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

Molecular Formula	C51H88O60S13
Molecular Weight	2078.053
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	29 / 29
E/Z Centers	0
Optical Activity	UNSPECIFIED

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
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
Heparanase Inhibition Reduces Glucose Levels, Blood Pressure, and Oxidative Stress in Apolipoprotein E Knockout Mice.	2017	29226146
Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth.	2017 Aug	28716813
The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression.	2017 Mar	28147305
A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.	2018 Apr	29531325
Prophylactic Antiheparanase Activity by PG545 Is Antiviral In Vitro and Protects against Ross River Virus Disease in Mice.	2018 Apr	29437628
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

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:55:42 UTC 2023` Edited by `admin` on `Sat Dec 16 11:55:42 UTC 2023`
Record UNII	66QR34C83N
Record Status	`Validated (UNII)`
Record Version

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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