OTX-008

Investigational

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

Structure Search

SMILES

CN(C)CCNC(=O)COC1=C2CC3=C(OCC(=O)NCCN(C)C)C(CC4=CC=CC(CC5=C(OCC(=O)NCCN(C)C)C(CC1=CC=C2)=CC=C5)=C4OCC(=O)NCCN(C)C)=CC=C3

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25042151 | https://www.ncbi.nlm.nih.gov/pubmed/23978989 | http://en.pharmacodia.com/web/drug/1_3420.html

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

Targets

Primary Target	Pharmacology	Condition	Potency
Galectin-1 3 Target ID: CHEMBL4915 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25042151 \| https://www.ncbi.nlm.nih.gov/pubmed/22575017 \|	Inhibitor 8504		30.0 µM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 147 Sources: https://clinicaltrials.gov/ct2/show/NCT01724320	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	1.48 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.48 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		OTX-008 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.7 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	1.06 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.06 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		OTX-008 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
6.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	1.48 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.48 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		OTX-008 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.2 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	1.06 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.06 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		OTX-008 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	1.48 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.48 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		OTX-008 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
21% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22413863/	unknown		OTX-008 plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01EOKC	https://www.1pchem.com/search?query=1P01EOKC
Axon MedChem	2332	https://www.axonmedchem.com/product/2332
Chem Scene	CS-0016572	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0016572
eMolecules	50580288	https://orderbb.emolecules.com/search/#?query=50580288
MedChem Express	HY-19756	https://www.medchemexpress.com/search.html?q=HY-19756&ft=&fa=&fp=
MolPort	MolPort-042-665-853	https://www.molport.com/shop/molecule-link/MolPort-042-665-853
MuseChem	I008493	https://www.musechem.com/product/I008493.html

PubMed

Title	Date	PubMed
Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine Model of Oxygen-Induced Retinopathy.	2017	28428895
Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment.	2016-10	27798864
OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis.	2014-09	25042151

Patents

Sample Use Guides

In Vivo Use Guide

PTX-008 (OTX008) given daily without interruption, subcutaneously. Starting dose: 65 mg/day

Route of Administration: Other

In Vitro Use Guide

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

OTX-008

Common Name

English

CALIXARENE 0118

Preferred Name

English

OTX008

Code

English

ACETAMIDE, 2,2',2'',2'''-(PENTACYCLO(19.3.1.13,7.19,13.115,19)OCTACOSA-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-DODECAENE-25,26,27,28-TETRAYLTETRAKIS(OXY))TETRAKIS(N-(2-(DIMETHYLAMINO)ETHYL)-

Systematic Name

English

PTX-008

Code

English

KM-0118

Code

English

Code System Code Type Description

SMS_ID

100000175616