT00879905	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
496 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
700 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
10108 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9712 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
20.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
17.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25625276	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		HSP-990 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=404904725	inconclusive [IC50 37.9083 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=404904725	yes [IC50 10.684 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=404904725	yes [IC50 6.7412 uM]

PubMed

Title	Date	PubMed
Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990.	2014-11-13	25368984
The novel oral Hsp90 inhibitor NVP-HSP990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo.	2012-03	22246440

Patents

Sample Use Guides

In Vivo Use Guide

Mice: In the GTL-16 xenograft model, a single oral administration of 15 mg/kg of HSP-990 induced sustained downregulation of c-Met and upregulation of Hsp70.

Route of Administration: Oral

In Vitro Use Guide

HSP-990 inhibited growth of all tumor cell lines evaluated irrespective of cancer types or genetics, with nanomolar potency (GI50 value of 4–40 nmol/L)

Name

Type

Language

HSP-990

Common Name

English

NVP-HSP990

Preferred Name

English

(R)-2-AMINO-7-(4-FLUORO-2-(6-METHOXYPYRIDIN-2-YL)PHENYL)-4-METHYL-7,8-DIHYDRO-6H-PYRIDO(4,3-D)PYRIMIDIN-5-ONE

Systematic Name

English

HSP 990 [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

934343-74-5