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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 of OTX-008

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)

HIDE SMILES / InChI
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
30.0 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.39 μg/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
31.4 h
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

PubMed

TitleDatePubMed
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

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.
Name Type Language
OTX-008
Common 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
CALIXARENE 0118
Code English
Code System Code Type Description
SMS_ID
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
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CAS
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
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MANUFACTURER PRODUCT INFORMATION
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.
DRUG BANK
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
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NCI_THESAURUS
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
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FDA UNII
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
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PUBCHEM
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
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