Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C24H32O2 |
Molecular Weight | 352.5097 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 2 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(\C=C\[C@@H]1C[C@]1(C)C2=CC3=C(C=C2)C(C)(C)CCC3(C)C)=C/C(O)=O
InChI
InChIKey=BOOOLEGQBVUTKC-NVQSDHBMSA-N
InChI=1S/C24H32O2/c1-16(13-21(25)26)7-8-18-15-24(18,6)17-9-10-19-20(14-17)23(4,5)12-11-22(19,2)3/h7-10,13-14,18H,11-12,15H2,1-6H3,(H,25,26)/b8-7+,16-13+/t18-,24-/m1/s1
Molecular Formula | C24H32O2 |
Molecular Weight | 352.5097 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 2 |
Optical Activity | UNSPECIFIED |
VTP-194204 (NRX 194204, IRX4204) is a second-generation retinoid X receptor (RXR) agonist that has no cross-reactivity with retinoic acid receptors, farnesoid X receptor, liver X receptors or peroxisome proliferator-activated receptor PPARγ. Rexinoid NRX 194204 selectively binds to and activates RXRs. Because RXRs can form heterodimers with several nuclear receptors (NRs), RXR activation by this agent may result in a broad range of gene expression depending on the effector DNA response elements activated. Rexinoid NRX 194204 may inhibit the tumour-necrosis factor (TNF)-mediated release of nitric oxide (NO) and interleukin 6 (IL6) and may inhibit tumour cell proliferation. This agent appears to be less toxic than RAR-selective ligands. VTP-194204 (IRX-4204) is in phase II clinical trials by Io Therapeutics for the treatment of prostate cancer. It is also in preclinical trials for the treatment of Alzheimer's disease, autoimmune diseases and multiple sclerosis.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26862735
Curator's Comment: Brain bioavailability studies demonstrate that VTP-194204 (IRX4204) can cross the blood brain barrier and reach the brain at nM concentration. IRX4204 represents a novel, potent and selective pharmacological means to activate cellular RXR-Nurr1 signaling and promote SN DA neuron survival in PD prevention and/or treatment.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2061 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11428923 |
0.2 nM [EC50] | ||
Target ID: CHEMBL1870 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11428923 |
0.8 nM [EC50] | ||
Target ID: CHEMBL2004 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11428923 |
0.08 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands. | 2004 |
|
Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. | 2004 Oct 29 |
|
Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes. | 2005 Dec 15 |
|
Combination therapy of insulin-like growth factor binding protein-3 and retinoid X receptor ligands synergize on prostate cancer cell apoptosis in vitro and in vivo. | 2005 Jul 1 |
|
Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways. | 2006 Feb 1 |
|
Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation. | 2006 Jun |
|
Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to PPAR ligands. | 2010 Nov 16 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02438215
VTP-194204 (IRX4204) 20 mg QD for Days 1-30
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26862735
VTP-194204 (IRX4204) can partially activate RXRs at a concentration of 0.1 nM and fully activates all three RXRs (α, β and γ) at a concentration of 1 nM
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 21:31:16 GMT 2023
by
admin
on
Fri Dec 15 21:31:16 GMT 2023
|
Record UNII |
877M97Z38Y
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Code | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
220619-73-8
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
PRIMARY | |||
|
877M97Z38Y
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
PRIMARY | |||
|
DB11806
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
PRIMARY | |||
|
C74076
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
PRIMARY | NCIT | ||
|
9863341
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
PRIMARY | |||
|
260262-39-3
Created by
admin on Fri Dec 15 21:31:16 GMT 2023 , Edited by admin on Fri Dec 15 21:31:16 GMT 2023
|
NON-SPECIFIC STEREOCHEMISTRY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TARGET -> AGONIST | |||
|
TARGET -> AGONIST | |||
|
TARGET -> AGONIST |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |