Details
Stereochemistry | ACHIRAL |
Molecular Formula | C52H72N8O8 |
Molecular Weight | 937.1769 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)CCNC(=O)COC1=C2CC3=CC=CC(CC4=CC=CC(CC5=CC=CC(CC1=CC=C2)=C5OCC(=O)NCCN(C)C)=C4OCC(=O)NCCN(C)C)=C3OCC(=O)NCCN(C)C
InChI
InChIKey=CQVAQQNDZCZBSU-UHFFFAOYSA-N
InChI=1S/C52H72N8O8/c1-57(2)25-21-53-45(61)33-65-49-37-13-9-14-38(49)30-40-16-11-18-42(51(40)67-35-47(63)55-23-27-59(5)6)32-44-20-12-19-43(52(44)68-36-48(64)56-24-28-60(7)8)31-41-17-10-15-39(29-37)50(41)66-34-46(62)54-22-26-58(3)4/h9-20H,21-36H2,1-8H3,(H,53,61)(H,54,62)(H,55,63)(H,56,64)
PTX-008 (OTX008) is a calixarene-based compound and galectin-1 (Gal-1) inhibitor with potential anti-angiogenic and antineoplastic activities. Upon subcutaneous administration, galectin-1 inhibitor OTX008 binds Gal-1 which leads to Gal-1 oxidation and proteosomal degradation through a not yet fully elucidated mechanism, and eventually downregulates Gal-1. This decreases tumor cell growth and inhibits angiogenesis. Gal-1, a multifunctional carbohydrate-binding protein, is often overexpressed on tumor cells and plays a key role in cancer cell proliferation, apoptosis, tumor angiogenesis and evasion of immune responses. PTX-008 had been in phase I clinical trials for the treatment of solid tumours. This compound was originally discovered by University of Minnesota and PepTx, then licensed to OncoEthix (acquired by Merck Sharp & Dohme in 2014). However, no recent developments has been reported.
Originator
Approval Year
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.39 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23978989 |
5 mg/kg 1 times / 2 days single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: SUNITINIB |
OTX-008 plasma | Mus musculus population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
31.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23978989 |
5 mg/kg 1 times / 2 days single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: SUNITINIB |
OTX-008 plasma | Mus musculus population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis. | 2014 Sep |
|
Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment. | 2016 Oct |
|
Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine Model of Oxygen-Induced Retinopathy. | 2017 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01724320
PTX-008 (OTX008) given daily without interruption, subcutaneously. Starting dose: 65 mg/day
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25042151
Exposure to 3 uM PTX-008 (OTX008) decreased Gal1 protein
expression in a time-dependent manner in SQ20B cells (p < 0.01 at 48 h relative to baseline), despite no significant changes in LGALS1 mRNA levels. Similar results were observed in A2780-1A9 ovarian cells after 24 h, 48 h and 72 h exposure to 170 uM OTX008.
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
100000175616
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | |||
|
286936-40-1
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | |||
|
OTX-008
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | Description: Selective allosteric inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumor angiogenesis. OTX008 inhibited galectin-1 expression and ERK1/2 and Akt-dependent survival pathways, and induced G2/M cell cycle arrest through CDK1. | ||
|
DB13123
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | |||
|
C103828
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | |||
|
8JI63CFH5V
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY | |||
|
11953346
Created by
admin on Sat Dec 16 09:48:26 GMT 2023 , Edited by admin on Sat Dec 16 09:48:26 GMT 2023
|
PRIMARY |
ACTIVE MOIETY