PIXATIMOD

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C51H88O60S13
Molecular Weight	2078.053
Optical Activity	UNSPECIFIED
Defined Stereocenters	29 / 29
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)O[C@]5([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]6([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]7([H])O[C@H](COS(O)(=O)=O)[C@@H](O[C@@]8([H])O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]8OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]7OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]6OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]5OS(O)(=O)=O)[C@H](C)CCCC(C)C

InChI

InChIKey=LNUFLCYMSVYYNW-ZPJMAFJPSA-N

InChI=1S/C51H88O60S13/c1-22(2)7-6-8-23(3)27-11-12-28-26-10-9-24-17-25(13-15-50(24,4)29(26)14-16-51(27,28)5)95-46-42(108-121(79,80)81)38(104-117(67,68)69)34(30(96-46)18-91-112(52,53)54)100-47-43(109-122(82,83)84)39(105-118(70,71)72)35(31(97-47)19-92-113(55,56)57)101-48-44(110-123(85,86)87)40(106-119(73,74)75)36(32(98-48)20-93-114(58,59)60)102-49-45(111-124(88,89)90)41(107-120(76,77)78)37(103-116(64,65)66)33(99-49)21-94-115(61,62)63/h22-49H,6-21H2,1-5H3,(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)(H,79,80,81)(H,82,83,84)(H,85,86,87)(H,88,89,90)/t23-,24+,25+,26+,27-,28+,29+,30-,31-,32-,33-,34-,35-,36-,37-,38+,39+,40+,41+,42-,43-,44-,45-,46-,47-,48-,49-,50+,51-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800019929 | https://www.ncbi.nlm.nih.gov/pubmed/21285983 | https://www.ncbi.nlm.nih.gov/pubmed/22101246 | https://www.ncbi.nlm.nih.gov/pubmed/29531325

PG-545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG-545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The anti- respiratory syncytial virus (RSV) activity of PG-545 was due to both partial inhibition of the virus attachment to cells and a more profound interference with some post-attachment steps as PG-545 efficiently neutralized infectivity of the cell-adsorbed virus. The anti-RSV activity of PG-545 was reduced when tested in the presence of human nasal secretions. Serial passages of RSV in the presence of increasing concentrations of PG-545 selected for weakly resistant viral variants that comprised the F168S and the P180S amino acid substitutions in the viral G protein. PG-545 has an immunomodulatory properties. PG-545 stimulates innate immune responses against tumours in preclinical cancer models. PG-545 is in phase I clinical trial for the treatment of pancreatic cancer.

Originator

Approval Year

PubMed

Title	Date	PubMed
PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models.	2011 Feb 15	21285983
PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.	2012	23300607
Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate.	2012 Jan	22101246
PG545, an angiogenesis and heparanase inhibitor, reduces primary tumor growth and metastasis in experimental pancreatic cancer.	2013 Jul	23696215
The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles.	2016 Feb	26643323
Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation.	2016 Jan	26649979
Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.	2016 Jan 19	26729870
A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.	2018 Apr	29531325
Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.	2018 Jun 14	29898788

Sample Use Guides

In Vivo Use Guide

25, 50, 100 and 150 mg once weekly for 28 days

Route of Administration: Intravenous

Name

Type

Language

PIXATIMOD

Official Name

English

Pixatimod [WHO-DD]

Common Name

English

pixatimod [INN]

Common Name

English

PG-545 FREE ACID

Code

English

Code System Code Type Description

PUBCHEM

57412325