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)
| Molecular Formula | C52H72N8O8 |
| Molecular Weight | 937.1769 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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 |
Sample Use Guides
PTX-008 (OTX008) given daily without interruption, subcutaneously. Starting dose: 65 mg/day
Route of Administration:
Other
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.
| Substance Class |
Chemical
Created
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admin
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Edited
Sat Dec 16 09:48:26 GMT 2023
by
admin
on
Sat Dec 16 09:48:26 GMT 2023
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| Record UNII |
8JI63CFH5V
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| Record Status |
Validated (UNII)
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100000175616
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286936-40-1
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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
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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. | ||
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DB13123
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C103828
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8JI63CFH5V
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11953346
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ACTIVE MOIETY |
RESULTS: In cultured cancer cells, OTX008 inhibited proliferation and invasion at micromolar concentrations. Antiproliferative effects correlated with Gal1 expression across a large panel of cell lines. Furthermore, cell lines expressing epithelial differentiation markers were more sensitive than mesenchymal cells to OTX008. In SQ20B and A2780-1A9 cells, OTX008 inhibited Gal1 expression and ERK1/2 and AKT-dependent survival pathways, and induced G2/M cell cycle arrest through CDK1. OTX008 enhanced the antiproliferative effects of Semaphorin-3A (Sema3A) in SQ20B cells and reversed invasion induced by exogenous Gal1. In vivo, OTX008 inhibited growth of A2780-1A9 xenografts. OTX008 treatment was associated with downregulation of Gal1 and Ki67 in treated tumours, as well as decreased microvessel density and VEGFR2 expression. Finally, combination studies showed OTX008 synergy with several cytotoxic and targeted therapies, principally when OTX008 was administered first.
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ACTIVE MOIETY |
Galectin-1 inhibitor OTX008: 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. Check for active clinical trials using this agent. (NCI Thesaurus)
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