General
Preferred name
PT-2385
Synonyms
79A ()
cpd 10i ()
PT2385 ()
P&D ID
PD062189
CAS
1672665-49-4
Tags
available
probe
drug candidate
Drug indication
Von hippel-lindau disease
Brain cancer
Recurrent glioblastoma
Drug Status
investigational
Probe info
Probe type
experimental probe
Probe sources
Chemical Probes.org
High-quality chemical probes
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT There are multiple lines of convincing evidence to support meaningful HIF2α modulation by PT-2385 in cell-free, cellular, and in vivo assays. This includes nanomolar cell-free target inhibition, x-ray crystal structures, ITC, convincing SAR, and activity consistent with HIF2α  engagement in multiple cellular and in vivo assays. I recommend including an inactive control analog in cellular assays, and in vivo assays if possible. May 20 2021 - 12:13pm; This is a promising HiF-2a antagonist with a high affinity to target, high cell potency, expected cellular effects (in vitro and in vivo), good in vivo PK and toxicology profiles, and very good selectivity properties. Jun 4 2021 - 11:52am
DESCRIPTION PT2385 is a small-molecule antagonist of HIF2α that was designed for antitumour activity . The molecule binds to an allosteric site on HIF2α and blocks its interaction with its dimerisation partner ARNT (aryl hydrocarbon receptor nuclear translocator, a.k.a. HIF1β). This action inhibits expression of HIF2α-dependent genes (e.g., VEGFA, PAI-1, and cyclin D1) in renal cancer models (cell lines and xenografts). (GtoPdb)
MOA Antagonist (Chemical Probes.org)
Compound Sets
12
Cayman Chemical Bioactives
21325
Chemical Probes.org
pt2385
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB16055
DrugMAP
DMCSN69
Guide to Pharmacology
12707
High-quality chemical probes
PD062189
MedChem Express Bioactive Compound Library
HY-12867
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
pt2385
External IDs
17
Properties
(calculated by RDKit )
Molecular Weight
383.04
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
3
Aromatic Ring Count
2
cLogP
3.12
TPSA
87.39
Fraction CSP3
0.24
Chiral centers
1.0
Largest ring
6.0
QED
0.88
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Member status
member
MOA
HIF2a / Hif-2 alpha inhibitor (gene: EPAS1)
HIF2A inhibitor (HIF-2 alpha inhibitor)
hypoxia inducible factor inhibitor
Target
EPAS1
HIF-2α
HIF/HIF Prolyl-Hydroxylase
HIF
Orthogonal probe
M1001
Pathway
Metabolic Enzyme/Protease
Target class
Transcription factor
Target subclass
Hypoxia-Inducible Factor
Control
9a
Source data